Technical Field

The present invention relates, in general terms, to a composite. The present invention also relates to methods of synthesising the composite and its use as a catalyst thereof.

Background

The production of high-value fine chemicals and specialty chemicals (e.g. pharmaceuticals, agrochemicals) usually involves multiple chemical conversion steps, where the preferential reaction of a chemical reagent with one of two or more different functional groups (so-called chemo-selectivity) is the key to retaining the (bio-)active functional groups intact. Considering the number of sulfone/sulfoxide-containing pharmaceuticals, selective oxidation of sulfides has become an important strategy to access functionalized sulfones/sulfoxides, especially in cases where traditional approaches using homogeneous catalysts and/or oxidants (e.g. meta-chloroperoxybenzoic acid, mCPBA) fail to deliver high chemo-selectivity with sulfides bearing oxidation-prone functionalities that include alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids, esters and amines. In the case of mCPBA and homogeneous catalysts, the removal of unreacted oxidants, side products and catalyst residuals from the reaction system is tedious, hindering their applications in industrial process.

In fact, sulfur-based functional groups are of paramount importance in drug discovery and development. Since the first sulfa antibiotic, Prontosil, was introduced to the market in the 1930’s, sulfonamides and other sulfur-containing drugs have become pervasive in medicines spanning all therapeutic areas. In fact, a recent analysis revealed that sulfur is the 5 ^th most common element in FDA-approved drugs, just behind the mainstays of organic chemistry: C, H, N, and O. Based on the prevalence of S-containing drugs, methods that enable the interconversion of common sulfur functional groups can have a meaningful impact in drug discovery. While selective oxidation of sulfide has been attempted using homogeneous molybdenum catalysts such as [Mo ₇ O ₂₂ (O ₂ ) ₂ ] ^6- , this requires complex synthetic procedures, and suffers from catalyst leaching during recovery of products.

It would be desirable to overcome or ameliorate at least one of the above-described problems, or at least to provide a useful alternative.

Summary

The present inventors have found that a composite as disclosed herein can advantageously be used as a heterogeneous catalyst in the conversion of sulphide moiety to its oxidised form. Further advantageously, the composite has good chemo-selectivity and activity compared to unmodified heterogeneous catalyst or homogenous catalyst. In this regard, sensitive functional groups such as alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids, boronic esters and amines can be retained while the sulphide moiety is oxidised. Notably, methyl 2-chloro-4-(methylthio)benzoate, which is an intermediate of the FDA- approved anti-metastatic cancer drug Vismodegib, can be synthesized in excellent yield (93%) by this method. Synthesis of other high-value intermediates are also applicable, for instance, Cariporide (cardiac surgery), Tinidazole (FDA-approved anti-trichomonal drug) and Dapsone (anti-bacteria).

In an aspect, the present invention provides a composite, comprising: a) a substrate; b) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and c) a plurality of transition metal atoms intercalated between the at least two TMD layers. In some embodiments, the at least two TMD layers are aligned in one plane and attached to the substrate at an edge of the plane. In some embodiments, the at least two TMD layers are aligned in one plane and perpendicularly attached to the substrate at an edge of the plane. In some embodiments, each of the at least two TMD layers has a thickness of about 5 nm.

In some embodiments, each of the at least two TMD layers has a plane dimension of about 400 nm. In some embodiments, the TMD is selected from the group consisting of molybdenum disulfide (MoS ₂ ), tungsten disulfide (WS ₂ ), titanium disulfide (TiS ₂ ), tantalum sulfide (TaS ₂ ), vanadium disulfide (VS ₂ ), molybdenum diselenide (MoSe ₂ ), tungsten diselenide (WSe ₂ ), tellurium sulphide (TeS ₂ ) and tellurium diselenide (TeSe ₂ ). In some embodiments, each of the plurality of transition metal atoms is coordinated to 4 chalcogens in the at least two TMD layers.

In some embodiments, the plurality of transition metal atoms occur as individual atoms within an interstitial space of the at least two TMD layers.

In some embodiments, the plurality of transition metal atoms are spaced apart about 5 Å from each other.

In some embodiments, the plurality of transition metal atoms are present at about 0.1 wt% to about 20 wt% of the total of the at least two TMD layers and the plurality of transition metal atoms.

In some embodiments, the plurality of transition metal atoms are selected from the group consisting of iron, cobalt, nickel, copper, palladium, platinum, gold, ruthenium, silver and a combination thereof. In some embodiments, the substrate is selected from carbon paper, graphite or carbon electrode, conductive glass (such as ITO, FTO) and metal-based electrodes (such as titanium, nickel, copper, stainless steel, PbO ₂ ).

In some embodiments, an interlayer spacing between the at least two TMD layers is about 0.56 nm to about 1.2 nm.

In some embodiments, the at least two TMD layers is at least two layers of MoS ₂ transition metal dichalcogenide (TMD).

In some embodiments, the plurality of transition metal atoms is a plurality of cobalt atoms.

In another aspect, the present invention provides a method of forming a composite, including: a) attaching at least two layers of transition metal dichalcogenide (TMD) on a substrate; b) electrochemically intercalating a plurality of transition metal precursor between the at least two TMD layers; and c) annealing the plurality of transition metal precursor to form a plurality of transition metal atoms between the at least two TMD layers.

In some embodiments, the at least two TMD layers are grown on the substrate via a hydrothermal process.

In some embodiments, the transition metal precursor is subjected to a negative voltage for intercalating the plurality of transition metal precursors between the at least two TMD layers.

In some embodiments, the method further includes a step after step (a) of contacting the at least two TMD layers with a co-intercalant.

In some embodiments, the co-intercalant is selected from the group consisting of cetyltrimethylammonium bromide (CTAB), tetrapropylammonium chloride (TRAC), tetramethylammonium salts (TMA), tetrabutylammonium salts (TBA) and tetraethylammonium salts (TEA).

In some embodiments, the co-intercalant is provided at a concentration of 0.1 mM to about 50 mM.

In some embodiments, transition metal precursor is a transition metal complex or a transition metal salt selected from the group consisting of metal phthalocyanine complex, metal 5,10,15,20-(tetra-N-methyI-4-pyridyI)porphyrin tetrachloride complex, metal 5,10,15,20- (tetraphenyl)porphyrin complex, metal 5,10,15,20-(tetra-N,N,N-trimethyl-4-anilinium) porphyrin tetrachloride complex, metallocene complexes, metal salen complex, metal phenanthroline complex, metal acetylacetonate complex, metal acetates, metal chlorides, metal nitrates, and a combination thereof. In some embodiments, the annealing step is performed at about 400 °C to about 1000 °C.

In another aspect, the present invention provides a method of catalysing a reaction, including, a) contacting a chemical entity comprising a sulphide moiety with a heterogeneous catalyst and an oxidant, the heterogeneous catalyst comprising: i) a substrate; ii) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and iii) a plurality of transition metal atoms intercalated between the at least two TMD layers; and b) oxidising the sulphide moiety.

In some embodiments, the sulphide moiety is oxidised to a sulfone moiety or a sulfoxide moiety.

In some embodiments, the reaction is performed at about 20 °C to about 70 °C. In some embodiments, the reaction is performed for about 10 min to about 180 min.

In some embodiments, the reaction has a conversion rate of at least 90%.

In some embodiments, the reaction is chemoselective for the sulphide moiety.

In some embodiments, the reaction has a selectivity of at least 90%. In some embodiments, the chemical entity further comprises at least one moiety which is not sulphide and/or sulfoxide; and wherein the at least one moiety which is not sulphide and/or sulfoxide is not modified by the method. In some embodiments, the at least one moiety is selected from the group consisting of alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids, esters, amines, benzyl alcohol, pyridine, quinolone and a combination thereof.

In some embodiments, the oxidant is selected from the group consisting of H ₂ O ₂ , ozone (O ₃ ), metal peroxides (such as Na ₂ O ₂ ), organic peroxides (such as tert-butylhydroperoxide, tBuOOH), and peroxycarboxylic acids (such as meta-chloroperoxybenzoic acid (mCPBA)).

In another aspect, the present invention provides a method of catalysing a reaction, including, a) contacting a chemical entity comprising a sulfoxide moiety with a heterogeneous catalyst and an oxidant, the heterogeneous catalyst comprising: i) a substrate; ii) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and iii) a plurality of transition metal atoms intercalated between the at least two

TMD layers; and b) oxidising the sulfoxide moiety.

In some embodiments, the sulfoxide moiety is oxidised to a sulfone moiety. Brief description of the drawings

Embodiments of the present invention will now be described, by way of non-limiting example, with reference to the drawings in which: Figure 1 is a representation showing the preparation of metal-intercalated transition metal dichalcogenide compounds by an electrochemical co-intercalation strategy;

Figure 2 illustrates the morphologies of an exemplary catalyst (composite) of the present invention;

Figure 3 illustrates (A) XRD patterns, (B) Co K-edge XANES spectra and (C) FT-EXAFS spectra of various exemplary composites of the present invention. Dotted lines represent the fitting of EXAFS spectra;

Figure 4 illustrates (A) comparative data comparing the composite of the present invention with other classes of catalysts; and (B) a plot of an exemplary catalytic reaction showing the cycling stability of the catalyst (composite) with regard to the conversion rate and selectivity; Figure 5 demonstrates an application of the composite in late-stage functionalization of Tamiflu®; and

Figure 6 illustrates (A) proposed radical mediated pathway for sulfide oxidation; (B) differential charge density of the optimized adsorption configuration (side view) of the sulfide lq at the edge of the composite; (C) difference in adsorption energies for various adsorption configurations of sulfide lq on the composite; (D) EPR experiments on trapping DMPO-OH adduct (marked as *) in sulfide oxidation in which (1) without H ₂ O ₂ and catalyst; (2) without H ₂ O ₂ ; (3) without sulfide la and (4) standard conditions.

Detailed description To overcome some of the problems in the prior art, the inventors have found that a heterogeneous catalyst is advantageous. In this regard, heterogeneous catalysts, when compared to homogeneous catalysts, will enables much higher activity and bypasses tedious separation and purification processes. However, the stability and utility of heterogeneous catalyst are often problematic. To this end, the inventors are of the opinion that intercalation of redox active or catalytic species can enhance the catalytic performance of heterogeneous catalyst. However, a drawback of such intercalated systems lies in the mass diffusion limitation since the catalyst is encapsulated; geometric constraint and confinement effect further affect reaction kinetics and turnover number. The inventors have found that the electronic structure of the heterogeneous catalysts can be modified by electrochemical intercalation to further enhance chemo-selectivity and activity compared to unmodified heterogeneous catalyst. This enhances the binding of the intercalating transition metal atoms with the transition metal dichalcogenides, which further results in a strong promoter effect of the transition metal atoms. Accordingly, the heterogeneous catalyst of the present invention provides a convenient way to access multifunctional sulfones and allows for good chemo-selectivity and activity for sulfide oxidation, where sensitive functional groups (alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids and esters, amines etc.) can be retained (not modified).

In an embodiment, the composite was fabricated by an electrochemical co-intercalation strategy as illustrated in Figure 1 to modify the electronic structure of the catalyst. For example, vertically grown transition metal chalcogenides (e.g. MoS ₂ ) on carbon paper (Toray-120) can be first prepared by a simple hydrothermal process that can be scale up to 50 cm ² . Such hydrothermal process can be a low temperature hydrothermal reaction, in which the grown structure is aligned and its edge sites are exposed, thus enabling a fast diffusion kinetics of reactants. Under a negative voltage and additionally the use of co- intercalant, soluble metal complex such as cobalt phthalocyanine (CoPc) can diffuse and intercalate into the layered spacing of MoS ₂ to form a ternary structure of MoS ₂ | CoPc | MoS ₂ . The resulting compound (CoPc-in-MoS ₂ ) on carbon paper support can be subjected to further annealing to transform the planar structure of CoPc into Co single atom (Co ₁ -in- MoS ₂ ), leading to the appearance of strong metal-substrate interaction (SMSI) and confinement effect between Co single atom and MoS ₂ .

Figure 2 shows the morphology of this exemplary catalyst (composite). Figure 2(a) shows typical CV patterns for an electrochemical intercalation process using CoPc and CTAB; Figure 2(b) shows SEM images of the Co ₁ -in-MoS ₂ catalyst and Figure 2(c) shows STEM images of the Co ₁ -in-MoS ₂ catalyst; Figure 2 (d) shows the ToF-SIMS mapping to prove the intercalation of Co single atoms in MoS ₂ ; and (e) Co _2p XPS spectrum showing the appearance of additional CoS _x peak due to intercalation.

In a particular embodiment, the morphology of metal-intercalated catalyst (composite) was verified by scanning electron microscopy (SEM) Figure 2b. Ultrathin MoS ₂ nanosheets were vertically grown on the surface of each carbon fiber in uniform with a typical thickness of 5 nm and dimension of -400 nm. Atomic resolution scanning transmission electron microscopy (STEM) image in Figure 2c confirmed the uniform distribution of individual Co atoms in between MoS ₂ layers, which were observed as bright spots overlapping with the Mo column in the lattice structure of MoS ₂ and marked with white circles. Uniform distribution of Co could be seen throughout the TMD nanosheet without any particle aggregation in the TEM/EDS mapping, indicating the good controllability of this approach. The encapsulation of Co confirmed by a sample disruptive technique (time-of-flight secondary ion mass spectroscopy, ToF-SIMS) using MoS ₂ single crystal in Figure 2d, where uniform Co ⁺ signal was clearly seen in the horizontal and perpendicular directions even after a long sputtering time. Changes in interlayer spacing of MoS ₂ was confirmed by XRD patterns in Figure 3A and from cross-section STEM imaging. After electrochemical intercalation, the {002} peak of the parent MoS ₂ at 14.2° became indiscernible, and a broad and relatively weak reflection at 8.6° from the intercalated species could be seen. The intercalated peak shifted slightly to 9.1° after annealing due to thermal decomposition of phthalocyanine skeleton and CTAB at high temperature. The increase in layer spacing from 0.6 to 1.1 nm is beneficial for edge-site promoted catalysis owing to a higher accessible surface area. The atomic dispersion of Co was validated by X-ray absorption near-edge structure (XANES) and the single atom nature of Co was further proven by extended X-ray absorption fine structure (EXAFS) profiles in Figure 3c. The Co K-edge XANES spectrum of CoPc-in-MoS ₂ was analogous to that of CoPc in terms of peak position, despite of a much lower white-line intensity and the absence of pre-edge signature due to the transfer of π- electron from CoPc to MoS ₂ . The CoPc complex was then converted to single atom after annealing, leading to an obvious shift in Co ₁ -in-MoS ₂ to that of CoS _x species. A prominent Co-S peak at ~ 1.6 Å was observed in the Fourier transformed spectrum, which was fitted with a coordination number of 4. No metallic Co-Co peak at 2.1 Å can be seen in Co ₁ -in- MoS ₂ , revealing that ah Co ₁ exists as isolated single atoms in-between MoS ₂ layers, consistent with the atomic resolution STEM data in Figure 2c. The loading of metal can be widely tuned from 0.1 ~ 20 wt%, depending on the type (maximum concentration) of metal precursor as well as its feeding ratio to TMDs. In other embodiments, the mass loading was ~ 1 wt% by ICP-OES when using CoPc as precursor and subsequent thermal decomposition.

The modification of electronic structure of MoS ₂ of the above exemplary composite was confirmed by X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS) and Raman spectroscopy. High-resolution Mo _3d , S _2s XPS and Raman spectra suggested a 2H-1T-2H phase conversion due to electron donation from CoPc and subsequent recovery of the 2H phase after reducing CoPc to Co single atoms. Owing to strong metal-substrate interaction (SMSI) and confinement effect, the Co _2p XPS spectrum of Co ₁ -in-MoS ₂ exhibits unique CoS _x and satellite features not seen in pure CoPc. This is consistent with the peak shift to lower energy direction of Co ₁ -in-MoS ₂ in the Co L _2,3 -edge XAS spectra.

Accordingly, in an aspect, the present invention provides a composite, comprising: a) a substrate; b) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and c) a plurality of transition metal atoms intercalated between the at least two TMD layers.

The transition metal dichalcogenides (TMDs) are 2-D materials and have a generalized formula of MX2 where M is a transition metal of groups 4-10 and X is a chalcogen (such as sulfur or selenium). In some embodiments, the TMD is selected from the group consisting of molybdenum disulfide (MoS ₂ ), tungsten disulfide (WS ₂ ), titanium disulfide (TiS ₂ ), tantalum sulfide (TaS ₂ ), vanadium disulfide (VS ₂ ), molybdenum diselenide (MoSe ₂ ), tungsten diselenide (WSe ₂ ), tellurium sulphide (TeS ₂ ) and tellurium diselenide (TeSe ₂ ).

In some embodiments, the at least two TMD layers are aligned in one plane and attached to the substrate at an edge of the plane. In this regard, the TMD layers are stacked one on top of the other and each of the at least two TMD layers is attached to the substrate.

The grown structure of the TMD on the substrate can be aligned with its edge sites exposed, thus can enable a fast diffusion kinetics of reactants. In some embodiments, the at least two TMD layers are aligned in one plane and perpendicularly (vertically) attached to the substrate at an edge of the plane. In this regard, the TMD layers are, for example, vertically aligned with respect to a surface of the substrate. In other embodiments, the at least two TMD layers are aligned in one plane and are attached to the substrate at an angle. The angle can be about 85°, about 80°, about 75°, about 70°, about 65°, or about 60°. The alignment of the TMD layers on the substrate advantageously allows for a catalyst with high active surface area and activity.

Depending on the type of TMD, the layer thickness of the TMD may vary. In some embodiments, each of the at least two TMD layers has a thickness of about 5 nm. In other embodiments, the thickness is about 4 nm, about 6 nm, about 7 nm, about 8 nm, about 9 nm, or about 10 nm.

In some embodiments, each of the at least two TMD layers has a plane dimension of about 400 nm. In other embodiments, the plane dimension is about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm or about 1 μm.

Similarly, depending on the type of TMD, the spacing between the TMD layers as formed may vary. For example, the interlayer spacing of MoS ₂ is 0.615 nm, MoSe ₂ is 0.646 nm, WS ₂ is 0.618 nm, WSe ₂ is 0.651 nm, TiS ₂ is 0.569 nm, VS ₂ is 0.573 nm, SnS ₂ is 0.589 nm, and TaS ₂ is 0.601 nm.

In some embodiments, the at least two layers of TMD is at least 3 layers, at least 4 layers, at least 5 layers, at least 6 layers, at least 7 layers, at least 8 layers, at least 9 layers, or at least 10 layers. In other embodiments, the at least two layers of TMD is at least 10 layers of TMD.

The plurality of transition metal atoms are intercalated between the at least two TMD layers. In this regard, the transition metal atoms are inserted between the TMD layers. In contrast to doping methods where a small amount of the TMD atoms are replaced with transition metal atoms are or surface functionalisation where the transition metal atoms are attached to an external surface of the TMD, the inventors have found that intercalation of transition metal atoms within the TMD layers enables the modification of electronic structure of the composite such that it can act as a catalyst to significantly improve catalytic activity and selectivity.

The intercalation of transition metal atoms may change the spacing between the TMD layers. For example, due to the repulsion between the electron densities of the TMD layers and the transition metal atoms, the spacing may be increased. The increase in layer spacing can be beneficial for edge-site promoted catalysis owing to a higher accessible surface area. In some embodiments, the interlayer spacing is about 0.56 nm, about 0.58 nm, about 0.6 nm, about 0.62 nm, about 0.64 nm, about 0.66 nm, about 0.68 nm, about 0.7 nm, about 0.75 nm, about 0.8 nm, about 0.85 nm, about 0.9 nm, about 0.95 nm, about 1 nm, about 1.05 nm, about 1.1 nm, or about 1.2 nm. In other embodiments, the interlayer spacing is about 0.56 nm to about 1.2 nm, about 0.58 nm to about 1.2 nm, about 0.6 nm to about 1.2 nm, or about 0.6 nm to about 1.1 nm.

The intercalation is preferably non-reversible. In some embodiments, each of the plurality of transition metal atoms is coordinated to 4 chalcogens in the at least two TMD layers. In this regard, 2 of the chalcogens are located on one TMD layer and the other 2 chalcogens are located on the other TMD layer. In other embodiments, each of the plurality of transition metal atoms has a valency of 3, 4, 5 or 6. In other embodiments, each of the plurality of transition metal atoms has a valency of 4.

The plurality of transition metal atoms occurs as individual atoms within the interstitial space of two TMD layers. In this regard, each of the transition metal atoms are isolated and spaced apart from each other. In some embodiments, the plurality of transition metal atoms are selected from the group consisting of iron, cobalt, nickel, copper, palladium, platinum, gold, ruthenium, silver and a combination thereof. In other embodiments, the plurality of transition metal atoms occurring as individual atoms is uniformly distributed within the interstitial space of two TMD layers.

Depending on the size of the transition metal atoms, the atom to atom distance may vary. In some embodiments, the plurality of transition metal atoms are spaced apart about 5 Å from each other. In other embodiments, the spacing is about 3 Å, about 4 Å, about 6 Å, about 7 Å, about 8 Å, about 9 Å, about 1 nm, about 1.1 nm, about 1.2 nm, about 1.3 nm, about 1.4 nm or about 1.5 nm.

In some embodiments, the plurality of transition metal atoms are present at about 0.1 wt% to about 20 wt% of the total of the at least two TMD layers and the plurality of transition metal atoms. In other embodiments, the plurality of transition metal atoms are present at about 0.1 wt% to about 18 wt% , about 0.1 wt% to about 16 wt%, about 0.1 wt% to about 14 wt%, about 0.1 wt% to about 12 wt%, about 0.1 wt% to about 10 wt%, about 0.1 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.1 wt% to about 4 wt%, about 0.1 wt% to about 2 wt%, or about 0.5 wt% to about 2 wt%. In other embodiments, the plurality of transition metal atoms are present at about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, or about 5 wt%.

In some embodiments, the substrate is carbon paper. In other embodiments, conductive and inert substrates can be used. For example, graphite or carbon electrode, conductive glass such as ITO and FTO can be used. In other embodiments, metal-based electrodes such as titanium, nickel, copper, stainless steel, PbO ₂ can be used. In some embodiments, a composite, comprising: a) a substrate; b) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and c) a plurality of cobalt atoms intercalated between the at least two TMD layers.

In some embodiments, a composite, comprising: a) a substrate; b) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and c) a plurality of cobalt atoms intercalated between the at least two TMD layers; wherein the TMD layers comprises molybdenum. In some embodiments, a composite, comprising: a) a substrate; b) at least two layers of MoS ₂ transition metal dichalcogenide (TMD), the at least two MoS ₂ TMD layers attached to the substrate; and c) a plurality of cobalt atoms intercalated between the at least two MoS ₂ TMD layers.

The present invention also provides a method of forming a composite, including: a) attaching at least two layers of transition metal dichalcogenide (TMD) on a substrate; b) electrochemically intercalating a plurality of transition metal precursor between the at least two TMD layers; and c) annealing the plurality of transition metal precursor to form a plurality of transition metal atoms between the at least two TMD layers.

In some embodiments, the at least two TMD layers are attached to the substrate by growing the TMD layers on the substrate. The grown of the TMD layers can be via a hydrothermal process. For example, the growth of the TMD layers can be conducted in a Teflon-lined stainless-steel autoclave with the substrate and TMD precursors placed within, sealed and heated at 160-200 °C for 2-24 h and then naturally cooled.

The composite is formed via an electrochemical process. In some embodiments, the soluble transition metal precursor is subjected to a negative voltage for intercalating the plurality of transition metal precursors between the at least two TMD layers. The negative voltage can also provide the energy for converting the transition metal precursors to the transition metal atoms and annealing to the TMD layers. The electrochemical process can be provided by a two or three electrode cell setup. The two/three-electrode cell can consist of a working electrode, a counter electrode, a reference electrode and electrolyte. In this setup, the working electrode is comprised of transition metal dichalcogenides in its crystal form, in powder rods, on carbon supports or on metal supports. The counter electrode can comprise, for example carbon counter electrode or metal counter electrode such as platinum, titanium or stainless steel. The reference electrode can comprise saturated calomel electrode (SCE), silver chloride electrode, mercury-mercurous sulfate electrode (Hg/Hg ₂ SO ₄ ) and non- aqueous reference electrode. The electrolyte is an organic solvent to dissolve metal complexes and organic molecules for electrochemical intercalation, which can be propylene carbonate (PC), acetonitrile (AN), tetrahydrofuran (THF), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). These organic solvents can be anhydrous, to allow for the avoidance of side reactions on hydrogen evolution that reduces intercalation efficiency and disrupts the layered structure of TMDs. Accordingly, when the substrate is immersed into the electrolyte, the intercalation of the transition metal precursor into the TMD layers on the substrate can be facilitated.

The electrochemical co- intercalation can be conducted at room temperature (21 °C) to elevated temperature such as 60 °C for 10 minutes to few days (72 hr). The negative voltage can be from about -0.01 V/cm ² to about -10 V/cm ² of electrode area (extreme voltage can be applied depending on the actual electrode area). The negative current can be from about -1 μA/cm ² to about -1 A/cm ² , depending on the applied voltage and electrode area.

In some embodiments, the transition metal precursor are soluble in the appropriate solvent. The solvents can be selected from propylene carbonate (PC), acetonitrile (AN), tetrahydrofuran (THF), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and a combination thereof. In other embodiments, the solvent is selected from PC and NMP.

In some embodiments, the concentration of the transition metal precursor is about 0.1 mM to about 10 mM. In other embodiments, the concentration is about 1 mM to about 10 mM, about 2 mM to about 10 mM, about 3 mM to about 10 mM, about 3 mM to about 9 mM, about 3 mM to about 8 mM, or about 3 mM to about 7 mM.

The inventors have found that the TMD layers and the guest molecules (metal complexes or atoms) form a bulk intercalated material with strong host-guest interaction and modified electronic structure. This is provided by the electrochemical process and is advantageous compared to physical mixing approaches (e.g., solution mixing) or doping of guest atoms into the lattice structure of hosts by chemical doping approaches (e.g., hydrothermal doping or chemical vapor deposition). In comparison, physical mixing approaches and doping were found to be unsuitable as the transition metal atoms are either weakly bonded to the TMD layers or are present only at very low levels. It is believed that this is the reason why a low chemoselectivity and low conversion rate are obtained when using catalysts made using these methods.

In some embodiments, the transition metal precursor can be a transition metal complex or a transition metal salt. In other embodiments, the transition metal precursor is selected from the group consisting of metal phthalocyanine complex, metal 5,10,15,20-(tetra-N-methyl-4- pyridyl)porphyrin tetrachloride complex, metal 5,10,15,20-(tetraphenyl)porphyrin complex, metal 5,10,15,20-(tetra-N,N,N-trimethyl-4-anilinium) porphyrin tetrachloride complex, metallocene complexes, metal salen complex, metal phenanthroline complex, metal acetylacetonate complex, metal acetates, metal chlorides and metal nitrates.

In some embodiments, the plurality of transition metal atoms is selected from the group consisting of iron, cobalt, nickel, copper, palladium, platinum, gold, ruthenium, silver and a combination thereof. In other embodiments, the plurality of transition metal atoms is selected from the group consisting of cobalt, nickel, iron, platinum and palladium.

As used herein, 'co-intercalant' are organic compounds that can intercalate or penetrate in between the TMD layers. The co-intercalant facilitates the penetration of the transition metal precursor in between the TMD layers by neutralising or minimising the effect of the electronic charges of the TMD layers on the transition metal precursor and vis versa. In some embodiments, the method further includes a step after step (a) of contacting the at least two TMD layers with a co-intercalant. Advantageously, the addition of co-intercalants can facilitate the intercalation process of metal precursor into TMD layered structure.

For example, a long-chain quaternary ammonium molecule (CTAB) can be chosen as a co- intercalant to further expand the interlayer spacing for assisting diffusional intercalation of CoPc. Successful intercalation can be confirmed by the appearance of CTAB intercalation peak at a concentration of 5 mM CTAB in the cyclic voltammograms (CV) in Figure 2A.

In some embodiments, the co-intercalant is selected from the group consisting of cetyltrimethylammonium bromide (CTAB), tetrapropylammonium chloride (TRAC), tetramethylammonium salts (TMA), tetrabutylammonium salts (TB A), tetraethylammonium salts (TEA) and a combination thereof. Examples of the ammonium salts can include anions such as bromide, chloride, fluoride and iodide.

In some embodiments, the co-intercalant is provided at a concentration of about 0.1 mM to about 50 mM. In other embodiments, the concentration is about 1 mM to about 50 mM, about 2 mM to about 50 mM, about 3 mM to about 50 mM, about 3 mM to about 40 mM, about 3 mM to about 30 mM, about 3 mM to about 20 mM, or about 3 mM to about 10 mM.

The annealing step allows for the thermal decomposition of the transition metal precursor to the transition metal atom. The annealing step also allows for the thermal decomposition of the co-intercalant, if present. This step ensures the complete conversion of the transition metal precursors to transition metal atoms within the TMD layers. This also allows for the increased binding of the transition metal atom to the TMD layers. In some embodiments, the annealing step is performed at about 400 °C to about 1000 °C. In other embodiments, the temperature is about 500 °C to about 1000 °C, about 600 °C to about 1000 °C, about 700 °C to about 1000 °C, or about 800 °C to about 1000 °C. In other embodiments, the annealing step is performed for about 0.5 hr to about 24 hr. In other embodiments, the time taken is about 1 hr to about 24 hr, about 1 hr to about 20 hr, about 1 hr to about 16 hr, about 1 hr to about 12 hr, or about 1 hr to about 8 hr.

Such intercalation strategy is found to be faster and more scalable when compared to traditional exfoliation strategy to functionalize TMD materials. The latter usually requires multiple washing steps to obtain functionalized TMD nanosheets, which can only be dispersed in good solvents at a very low concentration (e.g., 1 mg/mL in NMP), causing a huge difficulty in cost balance, storage and solvent waste. Meanwhile, the use of an external stimulus (electric field) as shown in this invention is found to promote the intercalation process as compared to concentration diffusion or ball milling, leading to a shorter period in material synthesis from several days to several hours. Such electrochemical intercalation also allows the intercalation of unconventional, bulky guest molecules (such as CoPc with a molecular weight of 571 g/mol), which has seldom been achieved in the past. The use of co- intercalant, a special organic cation such as cetyltrimethylammonium bromide (CTAB) that can intercalate into TMDs easily, is advantageous, which is shown by the CV patterns in Figure 2a. In the absence of co-intercalant, a limited current can be observed. The characteristic intercalation peak of CTAB appears when the concentration increases to 5 mM. Meanwhile, it is possible for direct intercalation of special porphyrins (e.g. cobalt(II) 5,10,15,20-(tetra-N-methyI-4-pyridyI)porphyrin tetrachloride) despite a longer preparation period, thus demonstrating the utility of the method.

In some embodiments, the metal intercalated composites can be used as a catalyst for the oxidation of sulfide to sulfone. An example of such a reaction (1a → 2a) is shown in Equation (1): Alternatively, the sulphide can be oxidised to a sulfoxide. As shown in Table 1, the reaction conditions was screened with various homogeneous or heterogeneous catalysts as comparators using the above transformation to sulfone as a model. Using the Co ₁ -in-MoS ₂ catalyst of the present invention as an example, the reaction can be completed within 20 minutes at 40 °C with conversion, selectivity and yield of > 99% (entry 2). The use of commercial MoS ₂ and MoO ₃ powders afford unsatisfactory results (entry 6 & 7). It was found that catalyst and/or oxidant (H ₂ O ₂ ) are needed for such oxidation reaction (entry 1 & 11). The usage of H ₂ O ₂ can be reduced from 5 (large excess) to 2.1 equivalents (minor excess) without appreciable effect on conversion and selectivity to sulfone. Other catalysts including the benchmark homogeneous catalyst Pd(PPh ₃ ) ₄ and heterogeneous catalyst 10% Pt/C gave negligible conversion of sulfide due to the lack of activation sites for sulfur (entry 11-13), and might prove the importance of the TMD layers for such conversion. Meanwhile, the oxidation reaction can also be completed within 10 minutes at 60 °C using Co ₁ -in-MoS ₂ catalyst or at room temperature by prolonging reaction time to 60 minutes (entry 14 & 15).

Table 1. Catalyst screening for selective oxidation of sulfide to sulfone ^a Condition: 0.1 mmol of 1a, 0.25 mmol of H ₂ O ₂ (25 μL), 4 mL of CH ₃ CN, 40 °C, 20 min; ^b Commercial MoS ₂ powder from Sigma Aldrich (69860); ^c Exfoliated MoS ₂ powder by BuLi lithiation and water exfoliation; ^d Single crystal MoS ₂ flake from HQ graphene; ^e Pt-MoS ₂ was prepared by the reaction of Na ₂ PtCl ₆ -6H ₂ 0 with Li _x MoS ₂ in anhydrous THF according to our previous report (Ref SI); ^f Catalyst degradation; ^g 60 °C, 10 min; ^h RT, 60 min; ¹ No H ₂ O ₂ ; Yield was determined by ¹ H NMR analysis of the crude reaction mixture.

These results highlight the importance of TMD layers attached to the substrate as it provides an accessible surface area and the promoter effect of transition metal atoms intercalant to sulfide oxidation. It is believed that the transition metal (single) atom encapsulation alters the electronic structure of TMD layers, leading to favourable adsorption of the sulphides to the composite and enhanced reaction activity.

Accordingly, the present invention provides a method of catalysing a reaction, including, a) contacting a chemical entity comprising a sulphide moiety with a heterogeneous catalyst and an oxidant, the heterogeneous catalyst comprising: i) a substrate; ii) at least two layers of transition metal dichalcogenide (TMD), the at least two TMD layers attached to the substrate; and iii) a plurality of transition metal atoms intercalated between the at least two

TMD layers; and b) oxidising the sulphide moiety.

In this regard, the composite of the present invention is used as a heterogenous catalyst. Such ternary composite when used as heterogeneous catalyst for sulphide (sulfide) oxidation can display good chemo-selectivity and activity to sulfones and sulfoxides, and can also allow for the bypass of tedious separation and purification processes. Further, the reaction can be completed within 20 minutes. Sensitive functional groups (alkenes, ketones, aldehydes, carboxylic acids, boronic acids, benzyl alcohol, pyridine, quinolone, esters, and amines) can also be retained (not modified).

In some embodiments, the method is chemoselective for sulphide and/or sulfoxide. Chemoselectivity refers to a preferential outcome of a chemical reaction over a set of possible alternative reactions. Chemoselectivity can also refer to the selective reactivity of one functional group in the presence of others. Chemoselectivity of a reaction is difficult to predict, as the physical outcome of a reaction is dependent on a number of factors that are practically impossible to predict to any useful accuracy (solvent, atomic orbitals, etc.).

In some embodiments, the chemical entity further comprises at least one moiety which is not sulphide and/or sulfoxide. The moiety can be alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids, esters, amines or a combination thereof. The at least one moiety is not modified by the method. In other words, the moiety is at least not oxidised or reduced by the method.

In some embodiments, the chemical entity further comprises at least one oxidizable moiety which is not sulphide and/or sulfoxide. The moiety can be ketone, aldehyde, amine, alkyne, alkene, benzyl alcohol, pyridine, quinolone or a combination thereof. The at least one moiety is not modified or oxidised by the method.

In some embodiments, the sulphide moiety is oxidised to a sulfone moiety or a sulfoxide moiety.

In some embodiments, the oxidant is H ₂ O ₂ . In other embodiments, the oxidant is selected from ozone (O ₃ ), metal peroxides (such as Na ₂ O ₂ ), organic peroxides (such as tert- butylhydroperoxide, tBuOOH), and peroxycarboxylic acids (such as meta- chloroperoxybenzoic acid (mCPBA)). In other embodiments, the oxidant is selected from H ₂ O ₂ and meta-chloroperoxybenzoic acid (mCPBA).

In some embodiments, the reaction is performed at about 30 °C to about 70 °C. In other embodiments, the temperature is about 40 °C to about 70 °C, or about 40 °C to about 60 °C.

In some embodiments, the reaction is performed for about 10 min to about 180 min. In other embodiments, the reaction is performed for about 10 min to about 160 min, about 10 min to about 140 min, about 10 min to about 120 min, about 10 min to about 100 min, about 10 min to about 80 min, or about 10 min to about 60 min. In other embodiments, the reaction is performed for at least about 5 min, at least about 10 min, at least about 15 min, at least about 20 min, at least about 25 min, at least about 30 min, at least about 35 min, at least about 40 min, at least about 50 min, at least about 55 min, at least about 60 min, at least about 70 min, at least about 80 min, at least about 90 min, at least about 100 min, at least about 120 min, at least about 140 min, at least about 160 min, or at least about 180 min.

Conversion (or conversion rate) is a term used in the art to describe as a ratio (or percentage) of how much of a reactant has reacted. Corollary, yield is a term used in the art to describe as a ratio (or percentage) of how much of a desired product was formed relative to the reactant consumed. Selectivity (or chemoselectivity) is a term used in the art to describe as a ratio (or percentage) of how much desired product was formed relative to the total products (desired + undesired).

In some embodiments, the reaction has a conversion rate of at least 90%. In other embodiments, the conversion rate is at least 92%, at least 94%, at least 96% or at least 98%. In other embodiments, the conversion rate is at least 99%.

Chemoselective oxidation of functionalized sulfides to sulfones is challenging owing to side reactions caused by oxidation-prone functional groups. To further illustrate the chemoselectivity and conversion rate of the catalyst of the present invention, Table 2 provides some comparison of the catalytic function of the composites of the present invention compared to prior art.

Considering that homogeneous oxidation using molybdenum/vanadium catalysts and/or external oxidants ( H ₂ O ₂ , mCPBA, etc) has achieved high oxidation efficiency but unsatisfactory chemo-selectivity with regards to preparation of functionalized sulfones (such as (2) ~ (6) in Table 2), a direct comparison on the chemo-selectivity was performed using Co ₁ -in-MoS ₂ catalyst and homogeneous mCPBA in its best conditions (as deemed from the literature). Congruent with earlier findings, the use of mCPBA generally gave a complex reaction mixture due to the oxidation of both sulfide and the oxidation-prone functional groups. For instance, boronic acid and ester can be readily oxidized and converted into hydroxyl group under excess amounts of mCPBA. Oxidation of amine to oxime, alkene or alkyne to epoxide, Baeyer-Villiger oxidation of carbonyl group to ester and Cope elimination of tertiary amine alkene, oxidation of N in pyridyl moiety to N-oxide and hydroxylation of arylboronic acid or pinacol ester to phenol were detectable side reactions in Table 2. This can pose a major technical problem to the synthesis of high-value chemicals containing sensitive functional groups such as alkynes, alkenes, ketones, aldehydes, carboxylic acids, boronic acids and esters as well as amines. More importantly, homogeneous oxidation typically requires tedious separation and purification processes to remove unreacted oxidants and catalyst residuals from products. In sharp contrast, all the above functional groups can be well-tolerated in using the heterogeneous catalyst with good conversions to the desired sulfones (>99%). Pure product can be easily isolated by simple removal of the carbon paper catalyst from the reaction system (using tweezer). Small amounts of excess H ₂ O ₂ was found to eventually be converted into water, thus bypassing tedious separation or purification steps in traditional sulfide oxidations. In this regard, the method of oxidation as presented herein has advantages pertaining to chemo-selectivity, substrate scope and ease-of-operation over reported methods.

To assess the generality of the reaction conditions, various sulfides were examined in Table 3. For instance, thioanisole, phenyl disulfide, diphenyl sulfide, dibenzyl sulfide, 2- (methylthio) thiophene and 2-(methylthio)pyridine can be effectively oxidized to the corresponding sulfones regardless of their electronic and steric attributes. Most commonly occurring and versatile functionalities, including those with potentially oxidizable functional groups such as ketone, aldehyde, amine, alkyne, alkene, benzyl alcohol, pyridine and quinoline, can be tolerated by the oxidation protocol, highlighting its remarkable chemo- selectivity compared to existing methods. Sulfones with synthetically valuable building blocks (phenol, hydroxyl, methoxy, carboxlic acid, bromide, silane, diazo and azide) can be accessed in excellent yields (90 ~ 99% except for diazo (~ 75%)). Likewise, boronic acid and ester substrates underwent oxidation to deliver the corresponding sulfones (2) & (3) without the occurrence of side reactions. Trifluoromethyl (CF ₃ )-functionalized substrates were suitable for such oxidative transformation. Notably, methyl 2-chloro-4- (methylthio)benzoate, which is an intermediate of the FDA-approved anti-metastatic cancer drug Vismodegib, can be synthesized in excellent yield (93%) by this method. Synthesis of other high-value intermediates are also applicable, for instance, Cariporide (cardiac surgery), Tinidazole (FDA-approved anti-trichomonal drug) and Dapsone (anti-bacteria). Sulfones bearing 1-phenyl-tetrazol scaffold can be synthesized in 91% and 82% yields, indicating that these can serve as good candidates in nickel-catalyzed radical cross-coupling reactions. It is also possible to synthesize sulfones without conjugated section in the molecule which are difficult to be isolated by traditional methods. The sulfide oxidation can be proceeded in excellent yields regardless of the electronic attributes of -OMe, -CN and -Br groups on aryl ring. Furthermore, the oxidation reactions occurred smoothly when replacing methyl group with trifluoromethyl (-CF ₃ ), benzyl and other groups bearing carboxylic acid, epoxide and azide moieties. One pot synthesis of deuterated sulfones with high deuterium ratio was achieved in alkaline solution using D2O as deuteration reagent, revealing the universal applicability of the composite of the present invention. Gram-scale reactions on 4-thioanisoleboronic acid and phenyl propargyl sulfide was performed using double usage of the composite (Co ₁ -in-MoS ₂ catalyst), where both sulfones can be obtained in nearly identical yields within 2 and 1 hours at 40 °C, indicating the potential for scaling up the reaction to an industrial level.

Some other examples in which the sulphide can be oxidised are: The reaction can be performed with 0.1 mmol of sulfide, 0.25 mmol of H ₂ O ₂ , 1 piece of Co ₁ - in-MoS ₂ catalyst (1 x 2 cm ² ) in 4 mL of CH ₃ CN at 40 °C for 20 min; or with 0.5 mmol of H ₂ O ₂ at 60 °C for 1 h; or with 4 mL of CH ₃ CN and 1 mL of DMF for 1 h; or at 60 °C for 4h, or at 40 °C for 1.5 h. In some embodiments, the utility of the method is further highlighted by controllable semioxidation to sulfoxides. 8 different representative examples with ketone, aldehyde, carboxylic acid, alkene, alkyne, heterocycles and boronic acid units were examined in Table 4. Similar to the results for sulfone oxidation, all of the substrates can be chemo-selectively oxidized to sulfoxides with excellent yields (83 ~ 91%) in a controllable manner. Notably, 4-(methyIthio)quinoIine is a colorful dye with blue color, where its semi- and full oxidation products with characteristic green and orange color can be obtained with stoichiometric amounts of H ₂ O ₂ .

Other examples of controllable semi-oxidation to sulfoxides include:

The reaction can be performed with 0.1 mmol of sulfide, 0.11 mmol of H ₂ O ₂ , 1 piece of Co ₁ - in-MoS ₂ catalyst (1 x 2 cm ² ) in 4 mL of CH ₃ CN at 40 °C for 20 min, or in 4 mL of CH ₃ CN and 1 mL of DMF for 1 h; or in 0.25 mmol of H ₂ O ₂ at 60 °C for 20 min; or at 60 °C for 4h. In some preferred embodiments, the solvent is acetonitrile (AN), water, hydrocarbyl aliphatic alcohols (such as methanol, ethanol, isopropanol), dioxane, N,N- dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). As is clear from the Examples, the catalytic oxidation of sulphide to either sulfone or sulfoxide can be controlled by varying the amount of oxidant. When an at least two or more equivalence of oxidant is added, sulphide is oxidised to sulfone. The at least two or more equivalence of oxidant can be at least about 2 equivalence, about 2.1 equivalence, about 2.2 equivalence, about 2.3 equivalence, about 2.4 equivalence, about 2.5 equivalence, about 3 equivalence, about 5 equivalence, or about 10 equivalence. When an at least one or less than two equivalence of oxidant is added, sulphide is oxidised to sulfoxide. The at least one or less than two equivalence of oxidant can be about 1 equivalence to less than 2 equivalence, about 1 equivalence to about 1.9 equivalence, about 1 equivalence to about 1.8 equivalence, about 1 equivalence to about 1.7 equivalence, about 1 equivalence to about 1.6 equivalence, about 1 equivalence to about 1.5 equivalence, about 1 equivalence to about 1.4 equivalence, about 1 equivalence to about 1.3 equivalence, about 1 equivalence to about 1.2 equivalence, or about 1 equivalence to about 1.1 equivalence. The at least one or less than two equivalence of oxidant can be about 1 equivalence, about 1.1 equivalence, about 1.2 equivalence, about 1.3 equivalence, about 1.4 equivalence, or about 1.5 equivalence.

If the sulphide is partially oxidised to a sulfoxide, the sulfoxide can be subsequently further oxidised to a sulfone. This can be performed by providing further oxidant (of at least 1 equivalence in the presence of the catalyst of the present invention) to the sulfoxide.

In some embodiments, the composite (Co ₁ -in-MoS ₂ catalyst) can be recycled for at least five times without any decrease in reaction efficiency and chemo- selectivity in Figure 4. This is part of the advantage of vertically structured catalyst, which reduces the sensitivity toward changes in the environment and minimizes catalyst loss in the recovery process; i.e. the composite is robust against changes in the environment and has minimal leaching. This is confirmed using SEM imaging, in which a recycled composite revealed no obvious difference to fresh composite. Inductively coupled plasma optical emission spectroscopy (ICP-OES) of the supernatant of reaction mixture also confirms no metal leaching after reaction completion.

Accordingly, in some embodiments, the reaction is chemoselective for the sulphide moiety. In this regard, only the sulphide moiety is oxidised to a sulfoxide moiety or a sulfone moiety. Other functional moieties such as alkyne, alkene, ketone, aldehyde, carboxylic acid, boronic acid and ester, amine and heterocycle are not oxidised. In some embodiments, the reaction has a selectivity (or chemoselectivity) of at least 90% for the sulphide moiety. In other embodiments, the selectivity is at least 92%, at least 94%, at least 96% or at least 98%. In other embodiments, the selectivity is at least 99%.

Owing to its high chemoselectivity and efficiency, the chemical products can be easily isolated by simple removal of the composite from the reaction medium. Small amounts of excess H ₂ O ₂ will be eventually converted into water, thus bypassing the tedious separation or purification steps in conventional sulfide oxidations. This is remarkably attractive for the synthesis of sulfone containing biomolecules.

Without wanting to be bound by theory, the inventors believe that sulfide oxidation by H ₂ O ₂ involves a radical pathway. A possible mechanism is proposed in Figure 6A. Figure 6A refers to Co ₁ -in-MoS ₂ as an exemplary example of the composite of the present invention. The preferred adsorption of sulfide lq at the edge of Co ₁ -in-MoS ₂ is supported by density functional theory (DFT) calculations. The enhanced absorption is attributed to the promoter effect of Co single atoms, which weakens the sulfur-molybdenum bonds at the edge and induces a higher electron density of the nearby Mo atoms (Figure 6B). The intercalation of Co may also introduce structural defects (such as S vacancy) due to its lower coordination number (4) than Mo atoms (6). As shown in Figure 6C, DFT studies show a much stronger adsorption of sulfide 1q in a vertical configuration on the sulfur site over other competing sites (such as OH site in boronic acid group), which is the basis for the excellent chemoselectivity toward sulfide oxidation in the system. Such promoter effect is universal and not affected by the location of intercalated Co single atoms. The basal plane of Co ₁ -in- MoS ₂ is relatively inactive, suggesting the oxidation reaction takes place at the active edge. Surface-absorbed sulfide species (I) is then attacked by the · OH radicals generated from the cleavage of H ₂ O ₂ to give the intermediate (II), which abstracts another · OH radical with the leaving of a H ₂ O molecule to give semi-oxidation product sulfoxide (III). Similar pathway is proposed for the subsequent oxidation of sulfoxide to sulfone (VII), where at least 2 equivalents of H ₂ O ₂ are required to complete the catalytic cycle. MoS ₂ serves as excellent promoter in catalytic decomposition of H ₂ O ₂ for advanced oxidation process involving Fenton-like radical mechanism. The existence of metallic Co single atoms further boosts the catalytic efficiency of radical generation. The radical pathway for sulfide oxidation is confirmed by electron paramagnetic resonance (EPR) measurements in Figure 6D. The radicals generated in the presence of H ₂ O ₂ and catalyst were trapped with 5, 5 -dimethyl- 1- pyrroline-N-oxide (DMPO) to form stable DMPOOH adducts, which show the fingerprint EPR signals (quartet peaks, α _N = α _H = 14.9 G, marked by *). However, hydroperoxyl adducts (DMPO-OOH) was not detected, excluding the heterolysis of H ₂ O ₂ in our Co ₁ -in-MoS ₂ system. This is distinct from conventional MoS ₂ and Co-doped MoS ₂ catalysts, where the existence of strongly oxidative hydroperoxyl radicals will lead to fast catalyst degradations and poor catalytic conversions due to the formation of non-oxidative H radicals. Upon the addition of substrate to our system, no additional EPR peaks could be observed in Figure 6D, which is reasonable owing to poor resolution of DMPO-S species. Time dependent EPR measurement also indicates a steady generation of DMPO-OH adducts in the course of reaction so that a small excess of H ₂ O ₂ is sufficient to complete full oxidation to sulfones. The radical pathway is further proved by 2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO) quenching experiment, where negligible yield of 2a could be observed in the presence of TEMPO molecule.

Examples Example 1. Synthesis of vertically grown MoS ₂ array on carbon paper:

In a typical hydrothermal synthesis, 726 mg of Na ₂ MoO ₄ -2H ₂ O and 609 mg of thiourea was dissolved in 50 mL of deionized water. After gentle stirring for 30 min, the solution was then transferred to a 80 mL Teflon-lined stainless steel autoclave with a piece of oxygen-treated carbon paper (10 cm ² ). The autoclave was sealed and heated at 190 °C for 24 h in an oven and then cooled down to room temperature naturally. Finally, the product was taken out, rinsed with deionized water and ethanol several times and dried at 60 °C in air. The loading for MoS ₂ nanosheet on carbon cloth was ~ 4.0 mg cm ^-2 by weight difference and ICP-OES.

Example 2. Synthesis of cobalt phthalocyanine intercalated MoS ₂ : The encapsulation of cobalt phthalocyanine in MoS ₂ matrix was conducted by an electrochemical co-intercalation method with a standard 2-electrode cell using a Pt plate as the counter/reference electrode and hydrothermal-grown MoS ₂ array on carbon paper (10 cm ² ) as the working electrode. Electrolyte was prepared by dispersing 28.6 mg of cobalt(II) phthalocyanine (CoPc) and 91.1 mg of cetyltrimethylammonium bromide (CTAB) in 50 mL of l-methyl-2-pyrrolidinone (NMP) with the aid of 30 min sonication. The electrochemical co-intercalation was performed by chronopotentiometry at a constant current density of -0.1 m A cm ^-2 or 300 mA for 2 h with a cut-off potential of - 4 V, where both CTAB and cobalt phthalocyanine molecules will intercalate into the layer spacing of MoS ₂ . The CoPc- modified electrode was rinsed by DMF, ethanol, water and acetone for 3 times and dried at 60 °C.

Example 3. Synthesis of cobalt single atom intercalated MoS ₂ :

To convert into cobalt single atom intercalated MoS ₂ , the CoPc-modified MoS ₂ electrode was loaded into a quartz tube mounted inside a tube furnace under Ar gas and then heated at 600 °C for 2 h at 5 °C min ¹ . The product (Co ₁ -in-MoS ₂ ) was rinsed by DMF, ethanol, water and acetone for 3 times and dried at 60 °C.

Example 4. Selective oxidation to sulfone:

1 piece of Co ₁ -in-MoS ₂ on carbon paper (~ 2 cm ² , 8 mg MoS ₂ loading) was loaded in a vial with 4.0 mL of acetonitrile (AN) and stirred at 40 °C. Then, 0.1 mmol of thioanisole (12.4 mg) and 0.25 mmol of 30% H ₂ O ₂ (~ 25 uL, 2.5 equilibrium) were added sequentially into the reactant vial. The reaction mixture was stirred at 40 °C for 20 min. The conversion yield and selectivity were determined by NMR.

Example 5. Gram-level synthesis of alkyne-functional sulfone:

2 piece of Co ₁ -in-MoS ₂ on carbon paper (~ 16 mg MoS ₂ loading) was loaded in a vial with 8.0 mL of AN and stirred at 40 °C. Then, 48 mmol of phenyl propargyl sulfide (1 g) was added into the reactant vial. The mixture was kept at 40 °C for 120 min where 0.25 mL of 30% H ₂ O ₂ was added every 10 min. Isolated compound was obtained by rotary evaporation and the conversion, yield and selectivity were determined by NMR. Example 6. Selective semi-oxidation to sulfoxide:

1 piece of Co ₁ -in-MoS ₂ on carbon paper (~ 2 cm ² , 8 mg MoS ₂ loading) was loaded in a vial with 4.0 mL of AN and stirred at 40 °C. Then, 0.1 mmol of 4'-(methylthio)acetophenone (16.6 mg) and 0.11 mmol of 30% H ₂ O ₂ (~ 11 uL, 1.1 equilibrium) were added sequentially into the reactant vial. The reaction mixture was stirred at 40 °C for 20 min. The conversion, yield and selectivity were determined by NMR.

Example 7. Synthesis of nickel complex-intercalated T1S ₂ : The encapsulation of nickel complexes in T1S ₂ was conducted by an electrochemical cointercalation method with a standard 2-electrode cell using a carbon nanorod as the counter/reference electrode and one piece of T1S ₂ crystal (2x5x0.1 mm ³ ) clamped by two Titanium sheets and fixed by Teflon tapes as the working electrode. Electrolyte was prepared by dispersing 128.4 mg of Nickel(II) acetylacetonate (Ni(acac)2) and 55.4 mg of tetrapropylammonium chloride (TRAC) in 50 mL of anhydrous propylene carbonate (PC) with the aid of 30 min sonication. The electrochemical co-intercalation was performed by chronopotentiometry at a constant current density of -0.1 m A cm ^-2 for 2 h with a cut-off potential of - 4 V, where both TP AC and nickel acetylacetonate molecules will intercalate into the layer spacing of MoS ₂ . The Ni complex-modified electrode was rinsed by DMF, ethanol, water and acetone for 3 times and dried at 60 °C.

Example 8. Electrochemical intercalation by modified porphyrins:

Direct intercalation of metal complexes can be realized by the use of modified porphyrins, avoiding the use of co-intercalant (CTAB, TPAC etc.). Cobalt(II) 5,10,15,20-(tetra-N- methyl-4- pyridyl)porphyrin tetrachloride or Cobalt(II) 5,10,15,20-(tetra-N,N,N-trimethyl- 4-anilinium) porphyrin tetrachloride at 0.002 M in l-methyl-2-pyrrolidinone (NMP) was employed as electrolyte. The electrochemical intercalation was performed in a two-electrode setup similar to example 1 by chronopotentiometry at a constant current density of -0.02 mA cm ^'2 for 2 h with a cut-off potential of - 4 V. The Co complex-modified electrode was rinsed by DMF, ethanol, water and acetone for 3 times and dried at 60 °C. Example 9. Sulfide Oxidation by 3-Chloroperbenzoic acid (mCPBA):

0.1 mmol of 4'-(methylthio)acetophenone (16.6 mg) was loaded in a vial with 4.0 mL of AN and stirred at 40 °C. Then, 0.25 mmol of mCPBA (43.1 mg, 2.5 equilibrium) were added sequentially into the reactant vial. The reaction mixture was stirred at 40 °C for 20 min. The conversion, yield and selectivity were determined by NMR. Additional purification steps were required to remove the excess mCPBA in solution. Multiple products were detected with a poor selectivity to 4'-(methylsulfonyl)acetophenone (< 50%).

Example 10. Comparison with Comparator

The oxidation reaction was implemented in acetonitrile (CH ₃ CN) by using sulfide la as model substrate, Co ₁ -in-MoS ₂ (lx 2 cm ² ) as catalyst and hydrogen peroxide (H ₂ O ₂ , 30% w/w, 2.5 equiv.) as oxidant. Full conversion of la and above 99% selectivity of sulfone 2a could be obtained within 20 minutes at 40 °C using the composite of the present invention. The use of commercial MoS ₂ , exfoliated MoS ₂ and M0O3 powders gave poor results. These results highlight the importance of TMD layers on the substrate to provide higher accessible surface area and the promoter effect of transition metal single atoms intercalant to sulphide oxidation. As aforementioned, Co single atom encapsulation alters the electronic structure of MoS ₂ , leading to favorable adsorption of the substrates and enhanced reaction activity. The promoter effect depends significantly on the nature of intercalated metals. Pt nanoparticles-in-MoS ₂ resulted in low efficiency due to the rapid decomposition of H ₂ O ₂ in the presence of noble metals. The existence of defect or edge also has a profound influence on catalytic activity, where negligible conversion was observed for single crystal MoS ₂ . Control experiments reveal that both catalyst and oxidant were essential for such oxidation reaction. Homogeneous Pd(PPh ₃ ) ₄ catalyst and heterogeneous 10% Pt/C catalysts gave negligible conversion of sulfide. Meanwhile, the oxidation reaction was completed within 10 minutes at slightly elevated temperature or at room temperature. Prolonging reaction time to 60 minutes gives similar yields and selectivities. As shown in Figure 4B, the Co ₁ -in-MoS ₂ catalyst can be easily recycled for five times without any decrease in reaction efficiency and chemoselectivity, thus the catalyst is robust against changes in the environment and has minimal leaching. The SEM images of recycled Co ₁ -in-MoS ₂ catalyst revealed no obvious difference to fresh catalyst. Inductively coupled plasma optical emission spectroscopy (ICP- OES) of the supernatant of reaction mixture also confirms no metal leaching after reaction completion.

Example 11. Late stage functionalisation of Tamiflu

The applicability of the oxidation protocol to the late-stage functionalization of Tamiflu ^® (a) in Figure 5, which has an electron-deficient alkene that is prone to traditional mCPBA oxidation. Tamiflu ^® was first subjected to sulfurization by 2-(phenylthio)acetyl chloride in anhydrous THF, followed by semi- or full oxidation with Co ₁ -in-MoS ₂ to give corresponding sulfoxide-modified and sulfonated Tamiflu ^® (4b & 4c) in 86% and 77% yields, respectively. Without using any purification process, both functionalized pharmaceuticals can be easily recrystallized to give ultrapure compounds (see single crystal data in Figure 5), which is a distinct advantage over homogeneous oxidation or cross-coupling reaction.

It will be appreciated that many further modifications and permutations of various aspects of the described embodiments are possible. Accordingly, the described aspects are intended to embrace all such alterations, modifications, and variations that fall within the spirit and scope of the appended claims.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.