Regiodivergence in Catalytic Asymmetric Allylic Alkylation: Access to Chiral Homoallylic Tertiary Fluorides

Abstract

Regiodivergent transformations are powerful tools for molecular diversification. However, achieving regiodivergence from identical starting materials while enabling control over multiple selectivity elements remains a fundamental challenge in organic synthesis. Herein, we report a regiodivergent asymmetric allylic alkylation between MBH carbonates and α-fluoro azaaryl carbonyl compounds, providing structurally distinct homoallylic tertiary fluorides. While the chiral Lewis acid catalysts govern enantio- and diastereoselectivity, the regiochemical outcome is modulated by the choice of Lewis base, with amines and phosphines favoring branched and linear products, respectively. By selecting an appropriate combination of a Lewis acid and a Lewis base, a diverse array of homoallylic tertiary fluorides is obtained with high enantio-, diastereo-, and regioselectivity. Mechanistic studies reveal that subtle differences in reactivity between two closely related onium species, ammonium and phosphonium, lead to divergent modes of electrophile engagement. In the branch-selective pathway, the in situ-generated ammonium intermediate reacts with the chiral enolate in the product-forming step, whereas in the linear-selective pathway, the chiral enolate reacts directly with the MBH carbonate, with the phosphonium species acting as a base shuttle. This work establishes a robust platform for regiodivergent asymmetric synthesis through orthogonal activation modes.