The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

Optically active sulfoxides are extensively used as chiral auxiliaries, chiral ligands for meta! complexes and organocatalysts. This unique moiety is also found in several marketed drugs such as Esomeprazole (proton pump inhibitor), Armodafini! (eugeroic) and Sulindac (anti- inflammation). Currently, there are two main strategies for the synthesis of enantioenriched sulfoxides - nucleophilic substitution of non-racemic sulfinates using organometallic reagents (the Andersen method) and direct oxidation of prochiral sulfides catalyzed by metal complexes (Kagan and Moderna methods). Recently, a metal-free approach using chiral imidodiphiosphoric acid catalysts for highly enantioselective sulfide oxidation employing aqueous H ₂ 0 ₂ has been demonstrated (e.g. see S. Liao, J. Am. Chem. Soc. 2012, 134, 10765-10768; and Z.-M. Liu, er a/., Synth. Cata!. 2012, 354, 1012-1022).

Due to the importance of such compounds, developments of catalytic and enantioselective methodologies with broad substrate scope are still highly desirable. In the classical Andersen method and its variants, the reactive sulfur center is electrophilic and a stoichiometric quantity of chiral auxiliaries is required (although recycling of auxiliary is possible in some cases). Recently, a complementary approach which is based on sulfenate anions (RSO ^" ) with a nucleophilic sulfur center has emerged as a viable method for enantio- and diasteroselective synthesis of sulfoxides. However, reports which exploit sulfenate anions in catalytic enantioselective synthesis of sulfoxides remain scant. Recent attempts with Cinchona alkaloid as a phase-transfer catalyst have been reported by Perrio and coworkers (see F. Gelat, et al., Org. Lett. 2011, 13, 3170-3173; and F. Gelat, er al., J. Sulfur Chem. 2013, 1-9), despite the high yield the ee-values do not exceed 60%. Asymmetric phase-transfer catalysis is a convenient, scalable and environmentally benign method to prepare compounds in high enantiopurity. Despite the success of several reported phase-transfer catalysts (PTCs) in the literature, it is still meaningful to design new ones with high level of stereocontrol. Recently, our group has developed structurally novel pentanidiums based on quaternized sp2-hybridized N- atoms as PTCs (see T. Ma, er al., J. Am. Chem. Soc. 2011 , 133, 2828-2831; Y. Y. Yang, et al., Org. Lett. 2012, 14, 4762-4765). Thiophene derivatives are important heteroaromatic compounds, which have been used prevalently in functional materials and pharmaceutical industry due to their distinct electronic and biological activities (Figure 1 ). Based on currently available methodologies for the synthesis of optically active sulfoxides, sulfoxides which contain thienyl group pose significant challenges (Figure 2; see also Reference Example 1). Although oxidation of sulfides is the most direct approach to sulfoxides, a sulfide with a thienyl substituent is vulnerable under the well-established Kagan method, leading to low yield and negligible enantioselectivity (Figure 1 a). On the other hand, in the classical Andersen approach, the use of organomagnesium reagents could potentially be problematic as sulfoxide that contains thiophene or furan could be displaced by such organometallic nucleophiles (Figure 1 b). Therefore, there remains a need for new methods of forming sulfoxides. Summary of Invention

In a first aspect of the invention, there is provided a compound of formula (1):

wherein:

A represents an anionic counterion; and

R represents a fragment of formula (II):

wherein:

the dotted line represents the point of attachment to the rest of molecule of formula

(I); and

each X independently represents Ci, Br or I.

In certain embodiments of the invention, each X is the same and may represent CI, Br or I. For example, all X groups may represent I.

In yet still further embodiments of the invention, the compound of formula (I) may be chrial. For example, the compound of formula (I) may be a compound of formula (la) or formula (lb):

In yet stili further embodiments of the invention, A may be an anionic counterion selected from the group consisting of CI ^" , Br ^" , Γ and F ^" . In still further embodiments of the invention, the compound of formula (!) may be selected from:

(a) (4S,5S)-2-(((4S _r 5S)-1 ,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5-diphenylimidazo lidin- 2-ylidene)amino)-1 ,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5-diphenyl-4,5-di hydro-1H- imidazol-3-ium chloride;

(b) (4S,5S)-2-(((4S,5S)-1 ,3-bis(2-bromo-3,5-di-tert-butylbenzyl)-4,5 diphenyiimidazolidin-

2- ylidene)amino)-1 ,3-bis(2-bromo-3,5-di-tert-butylbenzyl)-4,5-diphenyl-4,5-dih ydro-1 H- imidazol-3-ium chloride; and

(c) (4S,5S)-2-(((4S,5S)-1 ,3-bis(3,5-di-tert-butyl-2-iodobenzyl)-4,5-diphenylimidazoli din-2- ylidene)amino)-1 ,3-bis(3,5-di-tert-butyl-2-iodobenzyl)-4,5-diphenyl-4,5-dihy dro-1 H-imidazol-

3- ium chloride.

In a second aspect of the invention, there is provided a use of a compound of formula (I) as described hereinbefore as a catalyst for a chemical reaction. For example, the chemical reaction may result in one or more enantioenriched products, in particular embodiments of the invention, the chemical reaction is the preparation of sulfoxides (e.g. enantioenriched sulfoxides). In a third aspect of the invention, there is provided a method for preparing an enantoenriched sulfoxide, said method comprising, reacting a compound of formula (III): with a compound of formula (IV):

R ₃ -X ¹ (IV)

in the presence of a catalytic amount of a compound of formula (i) as defined in any one of

Claims 4 to 6, a base and a solvent, to provide the enantioenriched sulfoxide, wherein:

Ri represents a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or a substituted or unsubstituted alkyl group;

R ₂ represents and electron withdrawing group; and

R ₃ represents a substituted or unsubstituted alkyl group.

In certain embodiments, the solvent may comprise an ether (e.g. cyclopentyl methyl ether and/or diethyl ether). In still further embodiments, the solvent may further comprise water. In still further embodiments of the invention, the reaction may be conducted at a temperature of from -50°C to -80°C (e.g. from -60°C to -70°C). A catalytic amount of a compound of formula (I) may be from 0.0001 mol% to 20 mol%, such as from 0.001 to 2 mol%, e.g. 1 mol%.

In yet still further embodiments of the invention, the base may be a metal hydroxide, such as cesium hydroxide.

In yet still further embodiments of the invention, R ₂ may represent -C(0) ₂ Me, -C(0) ₂ Et, -0(0) ₂ ¾υ, -C(0) ₂ Ph, S0 ₂ Ph and -CN.

Drawings

The invention will be described with reference to the accompanying drawings.

Figure 1 depicts drugs containing thiophene moieties.

■ ^■ Figure 2 depicts approaches for the assymetric synthesis of 2-thienyl sulfoxide 3a.

Figure 3 depicts the general procedure for the synthesis of chiral pentanidium salts (using the pentanidium salt 1c as an example).

Figure 4 depicts a working model hypothesis for the sulfenate anion intermediate.

Figure 5 depicts the single crystal structure of the (R)-form of compound 6q. Description

The variant based on the nucleophilic displacement of alkyl halides by sulfenate anion catalyzed with pentanidiums that we herein report is able to circumvent the aforementioned problems to give the optically active thienyl sulfoxide in high yield and enantioselectivity.

We began by investigating the enantioselective benzylation of 2-thienyl sulfenate anion generated in situ with pentanidiums as phase-transfer catalyst by using benzyl bromide as the electrophile. Preliminary variation of reaction parameters such as pentanidiums, sulfenate anion precursors, solvent, inorganic base and temperature were performed (refer to supporting information). Eventually, it was found that iodinated pentanidium 1d is the best catalyst, providing sulfoxide 3a with excellent enantioselectivity of 91 % ee (Table 2, entry 10). Eventually, it was found that iodinated pentanidium 1d is the best catalyst, providing sulfoxide 3a with excellent enantioselectivity of 91 % ee {Example 1 , Table 2, entry 10; n attempt to prepare compound 3a by direct sulfoxidation was not satisfactory), in contrast, commercially available phase-transfer catalysts were also tested and low enantioselectivity was obtained (below 15% ee, Reference Example 2, Table 3).

A variety of alkyl halides was examined as electrophile under optimized conditions (Table 4; Example 2). With 1 mol % of pentanidium 1d, the alky!ation of 2-thienyl suifenate anion with various alkyl halides produced the corresponding sulfoxides in good yields and excellent enantioselectivities. Benzyl bromides with electron-withdrawing and electron-donating substituents are well tolerated {entries 1-6). It should be noted that benzyl bromides caused erosion of enantioselectivity in the previous report of a related reaction by Perrio group (a) F. Gelat, J. Jayashankaran, J. F. Lohier, A. C. Gaumont, S. Perrio, Org. Lett. 2011, 13, 3170- 3173; b) F. Gelat, A.-C. Gaumont, S. Perrio, J. Sulfur Chem. 2013, 1-9.). The construction of stereogenic sulfoxides bearing allylic and propargylic substituents could also be achieved in a similar manner (entries 7-9). Moreover, the alkylation of 2-theinyl suifenate anion with alkyl iodides provided sulfoxides 3J-3I with good enantioselectivities (77-81% ee, entries 10- 12). These results indicated that both alkyl and benzyl groups can be installed using this methodology. For specific benzyl bromide derivatives with electron-withdrawing substituents (entries 3-4) and alkyl iodides (entries 10-12), brominated pentanidium 1 c provided sulfoxides with marginally better enantioselectivities.

The practicality of this newly developed methodology was demonstrated by scaling-up the reaction to one-mmol and reducing the catalyst loading to 0.25 mol % 1 d. The sulfoxide 6q was obtained in 85% yield with an excellent enantioselectivity of 91% ee (Example 3).

The scope of this reaction was further examined under the optimized conditions with various β-heteroaryl and aryl su!finyl methyl esters (4a-e, 5a-f) as suifenate anion precursors (Table 5). They participated in the reaction efficiently to provide the anticipated sulfoxides in high yields with good to excellent enantioselectivities. The methyl substituted 2-thienyl sulfinyl esters 4a was transformed to the corresponding highly enantioenriched sulfoxides 6a-f. Interestingly, the reaction between the suifenate anion generated from β-sulfinyl ester 4a and m-xyiene dibromide produced the bis-sulfoxide 6g in reasonable yield (87%, dl/meso = 4.75:1 ) and excellent enantioselectivity (>99% ee). Sulfoxides 6k-v containing benzothiophene were also obtained with excellent enantioselectivities. Benzimidazoie sulfoxide 7a, reminiscence of the drug esomeprazole, was obtained in high enantioselectivity (90% ee). Suifenate anions containing fury!, benzofuryl, pyridyl moieties can be tolerated and converted into the sulfoxides 7c-f with a slightly decrease in enantioselectivities. As far as we are aware, this methodology allows the widest range of heterocyclic sulfoxides to be obtained in high optical purity and yield.

Additional experiments were carried out to provide more insights into the reaction mechanism (Table 6). Based on the experimental study, a working mechanism was proposed {Figure 4). The inorganic base promotes the deprotonation of β-sulfinyl methyl ester 2a to give the corresponding caesium enolate, which leads to the generation of sulfenate anion and the release of methyl acrylate via a retro-Michael process even without PTC. However, the sulfenate anion intermediate will undergo alkaline hydrolysis under basic conditions in the absence of PTC. In the presence of the chiral PTC, cationic exchange and retro-Michael processes lead to a chiral ion pair A. It readily reacts with electrophile RX (X = Br) to afford the product 3a (path a). When the reaction was performed in the presence of PTC but not the alkyl halides, 2a produced thiophene sulfenate 8 via oxygen-Michael addition of sulfenate anion to methyl acrylate released during the retro-Michael process (path b). Moreover, using non-halogenated pentanidium 1 a and benzyl chloride, a less active electrophile, only sulfenate 8 instead of sulfoxide 3a was observed (path b). However, it is noteworthy that sulfoxide 3a can be formed when halogenated pentanidiums were used as catalysts with benzyl chloride (path a). These results indicate the ability of halogenated pentanidiums to activate both the electrophile and the sulfenate anion nucleophile.

In summary, we have described a highly enantioseiective alkyiation of sulfenate anions to prepare enantioenriched sulfoxides using halogenated pentanidiums as catalysts. These heterocyclic sulfoxides could potentially be used as chiral ligands, chiral organocatalyst or bioactive molecules. Moreover, the work demonstrates the possibility of incorporating halogen bond as primary non-covalent interaction when designing organocatalysts.

Thus, there is provided a compound of formula (I):

wherein:

A represents an anionic counterion; and R represents a fragment of formula (II):

wherein:

the dotted line represents the point of attachment to the rest of molecule of formula

(I); and

each X independently represents CI, Br or I.

When used herein "anionic counterion" may refer to any anionic species that can form an ion pair with the positive charge on one of the nitrogen atoms of the compound of formula (I). For example, the anionic counter ion may be the anion of a carboxylic acid or it may be an anionic halogen ion (e.g. Br ^" , Γ, F ^" or, more particularly, CI ^" ). The substituent X may be the different or, more particularly, the same. For example, when each X is the same, X may represent one of CI, Br or, more particularly, i.

As noted above, the compounds of the current invention may be particularly useful as catalysts in enentioselective reactions. As such, the compound of formula (I) may be chiral. For example, the compound of formula (1) may be a compound of formula (la) or formula (lb):

In particular embodiments of the invention that may be mentioned herein, the compound of formula (I) may be selected from:

(a) (4S,5S)-2-(((4S,5S)-1 ,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5-diphenylimidazo lidin- 2-yifdene)amino)-1 ,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5-diphenyl-4,5-di hydro-1 H- imidazol-3-ium chloride;

(b) (4S,5S)-2-(({4S,5S)-1 ,3-bis(2-bromo-3,5-di-tert-butylbenzyl)-4,5 diphenylimidazolidin-

2- ylidene)amino)-1 ,3-bis(2-bromo-3,5-di-tert-buty!benzyl)-4,5-diphenyl-4,5-dih ydro-1H- imidazol-3-ium chloride; and, more particularly,

(c) (4S,5S)-2-(((4S,5S)-1 ,3-bis(3,5-di-tert-butyl-2-iodobenzyl)-4,5-diphenylimidazoli din-2- ylideneJamino^l .S-bisfS.S-di-tert-butyl^-iodobenzylH.S-diphenyl^.S-dihydro- I H-imidazol-

3- ium chloride. As described hereinbefore, the compound of formula (I) may be used as a catalysts for a chemical reaction. Thus, in a second aspect of the invention, there is provided a use of a compound of formula (I) as described hereinbefore as a catalyst for a chemical reaction. For example, the chemical reaction may result in one or more enantioenriched products. In particular embodiments of the invention, the chemical reaction is the preparation of sulfoxides (e.g. enantioenriched sulfoxides).

When used herein, the term "enantioenriched" is intended to refer to a product of a chemical reaction involving the compound of formula (I), wherein said product has an enantiomeric ratio that is greater than 50 : 50 but less than 100 : 0. In other words, the enantioenriched compound is not racemic and may, for example, have an enantiomeric excess (ee) of from 50% to 99.99% ee. In a third aspect of the invention, there is provided a method for preparing an enantoenriched sulfoxide, said method comprising, reacting a compound of formula (III): with a compound of formula (IV): R ₃ -X ¹ (IV)

in the presence of a catalytic amount (e.g. from 0.0001 mol% to 20 mol%, such as from 0.001 to 2 mol%, i.e. 1 mol%) of a compound of formula (I) as defined in any one of Claims 4 to 6, a base and a solvent, to provide the enantioenriched sulfoxide, wherein:

R ₁ represents a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or a substituted or unsubstituted alky! group;

R ₂ represents and electron withdrawing group; and

R ₃ represents a substituted or unsubstituted alkyl group.

Unless otherwise stated, the term "aryl" when used herein includes C ₆ .1 (such as C ₆ .io) aryl groups. Such groups may be monocyclic, bicyclic or tricyclic and have between 6 and 14 ring carbon atoms, in which at least one ring is aromatic. The point of attachment of aryl groups may be via any atom of the ring system. However, when aryl groups are bicyclic or tricyclic, they are linked to the rest of the molecule via an aromatic ring. C ₆ .14 aryl groups include phenyl, naphthyl and the like, such as 1,2,3,4-tetrahydronaphthyl, indanyl, indenyl and fluorenyl. Embodiments of the invention that may be mentioned include those in which aryl is naphthyl or, more particularly, phenyl.

Unless otherwise stated, the term "alkyl" refers to an unbranched or branched, cyclic, saturated or unsaturated (so forming, for example, an alkenyl or alkynyl)hydrocarbyl radical. Where the term "alkyl" refers to an acyclic group, it is preferably C _O alkyl and, more preferably, C _-6 alkyl (such as ethyl, propyl, (e.g. n-propyl or isopropyl), prop-1-eneyl, 2- methylisoprop-1-eneyl, butyl (e.g. branched or unbranched butyl), but-2-ynyl, pentyl ormethyl). Where the term "alkyl" is a cyclic group (which may be where the group "cycloalkyl" is specified), it is preferably C3. ₁ 2 cycloaikyl and, more preferably, C ₅ .io (e.g. C _5-7 ) cycloalkyl.

The term "heteroaryl" when used herein refers to an aromatic group containing one or more heteroatom(s) (e.g. one to four heteroatoms) preferably selected from N, O and S {so forming, for example, a mono-, bi-, or tricyclic heteroaromatic group). Heteroaryl groups include those which have between 5 and 4 (e.g. 10} members and may be monocyclic, bicyclic or tricyclic, provided that at least one of the rings is aromatic. However, when heteroaryl groups are bicyclic or tricyclic, they are linked to the rest of the molecule via an aromatic ring. Heterocyclic groups that may be mentioned include benzothiadiazolyl (including 2,1,3-benzothiadiazolyl), isothiochromanyl and, more preferably, acridinyl, benzimidazoiyi, benzodioxanyl, benzodioxepinyl, benzodioxolyl (including 1 ,3-benzodioxolyl), benzofuranyl, benzofurazanyl, benzothiazolyl, benzoxadiazolyl (including 2,1,3- benzoxadiazolyl), benzoxazinyl (including 3,4-dihydro-2H-1 ,4-benzoxazinyl), benzoxazolyl, benzomorpho!inyl, benzoselenadiazoiyl (including 2,1 ,3-benzoselenadiazolyl), benzothienyl, carbazolyl, chromanyl, cinnolinyl, furanyl, imidazolyl, imidazo[1 ,2-a]pyridyl, indazolyl, indolinyl, indolyl, isobenzofuranyl, isochromanyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiaziolyl, isoxazolyl, naphthyridinyl (including 1 ,6-naphthyridinyl or, preferably, 1,5- naphthyridinyl and 1,8-naphthyridinyl), oxadiazolyl (including 1 ,2,3-oxadiazolyl, 1 ,2,4- oxadiazolyl and 1 ,3,4-oxadiazolyl), oxazolyl, phenazinyl, phenothiazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridy!, pyrimidinyl, pyrrolyl, quinazo!inyl, quinoiinyl, quinolizinyl, quinoxalinyl, tetrahydroisoquinolinyl (including 1,2,3,4- tetrahydroisoquinolinyl and 5,6,7,8-tetrahydroisoquinolinyl), tetrahydroquinolinyl (including 1,2,3,4-tetrahydroquinolinyl and 5,6,7,8-tetrahydroquinolinyl), tetrazolyl, thiadiazolyl (including 1,2,3-thiadiazolyl, 1 ,2,4-thiadiazolyi and 1 ,3,4-thiadiazolyi), thiazolyl, thiochromanyl, thiophenetyl, thienyl, triazolyl (including 1 ,2,3-triazol l, 1 ,2,4-triazoiyl and 1 ,3,4-triazolyl) and the like. Substituents on heteroaryl groups may, where appropriate, be located on any atom in the ring system including a heteroatom. The point of attachment of heteroaryl groups may be via any atom in the ring system including (where appropriate) a heteroatom (such as a nitrogen atom), or an atom on any fused carbocyclic ring that may be present as part of the ring system. Heteroaryl groups may also be in the N- or S-oxidised form. Particularly preferred heteroaryl groups include pyridyl, pyrrolyl, quinoiinyl, furanyl, thienyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl, indazolyl, pyrimidinyl, thiophenetyl, thiophenyl, pyranyl, carbazolyl, acridinyl, quinoiinyl, benzoimidazolyl, benzthiazolyl, purinyl, cinnolinyl and pterdinyl. Particularly preferred heteroaryl groups include monocylic heteroaryl groups (e.g. furan, and thiophene). When used herein a "substituted" group refers to a group (e.g. an aryl, a heteroaryl or an alkyl group as defined hereinbefore) substituted with one or more substituents selected from halogen, an aikyl group, phenyl (which may be unsubstituted or substituted by halogen, -OAIky!, -COAIkyl, -C{0) ₂ Alkyl, -S0 ₂ alkyl and -CN), naphthyl (which may be unsubstituted or substituted by -OAIkyl, -COAIkyl, -C(0) ₂ Alkyl, -S0 ₂ alkyl and -CN), -OAIkyl, -COAIkyl, -C(0) ₂ Alkyl, -S0 ₂ alkyl and -CN.

The term "halogen", when used herein, includes fluorine, chlorine, bromine and iodine. In certain embodiments of the invention, the solvent may comprise an ether (e.g. cyclopentyl methyl ether and/or diethyl ether). In still further embodiments, the solvent may further comprise water.

As mentioned hereinbelow, the reaction may be conducted at a temperature of from -50°C to -80°C {e.g. from -60°C to -70°C).

In yet still further embodiments of the invention, the base may be a metal hydroxide, such as cesium hydroxide. When used herein, the term "electron withdrawing group" will be understood to mean a moiety that enables the deprotonation of the carbon atom alpha- to said electronwithdrawing group. Examples of electron withdrawing groups that may be mentioned herein includes -C(0) ₂ e, -C(0) ₂ Et, -C(0)2 ^l Bu, -C(0) ₂ Ph, S0 ₂ Ph and -CN, that is R ₂ may be any of these groups.

Advantages offered by the compound of formula (!) are listed below.

1. Optically active sulfoxides have extensive applications as chiral ligands, chiral organocatalyst, synthetic intermediates and bioactive drugs. The importance and the unique property of sulfoxide compounds promote the developing the synthetic approaches to them. Nowadays, there are two main strategies to synthesize enantioenriched sulfoxides: the classical Andersen method and the Kagan-Modena method. Many modification based on these two approaches also have been developed. However, the development of catalytic and enantioselective methodologies with broad substrate scope and using non-metallic chiral catalysts is still highly desirable, which has been developed herein.

2. Recently, the new emerging approach using the nucleophilic sulfenate anion species is potentially viable strategy for enantio- and d (stereoselective synthesis of sulfoxides. However, reports which employing the sulfenate anion in catalytic enantioselective synthesis of sulfoxide is still scant and only moderate results were obtained. We describe the surprisingly effective asymmetric alkylation reaction of a sulfenate anion intermediate using a pentanidium phase-transfer catalyst (i.e. the compound of formula (I)) for the synthesis of chiral heterocyclic sulfoxides.

3. In this methodology, a catalytic and highly enantioselective synthesis of various chiral heterocyclic sulfoxides using 1 mol % of pentanidium phase-transfer catalyst was achieved. The chiral heterocyclic sulfoxide which might not be compatible with the strong oxidation and organometallic reagents can be efficiently obtained with high yields and good to excellent enantioselecttvities with low loading of phase-transfer catalyst.

4. The chiral heterocyclic sulfoxides made using the compound of formula (1) could potentially be used as chiral organocatalyst, chiral ligand for metal complexes, biologically active molecules or drugs.

EXPERIMENTAL General

¹ H and ¹³ C N R spectra were recorded on Bruker AV-300 (300 MHz), BrukerAvance III 400 (400MHz) (100 MHz) spectrometer, 500 MHz Bruker DRX NMR spectrometer or AMX500 (500MHz) spectrometer. Chemical shifts are recorded as δ in units of parts per million (ppm). The residual solvent peak was used as an internal reference. ¹⁹ F NMR was performed on a Bruker Avance 111 400 (400MHz) spectrometer. Low resolution mass spectra (LRMS) were obtained on the ThermoFinnigan PolarisQ MS and ThermoFinnigan LCQ Fleet MS; High resolution mass spectra (HRMS) were obtained on the Q-Tof Premier mass spectrometer (Waters Corporation). LRMS and HRMS were reported in units of mass of charge ratio {m/z). Enantiomeric excess values were determined by HPLC analysis on Shimadzu LC-20AT and LC-2010CHT HPLC workstations. Optical rotations were measured in CHCI ₃ using a 1 mL cell with a 1 dm path length on a Jasco P-1030 polarimeter with a sodium lamp of wavelength 589 nm and reported as follows:(c = g/100 mL, solvent). Melting points (mp) were measured in OptiMelt MPA100 equipment and uncorrected. IR spectra were recorded with neat solid/liquid samples on a Shimadzu IR- Prestige-21 spectrometer and reported in wave numbers (cm ^'1 ). X-ray crystallography analysis was performed on Bruker XS APEX X- ray diffractionmeter. Flash chromatography separations were performed on Merck 60 (0.040 - 0.063mm) mesh silica gel. Analytical thin- layer chromatography (TLC) was performed on Merck 60 F254 silica gel plates. Visualization was performed using a UV lamp or potassium permanganate stain. Materials

THF were distilled over sodium/benzophenone under N _z atmosphere. Toluene, Acetonitrile and Dichloromethane were distilled over CaH ₂ under N ₂ atmosphere. The mercaptans were purchased from commercial suppliers or synthesized according to the literature procedures and used directly without further purification. Other reagents and solvents were commercial grade and were used as supplied without further purification, unless otherwise stated. Experiments involving moisture and/or air sensitive components were performed under a positive pressure of nitrogen in oven-dried glassware equipped with a rubber septum inlet. All compounds synthesized were stored in a -30 °C freezer.

Preparations Preparation

Syntheses and Characterization of Chiraf Pentanidium Salts

Representative procedure for chlorination or bromination of arene ((a) K. Tanemura, T. Suzuki, Y. Nishida, K. Satsumabayashi, T. Horaguchi, Chem. Lett. 2003, 32, 932-933; b) K. Kawamura, H. Fukuzawa, M. Hayashi, Bull. Chem. Soc. Jpn. 2011 , 84, 640-647): A mixture of 3,5- di-tert-butyl toluene (5.0 g, 24.4 mmol, 1.0 equiv.), FeCI ₃ (0.78 g, 4.9 mmol, 0.2 equiv.) and NBS (4.56 g, 25.6 mmol, 1.05 equiv.) in dry CH ₃ CN (50 mL) was stirred at 82 °C for 12 h, and the resulting solution was cooled to room temperature and then evaporated. The crude product was purified by silica gel column chromatography (hexane as the eluent) to give 2- bromo-1 ,5-di-tert-butyl-3-methylbenzene (6.83 g, 24.0 mmol) as colorless oil in 98% yield.

Preparation 2

Representative procedure for iodination of arene; Procedure modified from S. Stavber, P. Kralj, M. Zupan, Synthesis 2002, 15 3-15 8.

To a solution of 3.5-di-tert-butyl toluene (4.08 g, 20 mmol, 1.0 equiv.) in eCN (100 mL) were added l ₂ (3.8 g, 15.0 mmol, 0.75 equiv.) and Seiectfluor (5.3 g, 15.0 mmol, 0.75 equiv.) and the reaction mixture was stirred at 60 °C for 5 h. The solvent was removed under reduced pressure and the crude mixture was dissolved in CH ₂ CI ₂ (100 mL). After the filtration, the filtrate was washed with aqueous 10 % Na ₂ S ₂ 0 ₃ ^« 5H ₂ 0 ( 00 mL) and H ₂ 0 (100 mL), and dried (Na ₂ S0 ). The solvent was evaporated, and the crude product were purified by flash chromatography over silica gel (hexane), followed by distillation under reduced pressure (colourless oil, 3.21 g, 74% isolated yield) with the recovery of 3,4-di-tert- butyltoluene (1.4 g, 6.86 mmol). Preparation s

Syntheses of 1-(bromomethyl)-3,5-di-tert-butyl-2-iodobenzene:

Modified from procedures reported in: a) K. Hirai, K. Bessho, T. Kitagawa, H. Tomioka, J. Phys. Org. Chem. 2010, 23, 347- 356; and b) D. Sperandio, H. J. Hansen, Helv. Chim. Acta 1995, 78, 765-771.

To a stirred solution of 1 ,5-di-tert-butyl-2-iodo-3-methyibenzene (4.17 g, 12.6 mmol, 1.0 equiv.) in H ₂ S0 ₄ (6.86 mL), AcOH (21 mL), and Ac ₂ 0 (46 mL) was slowly added KMn0 ₄ (4.98 g, 31.5 mmol, 2.5 equiv.) at 40 °C over a period of 4 h and the mixture was stirred for 1 day at the same temperature. The mixture was poured into H2O and extracted with Et ₂ 0. The ethereal layer was washed with 10% NaOH solution and brine, dried over anhydrous Na ₂ S0 ₄ , and the solvent was removed under reduced pressure. The residue was chromatographed through a column of silica gel using hexane-CH ₂ CI ₂ (2:1 ) as the eluent to give 3,5-di-tert-buty!-2-iodobenzyl acetate(1.51 g, 3.90 mmol) as a yellow viscous liquid in 31% crude yield.

To a stirred solution of this acetate (1.51 g, 3.90 mmol 1.0 equiv.) in MeOH (20 mL) was added K ₂ C0 ₃ (270 mg, 1.95 mmol, 0.5 equiv.) and the mixture was stirred at room temperature for 3 h. The reaction mixture was quenched by the addition of 2 M hydrochloric acid. The mixture was extracted with ether, and the organic solution was washed with brine, dried over anhydrous Na ₂ S0 ₄ , and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography (silica gel, hexane-ethyl acetate 20:1-5:1 ) afford the product to give (3,5-di-tert-buty!-2-iodophenyl)methanol (1.24 g, 3.58 mmol) as a white solid in 92% yield.

(3,5-di-tert-butyl-2-iodophenyl)methanol (984 mg, 2.84 mmol, 1.0 equiv.) was suspended in a vigorously stirred solution of glacial AcOH (5.7 mL) and HBr (48% wt in H ₂ 0, 1.54 mL, 10 equiv.). The suspension was heated up to 100 °C for 1 h. Then the mixture was cooled to room temperature and poured onice-water and stirred again for 10 min. The mixture was extracted with ether, and the organic solution was washed with brine, dried over anhydrous Na ₂ S0 ₄ , and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography using hexane as an eluent to afford the product l-(bromomethyl)- 3,5- di-tert-butyl-2-iodobenzene(1.0 g, 2.45 mmol) as colourless oil in 87% yield.

Example 1 Representative procedure for the syntheses of chirai pentanidium salts (taking the pentanidium salt 1c as an example):

Step 1 : To a solution of chirai diamine A (1.23 g, 5.8 mmol, 1.0 equiv.) and K ₂ C0 ₃ (1.77 g, 12.8 mmol, 2.2 equiv.) in MeCN (15 mL), was added a solution of 2-bromo-3,5-di-tert- butylbenzyl bromide (4.30 g, 11.9 mmol, 2.05 equiv.) in MeCN (15 mL) by using a syringe pump during 1 h, and then the reaction mixture was stirred for 24 h at room temperature (monitored by TLC). After diamine A was completely consumed, reaction was quenched by water (20 mL) and extracted with CH ₂ CI ₂ (30 mL * 3). The combined organic layer was washed by brine and dried by Na ₂ S0 ₄ . Solvent was removed under reduced pressure. Compound B was obtained by flash chromatography (silica gel, hexane-ethyl acetate 50:1- 30:1 ), as a white solid, 3.55 g, 79% yield.

Step 2: A 50 ml flask was charged with 1.0 mL CH ₂ CI ₂ , compound B (522 mg, 0.67 mmol, 1.0 equiv.), and K ₂ C0 ₃ (205 mg, 1 ,48 mmol, 2.2 equiv.) in 1.5 mL H ₂ 0. The resulting mixture was stirred vigorously at 0 °C, followed by the dropwise addition of an anhydrous CH ₂ CI ₂ solution of triphosgene (1.0 M, 67 mg, 0.22 mmol, 0.33 equiv.). After the addition, the mixture was warmed to room temperature and further stirred for 2 h to complete the reaction. The reaction mixture was then extracted with CH ₂ CI ₂ (5 mL ^χ 3). The combined organic layer was washed by brine and dried by Na ₂ S0 ₄ . Solvent was removed under reduced pressure. Compound C was obtained by flash chromatography (silica gel, hexane-ethy! acetate 50:1- 30:1 ), as a white solid, 515 mg, 95% yield.

Step 3: To a solution of compound C (515 mg, 0.64 mmol, 1.0 equiv.) in 3.0 mL o-xylene was added Lawesson's reagent (518 mg, 1.28 mmol, 2.0 equiv.) under nitrogen atmosphere. Then the whole solution was heated to 145 °C for 24 h and cooled to room temperature. Upon the completion of compound C on TLC, the whole solution was directly loaded on a column. Firstly, all the o-xylene was allowed to drain by gravity and then hexane/ethyl acetate ( 00:1- 20:1 ) was used to flush out compound D as a pale-yellow foam, 508 mg, 96% yield.

Step 4: A 100 mL RBF was charged with a solution of D (508 mg, 0.62mmol, 1.0 equiv.) in toluene (3 mL) with a condenser under N ₂ atmosphere. (COCI) ₂ (0.43 mL, 4.97 mmol, 8.0 equiv.) was added via syringe in one portion. The mixture was refluxed overnight until D was completely reacted. Toluene was removed under reduced pressure and solid imidazoline salt was obtained for the next step without any purification. (Imidazoline salt is air and moisture sensitive, which should be stored under nitrogen atmosphere or vacuum.)

Step 5: To a solution of B (775 mg, 1 mmol, 1.0 equiv.) in dry MeCN (5 mL) under nitrogen atmosphere was added BrCN (106 mg, 1 mmol, 1.0 equiv.). The whole solution was heated to reflux for 12 h and cool to room temperature. Then solvent was removed under reduced pressure and compound E was obtained by flash chromatography (silica gel.DCM-Methanol 100:1-30:1 ), as a white hygroscopic powder, 703 mg, 87% yield. A mixture of theguanidinium salt E (0.87 mmol 1.0 equiv.) and 3 NaOH (13.05 mmol, 15 equiv.) in CH ₂ CI ₂ (13 mL) was vigorously stirred for 15 min at room temperature. The mixture was then extracted with CH ₂ CI ₂ (13 mL * 3). The combined organic phases were washed with water (20 mL), dried over MgS0 and concentrated to dryness under reduced pressure to provide the corresponding guanidine free base quantitatively as white solid.

Step 6: The imidazoline salt was dissolved in dry MeCN (3 mL) under nitrogen atmosphere, and then the guanidine free base of compound E (200 mg, 0.25 mmol, 0.4 equiv.) was added, followed by the addition of Et ₃ N (0.26 mL, 1.86 mmol, 3.0 equiv.). Then the whole solution was heated to reflux for 12 h and cooled to room temperature. Add 1 HCI (20 mL) to the reaction solution and the mixture was extracted by CH ₂ CI ₂ (10 mL * 3). The combined organic layer was dried by Na ₂ S0 ₄ . Solvent was removed under reduced pressure and PTC was obtained by flash chromatography (silica gel, DCM-Methanol 100:1-20 1 ), as a beige powder, 315 mg, 78% yield.

1,5-di-tert-butyl-2-chloro-3-methy1benzene Colourless oil; 80% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.35 (d, J - 2.4 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1 H), 2.42 (s, 3H), 1.53 (s, 9H), 1.33 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ = 148.49, 145.79, 137.15, 131.09, 125.93, 122.57, 36.52, 34.53, 31.36, 29.90, 21.99; IR: 2962, 2872, 1463, 1240, 1037, 873, 732 cm ^"1 ; LRMS (El) m/z 238.1 [M] +.

1-{bromomethyl)-3,5-di-tert-buty[-2-chlorobenzene[K. Kawamura, H. Fukuzawa, M. Hayasht, Bull. Chem. Soc. Jpn. 2011, 84, 640-647] Colourless oil; 93% yield; ¹ H NMR (400 MHz, CDCl ₃ ): δ = 7.45 (d, J = 2.4 Hz, 1 H), 7.31 (d, J = 2.4 Hz, 1H), 4.66 (s, 2H), 1.51 (s, 9H), 1.31 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 149.37, 146.88, 136.24, 131.06, 126.28, 125.70, 36.74, 34.70, 33.21 , 31.25, 29.87; IR: 2964, 1363, 1215, 1039, 881 cm ^-1

2-bromo-1, 5-di-tert-butyl-3-methylbenzene Colourless oil; 98% yield; 1 HNMR (400 MHz, CDCI ₃ ): δ = 7.33 (d, J = 2.5 Hz, 1 H), 7.13 (d, J = 2.4 Hz, 1 H), 2.44 (s, 3H), 1.54 (s, 9H), 1.30 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 149.18, 147.36, 139.22, 125.94, 122.91 , 122.61 , 77.32, 77.00, 76.68, 37.28, 34.56, 31.29, 30.10, 25.65; LRMS (El) m/z 283.1 [M] +.

2-bromo-1-{bromomethyl)-3,5-di-tert-butylbenzene [K. Kawamura, H. Fukuzawa, M. Hayashi, Bull. Chem. Soc. Jpn. 201 1 , 84, 640-647] Colourless oil; 83% yield; ¹ H NMR (300 MHz, CDC! ₃ ): δ = 7.45 (d, J - 2,5 Hz, 1 H), 7.33 (d, J - 2,5 Hz, 1 H), 4,72 (s, 2H), 1.55 (s, 9H), 1.32 (s, 9H); ¹³ C NMR (100 MHz, CDCi ₃ ): δ = 150.08, 148.48, 138,11 , 126.47, 125.97, 122.13, 77.42, 77.00, 76.58, 37.53, 36.78, 34.72, 31.19, 30.11.

1,5-di-tert-butyl-2-iodo-3-methylbenzene Colourless oil; 74% yield; ¹ H NMR (400 MHz, CDC ): δ - 7,29 (d, J = 2.4 Hz, 1 H), 7.16 (d, J = 2.2 Hz, 1 H), 2,53 (s, 3H), 1.61 (s, 9H), 1.31 (s, 9H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 150.27, 150.15, 142.97, 124.93, 122.55, 100.01 , 37.80, 34.54, 32.64, 31.23, 30.42; LRMS (El) m/z 330.0 [M] +.

(3,5-di-tert-butyl-2-iodophenyl)methanol White solid; 92% yield; mp: 89.9-91.0 °C; H NMR (400 MHz, CDCI ₃ ): 5 = 7.44 (d, J = 2.5 Hz, 1H), 7.35 (d, J = 2.5 Hz, 1H), 4.76 (d, J = 6.4 Hz, 2H), 2.28 (t, J = 6.6 Hz, 1 H), 1.61 (s, 9H), 1.33 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 150.87, 150.31 , 143.86, 124.70, 124.20, 96.61 , 72.28, 37.86, 34.76, 31 ,23, 30.44.

1-(bromomethyl)-3,5-di-tert-butyl-2-iodobenzene Colourless oil; 87% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.41 (d, J = 2.5 Hz, 1 H), 7,36 (d, J = 2.5 Hz, 1H), 4.79 (s, 2H), 1.60 (s, 9H), 1.31 (S, 9H); ³ C MR (100 MHz, CDCI ₃ ): δ = 151.45, 151.07, 141.56, 125.75, 125.54, 98.71 , 43.80, 38.09, 34,70, 31.14, 30.48; IR: 2962, 1639, 1394, 1363, 1263, 1121 , 1002, 881 , 732 cm ^"1 .

(1S,2S)-N1 ,N ₂ -bis(3,5-di-tert-butylbenzyl)-1,2-diphenylethane-1,2 diamine White solid; 83% yield; mp: 109.7-111.1 °C; [a]£ - + 6.4 (c 0.64, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.28 (t, J = 1.7 Hz, 2H), 7,16 (dd, J = 6.2, 4.5 Hz, 6H), 7,06 (dd, J = 9.4, 1 ,8 Hz, 8H), 3.73 (s, 2H), 3.63 (d, J = 13.0 Hz, 2H), 3.49 (d, J = 13.0 Hz, 2H), 1.29 (s, 36H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ ~ 150.53, 141 .48, 139.62, 128.08, 127.87, 126.80, 122.39, 120.73, 68.44, 52.08, 34.73, 31.48; IR: 3419, 2962, 1627, 1452, 1361 , 1247, 1 199, 698 cm ^"1 ; HRMS (ESI) calcd for C^Heo^ m/z [M+H] +: 617.4835; found: 617.4835. (1 S,2S)-N1,N ₂ -bis(3,5-di-tert-butyl-2-chlorobenz^

Colourless oil; 78% yield; [a]g = + 20.3 (c 1.24, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.33 (d, J = 2.4 Hz, 2H), 7.20 -7.12 (m, 6H), 7.09 (d, J = 1.8 Hz, 2H), 7.07 (dd, J = 4.1 , 1.9 Hz, 4H), 3.79 (d, J = 13.6 Hz, 2H), 3.66 (s, 2H), 3.56 (d, J = 13.6 Hz, 2H), 2.64 (s, 2H), 1 .45 (s, 18H). 1.26 (s, 18H); ¹³ C NMR (100 MHz, CDCI ₃ ): 0 = 148.41 , 145.89, 141.21 , 138.61 , 130.64, 128.02, 127.91 , 126.84, 125.72, 123.53, 68.41 , 50.84, 36.51 , 34.59, 31.33, 29.96; IR: 3419, 2962, 2360, 1653, 1454, 1394, 1363, 1265, 1199, 1035, 879, 738, 700 cm ^"1 ; HRMS (ESi) calcd for C44H ₅₈ C! _{2 2} m/z [M+H]+: 685.4055; found: 685.4050.

(1 S,2S)-N1,N ₂ ^is(2-bromo-3,5-di-tert-butylbenzyl)-1 ,2-diphenylethane-1,2-diamine

White hygroscopic foam; 79% yield; [α]£ = -22.1 (c 1.8, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.38 (d, J = 2.5 Hz, 2H), 7.24-7.1 1 (m, 10H), 7.08 (d, J = 2.5 Hz, 2H), 3.84 (d, J = 13.6 Hz, 2H), 3.71 (s, 2H), 3.63 (d, J = 13.6 Hz, 2H), 2.72 (s, 2H), 1.53 (s, 18H), 1.30 (s, 18H); ¹ C NMR (100 MHz, CDCI ₃ ): δ = 149.00, 147.33, 141.10, 140.31 , 128.01 , 127.92, 126.84, 126.07, 123.94, 121.85,68.22, 53.60, 37.27, 34.57, 31.26, 30.17; IR: 3415, 2964, 1629, 1458, 1396, 1363, 1199, 1014 cm ^"1 ; HRMS (ESI) calcd for C44H _5e Br ₂ N ₂ m/z [M+H] +: 775.3025; found: 775.3007.

(1S,2S}-N1,N ₂ -bis(3,5-di-tert-butyI-2-iodobenzyl)-1 ,2-diphenylethane-1,2-diamine White foam; 94% yield; = +18.2 (c 1.72, CHCI ₃ ); ¹ H NMR (400 MHz, CDCl ₃ ): δ = 7.33 (d, J = 2.3 Hz, 2H), 7.16 (dt, J = 13.7, 4.9 Hz, 10H), 7.00 (d, J = 2.3 Hz, 2H), 3.79 (d, J - 13.5 Hz, 2H), 3.69 (S, 2H), 3.63 (d, J = 13.5 Hz, 2H), 2.74 (s, 2H), 1.55 (s, 18H), 1.25 (s, 18H); ¹³ C NMR (100 MHz, CDCI3): δ = 150.19, 149.94, 143.63, 141.14, 128.16, 127.98, 126.88, 125.60, 123.85, 98.67, 68.12, 58.98, 37.85, 34.55, 31 .23, 30.55; IR: 3305, 2953, 2304, 1587, 1556, 1454, 1392, 1361 , 1 165, 1105, 999, 878 cm ^"1 ; HRMS (ESI) calcd for C^H^ z m/z [M+H] +: 869.2768; found: 869.2767.

(4S,5S)-1 ,3-bis(3,5-di-tert-butylbenzyl)-4,5-diphenylimidazolidin-2-o ne White solid;>99% yield; mp: 144.5-146.3 °C; = - 53.7 (c 1.2, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.25 (ddt, J = 8.8, 3.5, 1 .7 Hz, 8H), 7.01 - 6.96 (m, 4H), 6.96 (d, J = 1.7 Hz, 4H), 5.12 (d, J = 14.5 Hz, 2H), 3.99 (s, 2H), 3.62 (d, J = 14.5 Hz, 2H), 1 .28 (s, 36H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 159.85, 150.82, 139.41 , 135.70, 128.66, 128.14, 127.27, 122.98, 121.07, 65.34, 46.30, 34.70, 31.41 ; IR: 2962, 1697, 1697, 1600, 1444, 1361 , 1249, 1201 , 948, 702. cm ^"1 ; HRMS (ESI) calcd for C^H^O /z [M+H] +: 643.4627; found: 643.4631.

(4S,5S)-1,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5-dip henylimidazolidin-2-one White solid; 78% yield; mp:100.2- 101.3 °C; [α]? = -77.8 {c 0.6, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.30 (d, J = 2.3 Hz, 2H), 7.27-7.18 (m, 6H), 7.03 (dd, J = 7.3, 2.0 Hz, 4H), 6.85 (d, J = 2.3 Hz, 2H), 5.11 (d, J = 14.8 Hz, 2H), 4.02 (d, J = 14.8 Hz, 2H), 3.94 (s, 2H), 1.45 (s, 18H), 1.19 (s, 18H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 159.30, 148.42, 146.19, 139.92, 134.81 , 130.69, 128.71 , 128.06, 127.08, 126.24, 124.18, 66.09, 45.42, 36.52, 34.49, 31.21 , 29.8; IR: 3053, 2966, 2304, 1701 , 1419, 1037 cm ^"1 ; HRMS (ESi) calcd for m/z [M+H] +: 711.3848; found: 711.3849.

{4S,5S)-1,3-bis{2-bromo-3,5-di-tert-buty!benzyi)-4,5-diph enylimidazolidin-2-one

Colorless oil; 95% yield; = -69.8 (c 1.57, CHCI ₃ ); ¹ H NMR (400 MHz, CDCi ₃ ): δ = 7.39- 7.18 (m, 8H), 7.07 (dd, J = 6.4, 3.1 Hz, 4H), 6.82 (d, J = 2.4 Hz, 2H), 5.13 (d, J - 14.8 Hz, 2H), 4.09 (d, J = 14.8 Hz, 2H), 3.96 (s, 2H), 1.50 (s, 18H), 1.18 (s, 18H); ⁵³ C NMR (100 MHz, CDCIs): δ = 159.23, 149.05, 147.74, 139.92, 136.60, 128.75, 128.06, 127.07, 126.39, 124.59, 121.60, 66.08, 48.23, 37.32, 34.50, 31.15, 30.04; IR: 2962, 1697, 1629, 1460, 1265, 1201 , 1016, 881 cm ^"1 ; HRMS (ESI) calcd for C ₄ 5H ₅₆ Br ₂ N ₂ 0 m/z [M+H] +: 801.2817; found: 801.2822.

(4S,5S)-1,3-bis(3,5-di-tert-butylbenzyl)-4,5-diphenylimid azolidine-2-thione Pale yellow foam; >99% yield; = - 152.10 (c O.95, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.32-7.24 (m, 8H), 7.01 (d, J = 1.6 Hz, 4H), 6.97 (dd, J = 7.7, 1.6 Hz, 4H), 5.88 (d, J = 14.6 Hz, 2H), 4.24 (s, 2H), 3.74 (d, J = 14.6 Hz, 2H), 1.27 (s, 36H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 182.08, 150.96, 139.18, 135.14, 129.02, 128.57, 127.06, 122.88, 121.40, 68.73, 49.72, 34.75, 31.45; IR: 2964, 2904, 2304, 1598, 1448, 1417, 1363, 1300, 1219, 1199, 1080, 742 cm ^"1 ; HRMS (ESI) calcd for C45H5 ₈ N2S m/z [M+H] +: 659.4399; found: 659.4401. (4S,5S)-1,3-bis(3,5-di-tert-butyl·2-chlorobenzy!)-4,5-diphe nylimidazolidine-2-thione

Colourless oil; 78% yield; [a]J? = -164.64 (c 2.2, CHCI ₃ ); Ή NMR (400 MHz, CDCI ₃ ): δ = 7.33 (d, J = 2.3 Hz, 2H), 7.29 (dd, J = 5.0, .6 Hz, 6H), 7.06 (dd, J = 6.3, 2.8 Hz, 4H), 6.98 (d, J = 2.2 Hz, 2H), 5.79 (d, J = 14.9 Hz, 2H), 4.23 (d, J = 16.6 Hz, 4H), 1.44 (s, 18H), 1.22 (s, 18H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 182.51 , 148.57, 146.29, 139.36, 134.30, 130.69, 129.02, 128.44, 126.81 , 126.02, 124.39, 69.52, 48.62, 36.52, 34.52, 31.23, 29.78; IR: 3053, 2964, 2870, 1463, 1423, 1363, 1200, 1037 cm ^"1 ; HRMS (ESi) caicd for C ₄₅ H ₅₆ CI ₂ N ₂ S m/z [M+H] +: 727.3620; found: 727.3620.

(4S,5S)-1,3-bis(2-bromo-3,5-di-tert-butylbenzyl)-4,5-diph enylirnidazolidine-2-thione

Pale yellow foam; 96% yield; [α] - -145.0 (c 2.02, CHCI ₃ ); ¹ H N R (400 MHz, CDCI ₃ ): δ = 7.33 (d, J = 2.4 Hz, 2H), 7.31 -7.26 (m, 6H), 7.14-7.02 (m, 4H), 6.95 (d, J = 2.4 Hz, 2H), 5.77 (d, J = 15.0 Hz, 2H), 4.32 (d, J = 15.0 Hz, 2H), 4.22 (s, 2H), 1.47 (s, 18H), 1.20 (s, 18H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 182.65, 149.23, 147.83, 139.32, 136.11 , 129.09, 128.48, 126.86, 126.07, 124.83, 121.59, 69.58, 51.49, 37.36, 34.58, 31.22, 30.04; IR: 2964, 1421 , 1396, 1263, 1199, 1016, 883 cm ^"1 ; HRMS (ESI) calcd for C^HseBr^S m/z [M+H] +: 817.2589; found: 817.2587.

(4S,5S)- ,3-bis(3,5-di-tert-butyl-2-iodobenzyl)-4,5-diphenylimidazoli dine-2-thione: A 5 mL flask was charged with 1.5 ml_ CH ₂ CI ₂ , (1 S,2S)-N1 ,N ₂ -bis(3,5-di-tert-butyl-2-iodobenzy!)- 1 ,2- diphenylethane-1 ,2-diamine (305 mg, 0.35 mmol, 1.0 equiv.) and K ₂ C0 ₃ (106 mg, 0.77 mmol, 2.2 equiv.) in 1.5 mL H ₂ 0. The resulting mixture was stirred vigorously at 0 oC, followed by the dropwise addition of a solution of thiophosgene (1.0 M, 29.6 μ!_, 0.39 mmol, 1.1 equiv.) in anhydrous CH ₂ CI ₂ . After the addition, the mixture was warmed to room temperature and further stirred for 2 h to complete the reaction. The reaction mixture was then extracted with CH ₂ CI ₂ (5 mL * 3). The combined organic layer was washed by brine and dried by Na ₂ S0 ₄ . After removal of solvent under reduced pressure, the residue was subjected to flash chromatography (silica gel, hexane-ethyl acetate 50:1-30:1 ) to afford the product as colorless oil in 91 % yield; [a]£ = -126.4 (c 0.36,CHCI ₃ ); ¹ H NMR (400 MHz, CDCS ₃ ): δ = 7.30 (dd, J = 4.2, 2.3 Hz, 4H), 7.10 (dd, J = 6.5, 3.0 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1 H), 5.74 (d, J = 15.1 Hz, 1H), 4.43 (d, J = 15.2 Hz, 1H), 4.22 (s, 1 H), 1.51 (s, 8H), 1.19 (s, 8H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 182.99, 150.63, 150.14, 139.35, 139.21 , 129.13, 128.45, 126.94, 125.28, 124.65, 97.89, 69.64, 57.23, 37.90, 34.52, 31.15, 30.40; IR: 2964, 2870, 1633, 1556, 1487, 1454, 1396, 1361 , 1280, 1234, 1165, 1001 , 731 cm ^"1 ; HRMS (ESI) calcd for C4 ₅ H5 ₆ I2 2S m/z [M+H] +: 911.2332; found: 911.2335. (4S,5S)-1-(3,4-di ert-butylbenzyl)-3-{3,5-di-tert^utylbenzyl)-4,5-diphenylimid azolidin- 2-imine hydrobromide White foam; 98% yield; [α]? = - 125.3 (c 1.37, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 9.29 (s, 2H), 7.37-7.23 (m, 8H), 6.97 (d, J = 1.6 Hz, 4H), 6.95- 6.89 (m, 4H), 5.76 (d, J - 15.0 Hz, 2H), 4.25 (s, 2H), 3.89 (d, J = 14.9 Hz, 2H), 1.26 (s, 36H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 156.35, 151.24, 137.16, 132.47, 129.24, 129.17, 126.92, 123.37, 122.03, 68.24, 49.25, 34.74, 31.40; IR: 3423, 2964, 1662, 1600, 1363, 1265, 1201 , 734, 700 cm ^"1 ; HRMS (ESI) calcd for C ₄₅ H ₆ oBr ₃ m/z [M-Br- ]+: 642.4787; found: 642.4781. (4S,5S)-1,3-bis(3,5-di-tert-butyl-2-ch]orobenzyl)-4,5-diphen ylimidazolidin-2-imine hydrobromide White solid; 78% yield; mp: 167.1-168.8 °C; [α]? = -44.9 (c 2.6, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 9.19 (s, 2H), 7.35 (d, J = 2.3 Hz, 2H), 7.33 - 7.20 (m, 8H), 6.98 (d, J = 6.9 Hz, 4H), 5.89 (d, J = 14.6 Hz, 2H), 4.15 (d, J = 14.7 Hz, 2H), 3.96 (s, 2H), 1.52 (s, 18H), 1.10 (s, 18H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 156.32, 148.71 , 146.73, 137.57, 131.53, 131.16, 129.15, 128.98, 128.09, 127.07, 125.37, 68.73, 49.69, 36.62, 34.41, 31.03, 29.81 ; IR: 3396, 3053, 2966, 2358, 1666, 1558, 1363, 1124, 1037 cm ^"1 ; HRMS (ESI) calcd for C ₄₅ H ₅₈ BrCI ₂ N ₃ m/z [M-Br-] +: 710.4008; found: 710.3995. (4S,5S)-1 -(2-bromo-3,4-di-tert-butylbenzyl)-3-(2-bromo-3,5-di-tert-bu tylbenzyl)-4,5- diphenylimtdazolidin-2-imine hydrobromide White hygroscopic foam; 87% yield; [a]JF = -96.2 (c 0.42, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 9.26 (s, 2H), 7.34 (d, J = 2.3 Hz, 2H), 7.32-7.23 (m, 6H), 7.02 (d, J = 6.7 Hz, 4H), 6.44 (d, J = 2.3 Hz, 2H), 5.92 (d, J = 14.5 Hz, 2H), 4.25 (d, J = 14.6 Hz, 2H), 3.93 (s, 2H), 1.55 (s,18H), 1.06 (s, 18H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 156.34, 149.25, 148.25, 137.61 , 133.28, 129.16, 128.92, 128.61 , 127.07, 125.72, 122.20, 68.73, 52.28, 37.37, 34.37, 30.93, 29.99; IR: 3257, 2966, 1660, 1562, 1456, 1427, 1396, 1016, 883 cm ^"1 ; HRMS (ESI) calcd for m/z [M-Br-] +: 801.2817; found: 801.2822. (4S,5S)-1,3-bis(3,5-di-tert-butyl-2-iodobenzyl)-4,5-diphenyl imidazolidin-2-imine

hydrobromide Pale yellow foam; >99% yield; [a]g = -89.3 (c 1.36, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 9.23 (s, 2H), 7.36 - 7.16 (m, 8H), 7.07 (dd, J = 11.4, 5.7 Hz, 4H), 6.43 (d, J = 2.1 Hz, 2H), 5.72 (d, J = 14.5 Hz, 2H), 4.53 (d, J = 14.6 Hz, 2H), 3.95 (s, 2H), 1.53 (s, 18H), 1.03 (s, 18H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 156.90, 151.12, 150.04, 137.66, 136.69, 129.14, 128.80, 127.96, 127.03, 125.29, 98.85, 69.14, 57.09, 37.85, 34.31 , 30.88, 30.33; IR: 3325, 3188, 3034, 2964, 2872, 1651 , 1556, 1396, 1363, 1234, 1199, 1149, 11 19, 1001 , 734 cm ^"1 ; HRMS (ESI) calcd for C ₄₅ H ₅₈ Brl ₂ N3 m/z [M-Br-] +: 894.2720; found: 894.2723. (4S,5S)-2-({(4S _I 5S)-1,3-bis(3,5-di4ert-butylbenzyl) 5-diphenylimidazolidin-2- ylidene)amino)-1,3-bis(3,5-di-tert-butylbenzy[)-4,5-diphenyl -4,5-dihydro-1H-imidazol-3- ium chloride(la) Brown foam; 53% yield; [α]£ = -89.0 (c 1.05, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.38 (t, J = 7.4 Hz, 4H), 7.33-7.24 (m, 12H), 6.92-6.88 (m, 8H), 6.86 (d, J - 1.6 Hz, 8H), 5.20 (d, J = 14.8 Hz, 4H), 4.40 (s, 4H), 4.1 1 (d, J = 14.8 Hz, 4H), 1.11 (s, 72H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 157.24, 151.99, 136.27, 131.53, 129.78, 129.51 , 127.13, 123.17, 122.39, 68.04, 49.17, 34.66, 31.15; IR: 2964, 2868, 1600, 1456, 1363, 1201, 1139, 945, 734, 698 cm ^"1 ; HRMS (ESi) calcd for Ο ₉₀ Η ₁₁₆ ΟΙΝ ₅ m/z [M-CI-] +: 1266.9231 ; found: 1266.9229.

(4S,5S)-2-(((4S,5S)-1,3^is(3,5-di-tert-butyl-2-chlorobenz yl)-4,5-diphenyhmidazolidin-2- yIidene)amino)-1,3-bis(3,5-di-tert-butyl-2-chlorobenzyl)-4,5 -diphenyl-4,5-dihydro-1 H- imidazol- 3-ium chloride(lb) Pale yellow powder; 71 % yield; mp: 178.5-180.3 °C; [ ]^ = +5.3 (c 1.14, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.37 (d, J = 2.1 Hz, 4H), 7.33 - 7.27 (m, 1 H), 7.21 (t, J = 7.5 Hz, 8H), 6.94 (d, J = 7.3 Hz, 8H), 6.78 (d, J = 2.1 Hz, 1 H), 5.02 (d, J = 14.4 Hz, 4H), 4.62 (d, J = 14.4 Hz, 4H), 4.36 <s, 4H), 1.45 (s, 36H), 1.09 (s, 36H); ³ C NMR (100 MHz, CDC 1 ₃ ): δ = 157.93, 149.50, 147.08, 136.38, 131.21 , 130.36, 129.46, 129.34, 127.07, 126.45, 125.92, 70.01 , 49.30, 36.63, 34.55, 31.06, 29.73; IR: 2966, 2872, 1622, 1485, 1365, 1037, 947 cm ^"1 ; HRMS (ESI) calcd for C ₉₀ H ₁₁₂ CI ₅ N ₅ m/z [M-CI-] +: 1402.7672; found: 1402.7646. (4S,5S)-2-(((45,5S)-1 ,3-bis{2-bromo-3,5-di-tert-butyIbenzyl)-4,5 diphenylimidazolidin-2- ylidene)arnino)-1,3-bis(2-bromo-3,5-di-tert-butylbenzyl)-4,5 -diphenyl-4,5-dihydro-1H- imidazol-3-ium chloride (1c) Beige powder; 78% yield; mp:200.1-200.5 °C; [a¾ ^f = + 14.4 (c 1.43, CHCI ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.36 (d, J = 2.1 Hz, 4H), 7.29 (d, J = 7.4 Hz, 4H), 7.21 (t, J = 7.4 Hz, 8H), 6.96 (d, J = 7.3 Hz, 8H), 6.80 (d, J = 2.1 Hz, 4H), 5.00 (d, J = 14.4 Hz, 4H), 4.74 (d, J ~ 14.4 Hz, 4H), 4.41 (s, 4H), 1.48 (s, 36H), 1.07 (s, 36H); ¹³ C NMR (100 MHz, CDCI3): δ = 158.19, 150.05, 148.52, 136.21 , 132.95, 129.38, 129.31 , 127.10, 126.65, 126.19, 121.46, 77.32, 52.22, 37.39, 34.55, 31.01 , 29.91 , 17.41 ; IR: 2966, 1622, 1423, 1365, 1018 cm ^"1 ; HRMS (ESI) calcd for m/z [M-CI-J+: 1582.5610; found: 1582.5624.

(4S,5S)-2-{((4S,5S)-1,3-bis(3,5-di-tert-butyl-2- iodobenzyl)-4,5-diphenylimidazolidin-2- yIidene)amino)-1,3-bis(3,5-di-tert-butyl-2- iodobenzyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-3-lum chloride (1d) Brown powder; 27% yield; mp:195.2- 196.7 ^e C; [α]? = -9.4 (c 0.35, CHCl ₃ ); ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.32 (d, J = 2.2 Hz, 4H), 7.28 (d, J - 7.4 Hz, 4H), 7.22 (t, J = 7.4 Hz, 8H), 6.99 (d, J = 7.3 Hz, 8H), 6.76 (d, J = 2.1 Hz, 4H), 5.04 (d, J = 14.4 Hz, 4H), 4.87 (d, J = 14.4 Hz, 4H), 4.48 (s, 4H), 1.55 (d, 36H), 1.03 (s, 36H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 158.23, 151.64, 150.91 , 136.17, 136.02, 129.46, 129.40, 127.11 , 126.01 , 125.86, 98.62, 70.45, 57.99, 38.00, 34.50, 30.99, 30.32; IR: 2964, 2870, 1651 , 1556, 1504, 1454, 1361, 1201 , 1165, 1001 , 731 cm ^"1 ; HRMS (ESI) calcd for C ₉ oH ₁₁₂ CII ₄ N5 /z [M-CI-] +: 1770.5097; found: 1770.5073.

Preparation 4

Syntheses and Characterization of Sulfinyl Precursors Preparation of heteroaromatic thiols

Benzo[b]thiophene-2-thiol and 3-methylbenzo[b]thiophene-2-thiol ((a) K. Hirai, K. Bessho, T. Kitagawa, H. Tomioka, J. Phys. Org. Chem. 2010, 23, 347-356; (b) D. Sperandio, H. J. Hansen, Helv. Chim. Acta 1995, 78, 765-771 ), 3-methyl-thiophene-2 -thiol, 5- methy!thiophene-2-thiol and 3,5-dimethylthiophene-2-thiol (B. H.Zhong. et al. Acyclic nucleoside phosphonate derivative and its pharmaceutical use. Faming ZhuaniiShenqing, 101293899, 29 Oct 2008), furan-2-thiol and benzofuran-2-thiol (J. A. Wiles, A. S. Phadke, B. J. Bradbury, W. J. Pucci, J. A. Thanassi, M. Deshpande, J. Med. Chem. 2011 , 54, 3418- 3425.) were prepared according to the literature procedures and used directly in next steps without further purifications. Preparation of sulfanyl precursors Sulfanyl precursors were prepared according to the literature procedures (Method A, B or C) and used directly in next steps without further purifications. Preparation 4a

General procedure for Michael addition of electron-deficient olefins with thiols

9a

EWG = C0 ₂ Me, CCfcEt, C02 ^f Bu,

C0 ₂ Ph, SOzPh, CN

See, for example a) R. K. Haynes, S. C. Vonwiller, J, P. Stokes, L M. Mer!ino, Aust. J. Chem. 1988, 41 , 881- 895; b) C. Caupene, C. Boudou, S. Perrio, P. Metzner, J. Org. Chem. 2005, 70, 2812-2815; c) F. Gelat, J. Jayashankaran, J. F. Lohier, A. C. Gaumont, S. Perrio, Org. Lett. 2011 , 13, 3170-3173; d) Q. P. G. R. D. HUANG, 10555 Science Center DriveSan Diego, California, 92121 , US), RUi, Eugene, Yuanjin (Pfizer Global Research & Development, 10555 Science Center DriveSan Diego, California, 92121, US), PFIZER INC. (235 East 42nd Street, New York, New York, 10017, US), HUANG, Qinhua (Pfizer Global Research & Development, 10555 Science Center DriveSan Diego, California, 92121 , US), RUI, Eugene, Yuanjin (Pfizer Global Research & Development, 10555 Science Center DriveSan Diego, California, 92121 , US), 2009. Et ₃ N (5 mol %) was added to a solution of thiol (0.5mmol) and electron-deficient olefin 9a (0.5 mmol) in THF (0.1 mL) at 0 oC. The resulting reaction mixture was stirred for appropriate time at room temperature (monitored by TLC). After removing solvent under reduced pressure, the crude residue was used in next step without further purification. Preparation 4b (N. Furukawa, F. Takahashi, T. Kawai, K. Kishimoto, S. Ogawa, S. Oae, Phosphorous and Sulfur and the Related Elements 1983, 16, 167-180.)

reflux Methyl 3-bromopropanoate 9b (133 pL, 1.2 mmol, 1.2 equiv) was added dropwise to a solution of 2-mercaptopyridine (111 mg, 1 mmol, 1.0 equiv) and Et ₃ N (209 pL, 1.5 mmol, 1.5 equiv) in CH ₃ CN (0.2 mL) at room temperature. Then the mixture was stirred for 24 h at 82 oC. After the removal of solvent under reduced procure, the resulting residue was purified by flash chromatography to afford the desired compound as pale yellow oil in 76% yield. ¹ H NMR (400 MHz, CDCI ₃ ): δ = 8.42 (d, J = 4.2 Hz, 1 H), 7.49 (td, J = 7.8, 1.8 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 6.99 (ddd, J = 7.2, 5.0, 0.7 Hz, 1H), 3.69 (s, 3H), 3.44 (t, J * 7.1 Hz, 2H), 2.79 (t, J = 7.1 Hz, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 172.46, 158.05, 149.09, 136.24, 122.52, 1 19.53, 51.73, 34.42, 25.01 ; IR: 2951 , 1732, 1579, 1556, 1454, 1415, 1249, 1124, 985, 759 cm ^"1 ; HRMS (ESI) calcd for CgHnN0 ₂ S m/z [M+H] +: 198.0589; found: 198.0589.

Preparation 4c (N. Furukawa, F. Takahashi, T. Kawai, K. Kishimoto, S. Ogawa, S. Oae, Phosphorous and Sulfur and the Related Elements 1983, 16, 167-180.)

reflux

Methyl 3-bromopropanoate 9b (1.37 mL, 12.5 mmol, 1 .2 equiv.) was added dropwise to a solution of 5-methoxy-1-methyl-1 H-benzo[d]imidazole-2-thiol (2.03 g, 10.4 mmol, 1.0 equiv.) in MeOH (10 mL) at room temperature. Then the mixture was stirred for 24 h at 82 oC. After the removal of solvent under reduced procure, the resulting residue was purified by flash chromatography to afford the desired compound as a red solid in quantitative yield. ¹ H NMR (400 MHz, CDCI ₃ ): 5 = 7.16 (d, J = 2.3 Hz, 1 H), 7.09 (d, J = 8.7 Hz, 1 H), 6.84 (dd, J = 8.7, 2.4 Hz, 1 H), 3.83 (s, 3H), 3.69 (s, 3H), 3.61 (s, 3H), 3.57 (t, J = 6.8 Hz, 2H), 2.90 (t, J - 6.8 Hz, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 172.12, 155.92, 151.06, 144.03, 131.39, 1 11.37, 108.70, 101.09, 55.75, 51 .74, 34.41 , 29.98, 27.22; IR: 1732, 1647 cm ^"1 ; HRMS (ESI) calcd for C ₁₃ H ₁₆ N ₂ 0 ₃ S m/z [M+H] +: 281.0960; found: 281.0955.

Preparation 5

Preparation of sulfinyl precursors

EWG C0 ₂ e, C0 ₂ Et,C0 ₂ ⁱ Bu,

C0 ₂ Ph, S0 ₂ Ph, CN

General procedure for sulfides oxidation to sulfoxides To a 2 M solution of sulfide (1 mmol) in 2, 2, 2-trifluoroethanol (TFE) (1.0 mL) at 0 ^C C, H ₂ 0 ₂ (35% wt in water, 160 μΐ, 1.8 mmol, 1.8 equiv) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for appropriate time (monitor by TLC). Solid sodium sulfite (1.8 mmol, 1.8 equiv) was added then the reaction mixture was stirred for 30 min. The resulting mixture was filtered on ceiite, dried over MgS0 ₄ , filtered and evaporated under reduced pressure. The crude product was then purified by column chromatography on silica gel to afford the pure anticipated sulfoxide 2a-f, 4a-e and 5b-f. For the sulfide oxidation to sulfoxide 5a, additional ammonium molybdate tetrahydrate (5 mo! %) was added as a catalyst to promote this transformation.

Methyl 3-(thiophen-2-yisulfinyl)propanoate(2a) Colourless oil; 93% yield; ¹ H NMR (400 MHz, CDCI ₃ ): 6 = 7.80-7.73 (m, 1 H), 7.52 (dd, J = 5.1 , 3.0 Hz, 1 H), 7.22 (dd, J = 5.1 , 1.0 Hz, 1 H), 3.68 (S, 3H), 3.26 (ddd, J = 13.5, 8.2, 7.0 Hz, 1 H), 3.15-3.03 (m, 1 H), 2.89-2.76 (m, 1 H), 2.62 (ddd, J = 17.3, 8.2, 6.1 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): 5 = 171.58, 142.35, 128.63, 126.26, 122.80, 52.15, 50.50, 26.08; IR: 1732, 1436, 1406, 1359, 1224, 1176, 1041 cm ^"1 ; HRMS (ESI) calcd for ¾Η ₁₀ Ο ₃ 5 ₂ /z [M+H]+: 219.0150; found: 219.0147. Ethyl 3-(thiophen-2-ylsulfinyl)propanoate(2b) Colourless oil; 83% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.66 (dd, J = 5.0, 0.7 Hz, 1 H), 7.46 (dd, J = 3.6, 0.8 Hz, 1H), 7.13 (dd, J = 4.7, 3.9 Hz, 1 H), 4.14 (q, J = 7.1 Hz, 2H), 3.37 - 3.17 (m, 2H), 2.81 (dt, J = 17.2, 7.5 Hz, 1 H), 2.73 - 2.53 (m, 1 H), 1.25 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 170.82, 145.05, 131.17, 129.67, 127.48, 61.18, 52.59, 26.99, 14.08; IR: 2981 , 1732, 1373, 1234, 1043, 850, 719 cm ^"1 ; HRMS (ESI) calcd for m/z [M+H] +: 233.0306; found: 233.0305. tert-butyl 3-(thiophen-2-ylsulfinyl)propanoate{2c) Colourless oil; 82% yield; H NMR (400 MHz, CDCIa): δ = 7.65 (dd, J = 5.0, 1.1 Hz, 1 H), 7.46 (dd, J = 3.6, 1.1 Hz, 1 H), 7.13 (dd, J = 4.9, 3.7 Hz, 1 H), 3.24 (t, J = 7.3 Hz, 2H), 2.73 (dt, J = 17.2, 7.5 Hz, 1 H), 2.57 (dt, J = 17.2, 7.2 Hz, 1H), 1.44 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 169.99, 145.31 , 131.06, 129.57, 127.46, 81.64, 52.93, 28.16, 27.99; IR: 2978, 1730, 1367, 1247, 1155, 1043, 848, 725 cm ^"1 ; HRMS (ESI) calcd for CnHu jSa m/z [M+H] +: 261.0619; found: 261.0627. phenyl 3-(thiophen-2-ylsulfinyl)propanoate{2d) Colourless oil; 74% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.69 (d, J = 4.9 Hz, 1 H), 7.51 d, J = 3.6 Hz, 1H), 7.38 (t, J = 7.8 Hz, 2H), 7.24 (dd, J = 12.4, 4.8 Hz, 1 H), 7.19-7.12 (m, 1 H), 7.07 (d, J = 8.0 Hz, 2H), 3.49-3.25 (m, 2H), 3.19-3.04 (m, 1 H), 3.01-2.86 (m, 1 H); ¹³ C NMR (100 MHz, CDC! ₃ ): δ = 169.53, 150.38, 144.90, 131.26, 129.67, 129.44, 127.60, 126.06, 121.28, 52.31 , 27.05; IR: 3088, 1755, 1591 , 1492, 1401 , 1195, 1165, 1043, 850, 745, 719 cm ^"1 ; HRMS (ESI) calcd for Ci ₃ Hi ₂ 0 ₃ S ₂ m/z [M+H] +: 281.0306; found: 281.0300.

2-((2-(phenylsulfonyl)ethyl)sulfinyl)thiophene(2e) White solid; 82% yield; mp:121.9- 122.7 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.95-7,84 (m, 2H), 7.69 (dt, J = 4.9, 4.2 Hz, 2H), 7.59 (t, J = 7.7 Hz, 2H), 7.43 (dd, J = 3.7, 1.1 Hz, 1 H), 7.15 (dd, J = 4.9, 3.8 Hz, 1 H), 3.57- 3.46 (m, 1H), 3.40 (ddd, J = 14.1 , 8.5, 2.9 Hz, 1 H), 3.36- 3.30 (m, 1 H), 3.29-3.19 (m, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 143.83, 138.46, 134.30, 131.68, 129.74, 129.58, 128.05, 127.81 , 49.53, 48.82; IR: cm ^"1 ; IR: 2304, 1446, 1421 , 1323, 151, 1051 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₁₂ 0 ₃ S3 /z [M+H] +: 301 .0027; found: 301.0042.

3-(thiophen-2-ylsulfinyl)propanenitrile{2f) Colourless oil; 90% yield; H NMR (400 MHz, CDCI ₃ ): δ = 7.71 (dd, J = 5.0, 1.2 Hz, 1H), 7.50 (dd, J = 3.7, 1.2 Hz, 1 H), 7.17 (dd, J = 5.0, 3.7 Hz, 1 H), 3.35 - 3.12 (m, 2H), 2.89 (ddd, J = 17.3, 8.1 , 7.0 Hz, 1 H), 2.69 (ddd, J = 17.3, 8.4, 6.1 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 143.22, 131.91 , 130.13, 127.86, 116.87, 51.81 , 10.51 ; IR: 2241 , 1647, 1236, 1035, 854, 715 cm ^"1 ; HRMS (ESI) calcd for C ₇ H ₇ NOS ₂ m/z [M+H] +: 186.0047; found: 186.0044. Methyl 3-((3-methylthiophen-2-yl)sulfinyl)propanoate(4a) Orange oil; 62% yield; ¹ H NMR (300 MHz, CDCI ₃ ): 6 = 7.56 (d, J = 5.0 Hz, 1H), 6.90 (d, J = 5.0 Hz, 1H), 3.70 (s, 3H), 3.47 - 3.04 (m, 2H), 2.95 - 2.54 (m, 2H), 2.38 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.36, 141.49, 138.84, 130.46, 130.39, 52.19, 51.67, 27.20, 14.40; IR: 3099, 2953, 1732, 1436, 1361 , 1238, 1176, 1045, 829 cm ^'1 ; HRMS (ESI) calcd for C ₉ H ₁₂ 0 ₃ S ₂ m/z [M+H] +: 233.0306; found: 233.0303.

Methyt 3-{(5-methylthiophen-2-yl)sulfinyl)propanoate(4b) Colourless oil; 87% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.29 (d, J = 3.6 Hz, 1 H), 6.80-6.70 (m, 1H), 3.70 (s, 3H), 3.37- 3.17 (m, 2H), 2.88-2.73 (m, 1 H), 2.73-2.58 (m, 1 H), 2.55 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): 5 = 171.34, 147.28, 141.30, 130.93, 125.71, 52.16, 52.14, 27.08, 15.81 ; IR: 2953, 1737, 1732, 1440, 1359, 1222, 1176, 1041, 977, 808 cm ^'1 ; HRMS (ESI) calcd for C ₉ H ₁₂ 0 ₃ S ₂ m/z [M+H] +: 233.0306; found: 233.0305.

Methyl 3-((3,5-dimethylthiophen-2-yl)sulfinyl)propanoate(4c) Colourless oil; 53% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 6.58 (s, 1 H), 3.71 (s, 3H), 3.45 - 3.31 (m, 1 H), 3.23 (dt, J = 13.1 , 7.5 Hz, 1H), 2.87 - 2.66 (m, 2H), 2.50 (s, 3H), 2.31 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ - 171.36. 145.93, 142.64, 135.50, 128.89, 52.12, 51.55, 27.51 , 15.80, 14.41 ; IR: 2953, 2924, 1732, 1552, 1435, 1359, 1236, 1138, 1056, 1033, 831 cm ^"1 ; HRMS (ESI) calcd for C ₁₀ H ₁₄ O ₃ S ₂ /z [M+H] +: 247.0463; found: 247.0462.

Methyl 3-(benzo[b]thiophen-2-ylsu!finyl)propanoate(4d) Colourless oil; 80% yield; ¹ H NMR (400 MHz, CDCi ₃ ): δ = 7.93-7.86 (m, 1 H), 7.86-7.81 (m, H), 7.47-7.38 (m, 2H), 7.26 (s, 1 H), 3.68 (s, 3H), 3.45-3.35 (m, 1 H), 3.35-3.25 (m, 1 H), 2.88 (ddd, J = 17.3, 7.9, 7.1 Hz, 1 H), 2.69 (ddd, J = 17.3, 8.2, 6.1 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.31 , 145.52, 141.35, 138.16, 126.62, 126.36, 125.27, 124.89, 122.82, 52.20, 51.93, 26.50; IR: 1737, 1732, 1435, 1359, 1242, 1176, 1051 , 977, 831 cm ^'1 ; HRMS (ESI) calcd for C _l2 H ₁₂ 0 ₃ S ₂ m/z [M+H] +: 269.0306; found: 269.0299. Methyl 3-((3-methylbenzo[b]thiophen-2- yl)sulfinyl)propanoate(4e) Pale yellow oil; 93% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.92-7.85 (m, 1 H), 7.82-7.71 (m, 1 H), 7.51-7.39 (m, 2H), 3.68 (s, 3H), 3.42 (ddd, J = 13.9, 7.5, 6.4 Hz, 1 H), 3.31 (dt, J = 13.2, 7.4 Hz, 1 H), 2.86 (dt, J ~ 17.4, 7.4 Hz, 1 H), 2.74 (ddd, J = 17.4, 7.6, 6.5 Hz, 1 H), 2.56 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.28, 140.43, 140.34, 139.37, 135.98, 126.61 , 124.85, 123.06, 122.89, 52.19, 51.53, 27.18, 12.73; IR: 3055, 2953, 1737, 1517, 1438, 1319, 1105, 1047, 979, 731 cm ^"1 ; HRMS (ESI) calcd for C ₁₃ H ₁₄ 03S ₂ m/z [M+H] +: 283.0463; found: 283.0457. Methyl 3-((5-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)sulfinyl)pro panoate(5a)

Reddish oil; 84% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ - 7.30 (d, J = 8.9 Hz, 1H), 7.23 (d, J = 2.3 Hz, 1 H), 7.05 (dd, J = 8.9, 2.4 Hz, 1 H), 4.08 (s, 3H), 3.86 (s, 3H), 3.82-3.70 (m, 2H), 3.66 (s, 3H), 3.00 (m, 1H), 2.92-2.81 (m, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): 6 = 171.38, 157.01 , 150.16, 142.73, 131.53, 115.81 , 110.35, 101.99, 55.73, 52.17, 47.45, 30.93, 26.49; IR: 1735, 1646, 1614, 1010 cm ^"1 ; HRMS (ESI) calcd for C ₁₃ H ₁₆ N ₂ 0 ₄ S m/z [M+H] +: 297.0909; found: 297.0919.

Methyl 3-((3 _T 5-dimethylphenyl)sulfinyl)propanoate(5b) Colourless oil; quantitative yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.20 (s, 1 H), 7.1 1 (s, OH), 3.67 (s, 3H), 3.20 (ddd, J = 13.1 , 8.7, 6.5 Hz, 1 H), 3.01 - 2.76 (m, 2H), 2.55 (ddd, J = 17.0, 8.7, 5.5 Hz, 1 H), 2.38 (s, 6H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.76, 142.70, 139.33, 132.91 , 121.44, 52.06, 51.11, 26.12, 21.27; IR: 2953, 1730, 1606, 1436 ,1359, 1238, 1 174, 1049, 852, 686 cm ^"1 ; HRMS (ESi) calcd for C _l2 H ₁₆ 0 ₃ S m/z [M+H] +: 241.0898; found: 241.0901. Methyl 3-(furan-2-ylsulfinyl)propanoate(5c) Colourless oil; 85% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.69-7.62 (m, 1 H), 6.97 (dd, J = 3.5, 0.6 Hz, 1 H). 6.52 (dd, J = 3.4, 1.8 Hz, 1 H), 3.69 (s, 3H), 3.44 (dd, J = 7.8, 6.4 Hz, 1 H), 3.38 (dd, J = 7.7, 7.2 Hz, 1 H), 2.79 (t, J = 7.5 Hz, 1H), 2.71 (dd, J = 7.8, 6.5 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.27, 151.07, 146.99, 116.40, 111.40, 52.13, 47.09, 26.61 ; IR: 3128, 2954, 1737, 1732, 1438, 1365, 1242, 1128, 1041 , 1010, 908, 763 cm ^'1 ; HRMS (ESI) calcd for C ₈ Hi ₀ O ₄ S m/z [M+H] +: 203.0378; found: 203.0375.

Methyl 3-((2-methylfuran-3-yl)sulfinyl)propanoate(5d) Orange oil; 71 % yield; ¹ H NMR (400 MHz, CDCi ₃ ): δ = 7.40 (d, J = 2.0 Hz, 1 H), 6.66 (d, J = 2.0 Hz, 1H), 3.70 (s, 3H), 3.35- 3.20 (m, 1 H), 3.19-3.04 (m, 1H), 2.84-2.61 (m, 2H), 2.44 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.40, 154.75, 142.64, 121.67, 106.60, 52.16, 49.51 , 27.38, 12.38; IR: 2954, 1732, 1585, 1517, 1438, 1361 , 1232, 1128, 1039, 1012, 889, 744 cm ^"¾ ; HRMS (ESi) calcd for C ₉ H ₁₂ 0 ₄ S m/z [M+H] +: 217.0535; found: 217.0529.

Methyl 3-{benzofuran-2-ylsulfinyl)propanoate(5e) Pale yellow oil; 78% yield; H NMR (400 MHz, CDCI ₃ ): δ = 7.67 (d, J = 7.8 Hz, 1 H), 7.56 (d, J = 8.3 Hz, 1 H), 7.47 - 7.38 (m, 1H), 7.37 - 7.29 (m, 2H), 3.67 (s, 3H), 3.50 (t, J = 7.3 Hz, 2H), 2.90 (dt, J = 17.4, 7.4 Hz, 1 H), 2.72 (dt, J = 17.4, 7.1 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ = 171 ,30, 156.58, 153.62, 126.95, 126.48, 123.98, 122.31 , 112.23, 112.06, 52.21 , 47.22, 26.20; IR: 2953, 1732, 1444, 1359, 1236, 1168, 1053, 921, 827, 752 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₁₂ 0 ₄ S m/z [M+H] +: 253.0535; found: 253.0538.

Methyl 3-(pyridin-2-ylsulfiny!)propanoate(5f) Pale yellow oil; 78% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 8.62 (d, J = 4.5 Hz, 1 H), 8.00-7.86 (m, 2H), 7.38 (ddd, J = 6.9, 4.7, 1.7 Hz, 1 H), 3.64 (s, 3H), 3.49 (ddd, J = 13.7, 9.2, 6.1 Hz, 1 H), 3.19 (ddd, J - 13.7, 9.1 , 5.9 Hz, 1 H), 2.85 (ddd, J = 17.0, 9.1 , 6.1 Hz, 1H), 2.44 (ddd, J = 17.0, 9.2, 5.9 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 171.52, 163.72, 149.77, 137.86, 124.66, 120.24, 52.04, 47.94, 25.47; IR: 1737, 1732, 1423, 1361 , 1242, 1178, 1035, 829, 773 cm ^"1 ; HRMS (ESI) calcd for C ₉ HN0 ₃ S m/z [M+H] +: 214.0538; found: 214.0546.

Example 2

Thienyl group is a heterocyclic aromatic ring that can be used as a bioisostere of a phenyl group in order to either improve efficacy or change specificity of binding in medicinal chemistry. Some examples of commercially available drugs containing such a moiety are provided in Figure 1. initially, β-sulfinyl methyl ester 2a was chosen as the model substrate for reaction parameters screening (Table 1 and 2).

Base: The choice of base is crucial to this transformation (Table 1 ). One equivalent base was not efficient to promote the generation of su!fenate anion via retro-Michael reaction. 20 equivalent of CsOH base was chose in term of reaction rate and enantioselectivity which led a slightly improvement than 10 equivalent of that. Moreover, bases with less basicity such as NaOH, KOH, and RbOH usually cannot furnish the completion of reaction and low yield of sulfoxide was observed. On the other hand, in the presence of strong base NaO'Bu as well as KO'Bu, the reaction was too fast and most of the generated sulfenate anion intermediate underwent alkaline hydrolysis without trapping by the benzyl bromide electrophile. Therefore, the yield of desired sulfoxide product was still low.

Precursors and catalytst: The influence of the sulfenate anion precursors 2a-2f activated by different electron-withdrawing group (EWG) was first examined using catalyst 1 a bearing bulky benzyl groups on nitrogen (Table 2). The β-sulfinyl methyl ester 2a (EWG = C0 ₂ Me) was found to be the appropriate precursor in terms of reactivity and enantioselectivity (Table 2, entry 1 ). Attempts to use other bulkier β-sulfinyl esters did not lead to any improvements (entries 2-4). In particular, β-sulfinyl tert-butyl ester 2c (EWG = C0 ₂ tBu) was mostly recovered without undergoing the reaction. Both β-sulfinyl sulfone 2e (entry 5, EWG = S0 ₂ Ph) and β-sulfinyl nitrile 2f (entry 6, EWG = CN) did not lead to better results. Overall, only moderate results were obtained by using pentanidium 1a as catalyst. Further structural modification of pentanidium by the addition of halogens to ortho-position of the benzyl groups led to an increase in enantioselectivity relative to the parent catalyst 1a (entries 7-10). Eventually, it was found that iodinated pentanidium 1 d is the best catalyst, providing sulfoxide 3a with excellent enantioselectivity (91 % ee). These results indicate a stereocontrol enhancement induced by halogenated pentanidiums in comparison with non-halogenated pentanidium 1a.

CQ (h) (%)*

1 CsOH'H ₂ O(10 equiv) toluene -20 12 100 26

2 50% RbOH (10 equiv) toluene -20 12 100 29

3 50% CsOH (10 equiv) toluene -20 2 100 37

4 50% CsOH (10 equiv) toluene -30 10 100 42

5 50% CsOH (10 equiv) toluene -40 12 100 42

6 50% CsOH (20 equiv) toluene -40 12 100 43

7 67% CsOH (10 equiv) toluene -40 12 100 45

8 50% CsOH (10 equiv) toluene -60 48 80 54

9 50% CsOH (20 equiv) toluene -60 48 80 58

10 67% CsOH (20 equiv) toluene -60 48 100 59

1 1 67% CsOH (20 equiv) hexane -60 48 100 23

12 67% CsOH (20 equiv) pentane -60 48 100 37

13 67% CsOH (20 equiv) DCM -60 48 90 0

14 67% CsOH (20 equiv) MTBE -60 48 100 60

15 67% CsOH (20 equiv) CPME -60 48 100 61

16 67% CsOH (20 equiv) CPME -80 120 100 67

17 50% NaOH (20 equiv) CPME -60 48 50 37

18 50% KOH (20 equiv) CPME -60 48 80 61

19 50% RbOH (20 equiv) CPME -60 48 80 60

20 KO¾u (10 equiv) CPME -60 10 100 15^

21 NaO'Bu (10 equiv) CPME -60 10 100 35 ^d

Table 1 ^laJ [a] Reactions were performed by using 2a (0.02 mmol), and benzyl bromide (0.024 mmol) in the presence of 1 mol % of pentanidium 1a in solvent (0.4 mL). [b] Conversion was determined by TLC. [c] Determined by HPLC analysis using Chiralcel OD-H column, [d] The isolated yield of product 3a is very low. MTBE = Methyl tert-butyl ether. CPME = Cyclopentyl methyl ether.

Entry Catalyst 2 [EWG] Yield ee

1 la 2a [C0 ₂ Me] 76 61

2 la 2b [C0 ₂ Et] 39 61

3 la 2c [CC-2/Bu] trace 45

4 la 2d [C0 ₂ Ph] 39 58

5 la 2e [S0 ₂ Ph] 29 37

6 la 2f [CN] 73 57

7 lb 2a [COjMe] 67 79

8 lc 2a [C0 ₂ Me] 72 81

lc 2a [C0 ₂ Me] 86 88

10M Id 2a [C0 ₂ Me] 72 91

Table 2 ^la]

[a] Reactions were performed by using 2 (0,02 mmoi) and benzyl bromide (0.024 mmol) in the presence of 1 moi % of pentanidiums with 67 wt% aqueous CsOH solution(45 cL) in CPME (0.4 mL). [b] Yield of the isolated product, [c] Determined by HPLC analysis, [d] The reaction was conducted at -70 °C with saturated CsOH solution (24 L) in a solvent mixture of CPME (0.2 mL)/EtO (0.6 mL).

Reference Example 1 in contrast, commercially available phase-transfer catalysts were also tested and low enantioselectivity was obtained (below 15% ee, Table 3).

(RMS

Maruoka catalyst

entry base solvent temperature time yield (%) ^[ " ^] ee

O (fa)

33% NaOH Toluene/CH ₂ Cb rt 1.5 73 15

(10 equiv.) (7:3)(0.25 mL)

₂ w 67% CsOH CPME(0.4 mL) rt 0.5 82 10

(10 equiv.)

saturated CsOH CPME(0.4 mL) -60 28 86 9

(20 equiv.)

33% NaOH Toluene/CH ₂ Cl ₂ rt 12 45 1

(7:3)(0.25 mL)

[f] 33% NaOH Toluene(0.25 mL) rt 12 9 3

(10 equiv.)

67% CsOH CPME(0.4 mL) rt 2 50 3

(10 equiv.)

7M 67% CsOH CPME(0.4 mL) -60 48 70 1

(20 equiv.)

Table 3 ^[a}

[a] Reactions were performed by using 2a (0.02 mmol), and benzyl bromide (0.024 mmol) in the presence of 10 mol % of phase-transfer catalysts, [b] Isolated yield, [c] Determined by HPLC analysis using Chiralcel OD-H column, [d] The reaction was performed under the condition mentioned in reference 7c.[ej Cinchonidinium salt 1f was used as the phase- transfer catalyst, [f] Commercially available Maruoka Catalyst 1g was used as the phase- transfer catalyst.

Example 2

Experimental Procedures for Asymmetric Alkytation of Sulfenate Anions and Characterization of Sulfoxide Products Representative procedure for pentanidium 1d catalysed asymmetric alkylation of in situ generated sulfenate anions

A 5 mL RBF was charged with a solution of methyl 3-(thiophen-2-ylsulfinyi)propanoate 2a (13.1 mg, 0.06 mmol, 1.0 equiv.), benzyl bromide (8.6 pL, 0.072 mmol, 1.2 equiv.) and pentanidium 1d (1.1 mg, 0.0006 mmol, 1 mol %) in a solvent mixture of CPME (0.6 mL) and Et ₂ 0 (1.8 mL). The reaction mixture was stirred at -70 °C for 30 min, and then saturated CsOH solution (72 μΙ_, 1 ,2 mmol, 20.0 equiv.) was added by syringe in one portion. The reaction mixture was stirred at -70 °C and monitored by TLC. After 2a was completely consumed, reaction was quenched at 0 °C by addition of 1 aqueous HCI solution (1.5 mL) and extracted with CH ₂ CI ₂ (3 mL * 3). The combined organic layer was washed by brine and dried by Na ₂ S0 ₄ , filtered and concentrated. The sulfoxide 3a was obtained by flash chromatography (silica gel, hexane-ethyl acetate 10: 1-2:1 ), as colorless oil, 12.3 mg, 87% yield.

Corresponding examples were conducted using the starting materials listed in Table 4, along with the results.

l

sulfenate anion

Entry R Product Time [h] Yield [%] ^|aJ ee [%f ¹

1 PhCH ₂ 3a 12 87 92

2 4-MeC ₆ H ₄ CH ₂ 3b 12 88 94

3 4-CIC ₆ H ₄ CH2 3c 12 84 90 ^[cl

4 4-CF ₃ C ₆ H ₄ CH ₂ 3d 12 83 94 ^[cI

5 3- eOC ₆ H ₄ CH ₂ 3e 12 84 90

6 2-naphthylCH ₂ 3f 12 84 92

7 3g 36 82 92

8 Xx 3h 21 79 92

9 V 3i 21 77 82

10 ^M Me 3j 40 65 ₇₇ [c]

11 ^[dI CH ₃ CH ₂ CH ₂ 3k 28 66 ₈₁ [c]

₁₂ [d] CH3(CH ₂ )eCH ₂ 31 20 69 ₈₁ [c]

Tabled

[a] isolated yield, [b] Determined by HPLC analysis, [c] Data was obtained in the present of 1 mol% of pentanidium 1 c. [d] 2.5 equivalent of alkyl iodides was used. The absolute configuration of 3a was assigned to be R by single- crystal X-ray diffraction of 6q and DFT calculated specific optical rotation of 3a and 6q (see Example 4).

Characterisation data for the prepared sulfoxides are provided below. (R)-2-(benzylsulfinyl)thiophene(3a) Colorless oil; 87% yield; H NMR (400 MHz, CDCI ₃ ): δ = 7.62 (d, J = 4.8 Hz, 1 H), 7.36 - 7.19 (m, 3H), 7.16 - 6.96 (m, 4H), 4.36 (d, J = 12.4 Hz, 1 H), 4.14 (d, J = 12.4 Hz, 1 H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 144.94, 130.98, 130.19, 129.66, 129.24, 128.65, 128.42, 127.12, 65.07; IR: 1045 cm ^"1 ; HRMS (ESI) calcd for CnH ₁₀ OS2 m/z [M+H] +: 223.0251 ; found: 223.0255; [a]$ = -86.7 (c 0.85, CHCI ₃ ); HPLC analysis: Chiraicel OD-H (Hex/IPA = 90/10, 1.0 mUmin, 230 nm, 22°C), 20.7 (major), 29.1 min, 92% ee. {R)-2-((4-methylbenzyl)sulfinyl)thiophene(3b) Colorless oil. 88% yield; H NMR (400 MHz, CDCI ₃ ): 6 = 7.61 (dd, J = 4.9, 1.1 Hz, 1 H), 7.13 (dd, J ~ 3.6, 1.1 Hz, 1 H), 7.08 (d, J = 7.8 Hz, 2H), 7.03 (dd, J = 4.9, 3.7 Hz, 1H), 6.97 (d, J = 7.9 Hz, 2H), 4.32 (d, J = 12.5 Hz, 1 H), 4.11 (d, J = 12.5 Hz, 1 H), 2.32 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 145.16, 138.31 , 130.88, 130.07, 129.66, 129.35, 127.09, 126.13, 64.84, 21.16; IR: 2918, 1907, 1514, 1401 , 1224, 1087, 1045, 1001 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₁₂ OS ₂ m/z [M+H] +: 237.0408; found: 237.0418; [a]$ = -106.7 (c 1.06, CHCI ₃ ); HPLC analysis: Chiraicel OD-H (Hex/iPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 18.4 (major), 23.7 min, 94% ee.

(R)-2-((4-chlorobenzyl)sulfinyl)thiophene(3c) White solid; 84% yield; mp:96.0-97.5 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.63 (dd, J = 5.0, 1.2 Hz, 1H), 7.30 - 7.19 (m, 2H), 7.16 (dd, J = 3.7, 1.2 Hz, 1 H), 7.05 (dd, J = 5.0, 3.7 Hz, 1 H), 7.03 - 6.98 (m, 2H), 4.26 (d, J = 12.6 Hz, 1 H), 4.13 (d, J = 12.6 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 144.53, 134.62, 131.47, 131.17, 129.71 , 128.83, 127.65, 127.23, 64.03; IR: 2972, 1489, 1401 , 1224, 1087, 1045, 1033 cm ^"1 ; HRMS (ESI) calcd for C HeCIOSz m/z [M+H] +: 256.9862; found: 256.9875; [a]$ = - 56.9 (c 1.24, CHCI ₃ ); HPLC analysis: Chiraicel OD-H (Hex IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 22.1 (major), 30.1 min, 90% ee.

(/?)-2-((4-(trifluoromethyl)benzyJ)sulfinyl)thiophene(3d) White solid; 83% yield; mp: 161.9- 163.1 °C; ¹ H N R (400 MHz, CDCI ₃ ): δ = 7.64 (dd, J = 5.0, 1.2 Hz, 1 H), 7.55 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 7.18 (dd, J = 3.7, 1.2 Hz, 1 H), 7.06 (dd, J = 4.9, 3.7 Hz, 1 H), 4.32 (d, J = 12.6 Hz, 1 H), 4.22 (d, J = 12.5 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 144.38, 133.23, 131.33, 130.56, 130.49, 129.72, 127.31 , 125.52 (q, J = 3.7 Hz), 122.55, 64.21 ; 19F NMR (376 MHz, CDCI ₃ ): δ = -62.70; IR: 3049, 1417, 1126, 1066, 1047, 750 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₉ F ₃ OS ₂ m/z [M+H] +: 291.0125; found: 291.0115; = -106.5 (c 1.13, CHCI ₃ ); HPLC analysis: Chiraicel OD-H (Hex/IPA = 90/10, 1.0 mLmin, 230 nm, 22°C), 28.7 (major), 24.2 min, 93% ee. {/?)-2-((3-methoxybenzyI)sulfinyl)thiophene(3e) Colourless oil; 84% yield; H NMR (400 MHz, CDCI ₃ ): 6 = 7.62 (d, J = 5.0 Hz, 1 H), 7.19 (t, J = 7.9 Hz, 1 H), 7.15 (d, J = 3.6 Hz, 1 H), 7.07 - 6.99 (m, 1 H), 6.84 (dd, J = 8.3, 2.4 Hz, 1H), 6.69 (d, J = 7.5 Hz, 1 H), 6.59 (s, 1 H), 4.34 (d, J = 12.4 Hz, 1 H), 4.10 (d, J = 12.4 Hz, 1 H), 3.73 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 159.68, 145.04, 131.00, 130.63, 129.73, 129.65, 127.13, 122.47, 1 15.29, 114.35, 65.18, 55.19; IR: 1600, 1489, 1153, 1041 , 788 cm ^"1 ; HRMS (ESI) calcd for C^H-^C^ m/z [M+H] +: 253.0357; found: 253.0356; [a]$ = -91.5 (c 1.07, CHCI ₃ ); HPLC analysis: C Chiralcel OD-H (Hex/IPA - 90/10, 1.0 mUmin, 230 nm, 22°C), 25.3 (major), 36.9 min, 90% ee. (/¾)-2-((naphthalen-2-ylmethyI)sulfinyl)thiophene(3f) Beige powder; 84% yield; mp:93.9- 94.8 °C; H NMR (400 MHz, CDCI ₃ ): δ = 7.85 - 7.78 (m, 1 H), 7.75 (t, J = 5.4 Hz, 2H), 7.62 (dd, J = 5.0, 1.2 Hz, 1 H), 7.56 (s, 1 H), 7.52 - 7.43 (m, 2H), 7.18 (dd, J = 8.4, 1.6 Hz, 1 H), 7.11 (dd, J = 3.6, 1.2 Hz, 1H), 7.00 (dd, J = 4.9, 3.7 Hz, 1 H), 4.52 (d, J = 12.4 Hz, 1 H), 4.31 (d, J = 12.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCI3): δ = 144.94, 133.17, 132.98, 131.04, 129.76, 129.71 , 128.38, 127.86, 127.67, 127.42, 127.14, 126.69, 126.45, 126.39, 65.36; IR: 2983, 1508, 1419, 1406, 1224, 1045, 821 cm ^-1 ; HRMS (ESI) calcd for Ci ₅ Hi ₂ OS ₂ m/z [M+H] +: 273.0408; found: 273.0410; [«]# = -110.4 (c 1.32, CHCI ₃ ); HPLC analysis: Chiralcel OD- H (Hex/IPA = 90/10, 1.0 mUmin, 230 nm, 22°C), 30.5 (major), 41.3 min, 92% ee. (K)-2-(allylsulfinyl)thiophene(3g) Pale yellow oil; 82% yield; H NMR (400 MHz, CDCI ₃ ): δ = 7.65 (dd, J = 5.0, 1.2 Hz, 1 H), 7.43 (dd, J = 3.7, 1.2 Hz, 1 H), 7.12 (dd, J = 5.0, 3.7 Hz, 1 H), 5.71 (ddt, J = 17.6, 10.2, 7.5 Hz, 1 H), 5.37 (d, J = 10.2 Hz, 1 H), 5.29 (dd, J = 17.0, 1.2 Hz, 1 H), 3.79 (dd, J = 12.6, 7.4 Hz, 1 H), 3.70 (dd, J = 12.4, 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCIg): δ = 145.00, 131.08, 129.82, 127.22, 125.21 , 124.23, 62.08; IR: 3082, 1635, 1404, 1222, 1039, 933, 850, 711 cm ^'1 ; HRMS (ESI) calcd for C ₇ H ₈ OS ₂ m/z [M+H] +: 173.0095; found: 173.0101 ; [a]J? = +39.1 (c 0.45, CHCI ₃ ); HPLC analysts: Chiralcel OD-H (Hex IPA = 90/10, 1.0 mUmin, 254 nm, 22°C), 13.7 (major), 16.6 min, 92% ee.

(R)-2-((2-methytallyl)suifinyl)thiophene(3h) Pale yellow oil; 79% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.65 (dd, J = 5.0, 1.1 Hz, 1 H), 7.43 (dd, J = 3.6, 1.1 Hz, 1 H), 7.11 (dd, J = 4.9, 3.7 Hz, 1H), 5.08 - 4.98 (m, 1 H), 4.88 (s, 1 H), 3.82 (d, J = 12.2 Hz, 1H), 3.58 (d, J = 12.3 Hz, 1 H), 1.81 (S, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): 6 = 145.81 , 134.65, 130.98, 129.71 , 127.18, 118.98, 67.65, 22.79; IR: 3080, 2972, 2912, 1649, 1448, 1404, 1377, 1224, 1045, 902, 850, 715 cm ^"1 ; HRMS (ESI) calcd for C ₈ H ₁₀ OS ₂ m/z [M+H] +: 187.0251 ; found: 187.0257; [aft = +34.3(c 0.72, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex IPA = 90/10, 1.0 mL min, 230 nm, 22°C), 1 1.6 (major), 14.2 min, 92% ee. (/¾-2-<but-2-yn-1-ylsuifinyl)thiophene(3i) Pale yellow oil; 77% yield; H NMR (400 MHz, CDCI ₃ ): δ = 7.67 (d, J = 5.0 Hz, 1H), 7.52 (d, J = 3.6 Hz, 1 H), 7.17 - 7.10 (m, 1 H), 3.90 - 3.63 (in, 2H), 1.82 (t, J = 2.5 Hz, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 145.01 , 131.38, 130.04, 127.10, 85.26, 67.59, 49.46, 3.74; IR: 3080, 2902, 2235, 1404, 1224, 1047, 1001, 850, 713 cm- ; HRMS (ESI) calcd for C _a H ₈ OS ₂ m/z [M+HJ +: 185.0095; found: 185.0098; [ctYj = -103.3 (c 0.58, CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex/lPA = 90/10, 1.0 mL/min, 254 nm, 22°C), 11.6, 14.1 (major) min, 82% ee. (/?)-2-{methylsulfinyl)thiophene{3j) Colourless oil; 65% yield; H NMR (400 MHz, CDCI ₃ ): δ - 7.65 (dd, J = 5.0, 1.1 Hz, 1 H), 7.49 (dd, J = 3.6, 1.1 Hz, 1 H), 7.12 (dd, J = 4.9, 3.7 Hz, 1 H), 2.93 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 130.74, 129.19, 127.42, 44.55; IR: 1406, 1033, 954, 717 cm ^"1 ; HRMS (ESI) calcd for C ₅ H ₆ OS2 m/z [M+H] +: 146.9938; found: 146.9944; [α]? = +38.7 (c 0.15, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex lPA = 95/5, □ 1.0 mL min, 254 nm, 22°C), 34.1 (major), 38.2 min, 77% ee.

(R)-2-(propylsulfinyl)thiophene{3k) pale yellow oil; 66% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.65 (dd, J = 5.0, 1.2 Hz, 1 H), 7.47 (dd, J = 3.7, 1.2 Hz, 1 H), 7.12 (dd, J - 5.0, 3.7 Hz, 1 H), 3.12 (dt, J - 12.8, 7.3 Hz, 1 H), 2.91 (dt, J = 12.8, 7.7 Hz, 1 H), 1.84 - 1.67 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H); ³ C NMR (100 MHz, CDC! ₃ ): δ = 130.88, 129.67, 127.32, 60.22, 16.50, 13.18; IR: 1458, 1404, 1226, 1026, 848, 717 cm ^"1 ; HRMS (ESI) calcd for C ₇ H ₁₀ OS ₂ m/z [M+H] +: 175.0251 ; found: 175.0257; = +60.5 (c 0.18, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex lPA = 95/5, 1.0 mL/min, 230 nm, 22°C), 19.8 (major), 23.0 min, 81 % ee. (R)-2-(octylsulfinyl)thiophene(3l) pale yellow oil; 69% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.65 (dd, J = 5.0, 1.2 Hz, 1 H), 7.47 (dd, J = 3.6, 1.2 Hz, 1H), 7.12 (dd, J = 5.0, 3.7 Hz, 1 H), 3.11 (ddd, J = 12.9, 8.5, 6.4 Hz, 1 H), 2.94 (ddd, J = 12.8, 8.6, 7.1 Hz, 1 H), 1.81 - 1.58 (m, 2H), 1.43 (dd, J = 12.7, 5.9 Hz, 2H), 1.36 - 1.15 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 130.87, 129.69, 127.31 , 58.35, 31.68, 29.09, 28.95, 28.58, 22.74, 22.57, 14.04; IR: 2924, 2854, 1458, 1404, 1226, 1049, 848, 717 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₂₀ OS ₂ m/z [M+H] +: 245.1034; found: 245.1020; [α] = +34.7 (c 0.32, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/lPA = 95/5, 1.0 mL/min, 230 nm, 22°C), 13.2 (major), 15.9 min, 81 % ee. Example 3

One-mmol scale experiment for synthesis of sulfoxide 6q

1 mmol 18h 245 mg

85% yield 91% ee

A 50 mL RBF was charged with a solution of methyl 3-((3-methylbenzo[b]thiophen-2- yl)sulfinyl)propanoate 4e (282 mg, 1 mmol, 1.0 equiv.), benzyl bromide (143 DL, 1.2 mmol, 1.2 equiv.) and pentanidium 1 d (4.4 mg, 0.0025 mmol, 0.25 mol %) in Et ₂ 0 (20 mL). The reaction mixture was vigorously stirred at -60 °C for 30 min and then saturated CsOH (1.2 mL, 20 mmol, 20.0 equiv.) was added by syringe in one portion. The reaction mixture was stirred at -60 °C and monitored by TLC. After 4e was completely consumed within 18 h, the reaction was quenched by at 0 °C by addition of 1 M aqueous HC! solution (30 mL) and extracted with Et ₂ 0 (50 mL * 3). The combined organic layer was washed by brine and dried by a ₂ S0 ₄ , filtered and concentrated. The sulfoxide 6q was obtained by flash chromatography (silica gel, hexane-ethyl acetate 10:1-2:1 ), as a white solid (245 mg, 85% yield) with 91% ee. Characterisation data provided in Example 4.

Example 4

The general procedure outlined in Example 2 was repeated using different starting materials The results of which are outlined in Table 5.

o 1d (1 mol%) O R ² CH ₂ Br(1.2equiv.)

-St -R ^{2 R1'} . ^C _f ^¾Me saturated aq. CsOH ' ^R1'

4a-e.5a-f 6a.v 7a-f

CPME/Et ₂ 0 (1:3)

R ¹ = aryl, eteroaryl

R ² = aryl

Table 5 ^[al [a] Ratio of dhrneso ~ 4.75:1 , determined by ¹ H NMR analysis, [b] The reactions were conducted at -40 °C. [c] Data was obtained in the presence of pentanidium 1 c. The absolute configuration was assigned as R by analogy to 6q (see characterisation data below). Characterisation data for the resulting sulfoxides are presented below.

{R)-2-{benzylsuffinyl)-3-methylthiophene(6a> White solid; 85% yield; mp:63.1-63.9 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.53 (d, J = 5.0 Hz, 1 H), 7.31 - 7.20 (m, 3H), 7.02 (dd, J = 7.9, 1.4 Hz, 2H), 6.75 (d, J = 5.0 Hz, 1 H), 4.47 (d, J - 12.1 Hz, 1 H), 4.11 (d, J = 12.1 Hz, 1H), 1.80 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 142.22, 138.50, 130.36, 130.19, 129.83, 129.14, 128.62, 128.38, 64.64, 13.83; IR: 2983, 1465, 1419, 1045, 750 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₁₂ OS _z m/z [M+H] +: 237.0408; found: 237.0408; [a]? = -129.5 (c 1.3, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/!PA = 90/10, 1.0 mUmin, 230 nm, 22°C), 20.6 (major), 30.4 min, 91% ee.

(f?)-3-methyl-2-((4-methyibenzyI)sulfinyl)t iophene(6b) Colourless oil; 86% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.53 (d, J = 5.0 Hz, H), 7.05 (d, J = 7.8 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 5.0 Hz, 1H), 4.44 (d, J = 12.1 Hz, 1 H), 4.08 (d, J - 12.1 Hz, 1H), 2.31 (s, 3H), 1.82 (s, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 142.23, 138.61 , 138.29, 130.30, 130.08, 129.84, 129.30, 126.01 , 64.32, 21.15, 13.90; IR: 2920, 1614, 1514, 1444, 1381 , 1101, 1045, 821 , 732 cm ^"1 ; HRMS (ESI) calcd for C ₁₃ H ₁₄ OS ₂ m/z [M+H] +: 251.0564; found: 251.0562; [o¾ ^f = -162.9 (c 1.13, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 17.5 (major), 24.6 min, 95% ee. (R)-2-((4-chlorobenzyt)sulfinyl)-3-rtiethylthiophene(6c) Colourless oil; 87% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.54 (d, J = 5.0 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 2H), 6.97 (d, J = 8.2 Hz, 2H), 6.79 (d, J = 5.0 Hz, 1 H), 4.39 (d, J = 12.3 Hz, 1 H), 4.09 (d, J = 12.3 Hz, 1 H), 1.91 (s, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 142.09, 138.27, 134.58, 131.47, 130.59, 129.98, 128.80, 127.71 , 63.52, 14.02; iR: 1490, 1408, 1095, 1047, 1016 cm ^'1 ; HRMS (ESI) calcd for C ₁₂ HnClOS ₂ m/z [M+H] +: 271.0018; found: 271.0017; [α]# = -128.4 (c 1.35, CHCi ₃ ); HPLC analysis: Chiralcel OJ (Hex/IPA = 95/5, 1.0 mL/min, 230 nm, 22°C), 31.8 (major), 43.1 min, 92% ee.

(R)-3-methyl-2-((4-(trifluoromethyl)benzyl)sulfinyl)thiop hene(6d) White solid; 89% yield; mp.107.1-108.5 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.54 (dd, J = 8.5, 6.5 Hz, 3H), 7.18 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 5.0 Hz, 1 H), 4.44 (d, J - 12.1 Hz, 1 H), 4.18 (d, J = 12.1 Hz, 1 H), 1.92 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 141.95, 138.31 , 133.37, 130.64(q, J = 10.3 Hz), 130.58, 130.06, 125.50(q, J = 3.7 Hz), 125.22, 122.51 , 63.79, 14.00; 19F NMR (376 MHz, CDCI ₃ ): δ = -62.71 ; IR: 2368, 1618, 1419, 1325, 1168, 1126, 1066, 1049, 1018 cm ^-1 ; HRMS (ES!) calcd for C ₁₃ HiiF ₃ OS ₂ m/z [M+H] +: 305.0282; found: 305.0281; [a]$ = -78.0 (c 1.01, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex/IPA = 95/5, 1.0 mL/min, 230 nm, 22°C), 21.8 (major), 29.6 miri, 91% ee.

(R)-2-({3-methoxyb©nzyl)sulfinyl)-3-methylthiophene(6e) Colourless oil; 88% yield; ¹ H NMR (400 MHz, CDCI ₃ ): 6 = 7.54 (d, J = 5.0 Hz, 1 H), 7.16 (t, J = 7.9 Hz, 1H), 6.82 (dd, J = 8.3, 2.4 Hz, 1 H), 6.76 (d, J = 5.0 Hz, 1 H), 6.65 (d, J = 7.5 Hz, 1 H), 6.51 (s, 1 H), 4.45 (d, J = 12.0 Hz, 1 H), 4.06 (d, J - 12.0 Hz, 1 H), 3.70 (s, 3H), 1.84 (s, 3H); ^,3 C NMR (100 MHz, CDCI ₃ ): δ = 159.65, 142.18, 138.85, 130.57, 130.28, 129.86, 129.59, 122.49, 115.14, 114.38, 64.78, 55.18, 13.90; IR: 1600, 1490, 1165, 1045 crrT ¹ ; HRMS (ESI) caicd for C _l3 H ₁₄ 0 ₂ S ₂ m/z [M+H] +: 267.0513; found: 267.0512; [a]£ = -136.7 (c 1.38, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex IPA = 95/5, 1.0 mL min, 230 nm, 22*C), 53.1 (major), 61.8 min, 94% ee.

{ ?)-3-methyI-2-((naphthalen-2-ylmethyl)sulfinyl)thiophene(6f) Colourless oil; 87% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.87 - 7.76 (m, 1 H), 7.72 (t, J = 5.6 Hz, 2H), 7.54 (d, J = 5.0 Hz, 1H), 7.52 - 7.41 (m, 3H), 7.14 (dd, J = 8.4, 1.7 Hz, 1H), 6.72 (d, J = 5.0 Hz, 1 H), 4.63 (d, J = 12.1 Hz, 1 H), 4.28 (d, J = 12.1 Hz, 1 H), 1.74 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 142.17, 138.65, 133.14, 132.89, 130.40, 129.90, 129.68, 128.31 , 127.79, 127.64, 127.40, 126.62, 126.45, 126.42, 64.86, 13.94; IR: 1417, 1045, 1028 cm ^'1 ; HRMS (ESI) calcd for Ci ₆ H ₁₄ OS ₂ m/z [M+H] +: 287.0564; found: 287.0562; [α]? = -170.6 (c 1.22, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL/min, 254 nm, 22°C), 26.5 (major), 40.6 min, 92% ee.

1,3-bis(((RH3-methylthiophen-2-yl)sulfinyl)inethyl)benzen e(6g) Colourless oil; 87% yield; enantiomers: mesomer = 4.75:1 ; ¹ H NMR (400 MHz, CDCi ₃ ): δ - 7.54 (d, J = 5.0 Hz, 2H), 7.18 (t, J = 7.7 Hz, 1H), 7.01 (dd, J = 7.7, 1.6 Hz, 2H), 6.80 (d, J = 5.0 Hz, 2H), 6.75 (s, 1H), 4.32 (d, J = 12.3, 2H), 4.04 (d, J = 12.3 Hz, 2H), 1.94 (s, 6H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 141.91 , 138.83, 131.99, 130.47, 130.22, 130.08, 130.03, 128.94, 64.01 , 14.08; IR: 2991 , 1606, 1531 , 1487, 1446, 1384, 1217, 1099, 1041 , 1026 cm ^"1 ; HRMS (ESI) calcd for C ₁₈ H ₁₈ 0 ₂ S4 m/z [M+H] +: 395.0268; found: 395.0258; [α]% = -136.25 (c 1.84, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex/IPA = 80/20, 1.0 mL min, 230 nm, 22°C), 64.1 (major), 90.7 min, 99% ee. (/?}-2-(benzyl$ulfinyl)-5-methylthiophene(6h) White solid; 85% yield; mp: 109.3-110.8 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.33 - 7.27 (m, 3H), 7.12 (dd, J = 6.3, 2.7 Hz, 2H), 6.97 (d, J = 3.6 Hz, 1 H), 6.67 (d, J = 3.6 Hz, 1 H), 4.37 {d, J = 12.4 Hz, 1 H), 4.15 (d, J = 12.4 Hz, 1 H), 2.54 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 146.99, 141.23, 130.88, 130.17, 129.50, 128.65, 128.36, 125.40, 64.61 , 15.86; IR: 1494, 1440, 1213, 1072, 1041 cm ^"1 ; HRMS (ESI) calcd for Ci ₂ H ₁₂ OS ₂ m/z [M+H] +: 237.0408; found: 237.0439; [α]£ = -132.4 (c 1.0, CHCl ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 16.5 (major), 24.5 min, 91 % ee. ( ?)-2-((4-chlorobenzyl)suifinyl)-5-methylthiophene{6i) White solid; 86% yield; mp:1 18.2- 119.6 °C; H NMR (400 MHz, CDCI ₃ ): δ = 7.30 - 7.21 (m, 2H), 7.06 (s, 1 H), 6.99 (d, J = 3.6 Hz, 1 H), 6.69 (d, J = 3.6 Hz, 1 H), 4.28 (d, J = 12.5 Hz, 1 H), 4.12 (d, J = 12.6 Hz, 1 H), 2.55 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 147.20, 140.89, 134.54, 131.48, 130.94, 128.84, 127.97, 125.51 , 63.66, 15.87; IR: 1492, 1442, 1093, 1045, 1016 cm ^"1 ; HRMS (ESI) calcd for C ₁₂ H ₁₁ CIOS ₂ m/z [M+H] +: 271 .0018; found: 271.0013; = -93.8 (c 1.19, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex IPA = 90/10, 1.0 mL min, 230 nm, 22°C), 1 .5 (major), 23.7 min, 84% ee.

(R)-2-(benzylsulfinyl)-3,5-dimethylthiophene(6j) Colourless oil; 93% yield; *H NMR (400 MHz, CDCI ₃ ): δ = 7.34 - 7.16 (m, 3H), 7.06 (dd, J = 7.5, 1.8 Hz, 2H), 6.41 (s, 1 H), 4.44 (d, J = 12.0 Hz, 1 H), 4.08 (d, J = 12.0 Hz, 1 H), 2.49 (s, 3H), 1.73 (s, 3H); ³ C NMR (100 MHz, CDCI3): δ = 145.63, 142.91 , 135.43, 130.16, 129.56, 128.58, 128.34, 128.24, 64.50, 15.91 , 13.87; IR: 1556, 1494, 1454, 1242, 1215, 1055, 1033, 831 cm ^"1 ; HRMS (ESI) calcd for C ₁₃ H _l4 OS ₂ m/z [M+H] +: 251.0564; found: 251.0563; = -297.8 (c 1 .16, CHCI ₃ ); HPLC G analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 15.6 (major), 25.3 min, 95% ee.

(R)-2-(benzylsulfinyl)benzo[b}thiophene(6k) White solid; 89% yield; mp:166.0-167.1 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.96 - 7.84 (m, 1 H), 7.74 (dd, J = 6.8, 2.0 Hz, 1 H), 7.48 - 7.37 (m, 2H), 7.34 (s, 1 H), 7.33 - 7.22 (m, 3H), 7.12 (dd, J = 7.8, 1.3 Hz, 2H), 4.40 (d, J = 12.5 Hz, 1 H), 4.24 (d, J = 12.5 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 145.64, 141.26, 138.09, 130.23, 129.05, 128.71 , 128.55, 126.75, 126.21 , 125.10, 124.80, 122.84, 64.44; IR: 1651 , 1454, 1417, 1027, 1037 cnrf ¹ ; HRMS (ESI) calcd for C ₁₅ H ₁₂ OS ₂ m/z [M+H] +: 273.0408; found: 273.0405; [a]$ = -58.9 (c 1 .27, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 32.4 (major), 41.6 min, 92% ee. (R)-2-{{4-methylben2yl)sulfinyI)benzoIb]thiophene{6l) White solid; 91% yield; mp:152.0- 152.5 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.94 - 7.84 (m, 1H), 7.75 (dd, J = 6.7, 2.2 Hz, 1 H),

7.47 - 7.38 (m, 2H), 7.37 (s, 1 H), 7.07 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 4.37 (d, J = 12.5 Hz, 1 H), 4.21 (d, J = 12.5 Hz, 1 H), 2.31 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): 6 = 145.85, 141.28, 138.46, 138.12, 130.12, 129.42, 126.76, 126.16, 125.91, 125.07, 124.79, 122.85, 64.21 , 21.19; IR: 1506, 1417, 1049, 819 cm ^"1 ; HRMS (ESI) calcd for 0 ₁₆ Η ₁₄ 05 ₂ m/z [M+H] +: 287.0564; found: 287.0565; [a]£ = -84.5 (c 1.34, CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 20.3 (major), 27.3 min, 92% ee. (f?)-2-((4-chlorobenzyl)sulftnyI)benzo[b]thiophene(6m) White solid; 81% yield; mp:178.3- 179.0 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.95 - 7.82 (m, 1 H), 7.77 (dd, J = 6.5, 2.4 Hz, 1 H),

7.48 - 7.40 (m, 2H), 7.39 (s, 1H), 7.30 - 7.17 (m, 2H), 7.05 (d, J - 8.4 Hz, 2H), 4.31 (d, J = 12.7 Hz, 1 H), 4.23 (d, J = 12.7 Hz, 1 H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ = 145.18, 141.26, 138.01 , 134.75, 131.53, 128.89, 127.45, 126.90, 126.36, 125.23, 124.89, 122.86, 63.39; IR: 1247, 1037 cm ^-1 ; HRMS (ESI) calcd for C ₁₅ HnCIOS ₂ m/z [M+H] +: 307.0018; found: 307.0015; [ ]% = -20.3 (c 1.41 , CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 25.8 (major), 30.2 min, 90% ee.

( ?)-2-((4-(trifluoromethyl)benzyl)sulflnyl)benzo[b]thiophene( 6n) White solid; 80% yield; mp:205.9-207.2 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.90 (d, J = 7.6 Hz, 1 H), 7.80 - 7.71 (m, 1 H), 7.53 (d, J = 8.0 Hz, 2H), 7.44 (ddd, J = 7.1 , 6.2, 3.5 Hz, 2H), 7.40 (s, 1H), 7.26 (d, J = 7.8 Hz, 2H), 4.38 (d, J = 12.6 Hz, 1 H), 4.31 (d, J = 12.6 Hz, 1 H); ³ C NMR (100 MHz, CDCI ₃ ): 5 = 144.96(two peaks), 141.28, 137.98, 133.06, 130.61 , 126.96, 126.47, 125.59 (q, J = 3.8 Hz), 125.32, 124.92(two peaks), 122.87, 63.57; 19F NMR (376 MHz, CDCI ₃ ): δ = - 62.73; iR: 2358, 1421 , 1336, 1 1 16, 1070, 1033, 1018 cm ^"1 ; HRMS (ESI) calcd for Ci ₂ HnCIOS ₂ m/z [M+1] +: 271.0018; found: 271.0013. HRMS (ESI) calcd for CieHnF ₃ OS ₂ m/z [M+H] +: 341.0282; found: 341.0280; [a]Jf = +27.4 (c 0.81 , CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 mL min, 254 nm, 22°C), 19.9 (major), 24.8 min, 85% ee. (R)-2-((3-methoxybenzyl)sulfinyl)benzo[b]thiophene(6o) White solid; 81 % yield; mp:101.1-102.6 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.89 (d, J = 7.2 Hz, 1 H), 7.80 - 7.68 (m, 1 H), 7.47 - 7.37 (m, 2H), 7.36 (s, 1 H), 7.18 (t, J = 7.9 Hz, 1 H), 6.83 (dd, J = 8.3, 2.4 Hz, 1 H), 6.72 (d, J = 7.5 Hz, 1 H), 6.61 (s, 1H), 4.39 (d, J = 12.4 Hz, 1 H), 4.19 (d, J = 12.4 Hz, 1 H), 3.61 (s, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 159.69, 145.75, 141.23, 138.08, 130.46, 129.71 , 126.80, 126.23, 125.13, 124.80, 122.82, 122.50, 115.09, 114.66, 64.62, 55.06; IR: 1568, 1489, 1321 , 1166, 1155, 1039, 975 cm ^"1 ; HRMS (ESI) calcd for C ₁₆ H ₁₄ 0 ₂ S ₂ m/z [M+H] +: 303.0513; found: 303.0515; [a]£ = -71.8 (c 1.42, CHCI ₃ ); HPLC analysis: Chiralce! OD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 24.4 (major), 35.1 min, 92% ee.

(R)-2-{{naphthalen-2-ylmethyl)sulfinyi)benzo[b]thiophene( 6p) White solid; 90% yield; mp:198.3-199.7 °C; ¹ H NMR (400 MHz, CDCi ₃ ): 6 = 7.90 (d, J = 8.0 Hz, 1 H), 7.84 - 7.77 (m, 1 H), 7.71 (dd, J = 18.3, 8.0 Hz, 3H), 7.62 (d, J = 6.2 Hz, 1 H), 7.52 - 7.36 (m, 4H), 7.34 (s, 1 H), 7.21 (dd, J = 8.4, 1.7 Hz, 1 H), 4.57 (d, J = 12.5 Hz, 1 H), 4.41 (d, J = 12.5 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): 6 = 145.72, 141.28, 138.09, 133.17, 133.06, 129.83, 128.48, 127.89, 127.68, 127.43, 126.87, 126.53, 126.51, 126.43, 126.24, 125.11 , 124.84, 122.85, 64.80; IR: 1421 , 1047 cm ^-1 ; HRMS (ESI) calcd for C _t9 H ₁₄ OS ₂ m/z [M+H] +: 323.0564; found: 323.0569; [a]# = -95.3 (c 0.78, CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 mL min, 230 nm, 22°C), 32.8 (major), 42.6 min, 91% ee.

(R)-2-{benzylsulfiny])-3-methylbenzo[b]thiophene(6q) White solid; 83% yield; mp: 137.8- 138.7 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.90 (dd, J = 7.0, 1.1 Hz, 1 H), 7.60 (dd, J = 7.1 ,

1.5 Hz, 1 H), 7.50 - 7.37 (m, 2H), 7.27 (dt, J = 5.1 , 3.8 Hz, 1 H), 7.20 (dd, J = 10.1 , 4.7 Hz,

2H), 7.07 - 6.97 (m, 2H), 4.54 (d, J = 12.0 Hz, 1 H), 4.22 (d, J = 12.0 Hz, 1H), 1.90 (s, 3H);

¹³ C NMR (100 MHz, CDCI ₃ ): 5 = 140.47, 139.88, 139.05, 136.99, 130.20, 129.03, 128.67,

128.47, 126.42, 124.69, 123.12, 122.74, 64.12, 12.04; IR: 1454, 1107, 1045, 960 cm ^"1 ; HRMS (ES!) calcd for C ₁₆ H ₁₄ OS ₂ m/z [M+H] +: 287.0564; found: 287.0567; = -227.2 (c

1.3, CHCl ₃ ); HPLC analysis: Chiralcel OD-H (Hex/iPA = 90/10, 1.0 mL/min, 254 nm, 22°C),

31.4 (major), 64.6 min, 95% ee.

Crystal data for (R)-6q: [C ₁₆ H ₁₄ OS ₂ ], M = 286.39, monoclinic, P 1 21 1 , a = 11.0865(5), b = 5.5227(3), c = 11.5834(5) A, a = 90, β = 101.001 (2), γ = 90°, V = 696.19(6) A3, Z = 2, pealed = 1.366 g/cm3, p(CuKa) = 0.370 mm-1 , T = 103(2) , Wavelength - 0.71073 A, colourless blocks, Bruker X8 APEX X-ray diffractionmeter; 2431 independent measured reflections, F2 refinement, R1 (obs) = 0.0428, wR2(all) = 0.1296, 2188 independent observed absorption- corrected reflections, 173 parameters. CCDC 1006625 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data request cif.

( ?)-3-methyl-2-((4-methylbenzyl)sulfinyl)benzo[b]thiophene(6r ) White solid; 80% yield; mp:158.5-159.7 °C; ¹ H NMR (400 MHz, CDCI ₃ ): 6 = 7.94 - 7.87 (m, 1 H), 7.62 (dd, J = 6.9, 1.7 Hz, 1 H), 7.43 (pd, J = 7.1 , 1.3 Hz, 2H), 7.06 - 6.97 (m, 2H), 6.92 (d, J = 8.0 Hz, 2H), 4.50 (d, J = 12.1 Hz, 1 H), 4.19 (d, J = 12.1 Hz, 1 H), 2.30 (s, 3H), 1.94 (s, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 140.49, 140.06, 139.09, 138.38, 136.94, 130.08, 129.34, 126.37, 125.88, 124.65, 123.12, 122.75, 63.80, 21.15, 12.13; IR: 1427, 1255, 1105, 1039, 1010, 966 cm ^"1 ; HRMS (ESI) calcd for C _l7 H ₁₆ OS ₂ m/z [M+H] +: 301.0721 ; found: 301.0716; [a]$ = -240.2 (c 1.42, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex IPA - 95/5, 1.0 mL min, 254 nm, 22°C), 46.2, 64.5(major) min, 94% ee.

{ ?)-2-({4-chforoben2yl)sulfinyl)-3-methylbenzo[b]thiophene(6s ) White solid; 83% yield; mp:185.2-186.8 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.93 - 7.83 (m, 1 H), 7.69 - 7.60 (m, 1 H), 7.45 (dq, J = 7.3, 5.9 Hz, 2H), 7.19 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H), 4.46 (d, J = 12.2 Hz, 1 H), 4.20 (d, J = 12.2 Hz, 1 H), 2.03 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 140.47, 139.64, 139.01, 136.98, 134.67, 131.49, 128.87, 127.61 , 126.60, 124.84, 123.14, 122.86, 63.11 , 12.29; IR: 2985, 1421 , 1095, 1045 cm ^'1 ; HRMS (ESI) calcd for d ₆ H ₁₃ CIOS ₂ m/z [M+H] +: 321.0175; found: 321.0177; - -203.7 (c 1.73, CHCI ₃ ); HPLC analysis: Chiralcel OJ (ΗΘΧ/ΙΡΑ = 90/10, 1.0 mL/min, 254 nm, 22°C), 35.7, 39.9(major) min, 91% ee. (A¾)-3-methyI-2-{(4-{trifluoron(iethyl)benzyl)sulfinyI)benz o[b]thiophene(6t) White solid; 75% yield; mp:178.7-180.0 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.90 (dd, J = 6.9, 1.5 Hz, 1 H), 7.65 (dd, J = 6.9, 1.8 Hz, 1H), 7.54 - 7.37 (m, 4H), 7.20 (d, J - 8.0 Hz, 2H), 4.53 (d, J = 12.2 Hz, 1H), 4.28 (d, J = 12.2 Hz, 1 H), 2.04 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 140.46(two peaks), 139.52, 138.97, 136.91 , 133.27, 130.57, 126.70, 125.57 (q, J = 3.7 Hz), 124.92, 123.13, 122.87(two peaks), 63.31, 12.24; 19F NMR (376 MHz, CDCI ₃ ): δ = -62.72; IR: 1620, 1421 , 1325, 166, 122, 1066, 1039, 1018 cm ^-1 ; HRMS (ESi) calcd for C ₁₇ H ₁₃ F ₃ 0S ₂ m/z [M+H] +: 355.0438; found: 355.0446; [a]$ - -122.1 (c 1.5, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex IPA = 95/5, 1.0 mL/min, 254 nm, 22°C), 41.0, 49.4(major) min, 89% ee. {R)-2-((3-methoxybenzyl)sulfinyl)-3-methylbenzoEb]thiophene( 6u) Pale yellow oil; 90% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.90 (dd, J = 6.9, 1.6 Hz, 1 H), 7.69 - 7.58 (m, 1 H), 7.43 (pd, J - 7.1 , 1.4 Hz, 2H), 7.17 - 7.04 (m, 1 H), 6.80 (dd, J = 8.3, 1.9 Hz, 1 H), 6.66 (d, J = 7.5 Hz, 1 H), 6.50 - 6.35 (m, 1 H), 4.52 (d, J = 11.9 Hz, 1 H), 4.17 (d. J = 11.9 Hz, 1 H), 3.47 (s, 3H), 1.94 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 159.66, 140.42, 139.99, 139.05, 137.13, 130.42, 129.63, 126.46, 124.76, 123.09, 122.77, 122.50, 114.82, 114.76, 64.26, 54.92, 12.12; !R: 1600, 1490, 1438, 1165, 1105, 1045 crn ¹ ; HRMS (ESI) calcd for C ₁₇ H _1B 0 ₂ S ₂ m/z [M+H] +: 317.0670; found: 317.0674; [α}$ = -184.8 (c 1.66, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex/IPA = 90/10, 1.0 mL/min, 210 nm, 22°C), 37.5, 45.2(major) min, 95% ee.

(R)-3-methyl-2-({naphthalen-2-ylmethyl)sulfinyl)benzo[b]t hiophene(6v) White solid; 88% yield; mp:168.5-169.8 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.91 (d, J = 7.9 Hz, 1 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.67 (d, J = 8.4 Hz, 1 H), 7.62 (d, J = 7.7 Hz, 1 H), 7.53 (d, J = 7.3 Hz, 2H), 7.50 - 7.35 (m, 4H), 7.12 (dd, J = 8.4, 1.7 Hz, 1 H), 4.69 (d, J = 12.1 Hz, 1 H), 4.38 {d, J = 12.1 Hz, 1 H), 1.83 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 140.45, 140.09, 139.10, 136.93, 133.11 , 132.90, 129.70, 128.37, 127.75, 127.63, 127.36, 126.50, 126.49, 126.44, 124.70, 123.10, 122.75(two peaks), 64.40, 12.19; IR: 1102, 1037, 960, 746 cm ^"1 ; HRMS (ESI) calcd for C ₂₀ Hi ₆ OS ₂ m/z [M+H] +: 337.0721; found: 337.0724; [a]g = -249.3 (c 1.44, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex IPA = 70/30, 1.0 mL min, 254 nm, 22°C), 19.0 (major), 46.3 min, 92% ee.

(/^-5-methoxy-1-methyl-2-((4-methylbenzyl)sulfinyl)-1 H-benzoId]imidaz:ole(7a)

Colourless oil;99% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.27 (d, J = 6.6 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1H), 7.03 (t, J = 8.7 Hz, 3H), 6.94 (d, J = 7.5 Hz, 2H), 4.62 (d, J = 12.8 Hz, 1 H), 4.44 (d, J = 12.8 Hz, 1 H), 3.88 (s, 3H), 3.48 (s, 3H), 2.31 (s, 3H); ³ C NMR (100 MHz, CDCI ₃ ): δ = 157.00, 150.11 , 142.97, 138.66, 131.32, 130.43, 129.36, 125.81 , 115.35, 1 0.11, 102.07, 60.52, 55.77, 30.01 , 21.15; IR: 1490, 1411 , 1346, 1199, 1047, 1029 cm ^"1 ; HRMS (ESI) calcd for Ci ₇ H _{1 s} N ₂ 0 ₂ S m/z [M+H] +: 315.1167; found: 315.1171 ; [α]$ = +134.96 (c 1.35, CHCI ₃ ); HPLC analysis: Chiralcel OJ (Hex/IPA = 70/30, 1.0 mL/min, 230 nm, 22 ^e C), 25.3(major), 42.1 min, 90% ee.

( ?)-1-((4-chlorobenzyl)sulfinyl)-3,5-dimethylbenzene{7b) White solid; 88% yield; mp:98.7-100.4 °C; ¹ H NMR (400 MHz, CDCI ₃ ): δ - 7.30 - 7.18 (m, 2H), 7.10 (s, 1 H), 6.99 (s, 2H), 6.94 (d, J = 8.4 Hz, 2H), 3.98 (s, 2H), 2.33 (s, 6H); ¹³ C NMR (100 MHz, CDCI ₃ ): 6 = 142.20, 138.92, 134.32, 132.95, 131.65, 128.46, 127.87, 121.75, 62.59, 21.16; IR: 3049, 2920, 1606, 1492, 1408, 1097, 1051 cm ^"1 ; HRMS (ESI) calcd for C _l5 H ₁₅ CIOS m/z [M+H] +: 279.0610; found: 279.0612; [a] J? - +132.92 (c 1.47, CHCI ₃ ); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/ 0, 1.0 mL/min, 230 nm, 22°C), 10.6, 12.2(major) min, 88% ee.

(R)-2-((4-chlorobenzyl)sulfinyI)furan(7c) Colourless oil; 95% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.69 (dd, J = 1.7, 0.7 Hz, 1H), 7.30 - 7.19 (m, 3H), 7.10 - 6.96 (m, 2H), 6.75 (dd, J = 3.4, 0.6 Hz, 1 H), 6.46 (dd, J = 3.4, 1.8 Hz, 1 H), 4.41 (d, J = 12.6 Hz, 1H), 4.34 (d, J = 12.6 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ - 150.33, 146.83, 134.55, 131.31 , 128.91 , 127.72, 117.24, 11 1.45, 58.58; IR: 3051 , 1490, 1460, 1095, 1047, 1008 cm ^"1 ; HRMS (ESI) calcd for CnH _B CI0 ₂ S m/z [M+H] +: 241.0090; found: 241.0082; [a]$ = -77.5 (c 1.14, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mL min, 230 nm, 22°C), 20.6(major), 27.4min, 81 % ee. (/?)-3-(benzylsulfinyl)-2-methylfuran(7d) Colourless oil; 73% yield; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.37 (d, J = 2.1 Hz, 1 H), 7.31 - 7.20 (m, 3H), 7.06 (dd, J = 7.3, 2.1 Hz, 2H), 6.66 (d, J = 2.0 Hz, 1 H), 4.32 (d, J = 12.1 Hz, 1 H), 4.03 (d, J = 12.1 Hz, 1 H), 1.89 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 154.58, 142.36, 130.19, 129.46, 128.61, 128.26, 120.79, 106.69, 61.67, 1 1.70; IR: 1589, 1514, 1454, 1388, 1228, 1 126, 1043, 1012 cm ^'1 ; HRMS (ESI) calcd for Ci ₂ H ₁₂ 0 ₂ S m/z [M+H] +: 237.0408; found: 237.0401 ; [af = -41.6 (c 0.68, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mUmin, 254 nm, 22°C), 14.8(major), 21.1 min, 81 % ee.

(R)-2-((4-chlorobenzyl)sulfinyl)benzofuran(7e) White solid; 83% yield; mp:156.3-157.4 °C; H NMR (400 MHz, CDCI ₃ ): δ = 7.60 (dd, J = 8.1 , 4.6 Hz, 2H), 7.45 (dd, J = 11.5, 4.3 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 1 H), 7.22 (d, J = 8.4 Hz, 2H), 7.12 - 7.01 (m, 3H), 4.50 (d, J = 12.8 Hz, 1 H), 4.39 (d, J = 12.8 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 156.46, 153.22, 134.72, 131.45, 128.95, 127.41 , 126.98, 126.47, 124.00, 122.38, 112.90, 111.96, 58.71; IR: 1490, 1166, 1097, 1049, 2016 cm ^"1 ; HRMS (ESI) calcd for C ₁₅ HnCI0 ₂ S m/z [M+H] +: 291.0247; found: 291.0249; = -5.48 (c 0.73, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex/IPA = 95/5, 1.0 mUmin, 230 nm, 22°C), 37.8(major), 64.1 min, 79% ee. {R)-2-{(4-c lorobenzyl)suifinyl)pyridine(7f) Colourless oil; 84% yield; H NMR (400 MHz, CDCI ₃ ): δ = 8.66 (dd, J = 4.7, 0.7 Hz, 1 H), 7.78 (td, J = 7.7, 1.7 Hz, 1 H), 7.57 (d, J = 7.9 Hz, 1 H), 7.34 (ddd, J = 7.6, 4.7, 1.1 Hz, 1 H), 7.23 - 7.12 (m, 2H), 6.98 - 6.81 (m, 2H), 4.32 (d, J = 13.2 Hz, 1 H), 4.04 (d, J = 13.2 Hz, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ - 163.33,149.33, 137.73, 134.30, 131.48, 128.41 , 127.62, 124.65, 120.70, 58.70; IR: 3051 , 1575, 1490, 1423, 1095, 1051 , 1037, 1016 cm ^"1 ; HRMS (ESI) calcd for Ci ₂ H ₁₀ CINOS m/z [M+H] +: 252.0250; found: 252.0248; [α]# = +224.64 (c 1.27, CHCI ₃ ); HPLC analysis: Chiralcel OD-H (Hex IPA = 95/5, 1.0 mL/min, 230 nm, 22°C), 24.0, 28.0(major) min, 71 % ee.

Example 5

Mechanistic Study

1 (1 mol %)

BnX (1.2 equiv.)

X = Br, CI

CPME

-60 "C

Entry Catalyst X Time Product Yield ee [%] ^tc]

[h]

1 la - 24 8 40 -

₂ M . Br 1 - - -

3 la CI 48 8 27 -

4 lb CI 48 3a:8 (1:2)M 9 83

5 lc CI 24 3a 15 91

6 Id CI 24 3a 29 90

Table 6 ^Ial

[a] Reactions were performed by using 2a (0.02 mmol) and benzyl halides (0.024 mmol) in the presence of 1 mol % of pentanidiums in CPME (0.4 mL) and saturated aqueous CsOH (24 μ[_). [b] Yield of the isolated product, [c] Determined by HPLC analysis. [dj.The substrate 2a decomposed under basic conditions without phase-transfer catalysts, [e] The ratio was determined by ^" Ή NMR analysis.

Methyl 3-{(thiophen-2-ylthio)oxy)propanoate[8] Colorless oil; H NMR (400 MHz, CDCI ₃ ). δ = 7.75 (dd, J = 5.0, 1.3 Hz, 1H), 7.71 (dd, J - 3.8, 1.3 Hz, 1 H), 7.18 (dd, J = 4.9, 3.8 Hz, 1H), 3.67 (s, 3H), 3.59 - 3.46 (m, 2H), 2.88 - 2.74 (m, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 170.29, 139.46, 134.57, 134.47, 128.05, 52.91 , 52.36, 28.01 ; IR: 1732, 1438, 1402, 1367, 1317, 1261 , 1155, 1 132, 1020 cm ^"1 ; HRMS (ESI) calcd for C ₈ H ₁₀ O ₃ S ₂ m/z [M+H] +: 219.0150; found: 219.0141. Example 6

For the sulfoxides 7g-7m, about 50% enantioselectivity can be achieved by using pentanidium 1d (Table 7) using the reaction conditions used herein.

entry R Product Time(h) ee (%)

1 PhCH ₂ 7g 22 52 2 4-MeC ₆ H ₄ CH ₂ 7h 84 54 3 4-OMeC ₆ H ₄ CH ₂ 7i 84 52 4 4-ClC ₆ H4CH ₂ 7j 36 54 5 2-MCC ₆ H ₄ CH ₂ 7k 36 57 6 2-EtC ₆ H ₄ CH ₂ 71 36 64 7 'Bu _Tab 7 _| m _{e 7} , _aJ 24 53

[a] Reactions were performed by using 2a (0.02 mmol), and 4-ch!orobenzyl bromide (0.024 mmol) in the presence of 1 mol % of pentanidium 1 d and saturated aqueous CsOH solution (24 μΙ_) in CPME (0.4 mL). [b] Determined by HPLC analysis.

Characterisation data for the above-mentioned compounds is provided below.

7g; HRMS (ESI) calcd for C ₁₃ HnCIOS m/z [M+H] +: 251.0297; found: 251.0286; HPLC analysis: Chiralcel OD-H (Hex IPA = 95/5, 1.0 mL min, 230 nm, 22°C), 13.5(major), 15.7 min, 52% ee.

7h; HRMS (ESI) calcd for C ₁₄ H ₁₃ CIOS m/z [M+H] +: 265.0454; found: 265.0452; HPLC analysis: Chiralcel OD-H (Hex IPA = 90/10, 1.0 mL min, 230 nm, 22°C), 14.0(major), 15.5 min, 54% ee.

7i; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.34 - 7.27 (m, 2H), 7.24 - 7.15 (m, 2H), 6.97 - 6.91 (m, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.03 - 3.90 (m, 2H), 3.83 (s, 3H); ¹³ C NMR (100 MHz, CDCi ₃ ): δ = 162,11 , 134.25, 133.17, 131.63, 128.53, 127.62, 126.23, 114.43, 62.53, 55.47; HRMS (ESI) calcd for Ci ₄ H _t3 CI0 ₂ S m/z [M+H] +: 281.0403; found: 281.0405; HPLC analysis: Chiralcel OJ (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 22.0, 30.2(major) min, 52% ee. 7j; HRMS (ESI) calcd for Ci ₃ H _1Q CI ₂ OS m/z [M+HJ +: 284.9908; found: 284.9904; HPLC analysis: C iralcel AD-H (Hex/IPA = 90/10, 1.0 mL/min, 230 nm, 22°C), 11 .6, 12.9(major) min, 54% ee.

7k; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.60 (dd, J = 7.4, 1.8 Hz, H), 7.42 - 7.26 (m, 2H), 7.24 - 7.17 (m, 2H), 7.14 (d, J = 6.7 Hz, 1 H), 6.88 (d, J = 8.4 Hz, 2H), 4.13 - 3.84 (m, 2H), 2.17 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 140.82, 135.08, 134.39, 131.62, 130.98, 130.29, 128.52, 127.65, 127.08, 124.29, 60.70, 18.03; LRMS (ESI) m/z 265.06 (M + H+); HRMS (ESI) calcd for Ci H ₁₃ CIOS m/z [M+H] +: 265.0454; found: 265.0463; HPLC analysis: Chiralcel OD-H (Hex/IPA - 90/10, 1.0 mL/min, 230 nm, 22°C), 13.3(major), 15.4 min, 57% ee.

7\ NMR (400 MHz, CDCI ₃ ): δ = 7.61 (dd, J = 7.8, 1.0 Hz, 1 H), 7.41 (td, J ~ 7.4, 1.1 Hz, 1 H), 7.33 (t, J = 7.1 Hz, 1 H), 7.24 - 7.15 (m, 3H), 6.90 (d, J ~ 8.3 Hz, 2H), 3.98 (q, J = 12.8 Hz, 2H), 2.61 (dq, J = 15.0, 7.5 Hz, 1 H), 2.43 (dq, J = 14.9, 7.5 Hz, 1 H), 1.20 (s, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 141 .39, 140.33, 134.39, 131.62, 131.30, 128.54, 128.41 , 127.81 , 127.12, 124.32, 61 .51 , 24.47, 14.99; HRMS (ESI) calcd for C ₁₅ H ₁₅ CIOS m/z [M+H] +: 279.0610; found: 279.0613; HPLC analysis: Chiralcel OD-H (Hex/IPA = 90/10, 1.0 mlJmin, 230 nm, 22°C), 10.5(major), 12.7 min, 64% ee.

7m; ¹ H NMR (400 MHz, CDCI ₃ ): δ = 7.32 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 3.77 (d, J = 12.8 Hz, 1 H), 3.57 (d, J = 12.8 Hz, 1 H), 1.31 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ): δ = 134.08, 131.32, 130.49, 128.98, 53.82, 51.98, 23.00; HRMS (ESI) calcd for CnH ₁₅ CIOS m/z [M+H] +: 231.0610; found: 231.0607; HPLC analysis: Chiralcel AD-H (Hex IPA = 95/5, 1.0 mL min, 230 nm, 22°C), 15.4, 23.5(major) min, 53% ee.