An efficient chiral synthesis of (4R,5R)-4-(4-methoxybenzyloxymethyl)-2-heptene-1,5-diol (4), which corresponds to the C(11)-C(17) segment of mycinolide IV (1), is described. One of the key steps is the asymmetric pinacol-type rearrangement of a chiral glycerol-derived mesylate 12, promoted by a modified organoaluminum reagent (1:1 mixture of trimethylaluminium and diethyl ether). Stereospecific 1,2-shift of a three-carbon alkenyl group gave (R)-4-(4-methoxybenzyloxymethyl)-5-trimethylsilyl-7-(2-trimethylsilylethoxymethoxy)-5-hepten-3-one (13) 80 % yield. Reduction of 13 with lithium triethylborohydride followed by removal of silyl groups gave 4 in enantio- and diastereomerically pure form.
All Science Journal Classification (ASJC) codes
- Organic Chemistry