FIELD OF THE INVENTION The present invention relates to a novel metal free process for the synthesis of a- substituted carbonyl compound in good yields with excellent regio- selectivity via oxidative coupling, wherein said process employs N-bromosuccinimide in DMSO solvent as oxidative system.

BACKGROUND OF THE INVENTION

Functionalization of alkenes has become a popular methodology due to the significance of the products as building blocks in the synthesis of natural products and pharmaceutical molecules. Particularly, addition of heteroatoms across the olefins occupies an important place in synthetic organic chemistry. In this context, several Nobel reactions were developed. The formation of one C-0 bond (hydratization), one C-N bond (hydroamination), two C-0 bonds (epoxidation, dihydroxylation) and two C-N bonds (diamination) or the direct introduction of three C-0 bonds (oxo-acyloxylation and oxo-hydroxylation) has been the focus of oxidation chemistry for several years. Recently, more protocols were developed for one C-0 and one C-N bond (oxy-nitrogenation) formation across olefins regioselectivity. However, two C-0 bonds and one C-N bond (oxo-amination) formation across the alkenes which gives a-amino carobonyl compounds is not reported. a-Amino carbonyl compounds are important structural motifs existing widely in a large number of natural products and pharmaceuticals such as bupropion, pyrovalerone, which are the potential pharmacotherapies for antidepressant and cocaine addiction (Fig. 1).

amfepramone pyrovelerone bupropion

(psychoative drug) (psychoactive drug) (antidepressant drug)

effient spisulosine

Plavix (anti platlet agent) (anti prolifirative)

Fig. A: Representative examples for biologically significant a-amino ketones

Article titled,"One-Pot Cascade Leading to Direct a-Imidation of Ketones by a Combination of N-Bromosuccinimide and 1,8-Diazabicyclo [5.4.1] undec-7-ene" by Ying Wei, Shaoxia Lin, and Fushun Liang in Org. Lett., 2012, 14 (16), pp 4202- 4205 reports a one-pot cascade transformation of ketones into a-imidoketones, in which N-bromosuccinimide (NBS) provides both electrophilic bromine and nucleophilic nitrogen sources, and diazabicyclo[5.4.1]undec-7-ene (DBU) functions as a base and a nucleophilic promoter for the activation of NBS. a-Bromination is supposed as the key step in the process, which takes place between more electrophilic bromide active species and enolates.

Article titled,"N-Bromosuccinimide/l,8-Diazabicyclo[5.4.1] undec-7-ene Combination: β-Amination of Chalcones via a Tandem Bromoamination/Debromination Sequence" by Ying Wei, Shaoxia Lin, Fushun Liang, and Jingping Zhang in Org. Lett, 2013, 15 (4), pp 852-855 reports a one-pot cascade transformation of chalcones into β-imidoketones, in which NBS provides both electrophilic bromine and nucleophilic nitrogen sources, and DBU functions as a nucleophilic reagent to activate NBS to be a more electrophilic bromine species and to further remove the bromine of a-bromoketones. The whole process involves tandem bromoamination and debromination, which represents a unique example of preparing β-aminoketones by the reaction of chalcones with the NBS/DBU combination. In this prior art, the synthesis of β-imidoketones has been disclosed which is altogether different compound from a-imidoketones. In the prior art, essentially a Michael addition reaction takes place for the synthesis of β- imidoketones which cannot be extended to the synthesis of a-imidoketones.

Article titled, "N-Bromoimide/DBU Combination as a New Strategy for Intermolecular Allylic Amination" by Ying Wei, Fushun Liang, and Xintong Zhang in Org. Lett., 2013, 15 (20), pp 5186-5189 reports allylic amination reactions of alkenes, with an NBP (N-bromophthalimide) or NBS (N-bromosuccinimide)/DBU combination, in which both internal and external nitrogen nucleophiles can be installed directly. Dual activation of NBS or NBP by DBU leads to more electrophilic bromine and more nucleophilic nitrogen atoms simultaneously. This protocol may provide a novel and complementary access to allylic amination under mild conditions. Nonetheless, the allylic amination of trisubstituted amines which has been described is altogether different compound from α-imidoketones. Notably, the unsaturated C=C is not functionalized in the prior art.

Article titled, "Metal-free C-N cross -coupling of electrophilic compounds and N- haloimides" by Luyan Zhang, Yanru Li, Long-Yi Jin and Fushun Liang in RSC Adv., 2015, 5, 65600-65603 reports that when DBU is added, the cross-coupling reaction between alkyl halides (halogen = CI, Br and I) and N-haloimides (halogen = CI, Br) occurs, resulting in the formation of aminated products. The methodology represents an elegant example of applying the halogen bond activation strategy in an organic transformation. In this prior art, C-N cross-coupling of electrophilic compounds and N-haloimides to produce N-alkylimides has been described. The reaction uses imide (generated from N-haloimides and DBU) as the nucleophile.

Article titled, "Copper-catalyzed aerobic oxidative synthesis of a-ketoamides from methyl ketones, amines and NIS at room temperature" by Juan Zhang, Ying Wei, Shaoxia Lin, Fushun Liang and Pengjun Liu in Org. Biomol. Chem., 2012, 10, 9237-9242 report a simple, efficient and practical copper-catalyzed aerobic oxidative synthesis of a-ketoamides from aryl methyl ketones, aliphatic amines and N-iodosuccinimide (NIS). The one-pot reaction may proceed smoothly at room temperature in the open air. Molecular oxygen in air functions as both an oxidant and an oxygen source. The drawbacks of this prior art are: (i) it is not a metal-free protocol.

(ii) reaction is amidation reaction and not oxo-amination.

Article titled, "Transition-Metal-Free Oxidative a-C-H Amination of Ketones via a Radical Mechanism: Mild Synthesis of a-Amino Ketones" by Qing Jiang, Bin Xu, An Zhao, Jing Jia, Tian Liu, and Cancheng Guo in J. Org. Chem., 2014, 79 (18), pp 8750-8756 reports a transition-metal-free direct a-C-H amination of ketones using commercially available ammonium iodide as the catalyst and sodium percarbonate as the co-oxidant. A wide range of ketone ((hetero)aromatic or nonaromatic ketones) and amine (primary/secondary amines, anilines, or amides) substrates undergo cross-coupling to generate synthetically useful a-amino ketones. The utility of the method is highlighted through a concise one-step synthesis of the pharmaceutical agent amfepramone. The reported a-C-H amination of ketones requires higher temperature i.e 50 °C and also uses ketone as the raw material just like other reported prior art described earlier.

US 20060135790 Al discloses a process for the preparation of a-amino carbonyl compound by reacting an imine starting material with a suitable electrophile in the presence of a base. This process has the advantage that the imine starting materials can be prepared from glyoxylic acid esters or glyoxylic acid ester derivatives and a- hydrogen containing primary amines, which are usually cheap and readily available.

These imine starting materials can usually be prepared with a high yield and/or almost without the formation of any side products. It discloses the a-aminoketone formation by condensing amines and dicarbonyl compounds (glycolic esters) and hence is entirely different route to obtain the title compounds.

Article titled, "N-Heterocyclic Carbene Catalyzed Oxidative Coupling of Alkenes/a- Bromoacetophenones with Aldehydes: A Facile Entry to α,β-Epoxy Ketones" by Reddi RN, Prasad PK, Sudalai A in Angew Chem Int Ed Engl. 2015 Nov 16;54(47): 14150-3. doi: 10.1002/anie.201507363. Epub 2015 Sep 21 reports a novel, N-heterocyclic carbene (NHC) catalyzed direct oxidative coupling of styrenes with aldehydes for the synthesis of α,β-epoxy ketones in good yields. This unprecedented regioselective oxidative coupling employs NBS/DBU/DMSO (DBU=l,8-diazabicyclo [5.4. 0] undec-7-ene, DMSO=dimethylsulfoxide, NBS=N- bromosuccinimide) as an oxidative system at ambient conditions. Additionally, first NHC-catalyzed Darzens reaction of a-bromoketones and aldehydes under mild reaction conditions has also been described. Interestingly, mechanistic studies have revealed the preferred reactivity of NHC with alkene/a-bromoketone rather than aldehydes, thus proceeding via the ketodeoxy Breslow intermediate. The substituted a-amino ketones display numerous biological applications. Generally, a-amino ketones were prepared by substitution of a-halo-ketones with amines and a-amination of carbonyl compounds and their surrogates. However, these protocols require pre-functionalization of starting materials, metal catalysts, excess amount of amine sources and harsh reaction conditions. Therefore, it is the need to develop a simple, cheap and efficient metal free process for the preparation of a-substituted carbonyl compounds with high yields. OBJECTS OF THE INVENTION

The main object of the present invention is to provide a novel metal free process for the preparation of α-substituted carbonyl compounds directly from common and cheap raw materials like alkenes and amines, imides, amides etc. in high yields.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides a novel metal free process for the synthesis of α-substituted carbonyl compounds in good yields with excellent regio- selectivity via oxidative coupling, wherein said process employs N- bromosuccinimide in DMSO solvent as oxidative system.

In an embodiment, the present invention provides an improved process for the synthesis of compounds of formula I,

wherein,

X is selected from the following compounds

R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, heterocycloalkyl;

Ri is selected from H, substituted or unsubstituted alkyl, alkoxy, substituted/unsubstituted aryl, "=0" R ₂ and R ₃ is independently selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, acyl, substituted or unsubstituted alkoxy; or R ₂ and R ₃ combined to form a cyclic secondary amine structure, wherein cyclic secondary amine structure is selected from aromatic or cyclic amines with or without heteroatoms or heterocyclic secondary amines; comprising steps of: a) reacting an alkene compound of formula II,

II wherein, R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, alkyl, H, substituted or unsubstituted alkoxy; substituted or unsubstituted cycloalkyl, , heterocyclo alkyl ; wherein substitutions selected independently from aryl, alkyl, halo, nitro, alkoxy, and

Ri is selected from H, substituted or unsubstituted alkyl, alkoxy, substituted/unsubstituted aryl; with N-bromosuccinimide in a solvent, in the presence of a base to obtain the corresponding a substituted carbonyl compounds and their derivative.

In a preferred embodiment when imide or amide used as source of nitrogen the base is selected from Et ₃ N, DBU, KO ^l Bu, K ₃ C0 ₃ .

In another preferred embodiment the solvent for above reaction is selected from the group of aprotic polar solvent such as DMSO.

In still another preferred embodiment in the process for the synthesis of a substituted carbonyl compounds of formula IB, the base used is a compound of formula III, R ₂ -NH-R3 III wherein, R ₂ and R ₂ is independently selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, alkyl, H, acyl, substituted or unsubstituted alkoxy; or R ₂ and R ₃ combined to form a cyclic secondary amine structure, wherein cyclic secondary amine structure is selected from aromatic or cyclic amines with or without heteroatoms or heterocyclic secondary amines;.

In a more preferred embodiment formula III representative compounds are selected from piperidine (Ilia), morpholine (Illb), lH-imidazole (IIIc), 1H- benzo[d] imidazole (Hid), isoindoline- l,3-dione (Hie), lH-l,2,3-triazole (Illf), N- methylformamide (Illg), methanamine (ΙΙΠι), tert-butyl carbamate (Mi) or diethylamine (Illj).

In another embodiment the yield of compound of formula IA is in the range of 50 to 95% and compound of formula IB is in the range of 65 to 90%.

In yet another embodiment, a-substituted carbonyl representative compounds of formula IA is selected from: l-(2-oxo-2-phenylethyl) pyrrolidine-2,5-dione (IAa); l-(2-oxo-2-(p-tolyl)ethyl)pyrrolidine-2,5-dione (IAb); l-(2-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAc); l-(2-(4-methoxyphenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAd); l-(2-(4-nitrophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAe); l-(2-oxo-2-(m-tolyl)ethyl)pyrrolidine-2,5-dione (IAf); l-(2-(naphthalen-2-yl)-2-oxoethyl)pyrrolidine-2,5-dione (IAg); l-(l-oxo-l-phenylpropan-2-yl)pyrrolidine-2,5-dione (IAh); l-(l-oxo-2,3-dihydro-lH-inden-2-yl)pyrrolidine-2,5-dione (IAi); l-(2-oxohexyl)pyrrolidine-2,5-dione (IAj); l-(2-oxooctyl)pyrrolidine-2,5-dione (IAk);

1- (2-oxocyclohexyl)pyrrolidine-2,5-dione (IA1); ethyl 2-(2,5-dioxopyrrolidin-l-yl)acetate (IAm); 2-bromo-3,5-dimethoxybenzyl 2-(2,5-dioxopyrrolidin-l-yl)propanoate

(IAn).

In still another embodiment, α-substituted carbonyl representative compounds of formula IB is selected from:

2- (lH-imidazol-l-yl)- l-phenylethanone (IBp); 2-(lH-benzo[d]imidazol-l-yl)- l-phenylethanone (IBq);

2-( lH-benzo[d] [ 1 ,2,3] triazol- 1 -yl)- 1 -phenylethanone (IBr) ;

2-(methylamino)- 1 -phenylethanone (IB s) ;

1 -phenyl-2-(piperidin- 1 -yl)ethane- 1 ,2-dione (IB t) ;

1 -morpholino-2-phenylethane- 1 ,2-dione (IB u) ; l-(4-methylpiperazin-l-yl)-2-phenylethane-l,2-dione (IBv);

N,N-diethyl-2-oxo-2-phenylacetamide (IBw).

DETAILED DESCRIPTION OF THE INVENTION

The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

In view of above the present invention provides an improved process for the synthesis of α-substituted carbonyl compounds directly from common and cheap raw materials in high yields. In an embodiment, the present invention provides an improved process for the synthesis of compounds of formula I,

I wherein, selected from the following compounds

A

R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted heteroaryl, substituted or unsubstituted alkyl, H, substituted or unsubstituted alkoxy; substituted or unsubstituted cycloalkyl, , heterocycloalkyl

Ri is selected from H, alkyl alkoxy, substituted/unsubstituted aryl, "=0"

R ₂ and R ₃ is independently selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, acyl, substituted or unsubstituted alkoxy; or R ₂ and R ₃ combined to form a cyclic secondary amine structure, wherein cyclic secondary amine structure is selected from aromatic or cyclic amines with or without heteroatoms or heterocyclic secondary amines; comprising steps of: a) reacting an alkene compound of formula II,

II wherein, R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, substituted or unsubstituted alkoxy; substituted or unsubstituted cycloalkyl or heterocycloalkyl and

Ri is selected from H, substituted or unsubstituted alkyl, alkoxy, substituted/unsubstituted aryl with N-bromosuccinimide in in aprotic polar solvent such as DMSO , in the presence of a base to obtain the corresponding a substituted carbonyl compounds and their derivative.

In a preferred embodiment, the present invention provides a process, wherein compound of formula I is selected from:

The above process is shown below in Scheme 1:

Scheme: 1 wherein, R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, substituted or unsubstituted alkoxy; substituted or unsubstituted cycloalkyl or heterocycloalkyl and Ri is selected from H, substituted or unsubstituted alkyl, alkoxy, substituted/unsubstituted aryl, "=0"

In another preferred embodiment, the present invention provides a process for the synthesis of compound of formula IA wherein base is selected from Et ₃ N, DBU, KO ^l Bu, K ₃ C0 ₃ .

In yet another preferred embodiment, the present invention provides a process for the synthesis of compound of formula IB wherein base is a compound of formula in,

R ₂ -NH-R ₃ III wherein, R ₂ and R ₃ is independently selected from substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, H, acl, alkoxy; or R ₂ and R ₃ combined to form a cyclic secondary amine structure, wherein cyclic secondary amine structure is selected from aromatic or cyclic amines with or without heteroatoms or heterocyclic secondary amines;

In a more preferred embodiment, the present invention provides a process, wherein the examples for base is a compound of formula III are Piperidine (Ilia), Morpholine (Illb), lH-imidazole (IIIc), lH-benzo[d] imidazole (Hid), isoindoline- 1,3-dione (Hie), lH-l,2,3-triazole (Illf), N-methylformamide (Illg), methanamine (ΙΙΠι), tert-butyl carbamate (Illi) or Diethylamine (Illj).

In still another preferred embodiment, the present invention provides a process, wherein oxidative system is N-bromosuccinimide in DMSO solvent.

In still still another preferred embodiment, the present invention provides a process wherein yield of compound of formula IA is in the range of 50 to 95% and compound of formula IB is in the range of 65 to 90%.

In an aspect, the present invention provides a process wherein compound of formula IA is selected from the following: l-(2-oxo-2-phenylethyl) pyrrolidine-2,5-dione (IAa); l-(2-oxo-2-(p-tolyl)ethyl)pyrrolidine-2,5-dione (IAb); l-(2-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAc); l-(2-(4-methoxyphenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAd); l-(2-(4-nitrophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAe); l-(2-oxo-2-(m-tolyl)ethyl)pyrrolidine-2,5-dione (IAf); l-(2-(naphthalen-2-yl)-2-oxoethyl)pyrrolidine-2,5-dione (IAg); l-(l-oxo-l-phenylpropan-2-yl)pyrrolidine-2,5-dione (IAh);

1 -( 1 -oxo-2,3 -dihydro- 1 H-inden-2-yl)pyrrolidine-2,5 -dione (IAi) ;

1- (2-oxohexyl)pyrrolidine-2,5-dione (IAj); l-(2-oxooctyl)pyrrolidine-2,5-dione (IAk);

1 -(2-oxocyclohexyl)pyrrolidine-2,5-dione (IAI) ; ethyl 2-(2,5-dioxopyrrolidin-l-yl)acetate (IAm);

2- bromo-3,5-dimethoxybenzyl 2-(2,5-dioxopyrrolidin-l-yl)propanoate (IAn).

In another aspect, the present invention provides a process wherein compound of formula IB is selected from the following:

2-(lH-imidazol-l-yl)- l-phenylethanone (IBp);

2-( lH-benzo[d]imidazol- 1 -yl)- 1 -phenylethanone (IBq) ;

2-( lH-benzo [d] [ 1 ,2,3 ] triazol- 1 -yl)- 1 -phenylethanone (IBr) ; 2-(methylamino)- 1 -phenylethanone (IB s) ;

1 -phenyl-2-(piperidin- 1 -yl)ethane- 1 ,2-dione (IB t) ;

1 -morpholino-2-phenylethane- 1 ,2-dione (IB u) ;

1 -(4-methylpiperazin- 1 -yl)-2-phenylethane- 1 ,2-dione (IB v) ;

N,N-diethyl-2-oxo-2-phenylacetamide (IBw). The closest cited prior art titled, "One-Pot Cascade Leading to Direct a-Imidation of Ketones by a Combination of N-Bromosuccinimide and 1,8-Diazabicyclo [5.4.1] undec-7-ene" by Ying Wei, Shaoxia Lin, and Fushun Liang in Org. Lett., 2012, 14 (16), pp 4202-4205 reports a one-pot cascade transformation of ketones into a- imidoketones, in which N-bromosuccinimide (NBS) provides both electrophilic bromine and nucleophilic nitrogen sources, and diazabicyclo[5.4.1]undec-7-ene (DBU) functions as a base and a nucleophilic promoter for the activation of NBS. a- Bromination is supposed as the key step in the process, which takes place between more electrophilic bromide active species and enolates. But, the present invention has the following advantage over this prior art:

(i) The synthesis of a-imidoketones commences from the cheaply commercially available alkenes and not from the unsymmetrical ketones (which have to be synthesized).

(ii) In prior art, the reaction was limited to aromatic ketones whereas in the present invention, aliphatic alkenes have also been readily used to afford the corresponding a-imidoketones clearly increasing the substrate scope of the developed method.

(iii) In the present invention, the developed method is highly regio selective (place selectivity) whereas, the question of regio selectivity does not arise in the prior art because categorically only one a-position is made available for the reaction to take place (by using aryl alkyl ketones as the starting material of choice).

EXAMPLES

Following examples are given by way of illustration therefore should not be construed to limit the scope of the invention.

General Description

Solvents were purified and dried by standard procedures before use; petroleum ether of boiling range 60-80 °C was used. Melting points are uncorrected and recorded on a Buchi B -542 instrument. 1 H NMR and 13 C NMR spectra were recorded on Brucker AC-400 spectrometer unless mentioned otherwise. Deuterated solvent CDC1 ₃ was used as internal standard. HRMS data were recorded on a Waters SYNAPT G2 High Definition Mass Spectrometry System. Purification was done using column chromatography (230-400 mesh). The compounds Ila-o and Illa-j are commercially available and were procured from Sigma Aldrich and were used as such without any further purification.

Example 1

General procedure for the preparation of a-ketoimide derivatives (IAa-n)

To a stirred solution of alkene Ia-n (1 mmol) in DMSO (10 mL) at 0 °C was added NBS (1 mmol) followed by dropwise addition of DBU (1 mmol). The reaction mixture was then allowed to stir at 25°C for 8 h (monitored by TLC). After completion, the reaction mixture was then cooled to 0 °C and unreacted DBU was quenched with water. Organic layer was diluted with EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na ₂ S0 ₄ and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (7:3) as an eluent to afford corresponding a- ketoimide derivatives (IAa-o) in 52-91% yield. Example 2 l-(2-oxo-2-phenylethyl) pyrrolidine-2,5-dione (IAa)

Yield: 86% (186 mg); Colorless solid; mp: 162-163 °C; IR (KBr, cm-1): v 872, 1234, 1421, 1582, 1585, 1746, 1776, 2893, 2938 and 3056; IH NMR (400 MHz, CDC13): δ 2.87 (s, 4H), 4.96 (s, 2H), 7.45-7.57 (m, 2H), 7.58-7.68 (m, IH), 7.88- 8.04 (m, 2H);13C NMR (100 MHz, CDC13): δ 28.3, 44.7, 128.1, 128.9, 134.1, 176.7, 190.2; HRMS calcd for [(C12H11N03+Na)+] 240.0631; found: 240.0629.

Example 3 l-(2-oxo-2-(p-tolyl)ethyl)pyrrolidine-2,5-dione (IAb)

Yield: 89% (205 mg); Colorless solid; mp: 180-181 °C; IR (KBr, cm-1): v 720, 822, 1167, 1328, 1419, 1507, 1571, 1612, 1694, 1725, 2896, and 2986; IH NMR (400 MHz, CDC13) δ 2.42 (s, 3H), 2.85 (s, 4H), 4.92 (s, 2H), 7.29 (d, J = 7.8 Hz, 2 H), 7.86 (d, = 7.8 Hz, 2H); 13C NMR (100 MHz, CDC13): δ 21.7, 28.3, 44.6, 128.1, 129.5, 131.8, 145.0, 176.7 189.8;HRMS calcd for [(C13H13N03+Na)+] 254.0788; found: 254.0786.

Example 4 l-(2-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAc)

Yield: 91% (228 mg); Colorless solid; mp: 158-159 °C; IR (KBr, cm-1): v 714, 912, 1242, 1481,1573, 1596, 1696, 1722, 1778, 2789, 2940 and 2980; IH NMR (400 MHz, CDC13): δ 2.85 (s, 4H), 4.89 (s, 2H), 7.46 (m, = 8.7 Hz, 2H), 7.89 (m, = 8.7 Hz, 2H); 13C NMR (100 MHz, CDC13): δ 28.3, 44.5, 129.2, 129.4, 132.5, 140.6, 176.6, 189.2; HRMS calcd for [(C12H10ClNO3+Na)+] 274.0241; found: 274.0243. Example 5 l-(2-(4-methoxyphenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAd)

Yield: 84% (207 mg); Colorless solid; mp: 149-150 °C; IR (KBr, cm-1): v 668, 884, 1134, 1372, 1458, 1571, 1598, 1684, 1704, 1726, 2586, 2891 and 2946; 1H NMR (400 MHz,CDC13):5 2.86 (s, 4H), 3.89 (s, 3H), 4.91 (s, 2H), 6.97 (m, 7 = 8.80 Hz, 2H), 7.95 (m, 7=9.05 Hz, 2H); 13C NMR (101 MHz, CDC13) δ 28.4, 44.4, 55.5, 114.1, 127.4, 130.4, 164.2, 176.8, 188.6; HRMS calcd for [(C13H13N04+Na)+] 270.0737; found: 270.0735

Example 6 l-(2-(4-nitrophenyl)-2-oxoethyl)pyrrolidine-2,5-dione (IAe)

Yield: 52% (136 mg); Colorless solid; mp: 178-179 °C; IR (KBr, cm-1): v 914, 1231, 1388, 1426, 1531, 1621, 1691, 1718, 2727, 2865, 2943, and 2986; 1H NMR (400 MHz,CDC13):5 2.86 (s, 4H), 5.81 (s, 2H), 8.17-8.21 (m, 2H), 8.25-8.31 (m, 2H); 13C NMR (101 MHz, CDC13) δ 28.2, 62.1, 123.6, 129.7, 131.0, 134.3, 163.4, 175.5; HRMS calcd for [(C12H10N2O5+Na)+] 285.0487; found: 285.0482

Example 7 l-(2-oxo-2-(m-tolyl)ethyl)pyrrolidine-2,5-dione (IAf)

Yield: 90% (207 mg); Colorless solid; mp: 145-146 °C; 1H NMR (400 MHz, CDC13): δ 2.41 (s, 3H), 2.84 (s, 4H), 4.92 (s, 2H), 7.32-7.49 (m, 2H), 7.64-7.84 (m, 2H); 13C NMR (100 MHz, CDC13): δ 21.3, 28.3, 44.7, 125.2, 128.5, 128.7, 134.3, 134.8, 138.7, 176.7, 190.4 ; HRMS calcd for [(C13H13N03+Na)+] 254.0788; found: 254.0785. Example 8 l-(2-(naphthalen-2-yl)-2-oxoethyl)pyrrolidine-2,5-dione (IAg)

Yield: 85% (226 mg); Colorless solid; mp: 157-159 °C; IR(KBr, cm-1): v 726, 891, 1171, 1420, 1469, 1595, 1628, 1702, 2853, 2938, 2978 and 3059; IH NMR (400 MHz, CDC13): δ 2.88 (s, 4H), 5.08 (s, 2H), 7.54-7.66 (m, 2H), 7.85-7.93 (m, 2H), 7.94-8.01 (m, 2H), 8.48 (s, 1 H); 13C NMR (100 MHz, CDC13): δ 28.3, 44.7, 123.4, 127.0, 127.8, 128.8, 129.0, 129.6, 130.0, 131.6, 132.3, 135.9, 176.7, 190.2; HRMS calcd for [(C16H13N03+Na)+] 290.0788; found: 290.0786.

Example 9 l-(l-oxo-l-phenylpropan-2-yl)pyrrolidine-2,5-dione (IAh)

Yield: 85% (196 mg); Colorless solid; mp:154-155 °C; IR (KBr, cm-1): v 729, 821, 1186, 1366, 1454, 1576, 1599, 1688, 1717, 1768, 2896, 2989, and 3049: IH NMR(400 MHz, CDC13): δ 1.61 (d, = 7.1 Hz, 3H), 2.64 (q, = 2.7 Hz, 4H), 5.47 (q, = 7.1 Hz, IH), 7.41 (t, = 7.7 Hz, 2H), 7.53 (t, = 7.5 Hz, 1 H), 7.66-7.78 (m, 2H); 13C NMR (100 MHz, CDC13): δ 13.9, 28.0, 51.6, 127.7, 128.6, 133.0, 135.1,

176.2, 195.8; HRMS calcd for [(C13H13N03+Na)+] 254.0788; found: 254.0786.

Example 10 l-(l-oxo-2,3-dihydro-lH-inden-2-yl)pyrrolidine-2,5-dione (IAi)

Yield: 81% (185 mg); Colorless solid; mp: 177-178 °C; IR(KBr, cm-1): v 733, 896, 1184, 1433, 1471, 1598, 1631, 1684, 1712, 2893, 2948, 2968 and 3062; IH NMR (500 MHz, CDC13) δ 2.69- 2.79 (m, 4 H), 3.00-3.04 (m, 2H), 5.76-5.94 (m, IH), 7.34 (dd, = 7.8, 0.9 Hz, IH), 7.61 (td, = 7.6, 0.9 Hz, IH), 7.81 (d, = 7.6 Hz, IH); 13C NMR (125 MHz, CDC13): δ 28.0, 40.3 47.9, 123.7, 124.5, 129.3, 135.1,

137.3, 150.7, 176.4, 202.0; HRMS calcd for [(C13H11N03+Na)+] 252.0631; found:252.0629. Example 11 l-(2-oxohexyl)pyrrolidine-2,5-dione (IAj)

Yield: 84% (165 mg); Colorless gum; IR(KBr, cm-1): v 761, 844, 1254, 1343, 1461, 1592, 1654, 1691, 1718, 2896; 1H NMR (400 MHz, CDC13): δ 0.89 (t, J = 7.3 Hz, 3H), 1.23-1.39 (m, 2H), 1.58 (dt, = 15.1, 7.6 Hz, 2H), 2.39-2.51 (m, 2H), 2.77 (s, 4H), 4.28 (s, 2H); 13C NMR (100 MHz, CDC13): δ 13.7, 22.1, 25.4, 28.2, 39.7, 46.9, 176.5, 201.4; HRMS calcd for [(C10H15NO3+Na)+] 220.0950; found:220.0942.

Example 12 l-(2-oxooctyl)pyrrolidine-2,5-dione (IAk)

Yield: 82% (184 mg); Colorless oil; IR(KBr, cm-1): v 741, 834, 1164, 1257, 1383, 1401, 1491, 1586,1624, 1694, 1722, 2899, 2984; 1H NMR (500 MHz, CDC13): δ 0.88 (t, = 7.0 Hz, 3H), 1.24-1.34 (m, 7H), 1.52-1.71 (m, 3H), 2.48 (t, = 7.3 Hz, 2H), 2.80 (s, 4H), 4.31 (s, 2H); 13C NMR (125 MHz, CDC13): δ 14.0, 22.4, 23.4, 28.2, 28.7, 31.4, 40.1, 47.0, 176.5, 201.4; HRMS calcd for [(C12H19N03+Na)+] 248.1257; found: 248.1256.

Example 13 l-(2-oxocyclohexyl)pyrrolidine-2,5-dione (IA1)

Yield: 79% (154 mg); Colorless solid; mp: 137-138 °C; IR (KBr, cm-1): v 761, 854, 1296, 1356, 1475, 1584, 1711, 1738, 2866, and 2945; 1H NMR (500 MHz, CDC13): δ 1.70-1.83 (m, 2H), 1.99-2.12 (m, 3H), 2.33 (td, = 14.3, 6.6 Hz, 1H), 2.49-2.65 (m, 2H), 2.75 (s, 4H), 4.63 (dd, 7 =13.4, 6.1 Hz, 1H); 13C NMR (125 MHz, CDC13): δ 24.5, 25.5, 28.1, 29.3, 40.8, 58.1, 176.7, 202.1; HRMS calcd for [(C10H13NO3+Na)+] 218.0788; found:218.0784. Example 14 ethyl 2-(2,5-dioxopyrrolidin-l-yl)acetate (IAm)

Yield: 82% (151 mg); Colorless oil; IR(KBr, cm-1): v 691, 846, 1171, 1422, 1476, 1596, 1628, 1702, 1746, 2869, 2964. 1H NMR (500 MHz, CDC13): δ 1.27 (t, = 7.2 Hz, 3H), 2.79 (s, 4H), 4.19 (q, = 7.0 Hz, 2H), 4.23 (s, 2H); 13C NMR (125 MHz, CDC13): δ 14.0, 28.2, 39.5, 61.9, 166.6, 176.3; HRMS calcd for [(C8H11N04+Na)+] 208.0586; found:208.0579.

Example 15 2-bromo-3,5-dimethoxybenzyl 2-(2,5-dioxopyrrolidin-l-yl)propanoate (IAn)

Yield: 71% (284 mg); Colorless solid; mp: 205-206 °C; IR(KBr, cm-1): v 694, 777, 864, 1268, 1496, 1564, 1579, 1698, 1729, 1739, 2596, 2894 and 2964; 1H NMR (400 MHz, CDC13): δ 1.57 (d, = 7.3 Hz, 3H), 2.73 (s, 4H), 3.84 (s, 3H), 3.90 (s, 3H), 4.82 (q, = 7.2 Hz, 1H), 5.09 (s, 2H), 6.45 (s, 1H), 7.37 (s, 1H); 13C NMR (100 MHz, CDC13): δ 14.2, 28.1, 48.1, 55.7, 56.3, 62.0, 96.2, 101.3, 117.2, 133.8, 156.9, 158.0, 168.9, 176.1; HRMS calcd for [(C16H18BrN06+Na)+] 422.0215; found:422.0208.

Example 16 Experimental procedure for the preparation of a-substituted carbonyl compounds (IBp-w)

To a stirred solution of styrene (1 mmol, 104 mg) in dry DMSO (10 mL) at 0 °C was added NBS (1 mmol, 178 mg) followed by slow addition of amine III (1 mmol). The reaction mixture was then allowed to stir at 25 °C for 8 hours (monitored by TLC). After completion, the reaction mixture was diluted with water and EtOAc. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extracts were repeatedly washed with saturated brine solution, dried over anhyd. Na ₂ S0 ₄ and concentrated under reduced pressure to give crude products which were purified by column chromatography [silica gel (230-400 mesh)] using petroleum ether: EtOAc (6:4) as eluent to afford corresponding a-substituted carbonyl compounds (IBp-w) in good yield.

Example 17 2-(lH-imidazol-l-yl)-l-phenylethanone (IBp)

Yield: 86% (160 mg); Colorless solid; mp: 117-119 °C; 1Η NMR (200 MHz, CDC13): δ 5.41 (s, 2H), 6.88-6.99 (m, IH), 7.09-7.15 (m, IH), 7.45-7.59 (m, 3H), 7.60-7.75 (m, IH), 7.90-8.02 (m, 2H); 13C NMR (50 MHz, CDC13): δ 52.4, 120.3, 127.9, 129.1, 129.4, 134.4, 138.1, 191.5: HRMS calcd for [(Cl lH10N2O+Na)+] 209.0691; found: 209.0695.

Example 18

2-( lH-benzo[d]imidazol- 1 -yl) - 1 -phenylethanone (IB q)

Yield: 85% (200 mg); Colorless solid; mp: 150-151 °C; 1Η NMR (200 MHz, CDC13): δ 5.57 (s, 2H), 7.19-7.33 (m, 4H), 7.33-7.41 (m, IH), 7.50-7.62 (m, 2H), 7.64-7.76 (m, IH), 7.78-7.88 (m, IH), 7.93 (s, IH), 7.99-8.06 (m, 2H); 13C NMR (100 MHz, CDC13): δ 50.5, 109.5 115.0, 120.0, 122.7, 123.6, 124.2, 128.0, 129.1, 134.5, 142.3, 143.7, 191.1 HRMS calcd for [(C15H12N20+Na)+] 259.0847; found: 259.0836.

Example 19

2-(lH-benzo[d][l,2,3]triazol-l-yl)-l-phenylethanone (IBr)

Yield: 83% (196 mg); Colorless solid; mp: 114-115 °C; 1Η NMR (200 MHz, CDC13): δ 6.21 (s, 2H), 7.36-7.47 (m, 2H), 7.48-7.59 (m, 2H), 7.61-7.73 (m, IH), 7.84-7.96 (m, 2H), 7.98-8.08 (m, 2H); 13C NMR (50 MHz, CDC13): δ 53.7, 109.5, 119.9, 123.9, 127.7, 128.2, 129.0, 133.7, 133.9, 134.4, 145.9, 190.4; HRMS calcd for [(C14H11N30+Na)+] 260.0800; found: 260.0802. Example 20

2-(methylamino) - 1 -phenylethanone (IBs)

Yield: 79% (117 mg); Colorless oil; IH NMR (200 MHz, CDC13): δ 2.82 (s, 3H), 4.89 (s, 2H), 7.45-7.70 (m, 3H), 7.93 (d, = 7.96 Hz, 2H); 13C NMR (50 MHz, CDC13): δ 39.7, 65.4, 127.7, 129.0, 134.3, 198.4; HRMS calcd for [(C9H11N0+Na)+] 172.0738; found: 172.0740.

Example 21 l-phenyl-2-(piperidin-l-yl)ethane-l,2-dione (IBt)

Yield: 72% (146 mg); Colorless oil; IR(KBr, cm-1): v 786, 1052, 1286, 1391, 1644, 1745, 2889, 2976, 2964; IH NMR (200 MHz, CDC13): δ 1.47-1.62 (m, 2H) 1.65- 1.74 (m, 5H) 3.25-3.35 (m, 2H) 3.65-3.78 (m, 2H) 7.45- 7.57 (m, 2H) 7.60-7.70 (m, IH) 7.89-8.01 (m, 2H); 13C NMR (50 MHz, CDC13): δ 24.2, 25.3, 26.1, 42.0, 46.9, 128.9, 129.4, 133.1, 134.5, 165.3, 191.8; HRMS calcd for [(C13H15N02+Na)+] 240.0995; found: 240.0992.

Example 22 l-morpholino-2-phenylethane-l,2-dione (IBu)

Yield: 74% (153 mg); Colorless solid; mp: 50-52 °C; IR(KBr, cm-1): v 776, 1126, 1216, 1447, 1636, 1665, 1722, 1771, 2862, 3446 IH NMR (200 MHz, CDC13) δ 3.34-3.45 (m, 2H), 3.62-3.72 (m, 2H), 3.81 (s, 4H), 7.49-7.60 (m, 2H), 7.61-7.75 (m, IH), 7.98 (d, = 7.20 Hz, 2H): 13C NMR (100 MHz, CDC13): δ 41.7, 46.4, 66.8, 66.8, 129.2, 129.8, 133.1, 135.0, 165.5, 191.2; HRMS calcd for [(C12H13N03+Na)+] 242.0793; found: 242.0789. Example 23 l-(4-methylpiperazin-l-yl)-2-phenylethane-l,2-dione (IBv)

Yield: 71% (154 mg); Colorless solid; mp: 68-69 °C; IR(KBr, cm-1): v 694, 774, 895, 1062, 1272, 1396, 1654, 1722, 1745, 2899, 2956, 2969; IH NMR (200 MHz, CDC13): δ 2.30-2.41 (m, 5H), 2.48-2.57 (m, 2H), 3.31-3.47 (m, 2H), 3.73-3.88 (m, 2H), 7.44-7.58 (m, 2H), 7.60-7.74 (m, IH), 7.95 (d, = 8.59 Hz, 2H); 13C NMR (50 MHz, CDC13): δ 41.1, 45.7, 45.9, 54.3, 54.8 , 129.0, 129.5, 133.0, 134.7, 165.3, 191.4; HRMS calcd for [(C13H16N202+Na)+] 255.1104; found: 255.1107.

Example 24

N,N-diethyl-2-oxo-2-phenylacetamide (IBw)

Yield: 68% (134 mg); Colorless gum; IR(KBr, cm-1): v 894, 974, 995, 1042, 1262, 1395, 1659, 1742, 1739, 2892, 2966, 2979; IH NMR (200 MHz, CDC13): δ 1.15 (t, = 7.1 Hz, 3H), 1.28 (t, / = 7.1 Hz, 3H), 3.11-3.30 (m, 2H), 3.47-3.63 (m, 2H), 7.50 (t, = 7.8 Hz, 2H), 7.54-7.74 (m, IH), 7.84-8.07 (m, 2H); 13C NMR (100 MHz, CDC13): δ 12.8, 14.1, 38.8, 42.1, 128.9, 129.6, 133.3, 134.6, 166.7, 191.6; HRMS calcd for [(C12H15N02+Na)+] 228.1000; found: 228.1006.

ADVANTAGES OF THE INVENTION

(1) Metal-free synthesis process.

(2) Milder reaction conditions.

(3) Functional group tolerance and excellent regioselectivity

(4) Practical and economically viable, as it is utilizes the readily available alkenes as starting material