Epoxide with lithium dimethylcuprate

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

Elaboration of 248 to 257 is depicted in Scheme 32. Acidic deketalization, basic epoxide formation, and silylation of the remaining hydroxyl group led to 249, which was subjected to ring opening with lithium dimethylcuprate in a regioselective (78 15) fashion to provide the desired alcohol 250 as the major... 

Selective opening of allylic epoxides (9, 329-330). The reaction of the trimethyl-silyl enol ether (I) of a, /Tepoxycyclohexanone with lithium dimethylcuprate (or di-n-butylcuprate) in THF proceeds as expected to give 2.25,26 However when the reaction is conducted in ether, 2 and 3 are formed in about equal amounts.26... 

As shown below, the attack of epoxide 6 with lithium dimethylcuprate is a key step of Hanessian et al. s erythronolide synthesis [23]. This methodology was also applied to the preparation of other polyketide-derived macrolides. Specific to erythronolide, introduction of the methyl group at C2 was achieved according to Scheme 11.3. 

Interest in the synthesis of desether muscarine derivatives (6) has developed owing to their activity and specificity, which parallel those of the muscarines. In order to overcome deficiencies in overall yield of a previous photochemical synthesis, a new stereoselective route has been devised (Scheme 1). The readily available cyclo-pentene amide (3) was epoxidized to give (4), which upon treatment with lithium dimethylcuprate provided the amido-alcohol (5). Metal hydride reduction followed... 

A A 24-methyl-25,26-dihydroxysteroidal side-chain was found in a highly polyhydroxysteroid (161) from the extracts of the New Caledonian starfish Arc/iasfer typicus (126). Simplified side-chain models were synthesized by epoxidation of ( )-2-methyl-2-pentenol followed by reaction with lithium dimethylcuprate to give the (2R,3R)/(2S,3S)-2, 3-dimethylpentane-1,2-diol enantiomeric pair (197a, b) (Fig. 22). This was converted into the (2S,3R)/(2R,3S)-enantiomeric pair (198a, b) by... 

Diethyl D-tartrate (2b), treated similarly with 30% hydrobromic acid in acetic acid followed by acidic hydrolysis, is converted to diethyl 6 y /fro-(2R,3R)-2-bromo-3-hydroxysuccinate (824) in an overall yield of 73%. Sodium ethoxide cylization affords (2 S, 3 S)-2,3-epoxysuccinate (825), which is the enantiomeric epoxide of 821. Epoxide cleavage with lithium dimethylcuprate provides in 78% yield diethyl (2S,3R)- eo /zro-3-methylmalate (826), which is converted in eight steps to ( —)-(l S, 2 S, 4iS, 5R)-2,4-dimethyl-5-ethyl-6,8-dioxobicyclo-[3.2.1]octane or ( —)-(5-multistriatin (827), one of the eight possible stereoisomeric forms for this pheromone component responsible for the aggregation of the North American... 

Indeed, in diethyl ether, lithium dimethylcuprate usually reacts with the a-enone group to give a methyl-substituted bromo ketone. Addition of hexamethylphosphoric triamide (HMPT), however, slows down this reaction to such an extent that displacement of the bromo substituent takes place [698], Another remarkable example of the influence of HMPT on chemoselectivity is the reaction of an arsonium ylide, Ph3As= CH-CH=CH-Ph, with benzaldehyde in tetrahydrofuran solution, yielding either an epoxide (in THE) or an alkene (in THF/HMPT) [699],... 

Two new preparations of 1,8-cineole (553) [the biogenesis of which from geraniol (25) in Rosmarinus officinalis has been elucidated ] have been recorded. A Diels-Alder adduct 625 (R = Me) of methyl vinyl ketone and isopropenyl methyl ketone was converted to the diazoketone (R = CH = N2) with diethyl oxalate/base, then toluenesulfonyl azide, and treatment of the latter with [Rh(OAc)2]2 in methylene chloride at room temperature for five minutes converted it in very high yield to the tricyclic compound 626. Lithium dimethylcuprate then yielded the ketone 627, conversion of which to 1,8-cineole (553) was known.The other 1,8-cineole synthesis was a by-product of an observation which enabled the two stereoisomers of limonene 1,2-epoxide to be separated. The cjs-epoxide 549 was brominated to stereoisomers of a dibromocineole 628, under conditions when the rran.s-epoxide did not react, and could be distilled pure afterward. The dibromo compound 628 yielded 1,8-cineole (553) with tributyltin hydride. 

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