Decarboxylative thiolation

SCHEME 5.15 Decarboxylative thiolation of alkyl carboxylic acids [16]. 

Due to the stability and availability of carboxylic acids, they remain some of the most attractive starting points for the synthesis of complex organic compounds. Using these compounds as substrates, the decarboxylative thiolation of carboxylic acids has been achieved using silver nitrate as a promoter (Scheme 5.15) [16]. Disulfides served as the sulfur source for this chemistry, and moderate to good yields of the thioethers from a host of aUcyl carboxylic acids. 

A reasonable entry point to the chemistry would be to convert the carboxylic acids into sulfinate salts [12]. Alternatively, a silver-catalyzed decarboxylative thiolation will generate sulfone precursors [16]... 

As has been mentioned above, thermal decarboxylation of heterocycle 36 can be coupled with electrophilic trapping with either bromine or nitro groups to yield the substituted analogues. The same heterocyclic system 59 can be thiolated by treatment either with elemental sulfur (followed by alkylation with an alkyl halide) to afford 60, or the electrophilic thiolating reagent 58 to generate 57 (Scheme 5) <2005HCA1208>. 

In the first half of the ping-pong bi-bi reaction, the active site cysteine is acylated by either an acyl-ACP (KAS I and KAS II) or an acetyl-CoA (KAS III), or in the case of the M. tuberculosis KAS III (FabH) a long-chain acyl-CoA. Attack of the active site cysteine thiolate on the donor acyl thioester is aided by the dipole of the active site helix and an oxyanion hole composed of two backbone NH groups. The additional catalytic residues (His, His or His, Asn) are thought to primarily function in the decarboxylation of malonyl-ACP and stabilization of the acetyl-ACP carbanion that is formed. The carbanion subsequently attacks the acyl-enzyme thioester leading to the formation of the (3-ketoacyl-ACP product. 

This type of reaction is essentially similar to that of replacement of an aromatic halogen by a thiolate group. Halogen compounds studied include 3,4-dimethyl-5-bromo-2(N,N-dimethylaminomethylene)-2H-pyrrole and chlorofuro-[2,3-d]pyridazines . Copper(i) alkylthiolates have been used to form thioethers with 2-bromothiophene, 2-bromopyridine and 2-bromofuroic acid, the latter with concomitant decarboxylation . 

Olefins are obtained from S -(2-pyridyl)thiolates by a novel nickel-catalysed decarboxylation pathway (Scheme 31). The products are formed in good yield at reasonable temperatures, and since the thiolates are readily obtainable from the parent acids the overall process is therefore one of mild conversion of an acid into an olefin. ... 

---