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.
Whereas C-2- and 4-ulopyranosyl compounds (C-2- and C-4-ulosides) can be converted to cyclopentenones under base conditions through beta-elimination and ring contraction, base-initiated beta-elimination of C-glycosyl 2'-aldehydes and 2'-ketones results in the formation of acyclic alpha,beta-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 alpha- and beta-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 beta-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 beta-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.
Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON, Canada K1A 0R6. wei.zou@nrc.cnrc.gc.ca
Wei
W
Zou
Huawu
H
Shao
Shih-Hsiung
SH
Wu
D002241:Carbohydrates / Q000737:chemistry*; D003500:Cyclization; D034242:Cyclooctanes / Q000138:chemical synthesis; D003517:Cyclopentanes / Q000138:chemical synthesis; D007659:Ketones / Q000138:chemical synthesis*
D002241:Carbohydrates; D034242:Cyclooctanes; D003517:Cyclopentanes; D007659:Ketones; C007201:cyclopentanone; C044494:cyclooctanone