Open AccessCu-Catalyzed Hydroboration of Benzylidenecyclopropanes: Reaction Optimization, (Hetero)Aryl Scope, and Origins of Pathway Selectivity
Author(s) -
Jose M. Medina,
Taeho Kang,
Tuğçe Erbay,
Huiling Shao,
Gary M. Gallego,
Shouliang Yang,
Michelle TranDube,
Paul Richardson,
Joseph Derosa,
Ryan Helsel,
Ryan L. Patman,
Fen Wang,
Christopher P. Ashcroft,
John Braganza,
Indrawan McAlpine,
Peng Liu,
Keary M. Engle
Publication year - 2019
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.9b03557
Subject(s) - hydroboration , chemistry , phosphine , catalysis , steric effects , derivatization , combinatorial chemistry , aryl , selectivity , cyclopropane , organic chemistry , reductive elimination , ring (chemistry) , alkyl , high performance liquid chromatography
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.