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

preprint
submitted on 12.08.2020 and posted on 12.08.2020 by Taeho Kang, Tuğçe Erbay, Kane Xu, Gary Gallego, Alexander Burtea, Sajiv Nair, Ryan Patman, Ru Zhou, Scott Sutton, Indrawan McAlpine, Peng Liu, Keary Engle
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.

Funding

NIH-R35GM12505

NIH-R35GM128779

Kwanjeong Educational Foundation Graduate Fellowship

History

Email Address of Submitting Author

keary@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0003-2767-6556

Declaration of Conflict of Interest

No conflict of interest to declare.

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