Ternary Catalysis Enabled Three-Component Asymmetric Allylic Alkylation as a Concise Track to Chiral α,α-Disubstituted Ketones

Multicomponent reactions that involve interception of onium ylides through Aldol, Mannich, and Michael addition with corresponding bench-stable acceptors have demonstrated broad applications in synthetic chemistry. However, because of the high reactivity and transient survival of these in situ generated intermediates, the substitution-type interception process, especially the asymmetric catalytic version, remains hitherto unknown. Herein, a three-component asymmetric allylation of alpha-diazo carbonyl compounds with alcohols and allyl carbonates is disclosed by employing a ternary cooperative catalysis of achiral Pd-complex, Rh-2(OAc)(4), and chiral phosphoric acid CPA. This method represents the first example of three-component asymmetric allylic alkylation through an S(N)1-type trapping process, which involves a convergent assembly of two active intermediates, Pd-allyl species, and enol derived from onium ylides, providing an expeditious access to chiral alpha,alpha-disubstituted ketones in good to high yields with high to excellent enantioselectivity. Combined experimental and computational studies have shed light on the mechanism of this novel three-component reaction, including the critical role of Xantphos ligand and the origin of enantioselectivity.

Automated summary

The study presents a novel asymmetric allylation reaction through ternary cooperative catalysis, enabling the expedient access to chiral alpha,alpha-disubstituted ketones with high enantioselectivity. Experimental and computational studies have elucidated the mechanism and origin of enantioselectivity in this three-component reaction.