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Asymmetric remote C–H borylation of aliphatic amides and esters with a modular iridium catalyst

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Science  21 Aug 2020:
Vol. 369, Issue 6506, pp. 970-974
DOI: 10.1126/science.abc8320

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Targeting a distant C–H bond

Enzymes often have intricate active sites that bind one portion of a molecule to orient a distant portion for optimal reactivity. This type of orienting effect has proven a much greater challenge for small-molecule catalysts. Reyes et al. now report a simple ligand that can simultaneously bind to an iridium catalyst through a pyridine substituent while positioning an amide or ester reactant through a hydrogen-bonding urea. As a result, the catalyst exclusively borylates the site three carbons away from the carbonyl, with a second chiral ligand inducing high enantioselectivity.

Science, this issue p. 970

Abstract

Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

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