Organocuprates, reaction with epoxides

Hydroxy stannanes can be prepared by cleavage of epoxides with BusSnLi or cleavage of epoxy stannanes with organocuprates (equation 33)72. The two methods are stere-ochemically complementary. The higher order cyanocuprate, Bu3Sn(Bu)Cu(CN)Li2, also affords /1-hydroxy stannanes by reaction with epoxides54. 

In addition to their reactions with acid chlorides, epoxides, and a,P-unsaturated carbonyl compounds (Sections 20.13-20.15), organocuprate reagents (R2CuLi) also react with organic halides R X to form coupling products R-R that contain a new C-C bond. Only one R group of the organocuprate is transferred to form the product, while the other becomes part of RCu, a reaction by-product. 

The reaction is completely regioselective in favor of the 8 2 product, and the cross-coupling of propargyl epoxides with organocuprates give nearly an exclusive anti-product when dimethyl sulfur is present, but give mixtures of syn- and anti-products in its absence. 

Reactions of substituted epoxides with Grignard reagents are often accompanied by rearrangement. Thus, organocuprates are better suited for carbon-carbon bond forming reactions with epoxides. For a detailed discussion of the preparation and reactions of organocuprates, see Section 7.5. 

Diastereomerically enriched P-hydroxy silanes are also accessible from a,P-epoxy silanes and reaction of these with organocuprate reagents. The epoxy silanes are synthesized by epoxidation of (E)- or (Z)-vinylsilanes with m-chloroperbenzoic acid. The required (Z)- and ( )-vinylsilanes can be obtained by hydroboration-protonolysis of 1-trimethylsilyl-l-alkynes or by hydrosilylation of 1-alkynes, respectively. 

The reaction of a, P-epoxysilanes with organocuprate reagents proceeds with the regioselective opening of the epoxide ring to form P-hydroxyalkylsilanes, which are then converted to stereodefmed alkenes, as exemplified below. 

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%. 

Reaction of a,fi-epoxysilanes with organocuprates. Hudrlik et al have shown that the reaction of di-n-propylcopperlithium with a, 3-epoxysilanes is both regio- and stereospecific. Thus the cii-epoxide (1) is converted into the erythro-alc6ho (2), whereas the frans-epoxide (3) is converted into the threo-alcohol (4). ... 

The reaction of organocuprates with epoxides is therefore useful for stereospecific synthesis of olefins. 

There are limited data on 1,2-epoxy of glycal epoxide ring opening reaction with C-nucleophiles other than organocuprate, e.g., Grignard reagents [217, 218], organolithium compounds [217-219], aUylstannane [217], and sodio di-tert-butyl malonate [219, 220]. 

Since they are nucleophiles, organocuprates react with electrophiles. For example, in the following reactions, the organocuprate reacts with an epoxide in a nucleophilic substitution reaction. 

An organocuprate undergoes a nucleophilic substitution reaction with an epoxide. 

Asymmetric ring-opening of saturated epoxides by organocuprates has been studied, but only low enantioselectivities (< 15% ee) have so far been obtained [49, 50]. Muller et al., for example, have reported that the reaction between cyclohexene oxide and MeMgBr, catalyzed by 10% of a chiral Schiff base copper complex, gave trans-2-methylcyclohexanol in 50% yield and with 10% ee [50]. 

An extension was reported215 of the preparation of 11 -substituted compounds (242) through reaction of A9 (11>-5,10-epoxides with lithium organocuprates.216 A... 

Epoxide opening. A stereoselective alkene synthesis starts from reaction of triethylsilyloxirane with an organocuprate reagent, and it is concluded by oxidation of the j8-silyl alcohol to the aldehyde, Grignard reaction and elimination of [Et Si/OH]. The elimination leads to either the ( )- or the (Z)-alkene by using different reagents. 

The rate of nucleophilic ring opening of epoxides with unreactive organocuprates has been demonstrated to be vastly enhanced by the addition of boron trifluoride etherate to the reaction mixture. 

Thus, the reaction of glycal epoxides with strong nucleophiles, such organocuprates, allylmagnesium bromide, and allyllithium, did not require the use of Lewis acid and proceeded with the formation of l,2-tra s-C-glycosides. 

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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