Stereoselective synthesis of 3(2H)-dihydrofuranones by addition of lithiated methoxyallene to chiral aldehydes

Article abstract of DOI:10.1021/jo00080a013

Lithiated methoxyallene 2 adds to chiral aldehydes such as 2- phenylpropanal and N,N-dibenzylated α-amino aldehydes 4-8 to give products 9-14 in good yields and with excellent anti-selectivity. The stereochemical outcome of these reactions can be explained by the Felkin-Anh model in a straightforward manner. The crude reaction products can either be transformed to enones by hydrolysis with acid or be converted into 2,5-dihydro-3- methoxyfuran derivatives 19-24 by treatment with potassium tert-butoxide in DMSO. The latter can be hydrolyzed to give 3(2H)-dihydrofuranones 25-29. The diastereoselectivity of the initial addition step is transferred to the dihydrofuran derivative without a major change in the isomer ratio. Compounds derived from α-amino aldehydes 5, 6, and 8 are assumed to be enantiomerically pure. Sodium borohydride reductions of and Grignard additions to 3(2H)-dihydrofuranones 27a and 28a demonstrate that these chiral ketones react in a highly diastereoselective manner. In summary, this paper shows that lithiated methoxyallene 2 can serve as a very useful equivalent for α,β-unsaturated acyl anions and 1,3-dipolar synthons in asymmetric synthesis.