Regio- and Enantioconvergent Hydroallylation of Acrylates Enabled by γ-Silyl-Substituted Allyl Acetates

Abstract

Transition-metal-catalyzed asymmetric allylic substitution provides an efficient route to chiral organic molecules featuring an allyl moiety, key intermediates in the synthesis of biologically active compounds. However, the use of unsymmetrical 1,3-disubstituted allyl electrophiles has been severely constrained by the challenges of achieving both regio- and stereoselectivity simultaneously. Herein, we present γ-silyl-substituted allyl acetates as highly effective electrophiles for a regio- and enantioconvergent hydroallylation, enabling the construction of vicinal stereogenic centers. This method delivers allylated products in 44%-93% yield with 79:21 to >95:5 dr and 88% to >99% ee. Additionally, the silyl group in the products can be readily converted into other functional groups, such as acyl and aryl groups, enhancing their synthetic utility.

Keywords: Copper; Enantioconvergent catalysis; Hydroallylation; Palladium; Vinylsilanes.

Scheme 1

Enantioconvergent allylic substitutions using unsymmetrical 1,3‐disubstituted allyl electrophiles.

Scheme 2

Substrate scope for regio‐ and enantioconvergent hydroallylation of acrylates with unsymmetrical 1,3‐disubstituted allyl acetates.^a) a) Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), Cu(OAc)₂ (5.0 mol%), Cu‐L2 (5.5 mol%), Pd(dba)₂ (3.0 mol%), Pd‐L3 (3.3 mol%), and HBpin (0.3 mmol) were reacted in DME (0.8 mL) at 40 °C for 18 h, unless otherwise noted. b) 1 mmol scale. c) 5 mmol scale. d) THF was used instead of DME.

Scheme 3

Derivatization of pent‐4‐enoate 3, preliminary mechanistic investigations, and plausible reaction mechanism.