Palladium-Catalyzed Enantioselective C_(sp)^3–C_(sp)^3 Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks

Abstract

A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed decarboxylative allylic alkylation is described. The stereoselective C_(sp)^3–C_(sp)^3 cross-coupling reaction delivers five- and six-membered ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral centers in high yields and enantioselectivities. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents.

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