Sulfones, aryl coupling reactions

The most important palladium-catalyzed processes include Heck vinylation of halides and sulfonates and various cross-coupling reactions in which a nucleophilic intermediate (stannane, organo-zinc halide or boronic acid) is coupled with an electrophile (halide or sulfonate). These coupling reactions are usually restricted to arylation and vinylation because of the tendency of alkylpalladium species to undergo elimination. The pyrrole and indole rings can participate in cross-coupling as either the nucleophilic or electrophilic component. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

In the early solution phase syntheses of oligonucleotides, coupling of phosphate diesters was used. A mixed 3 -ester with one aryl substituent, usually o-chlorophenyl, was coupled with a deprotected 5 -OH nucleotide. The coupling reagents were sulfonyl halides, particularly 2,4,6-tri-i-propylbenzenesulfonyl chloride,53 and the reactions proceeded by formation of reactive sulfonate esters. Coupling conditions... 

Mulhaupt et al. synthesized novel soluble copoly-arylenes via a Ni(0)-catalyzed coupling reaction of aryl chlorides. Molar ratios of dichlorodiphenyl sulfone (a) to m-dichlorobenzene (y) were used to vary the amount of m-phenylene in the final copolymer. Then these copolymers were dissolved in chloroform and sulfonated with chlorosulfonic acid. The synthe-... 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

From the synthetic point of view, choice of the starting halide or sulfonate is usually based on availability. Reactivity and economy usually work antiparallel with bromides being the most frequently used substrates. The recent invention of highly active catalyst systems, on the other hand, broadened the applicability of aryl chlorides considerably in cross-coupling reactions.3... 

The first step in the cycle, analogous to the cross-coupling reactions, is the oxidative addition of an aryl (vinyl) halide or sulfonate onto the low oxidation state metal, usually palladium(O). The second step is the coordination of the olefin followed by its insertion into the palladium-carbon bond (carbopalladation). In most cases palladium is preferentially attached to the sterically less hindered end of the carbon-carbon double bond. The product is released from the palladium in a / -hydrogen elimination and the active form of the catalyst is regenerated by the loss of HX in a reductive elimination step. To facilitate the process an equivalent amount of base is usually added to the reaction mixture. 

A number of methods for the preparation of vinyl and allyl sulfones are available [1U9, 110], and the syntheses of vinyl sulfones from alkenes has been reviewed [116]. A simple one-step procedure of wide applicability makes use of a palladium-catalysed cross-coupling reaction between aryl and alkyl sulfonyl chlorides and substituted vinyl and allyl stannanes... 

Table 5.5 Scope of aryl chlorides and sulfonates in iron-catalyzed cross-coupling reaction with RMgBr.

Palladium-catalyzed cross-coupling reactions of diaryliodonium tetrafluo-roborates have recently been employed for conversions of mercaptans to aryl-and diaryl sulfides, sodium arenesulfinates to diaryl sulfones, and dialkyl phosphites to aryl phosphonates (Scheme 43) [120-122]. 

De Carolis, M., Protti, S., Fagnoni, M. and Albini, A. (2005) Metal-free cross-coupling reactions of aryl sulfonates and phosphates through photoheterolysis of aryl-oxygen bonds. Angewandte Chemie, International Edition, 44, 1232-1236. 

One of the challenges in the Suzuki-type cross-coupling is to extend this reaction from electron-rich aryl iodides, bromides, and triflates to less reactive aryl sulfonates and aryl chlorides, which show poor reactivity in terms of oxidative addition in the catalytic cycle. Aryl mesylates, benzenesulfonates, and tosylates are much less expensive than triflates, and are unreactive toward palladium catalysts. The Ni(0)-catalyzed Suzuki-type cross-coupling reaction of aryl sulfonates, including mesylates, with arylboronic acids in the presence of K3P04 has been reported [123]. 

Transition metal-catalyzed cross-coupling reaction has become the most important method for the formation of aryl-aryl bonds. The reaction of aryl halides and sulfonates with organomagnesium compounds is usually referred... 

Oxidative Pd insertion into electron-poor aryl sulfonates is a key step in Pd(0)-mediated C-C coupling reactions. This principle has been turned into a traceless linker concept in which phenols are attached via sulfonates to a solid support [107]. The system has been optimized by employing a perfluoroalkylsulfonyl linker that closely resembles the commonly applied inflates (90, Scheme 41). In this respect, the linker acts as a protecting group and as an activating entity. Reductive cleavage of 91 with Pd(0) and formic acid led to arenes 92 [108]. 

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