Organocuprates mixed

Viprostol (81) also incorporates a hydroxy group moved to C-16 and protects this from facile metabolic oxidation by vinylation. It is a potent hypotensive and vasodilatory agent both orally and transdermally. The methyl ester moiety is rapidly hydrolyzed in skin and in the liver so it is essentially a prodrug. It is synthesized from protected E-iodo olefin 78 (compare with 75) by conversion to the mixed organocuprate and this added in a 1,4-sense to olefin 79 to produce protected intermediate 80. The synthesis of viprostol concludes by deblocking with acetic acid and then reesterification with diazomethane to give 81 [19]. 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

B.H. Lipshutz, Application of Higher-Order Mixed Organocuprates to Organic Synthesis, Synthesis 1987, 325, s.d.S.335ff. 

In contrast to their reaction with R R CuLi (R = alkyl, R = alkyl or CN), the reactions of epoxides with the higher order mixed organocuprates R2Cu(CN)Li2 (R = various alkyl or aryl) give excellent yields of ring-opened products. The trisubstituted oxiran (190), on reaction with Pr"Cu(CN)Li, affords only 23% of (191), but with Pr"2Cu(CN)Li2 the yield is increased to 86%. 

Lipschutz BH, Wilhellm RS, Kozlovski JA, Parker D (1984) Substitution reaction of secondary halides and epoxides with higher order, mixed organocuprates, R2Cu(CN)Li2 synthetic, stereochemical, and mechanistical studies. J Org Chem 49 3928-3938... 

The only product isolated (32) arises from transfer of the aryl group to the enone. This complements the behaviour of mixed organocuprates which will transfer unsaturated alkyl groups in preference to saturated ligands. 

Selective group transfer is observed from mixed organocuprates of the type (41) acetylenic residues are always retained, and the resulting copper(i) acetylide is produced as its water-soluble phosphine complex (Scheme 101). 

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