Abstract
Biocatalysis offers compelling advantages in synthesis, often becoming the method of choice based on sustainability, safety, and selectivity considerations. Despite these advantages, enzymes in synthesis are typically dedicated to functional group interconversions in linear synthetic sequences and have not been broadly integrated into the retrosynthetic logic for carbon skeleton assembly. In this article, we disclose a biocatalytic platform for fragment coupling to assemble target molecules convergently. Specifically, we report a strategy for biocatalytic phenolic cross-coupling through oxidative C–C bond formation. Using cytochrome P450 enzymes, we demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates and further demonstrate the ability to tune these catalysts to possess the desired reactivity, site-, and atroposelectivity. This streamlined method for constructing sterically-hindered biaryl bonds provides an engineerable platform for assembling molecules with programmable catalyst-controlled reactivity and selectivity unprecedented with small molecule catalysts.
Supplementary materials
Title
Biaryl bond formation through biocatalytic oxidative cross-coupling reactions- SI
Description
Supplementary Information
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