posted on 2021-12-22, 15:06authored byQiang Huang, Yu-Xuan Su, Wei Sun, Meng-Yang Hu, Wei-Na Wang, Shou-Fei Zhu
Organozinc reagents are among the
most commonly used organometallic
reagents in modern synthetic chemistry, and multifunctionalized organozinc
reagents can be synthesized from structurally simple, readily available
ones by means of alkyne carbozincation. However, this method suffers
from poor tolerance for terminal alkynes, and transformation of the
newly introduced organic groups is difficult, which limits its applications.
Herein, we report a method for vinylzincation of terminal alkynes
catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine
ligands. This method provides efficient access to novel organozinc
reagents with a diverse array of structures and functional groups
from readily available vinylzinc reagents and terminal alkynes. The
method features excellent functional group tolerance (tolerated functional
groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal,
phosphono, pyridyl), a good substrate scope (suitable terminal alkynes
include aryl, alkenyl, and alkyl acetylenes bearing various functional
groups), and high chemoselectivity, regioselectivity, and stereoselectivity.
The method could significantly improve the synthetic efficiency of
various important bioactive molecules, including vitamin A. Mechanistic
studies indicate that the new iron-1,10-phenanthroline-imine catalysts
developed in this study have an extremely crowded reaction pocket,
which promotes efficient transfer of the vinyl group to the alkynes,
disfavors substitution reactions between the zinc reagent and the
terminal C–H bond of the alkynes, and prevents the further
reactions of the products. Our findings show that iron catalysts can
be superior to other metal catalysts in terms of activity, chemoselectivity,
regioselectivity, and stereoselectivity when suitable ligands are
used.