Higher order mixed

This reagent is perhaps best thought of as a higher-order mixed cuprate of the type (R3Si)2Cu(CN)Li2 (7). 

Thienyl(cyano)copper lithium S Cu(CN)Li xhe reagent is obtained by reaction of thiophene with BuLi in THF at - 78° and then with CuCN at - 40°. The reagent is fairly stable and can be stored in THF at - 20° for about 2 months. It is inert, but is readily converted by addition of RLi or RMgX into a higher-order mixed cuprate, which is as efficient as the freshly prepared cuprate."1... 

General procedure for the 1,4-addition of higher-order mixed cyanocuprates to enones followed by O-functionalization ... 

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

Lipshutz, B. H. Kozlowski, J. Wilhelm, R. S. Chemistry of higher order mixed organocup-rates. 2. Reactions of epoxides./. Am. Chem. Soc. 1982, 104, 2305-2307. 

RR Cu(CN)LiMgX w a higher order mixed metal cyanocuprate... 

O Donnell et al have examined benzophenone-derived glycine acetate (85) as a glycine cation equivalent. Higher order mixed cuprates [R2Cu(CN)Li2] react with (85) to afford alkylated Schiff base (86) in moderate yields. The reaction is sensitive to reaction conditions and reduction competes with or-ganometallic addition. Hydrolysis of (86) provides access to aryl- or alkyl-substituted amino acids (87 Scheme 16). 

In high ligand variety systems, equation 1 can be replaced with an equation which Implicitly accounts for the formation of ternary and higher order mixed complexes (2). 

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%. 

Lithium-cuprate complexes obtained by the reaction of Cu(I) iodide and the corresponding aryllithium were also successfully applied in the synthesis of unsymmetrical biaryls [23]. An alternative strategy involves the low temperature oxidative coupling of higher order mixed diarylcuprates [24]. The classical Ullmann reaction can be accelerated by using, instead of copper... 

Cuprates are very useful but there are a few problems associated with them. In an attempt to circumvent these problems, Lipshutz developed the so-called higher order mixed cuprates (R2Cu(CN)Li2), prepared by reaction of 2 equivalents of organolithium reagent with cuprous cyanide (CuCN). 35 Mixed cuprates react... 

One of the most recent developments in the area of biaryl coupling is the use of higher order mixed diarylcyanocuprates these kinetically prepared higher-order cuprates function well at very low temperatures to yield unsymmetrical coupling products (Scheme 135) <94TL815>. Two dissimilarly substituted thiophenes have also been coupled by this procedure. 

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... 

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