Asymmetric Catalytic Formal 1,4‐Allylation of β,γ‐Unsaturated α‐Ketoesters: Allylboration/Oxy‐Cope Rearrangement

Abstract

Ah ighly enantioselective formal conjugate allyl addition of allylboronic acids to b,g-unsaturated a-ketoesters has been realized by employing ac hiral Ni II /N,N'-dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy-Cope rearrangement sequence,p roviding af acile and rapid route to g-allyl-a-ketoesters with moderate to good yields (65-92 %) and excellent ee values (90-99 %ee). The isolation of 1,2-allylboration products provided insight into the mechanism of the subsequent oxy-Cope rearrangement reaction:s ubstrate-induced chiral transfer and ac hiral Lewis acid accelerated process.Based on the experimental investigations and DFT calculations,arare boatlike transition-state model is proposed as the origin of high chirality transfer during the oxy-Cope rearrangement.

Copper(I)-catalyzed asymmetric 1,6-conjugate allylation

“…Among the various carbon-based metal reagents, allyl metal reagents exhibit advantages over other alkyl metal reagents as the olefin moiety is more synthetically versatile. Non-enantioselective methods based on different allyl metal (such as, Si, B, Zn, and Sn) species have been disclosed in the past several decades 4 . However, the catalytic asymmetric conjugate addition with allyl metal reagents is still in its infancy as such a reaction is not easy to achieve due to the competitive 1,2-addition and the difficulty in the asymmetric induction.…”

“…In 2011, the Feng group achieved an asymmetric conjugate allylation of activated unsaturated lactones with a bimetallic catalytic system 32 . In 2019, the same group reported a formal catalytic asymmetric 1,4-allylation of β,γ-unsaturated α-ketoesters 4 . In fact, the formal conjugate allylation was enabled by the allylation of the ketone group and the following oxy-Cope rearrangement.…”

Enantioselective N‐Heterocyclic Carbene Catalyzed α‐Oxidative Coupling of Enals with Carboxylic Acids Using an Iodine(III) Reagent

“…[3] Recently, Liu and co-workers reported the asymmetric OÀ H insertion of β,γunsaturated α-diazoester with carboxylic acid via Rh/ guanidine catalysis (Scheme 1c). [4] Asymmetric allylation of β,γ-unsaturated α-ketoesters via Lewis acid catalysis to provide α-hydroxy β,γ-unsaturated esters were disclosed by Feng [5] and Li, [6] respectively (Scheme 1d). Despite these encouraging advances, methods for rapid asymmetric synthesis of α-oxyl-β,γ-unsaturated acid and derivatives are still highly desirable.…”