Asymmetric Synthesis of All Eight Seven-Carbon Dipropionate Stereotetrads

• Published in: Journal of the American Chemical Society Vol. 129; no. 29; pp. 9086 - 9093
• Main Authors: El-Awa, Ahmad, du Jourdin, Xavier Mollat, Fuchs, Philip L
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.07.2007; Amer Chemical Soc
• Subjects: Catalysis; Chemistry; Chemistry, Multidisciplinary; Epoxy Compounds - chemical synthesis; Indicators and Reagents; Methylation; Oxidation-Reduction; Physical Sciences; Propionates - chemical synthesis; Propionates - chemistry; Science & Technology; Stereoisomerism; Steroids - chemical synthesis; Steroids - chemistry; Sulfones - chemistry; SN2' ADDITIONS; ALCOHOLS; EPOXIDES; VINYL SULFONES; ORGANOMETALLIC REAGENTS; APLYRONINE-A; POTENT ANTITUMOR SUBSTANCE; STEREOCHEMISTRY; ALKYLATIVE OXIDATION; BASE-INDUCED REARRANGEMENT
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja071217x

Enantiopure cycloheptadienyl sulfones 6 and 7 are diastereoselectively epoxidized to yield epoxyvinyl sulfones 8, 9, 14, and 16 in high yields and diastereomeric ratios. Syn and anti methylation of epoxides 8, 9, 14, and 16 enables access to all eight possible diastereomeric stereotetrads, seven of which are commonly found in polypropionate natural products. Anti methylations of the above epoxides are possible by either the reaction of methyl organometallics promoted by copper(I), or via reaction with trimethylaluminum to yield stereotetrads 11, 12, 22, and 24. Syn methylations are achieved via Lawton SN2‘ reaction in the case of stereotetrads 10, 15, and 38, while stereotetrad 13 is accessed by an oxidation/reduction alcohol inversion sequence from stereotetrad 11. All stereotetrads were obtained in high diastereomeric ratios and yields, and their relative stereochemistry was confirmed by X-ray crystallography. Oxidative cleavage of the cyclic stereotetrads yields termini-differentiated acyclic heptanyl stereotetrads ready for use in building larger fragments in the course of target syntheses.