Cecilia Anaya de Parrodi, Angel Clara Sosa, Lydia Pérez, Leticia Quintero Cortés, Virginia Marañón, Rubén A. Toscano, Judit A. Aviña, Susana Rojas-Lima, Eusebio Juaristi y Cosio. Highly diastereoselective alkylation, acylation and aldol condensation of cis- and trans(N-Acyloyl)hexahydrobenzoxazolidin-2-ones Tetrahedron: Asymmetry, 12, 69-79 (2001). DOI: http://dx.doi.org/10.1016/S0957-4166(00)00492-4
The potential of hexahydrobenzoxazolidinones 1ad as chiral auxiliaries was explored. N-Acylation of 1ad, 2ad and 3ad was followed by methylation and benzylation via the corresponding sodium enolates generated by treatment with NaHMDS. Diastereoselectivities of 98% or higher were observed. The absolute configuration of the newly created stereogenic center was established by chemical correlation with 2-benzyl-1-propanol. The stereochemical results are congruent with addition to the electrophile from the less hindered face of a (Z)-configured enolate, the sodium cation being coordinated by both carbonyl oxygens of the substrate. cis- and trans-N-Propionyl derivatives 2ad were treated with Bu2BOTf/Et3N to give dialkylboron enolates 6ad, which were then reacted with acetaldehyde and benzaldehyde. 1H and 13C NMR analyses showed the formation of a single diastereomeric aldol addition product, whose relative configuration was ascertained as syn from the measurement of the 3JH(2?)/H(3?) coupling constants, and whose absolute configuration was determined by X-ray crystallographic analysis. The results are rationalized in terms of a ZimmermanTraxler transition state, with a (Z)-configured enolate where boron is coordinated to the aldehyde carbonyl rather than the oxazolidinone carbonyl. Substrate 2a was also reacted with acyl chlorides via the sodium enolate (NaHMDS). The effect of reaction conditions on O- versus C-acylation, as well as the influence of solvent and additives on diastereoselectivity, are discussed.