A new, non-iterative asymmetric synthesis of long-chain 1,3-polyols

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-acet-oxycyclohept-3-en-1-yl]bis(4-metho xy-benzoate) (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,6S,6R)-tetrahydro-2-hydroxy-6-{(4S,6S)-{6-hydroxy-4-[(4-methoxybenzoy l)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.