Substrate Directable Heck-Matsuda Reactions: A Short and Stereoselective Total Synthesis of S1P1 Agonist

Our approach began with the preparation of multigram quantities of 4 from dimethyl malonate (2) in four steps: diallylation of 2 with allyl bromide (98% yield), ring-closing metathesis (98% yield), followed by monohydrolysis to provide the half-ester 3 (95% yield). The last step consisted in the Curtius rearrangement, and was carried out according to the one-pot methodology developed by Label (42% yield). 3