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Cu-Catalyzed Hydroboration of Benzylidenecyclopropanes: Reaction Optimization, (Hetero)Aryl Scope, and Origins of Pathway Selectivity

preprint
submitted on 28.06.2019 and posted on 28.06.2019 by Jose Medina, Taeho Kang, Tuğçe Erbay, Huiling Shao, Gary Gallego, Shouliang Yang, Michelle Tran-Dubé, Paul Richardson, Joseph Derosa, Ryan Helsel, Ryan Patman, Fen Wang, Christopher Ashcroft, John Braganza, Indrawan McAlpine, Peng Liu, Keary Engle
The copper-catalyzed hydroboration of benzylidenecyclopropanes, conveniently accessed in one step from readily available benzaldehydes, is reported. Under otherwise identical reaction conditions, two distinct phosphine ligands grant access to different products by either suppressing or promoting cyclopropane opening via β-carbon elimination. Computational studies provide insight into how the rigidity and steric environment of these different bis-phosphine ligands influence the relative activation energies of β-carbon elimination versus protodecupration from the key benzylcopper intermediate. The method tolerates a wide variety of heterocycles prevalent in clinical and pre-clinical drug development, giving access to valuable synthetic intermediates. The versatility of the tertiary cyclopropylboronic ester products is demonstrated through several derivatization reactions.

Funding

NIH-5R35GM125052-02

NIH-1R35GM128779

Kwanjeong Educational Foundation Graduate Fellowship

NSF/DGE-1346837

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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