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 products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

More with boron: The title reaction was developed to generate quaternary carbon stereogenic centers through the use of commercially available vinylboron reagents (see scheme, MOM=methoxymethyl, NHC=N‐heterocyclic carbene, pin=pinacolato). Application of the method to the two isomeric forms of an intermediate in morphine biosynthesis demonstrates its utility.

The total syntheses of (±)-aspercyclide A (1) and its C19 methyl ether derivative (15a) are described. ELISA studies show that both compounds display comparable antagonist activity against the IgE–FcεRI protein–protein interaction.

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