Intramolecular aldol cyclization of C-4-ulopyranosyl-2′-oxoalkanes controlled by steric effects. Asymmetric synthesis of substituted 8-oxabicyclo[3.2.1]octanones and -octenones and cyclopentenones Original Research Article

Whereas C-2- and 4-ulopyranosyl compounds (C-2- and C-4-ulosides) can be converted to cyclopentenones under base conditions through β-elimination and ring contraction, base-initiated β-elimination of C-glycosyl 2′-aldehydes and 2′-ketones results in the formation of acyclic α,β-unsaturated aldehydes or ketones. By combining both molecular features we synthesized 1-C-(4-ulopyranosyl)-2-oxoalkanes 6, 13, and 20 and investigated their reactions when they were treated with base. Both α- and β-anomers of C-(4-ulopyranosyl)acetaldehydes 6 and 13 underwent a fast intramolecular aldol reaction between the C-5 enolate and 2′-aldehyde to form optically pure 8-oxabicyclo[3.2.1]octanones, which further transformed to 8-oxabicyclo[3.2.1]octenones 14 and 15 by β-elimination. However, this aldol reaction did not occur when 1-C-(4-ulopyranosyl)propan-2-one 20 was treated with base because of steric hindrance exerted by the additional methyl group. Instead, an alternate C-3 enolization led to β-elimination and further electro-ring opening to form an acyclic enol, which was then converted through a disrotatory intramolecular aldol cyclization to a cis-substituted cyclopentenone 21.