A New, Non-Iterative Asymmetric Synthesis of Long-Chain 1,3-Polyols

Abstract

A new approach to the asymmetric synthesis of pentadeca-1,3,5,7,9,11,13,15-octols and their derivatives is presented. It is based on the Sharpless asymmetric dihydroxylation (AD) of 4,4'-methylene[(1R,1'S,6R,6'S)-6-acetoxycyclohept-3-en-1-yl]bis(4-methoxybenzoate) (9), derived from a double [3+4] cycloaddition of the 1,1,3-trichloro-2-oxyallyl cation with 2,2'-methylenedifuran (1). The diol (-)-10, obtained in 98.4% ee from 9 with "AD-mix-beta(5x), was oxidised into (2R and 2S,4S,6R)-tetrahydro-2-hydroxy-6-((4S,6S)-(6-hydroxy-4-[(4-methoxybenzoyl)oxy]cyclohept-1-en-1-yl)-2-oxopropyl)-2H-pyran-4-yl 4-methoxybenzoates ((-)-18). By the combinations of Evans' anti and Nasaraka's syn reductions of aldol (-)-18 with the double Mitsunobu reaction, 16 diastereomeric pentadeca-1,3,5,7,9,11,13,15-octols and analogues can be obtained, in principle, with high enantio- and diastereoselectivities.

8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐ones: Application to the Asymmetric Synthesis of Polyoxygenated Building Blocks

“…Desymmetrization of meso ‐configured dimer 104 by using the Sharpless asymmetric dihydroxylation method was accomplished by Schwenter and Vogel 64. The dicycloheptene meso ‐ 104 is accessible in five steps from oxabicyclic dimer meso ‐ 103 (Scheme ), which in turn results from a double [4+3] cycloaddition by employing 2,2′‐methylenefuran as the bisdiene.…”

Spongistatins: Biological activity and synthetic studies

“…35). Oxidative cleavage of diol 280 [36], followed by diastereoselective reduction of the intermediate keto aldehyde installed the C(7)eC (15) fragment. Ozonolysis of the remaining olefin and in situ selective reduction of the resulting aldehyde delivered hemiketal 283.…”

Preparation and Synthetic Applications of 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives

“…[25] A SN 2 '-type-8oxa bridge cleavage induced by BCl 3 , followed by esterification of the intermediate dichlorodiol and radical reduction provided diolefin 35. [26] Desymmetrization was then achieved by means of the Sharpless asymmetric dihydroxylation to deliver the corresponding diol 36 with 98.4% enantiomeric excess. At that stage, the double elongation strategy proceeded through sequential sequences of oxidative opening of the sevenmembered ring/diastereoselective reduction of the intermediate keto-aldehyde to provide a 15-carbon polyolic chain 38.…”