Photoredox-enabled 1,2-dialkylation of α-substituted acrylates via Ireland-Claisen rearrangement

Herein, we report the 1,2-dialkylation of simple feedstock acrylates for the synthesis of valuable tertiary carboxylic acids by merging Giese-type radical addition with an Ireland-Claisen rearrangement. Key to success is the utilization of the reductive radical-polar crossover concept under photocatalytic reaction conditions to force the [3,3]-sigmatropic rearrangement after alkyl radical addition to allyl acrylates. Using readily available alkyl boronic acids as radical progenitors, this redox-neutral, transition-metal-free protocol allows the mild formation of two C(sp(3))-C(sp(3)) bonds, thus providing rapid access to complex tertiary carboxylic acids in a single step. Moreover, this strategy enables the efficient synthesis of highly attractive alpha,alpha-dialkylated gamma-amino butyric acids (GABAs) when alpha-silyl amines are used as radical precursors - a structural motif that was still inaccessible in related transformations. Depending on the nature of the radical precursors and their inherent oxidation potentials, either a photoredox-induced radical chain or a solely photoredox mechanism is proposed to be operative.

Automated summary

The study reports a new method for synthesizing valuable tertiary carboxylic acids by combining radical addition with rearrangement reactions under photocatalytic conditions, enabling rapid access to complex carboxylic compounds in a single step. This method also allows for the efficient synthesis of GABA analogs, a structural motif that was previously inaccessible in related transformations.