ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
4 files

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

preprint
submitted on 12.08.2020, 04:30 and posted on 12.08.2020, 09:54 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.

Exports