In the past decade, there has been significant interest in the development of synthetic methods for the preparation of optically enriched chiral organoboronates as precursors of enantioenriched compounds. Our group has developed a number of new catalytic enantioselective methods for the preparation of acyclic and cyclic secondary alkyl- and allyl- boronates, such as conjugate additions, allylic alkylations, and a unique borylative alkene isomerization reaction that produces optically enriched heterocycles. One remaining challenge in the chemistry of alkylboronate derivatives is their cross-coupling, especially with control of stereoselectivity. With unsymmetrical allylic boronates, this challenge is further complicated by the possibility of forming either the a or ? regioisomers. As part of our ongoing efforts to address this problem, we have optimized a stereospecific and regioselective Suzuki-Miyaura cross-coupling of heterocyclic allylic boronates formed by a catalytic enantioselective borylative isomerization (Angew. Chem. Int. Ed. 2013, 52, 8069). By way of a ligand-controlled regiodivergent mechanism, this Pd-catalyzed cross-coupling methodology provides 2- or 4-substituted dehydro pyran and piperidine products in high yields with high regioselectivity without any significant enantiomeric erosion. These new Csp2�Csp3 coupling methods can be applied to the synthesis of complex heterocyclic natural products and pharmaceutical drugs. 

Merging stereocontrol and regiodivergent selectivity in Suzuki-Miyaura cross-coupling of allylic boronates for the synthesis of biologically privileged non-aromatic heterocycles

248th National Meeting (2014)

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