A concise and scalable synthesis of high enantiopurity (-)-D-erythro-Sphingosine using peptidyl thiol ester-boronic acid cross-coupling

A short and efficient synthesis of high enantiopurity (-)-D-erythro-sphingosine has been achieved in 71% yield over 6 steps from N-Boc-L-serine. The key steps are high yield, racemization-free, palladium-catalyzed, copper( I)- mediated coupling of the thiophenyl ester of N-Boc-OTBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAl(O-t-Bu) H-3. By using this concise route (-)-D-erythro-sphingosine can be prepared on large scale and in high enantio- and diastereopurity (ee > 99%, de up to 99%).