Enantioselective Catalytic Crotylboration Based Syntheses of the C(7)-C(18(20)) Fragments of Polyketides Isolated from Streptomyces gramineus

A general modular enantioselective synthetic approach to the C(7)-C(18) and the C(7)-C(20) fragment belonging to E-492, actinofuranone A, and JBIR-108 was developed. The crucial synthetic step relies on highly enantioselective crotylboration of aldehydes catalyzed by a chiral TRIP PA giving rise to highly enantioenriched terminal alkenes (86 and 88 % ee on the preparative scale). The alkenes were subsequently converted into the title products. Further important synthetic steps included Ru-catalyzed alkene cross-metathesis and Suzuki coupling reactions. The approach consists of five synthetic steps starting from easily available aldehydes and other reaction partners.

Automated summary

A general modular enantioselective synthetic approach was developed for the C(7)-C(18) and the C(7)-C(20) fragments belonging to E-492, actinofuranone A, and JBIR-108. The key step involves highly enantioselective crotylboration of aldehydes catalyzed by a chiral TRIP PA, leading to highly enantioenriched terminal alkenes. Followed by additional synthetic steps including Ru-catalyzed alkene cross-metathesis and Suzuki coupling reactions, the approach starts from easily available aldehydes and other reaction partners.