Thioketones, 4-alkyl synthesis

Another indole/oxindole synthesis achieves the critical ortho-substitution by Sommelet-Hauser rearrangement of an anilinosiilfonium ion intermediate. Use of P-thioketones (G = R, an alkyl group) generates 2-substituted indoles, whereas P-thioesters (G = OR) lead to oxindoles. In each case, a 3-thio substituent must be removed by desulfuri2ation. 

The synthesis of 4-alkyl thioketones is possible by exploiting the stabilizing effect of a sulfur atom upon an adjacent carbanionic center. Ambident allylic anions react so that conjugate addition proceeds exclusively with the a-carbon of the nucleophile,129 243 244 as illustrated in equation (S3) 245 arylsulfinyl and arylsulfonyl groups normally246 behave similarly.247-249 Sulfur-stabilized vinylic carbanions can be prepared and function as Michael donors in difunctionalization sequences.250... 

Aryl alkyl thioketones undergo intramolecular hydrogen abstraction from the 5-carbon atom, and the resulting biradicals cyclize to cyclopentanethiols rather than to the cyclobutanols more usually observed in the Norrish Type II reaction. This principle has been utilized in a synthesis of cuparane (98) (Scheme 32). 

A variation of the use of thiourea for converting alkyl halides into thiols uses N-acetylthiourea although reaction with an alkyl halide in refluxing EtOH is slow, a separate hydrolysis step is not required and the method may prove useful for the synthesis of water- or alkali-sensitive thiols. Other methods based upon thiocarbonyl derivatives are exemplified by the addition of allylic Grignard reagents to thioketones, giving 7-unsaturated... 

Isothiazolopyridines.—A general synthesis of isothiazolo[2,3-n]pyridinium salts involves a cyclization by the formation of an S—bond as the final step. Thus, oxidation of the substituted thioacetamide (130) with hydrogen peroxide-perchloric acid or bromine, yields 2-dimethylaminoisothiazoIo-[2,3-a]pyridinium perchlorate (131) or its 3-bromo-derivative, respectively. Applied to suitable thioketones, e.g. (132), the method affords a 2-alkyl-com-pound, e.g. (133), but is of restricted applicability because of the lack of efficient routes to the starting thiones (132). ... 

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