Reaction of Carboxylic Acids and Dehydroalanine Allyl Esters via One‐Pot Sequential Decarboxylative Couplings

In this study, a protocol for a one-pot photocatalytic decarboxylative alkylation of dehydroalanine (Dha) allyl esters, followed by a sequential photoredox/Pd dual-catalyzed allylation, allows for the synthesis of densely functionalized, synthetically valuable, homoallylic amines and/or 1,3-diamine products. This protocol leverages temporally separated decarboxylative couplings to form two new C─C bonds, all while obviating isolation of intermediates.

Abstract

A protocol for the iterative decarboxylative cross-coupling of carboxylic acids with dehydroalanine (Dha) allyl esters is described. A procedure for decarboxylative Giese addition to dehydroalanine allyl esters that avoids 5-exo-trig radical cyclization onto the allyl moiety was developed. This results in complex, substituted alanine allyl esters that are poised for a second decarboxylative coupling. Thus, following the photocatalytic decarboxylative alkylation of Dha, the resulting amino acid allyl esters were subjected to decarboxylative allylation under metallaphotoredox/palladium catalysis. The Giese addition and decarboxylative allylation can be performed in one pot simply by triggering the decarboxylative allylation by addition of a palladium catalyst. These one-pot decarboxylative couplings leverage temporally controlled carboxylate formation to allow controlled, sequential photoredox activation of the carboxylates. The ability to perform sequential, one-pot photoredox C─C bond formations obviates the need for isolation of intermediates. The final products of these coupling reactions are densely functionalized homoallylic amines and/or unsymmetric, differentiated 1,3-diamines, both known for their high synthetic value.

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