Organic Chemistry

Multifaceted Substrate–Ligand Interactions Promote the Copper-Catalyzed Hydroboration of Benzylidenecyclobutanes and Related Compounds

Abstract

A unified synthetic strategy to access tertiary four-membered carbo/heterocyclic boronic esters is reported. Use of a Cu(I) catalyst in combination with a modified dppbz ligand enables regioselective hydroboration of various substituted benzylidenecyclobutanes and carbo/heterocyclic analogs. The reaction conditions are mild, and the method tolerates a wide range of medicinally relevant heteroarenes. The protocol can be conveniently conducted on gram-scale, and the tertiary boronic ester products undergo facile diversification into valuable targets. Reaction kinetics and computational studies indicate that the migratory insertion step is turnover-limiting and accelerated by electron-withdrawing groups on the dppbz ligand. Energy decomposition analysis (EDA) calculations reveal that electron-deficient P-aryl groups on the dppbz ligand enhance the T-shaped π/π interactions with the substrate and stabilize the migratory insertion transition state.

Content

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Supplementary material

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Supporting Info
Thumbnail image of (4-CF3-dppbz)CuCl dimer.txt
(4-CF3-dppbz)CuCl dimer
Thumbnail image of (4-F-dppbz)CuCl dimer.txt
(4-F-dppbz)CuCl dimer