Direct Enantioselective and Regioselective Alkylation of β,γ-Unsaturated Carboxylic Acids with Chiral Lithium Amides as Traceless Auxiliaries

Abstract

Efficient asymmetric alkylation of β,γ-unsaturated carboxylic acids without prior functionalization is enabled by chiral lithium amides. Enantioselectivity is imparted by a putative mixed lithium amide−enediolate aggregate that acts a traceless auxiliary formed in situ, allowing for a direct asymmetric alkylation and a simple recovery of the chiral reagent.

Visible-Light-Driven α-Allylation of Carboxylic Acids

“…Hence, efficient methods, especially catalytic methods, for upgrading the feedstock carboxylic acids to value-added compounds are of great interest. While catalytic α-functionalization of carbonyl compounds has been studied extensively for decades, mild and catalytic methods applicable to carboxylic acids are rare despite their utility. − The difficulty stems mainly from the low acidity of the carboxylic acid α-protons, which hampers the formation of enolates required for application to polar reactions . Moreover, radical reactions, which exhibit intriguing reactivity complementary to polar reactions, have largely been neglected partly due to their tendency for decarboxylation .…”

Palladium-Catalyzed Direct C–H Arylation of 3-Butenoic Acid Derivatives

“…Such bioactivities have generated interest in 4-phenyl-3-butenoic acid analogues. There are two main approaches to synthesize the analogues . One is the condensation of aryl acetaldehyde with malonic acid and another is through the Wittig reaction of aryl acetaldehyde with 2-(carboxy-ethyl)­triphenylphosphonium bromide as the coupling partner.…”

The Enediolate Chemistry of Free Carboxylic Acids

“…When applying β,γ‐unsaturated carboxylic acids as substrates in the alkylation reaction with halides, chiral amine L6 was able to direct high enantioselectivities preferably at α‐position (Scheme 11). [25] …”