A Domino Approach to the Enantioselective Total Syntheses of Blennolide C and Gonytolide C

Abstract

The first enantioselective total syntheses of the tetrahydroxanthenone (-)-blennolide C (ent-4) and related gamma-lactonyl chromanone (-)-gonytolide C (ent-3) are reported. Key to the syntheses is an enantioselective domino-Wacker/carbonylation/methoxylation reaction to set up the stereocentre at C-4a. Various chiral BOXAX ligands were investigated, including novel (S,S)-iBu-BOXAX, and allowed access to chromane 8 in an excellent enantioselectivity of 99%. The second stereocentre at C-4 was established employing a diastereoselective Sharpless dihydroxylation. An extensive survey of (DHQ)- and (DHQD)-based ligands enabled the preparation of both the anti-isomer 14a and the syn-isomer 14b in very good to reasonable selectivities of 13.7:1 and 1:3.7, respectively. While 14a was further converted to ent-3 and ent-4, 14b was elaborated to syn-acid 25 and 2'-epi-gonytolide C 28.