Journal Article

Biocatalytic oxidative cross-coupling reactions for biaryl bond formation

Yazarians, Jessica A., Joyce, Leo A., Lukowski, April L., Narayan, Alison R. H., Hinze, Meagan E., Murray, Lauren A. M., Zetzsche, Lara E., Chakrabarty, Suman

2022

Overview

Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis 1 , 2 . The necessity of joining arene building blocks to access these valuable compounds has inspired several approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task 3 . Oxidative coupling of two C–H bonds offers an efficient strategy for the formation of a biaryl C–C bond; however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates 4 , 5 . Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to numerous small-molecule-mediated methods by providing a paradigm with catalyst-controlled selectivity 6 . Here we disclose a strategy for biocatalytic cross-coupling through oxidative C–C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyse cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site selectivity and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity. A study presents a biocatalytic method for the formation of sterically hindered biaryl bonds, providing a tunable approach for assembling molecules with catalyst-controlled reactivity, site selectivity and atroposelectivity.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 140/131 / 631/45/603 / 639/638/77/603 / Aromatic compounds / Biocatalysis / Biocatalysts / Carbon - chemistry / Catalysts / Chemical bonds / Chemical reactions / Chemistry Techniques, Synthetic / Chemists / Coumarins - chemistry / Coupling (molecular) / Cross coupling / Cytochrome P-450 Enzyme System - chemistry / Cytochrome P-450 Enzyme System - genetics / Cytochrome P-450 Enzyme System - metabolism / Cytochrome P450 / Cytochromes P450 / Engineering / Enzymes / Humanities and Social Sciences / Hydrogen - chemistry / Materials science / multidisciplinary / Oxidants - chemistry / Oxidation-Reduction / Phenolic compounds / Phenols / Potassium channels / Reactivity / Science / Science (multidisciplinary) / Selectivity / Substrate Specificity / Substrates