Substitution with organocuprates

Scheme 6.32. Different stereochemical results with mesylate (156) and carbamate (158) leaving groups upon allylic substitution with organocuprates.

Remarkable y-syn-substitution preference is observed in the reaction of allylic carbamates with organocuprates. 

When treated with organocuprates, 2,3-epoxy alcohols can be converted to substituted 1,3-diols with high regioselectivity and stereoselectivity. Thus, as... 

Scheme 2.3 Formation of pharmacologically active target molecules by Sn2 substitution of propargylic electrophiles with organocuprates.

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

Only few examples have been reported so far on nucleophilic addition reactions to acceptor-substituted polyenes123,124,186 188. In 1933, Farmer and Martin186 examined the reaction of methyl 2,4,6-octatrienoate with sodium dimethyl malonate and isolated the 1,4-adduct as major product (equation 81). In contrast to this, 3,5,7-nonatrien-2-one and ethyl 2,4,6-octatrienoate react with organocuprates under 1,8-addition to provide the 4,6-dien-2-ones and 3,5-dienoates, respectively (equation 82)187. 

Bicyclic or polycyclic enones may give slow or inefficient reaction with organocuprates. In particular, it is those enones which contain substituents arranged so as to create a steric hindrance on the carbon 3 to the carbonyl that see the greatest effect. The yields are often low to moderate, unless additional activation is provided. For example, when the bicyclic enone (23) was treated with R2C11U (R = 3-pentynyl), the -substituted product was formed in only 46% yield,69 while exposure of the same enone to RQ1BF3 (R = 3-pentynyl) gave the same (3-alkylated product in 76% yield (Scheme 9).70... 

The reaction of the 2-substituted cyclopropenes (R = Et, Ph) with organocuprates favored, after hydrolysis, the 2,2- over 2,3-dialkyl adducts in a 29 1 to > 99 1 ratio [134] (Scheme 7-115). 

Substitution. Reaction of the diepoxides derived from aUenes with organocuprates to afford a-hydroxy ketones is stereoselective. ... 

The enol ethers of substituted 2,3-epoxycyclohexanones, e.g. (192), react with organocuprates, e.g. MeCu(CN)Li, in a regio- and stereo-specific manner to yield (in most cases) the l,4-rra s-adducts (193) (95%). ... 

Substituted 1,2,3,4-tetrahydropyridines. Enol triflates are readily prepared from V-alkoxycarbonyl-2-piperidones by successive treatment with LHMDS and reagent (1). The triflyloxy group can be replaced on reaction with organocuprates and carbonylation the product from the latter reaction is a precursor of pipecolic acid. 

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