Ketene dithioacetals 7-selectivity

Given the selection of an appropriate substrate, the generation of a carbon centred radical from such a substrate can initiate a series of bond-making and bond-breaking processes which are sometimes referred to as radical cascade reactions. These can be of great synthetic value. Thus, treatment of the ketene dithioacetal 1 with a five fold excess of tributyltin hydride in hot benzene under nitrogen and in the presence of a catalytic amount of AIBN gave the metallated benzo[ fc]thiophene 2, itself a valuable synthetic intermediate, in 70% yield. 

Ketene dithioacetals and diselenoacetals are obtained under the same conditions from orthothioesters and orthoselenothioesters (equation II).2 These products undergo selective C-Se bond cleavage on treatment with n-butyllithium to give a lithio... 

Chirahty transmission can also be induced in thio-Claisen reactions by a chiral center adjacent to the allyl vinyl sulfide core. The group of Metz-ner examined the diastereoselectivity of the rearrangement of acyclic S-allyl ketene dithioacetals bearing a chiral center adjacent to carbon 6. hi these substrates, the sigmatropic shift proceeded smoothly and with modest syn anti diastereoselectivity [74]. In contrast, higher selectivities are foimd for thio-Claisen precursors bearing a chiral center adjacent to carbon 1 mainly due to steric effects and allylic strain [75]. In 1991, the group of Beslin examined the effect of a hydroxyl substituted chiral center attached to C-1 of Z and E S-allyl ketene dithioacetals [76,77] (Scheme 7). Under the reaction conditions, these... 

Reaction of ketene dithioacetals 260 with thioamides gave 5-substituted 2-methyl(phenyl)-6-methylthio-4-thioxopyrimidine (262) (92H1573). The reaction mechanism involves the addition of the thioamide to the ketene dithioacetal 260 to afford 2-cyano-3-methylthio-3-thioamido-propenoni-trile or -propenoate intermediate, which cyclizes in situ by site-selective nucleophilic attack of the sulfur on the cyano group to give 6-imino-l,3-thiazine 261, which rearranged to 262 (Scheme 84). 

Defunctionalization of heteroalkenes. The C-X bonds of alkenyliodonium salts, l,2-bis(phenyltelluro)alkenes, and ketene bis(methylthio)acetals, which carry an electron-deficient substituent, are selectively replaced. Only one group of the chalcogenides is affected, and the ketene dithioacetals undergo reductive cleavage. However, the alkenylcopper intermediates can be acylated. ... 

A different approach to a-methylenebutyrolactones is a further development of the chemistry of 2-silyloxycyclopropane carboxylates (393), which, when treated with the trifluoromethanesulphonate analogue of Eschenmoser s salt and a Lewis acid (TMSOTf), are converted into 8-amino-esters (394) and thence lactones (395) following borohydride reduction and elimination.33 Overall yields are reasonable for this multi-step approach. A carbanion based approach to monosubstituted lactones. (390) begins by metallation and regio-selective condensation of ketene dithioacetal (396) with an aldehyde. 

Careful acid-catalysed cyclisation of ketene dithioacetals (460) can take place with > 90% selectivity in favour of isomers (461)... 

The alkylation of O-silylated dienolates with 1,3-dithienium tetrafluoroborate shows useful y-selectivity [equation (59)]. The y-alkylated products are selectively protected 1,5-dicarbonyl compounds. Unsaturated 1,5-diketones, precursors of various heterocycles, can be prepared by the reaction of the potassium enolates of methyl ketones with acyl keten dithioacetals [equation (60)]. ... 

Dithiolane Formation. 1,2-Ethanedithiol (1) condenses with aldehydes, ketones, and acetals to afford 1,3-dithiolanes, - useful for carbonyl protection (eqs 1 and 2). Stability, condensation selectivity, and conditions for carbonyl regeneration parallel those discussed for 1,3-Propanedithiol. Esters and lactones can be protected as ketene dithioacetals and/or dithioortholactones, resistant to nucleophilic attack, using the bis(dimethylalanyl) derivative of (1). ... 

Ketene Dithioacetal Formation. These versatile intermediates arise from 1,3-dithiane anions by elimination (eq 8) or vinylogous alkylation (eq 4), and by condensation of carboxylic acid derivatives with (1) (eq 13). Ketene dithioacetals derived from lactones can cyclize to give dithio orthoesters, which can be selectively deprotected (eq 16). ... 

Similar reactions could also be carried out with ketene diethyl dithioacetal S-monooxide (251). The Michael addition of nitroalkanes 246 to 251 afforded the selective monoadducts 252, but that to 247 (R = H) yielded a mixture of the mono- (248) and diadducts. 

Additive Pummerer reactions of the type described above using racemic a,P-unsaturated sulfoxides can be accomplished using the following electrophiles acyl chlorides [205,206], dithioacetic acid [207], acetic anhydride [208], mineral acids/alcohols [209], phosphorus pentachloride [210], silyl ketene acetals/zinc iodide [211], thionyl chloride [212], oxalyl chloride [213], trifluoroacetic acid and its anhydride [214-218], triflic anhydride/sodium acetate [219], and dichloroketene (see below). Selected recent examples of work in this area are presented here. 

The efFicienqr of sulfoxides as chiral inductors for the thio-Claisen rearrangement has been demonstrated with N,S-ketene acetals derived from racemic 2-sulfinyl dithioacetates [72], Moreover, these reactions were successfully extended to the enantiopure series using chiral thioamides as substrates [125]. The source of chirality is the easily available and cheap D-glucose [126]. Remarkably, both enantiomers of the starting 2-sulfinyl thioacetamides can be selectively obtained from the same D-glucose. 

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