A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient Site- and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

摘要

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene productsin good yield and with high enantioselectivity despite the presenceof a sensitive stereogenic tertiary carbon center that could be consideredprone to epimerization. In most instances, the alternative approachof utilizing an alkenylmetal reagent (e.g., an Al-based species) representsan incompatible option. The utility of the approach is illustratedthrough applications to enantioselective synthesis of natural productssuch as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuolE.