Asymmetric Synthesis of All Eight Seven-Carbon Dipropionate Stereotetrads

Abstract

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.

Reagent-Directed Allylic Quadraselection. Chemoselective Anti- and Syn-Lawton SN2′ Methylation of Seven-Membered Epoxyvinylsulfones

“…A previous report featured 1,2-syn and 1,2-anti additions to four functionalized seven-membered epoxyvinylsulfones I which provided stereoselective synthesis of all eight possible homoallylic stereotetrads of the 1,3-dimethyl-2,4-diol moiety II (Scheme 1). 2 This communication reveals the complementary 1,4syn and 1,4-anti additions to epoxyvinylsulfones I, thus completing the first 16-member "quadraset" of reagent-directed stereotetrads III.…”

Aplyronine A, a potent antitumour macrolide of marine origin, and the congeners aplyronines B–H: chemistry and biology

“…In 2007, Fuchs and co-workers achieved asymmetric synthesis of all eight diastereomeric seven-carbon dipropionate stereotetrads including the above-mentioned compound 106, and made possible access to all 16 enantiomers of these eight diastereomeric tetrads. 34 The Fuchs group reported a novel method for the conversion of cyclic vinyl sulfones to transposed vinyl phosphonates in 2007, and this method was applied for the preparation of a complementary set of termini-differentiated ester-aldehydes, 107 and 110, corresponding to the C15-C20 part of aplyronine A (1) (Scheme 24). 35…”

Citric acid mediated catalytic osmylation/oxidative cleavage of electron deficient olefins: a vinyl sulfone study

“…1 The vinyl sulfone polypropionate methodology has been utilized to provide cyclic vinyl sulfones for use as termini differentiated polyketide precursors primarily via ozonolysis. 2 Ozonolysis of electron-rich olefins is widely used and fully documented, as electron-rich olefins are an estimated 10,000 times more reactive to ozone than electron-deficient olefins. 3 Oxidative cleavage of electronically deactivated and/or sterically hindered olefins has proven historically quite difficult.…”