Thiol lactones synthesis from thiols

Masamune S, Kamata S, Schilling W (1975) Syntheses of Macrolide Antibiotics. III. Direct Ester and Lactone Synthesis from 5-/ert-Butyl Thioate (Thiol Ester) J Am Chem Soc 97 3515... 

Monothioacetals 1,3-Oxathiolanes Thiolactams S extrusion, 59-60, 261 Thiols synthesis from haloalkanes, 169, 269 Thionation of lactones, 110-111 Thiones olefination of, 35 Thionocarbonates. See Carbonothioates Thionolactones, 110-111 Thionyl chloride prepn. of acyl halides, 143 prepn. of carboxylic esters, 347 prepn. of haloalkanes from alcohols, 32 Thiophenoi. See Benzenethiol Thiotosylatc. See Benzenesulfonothioic add... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Acylation of a simple thiol with an alkyl carboxylate is not a very suitable method for preparation of S-alkyl thiocarboxylates. Transesterification is, however, possible if either the thiol or the carboxylic ester is activated. The enhanced reactivity of boron, aluminum and silicon thiolates has been utilized for the synthesis of a large variety of thiocarboxylic S-esters, including hydroxy derivatives (from lactones). a,P-Unsaturated thiol esters, e.g. cinnamoyl or 2-butenoyl derivatives, are also accessible. Michael addition, an undesirable side reaction of thiols, is completely avoided if alkyl trimethylsilyl sulfides ortris(arylthio)boranes are applied. ... 

Lactone ring expansion. The lithio derivative from this sulfoxide (LDA) reacts with lactones to form adducts which on further treatment with KH and then r-BuLi are transformed into ketenes. Acidification regenerates lactones of one size larger. This reaction sequence works well for expansion of 5- and 6-membered lactones. For the synthesis of macrolides, it is necessary to quench the ketene with pyridine-2-thiol and use the Corey-Nicolaou method to effect reclosure of the lactone ring. 

Very recently, the concise synthesis of a range of disubstituted 2-pyrones 96 from (thiophenyl)acetic acids and readily available trifluoromethyl enones via an isothio-nrea mediated one-pot Michael addition/lactonization/thiol elimination sequence has been demonstrated. Derivatization of these reactive pyrones to generate additional high-value products was next investigated and compounds 96a-c were prepared in good yields [39b] (Scheme 31). 

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