Tosyl displacement with cuprates

The tosylate group can be displaced from alkyl tosylates by dialkyl-cuprates 256, 297, 301), presumably by attack at carbon by the d electrons of copper. A transient copper(III) intermediate may be formed [Eq. (87)], as suggested for similar reactions with alkyl halides. An analogous reaction was reported between a copper(I) carboxylate and an alkyl tosylate 185). (Carboxyethyl)methylcopper, C2H5O2CCH2CU, failed to react with butyl tosylate in THF 181). However, copper compounds of the type RCu are generally less reactive than the cuprates. 

It should be noted that direct substitution of sulfonate or iodide derivatives at C6 is sensitive to steric hindrance. Kishi reported a failure in the substitution of a primary tosylate by vinyl cuprate in the synthesis of mycalamides where C4 had two geminal methyl substituents. An alternate five step route was developed to introduce the vinyl substituent [119]. Direct substitution of a primary triflate by an aryl Grignard reagent is a key step in the formal synthesis of (+)-apicularen A from D-glucal [194]. Displacement of a triflate with an alkynyllithium has also been used in the total synthesis of (+)-panaxacol [195]. 

The gastric antisecretory properties of 15-deoxy-l 6-methyl-16-a,iS-hydroxyprostaglandin El methyl ester are associated exclusively with the 16(S) diastereomer 1054. Diol 1053, a key chiral synthon for the synthesis of 1054, is readily prepared from 1031 by conversion of the primary alcohol to a tosylate, displacement of the tosylate by mixed cuprate to give 1052, and then hydrolysis of the acetonide (Scheme 156) [222]. The overall yield of the sequence starting from (5)-citramalic acid is 50.4%. 

The corresponding reaction with PlnSnM proceeds with complete inversion regardless of addition mode (equation 21). In this case, radical reactions appear unimportant. Displacement of the tosylate by a trimethyltin cuprate was also found to take place by inversion. 

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