CuH-Catalyzed Regio- and Enantioselective Hydrocarboxylation of Allenes: Toward Carboxylic Acids with Acyclic Quaternary Centers

Abstract

We report a method to prepare α-chiral carboxylic acid derivatives, including those bearing all-carbon quaternary centers, through an enantioselective CuH-catalyzed hydrocarboxylation of allenes with a commercially available fluoroformate. A broad range of heterocycles and functional groups on the allenes were tolerated in this protocol, giving enantioenriched α-quaternary and tertiary carboxylic acid derivatives in good yields with exclusive branched regioselectivity. The synthetic utility of this approach was further demonstrated by derivatization of the products to afford biologically important compounds, including the antiplatelet drug indobufen.

Progress on transition metal catalyzed asymmetric hydroesterification, hydrocarboxylation, and hydroamidation reactions of olefins

“…37 Scheme 62 Asymmetric hydrocarboxylation with HCO 2 H. 59 Scheme 63 CuH-catalyzed asymmetric hydroesterification of allenes with fluoroformate. 60 Scheme 64 Synthesis of (S)-indobufen. 60 with a commercially available fluoroformate 129 as a carbonyl source.…”

Acyclic Quaternary Carbon Stereocenters through Transition-Metal-Catalyzed Enantioselective Functionalization of Unsaturated Hydrocarbons

“…Buchwald and co-workers further showed that the -allylcopper intermediate obtained from hydrocupration of allene can be trapped to form ester products (Scheme 11). 18 Using 1,1-disubstituted allene as the substrate and a fluoroformate as the carboxylation reagent, enantioenriched carboxylation products bearing an acyclic quaternary carbon stereocenter were obtained with high enantioselectivities. Similar to previous observations, exclusive branched selectivity was observed.…”

Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State‐of‐The‐Art Survey

“…Conversely, the pronounced nucleophilicity of allylcopper species unlocks diverse enantioselective allene‐C=X reductive couplings beyond aldehyde addition (Scheme 2). [25b,29a,37a–d] For example, following work on enantioselective copper‐catalyzed acrylate‐ketone [26,27] and vinyl azine‐ketone [28] reductive couplings mediated by silane, Buchwald and coworkers reported highly diastereo‐ and enantioselective allene‐mediated ketone allylations using (MeO) 2 MeSiH as reductant (Scheme 2, Eq. A) [29a] .…”

“…E) [37c] and fluoroformates (Scheme 2, Eq. F), [37d] as described by Ma and Buchwald, respectively. Catalytic enantioselective allene‐mediated reductive imine allylation remains an unresolved challenge [38] …”