Chiral diarylalkanes are an important structural motif in the pharmaceutical industry, but synthetic limitations have made it difficult to carry out the stereoselective synthesis of this valuable structural motif. This limitation often results in drug candidates that are either used as racemates or that are prepared in enantiomerically enriched from through classic resolution routes. Herein, iron complexes supported by chiral cyano bis(oxazoline) ligands are disclosed that effect the stereoselective assembly of benzylic halides and unactivated aryl boronic esters to give enantiomerically enriched diarylalkanes. Reactions between a variety of benzylic halide substrates and aryl boronic esters were possible leading to good yields of the cross-coupling products (up to 90%) with high levels of stereoselectivities (up to 92:8 er). Mechanistic studies revealed that the cross-coupling reaction proceeded through a free radical intermediate, was stereoconvergent, and involved a monometallic stereodetermining step. A key step to make this Suzuki-Miyaura cross coupling reaction possible was the use of lithium amide bases, which greatly enhanced transmetalation rates and prevented deleterious aggregates from forming. Application of this cross coupling reaction for the stereoselective assembly of other chiral substrates and the challenges associated with developing a general strategy for stereoselective cross-coupling reactions catalyzed by iron-based complexes will be discussed.

Synthesis of enantiomerically enriched diaryl alkanes through a stereoconvergent Suzuki-Miyaura cross coupling reaction catalyzed by iron-based complexes

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.