Large-scale synthesis of the anti-cancer marine natural product (+)-discodermolide. Part 4: Preparation of fragment C7-24

Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.