General Allylic C–H Alkylation with Tertiary Nucleophiles

A general
method for intermolecular allylic C–H alkylation of terminal
olefins with tertiary nucleophiles has been accomplished employing
palladium­(II)/bis­(sulfoxide) catalysis. Allylic C–H alkylation
furnishes products in good yields (avg. 64%) with excellent regio-
and stereoselectivity (>20:1 linear:branched, >20:1 E:Z). For the first time, the olefin scope encompasses unactivated
aliphatic olefins as well as activated aromatic/heteroaromatic olefins
and 1,4-dienes. The ease of appending allyl moieties onto complex
scaffolds is leveraged to enable this mild and selective allylic C–H
alkylation to rapidly diversify phenolic natural products. The tertiary
nucleophile scope is broad and includes latent functionality for further
elaboration (e.g., aliphatic alcohols, α,β-unsaturated
esters). The opportunities to effect synthetic streamlining with such
general C–H reactivity are illustrated in an allylic C–H
alkylation/Diels–Alder reaction cascade: a reactive diene is
generated via intermolecular allylic C–H alkylation
and approximated to a dienophile contained within the tertiary nucleophile
to furnish a common tricyclic core found in the class I galbulimima
alkaloids.