Copper(I)–Thiazol-2-ylidenes: Highly Reactive N‑Heterocyclic Carbenes for the Hydroboration of Terminal and Internal Alkynes. Ligand Development, Synthetic Utility, and Mechanistic Studies

In the last 15 years, copper-catalyzed borylative transformations
utilizing boryl–copper have been established as a powerful
activation mode in organic synthesis and catalysis, enabling direct
transformations of various π-systems. Although many of these
transformations use NHC (N-heterocyclic carbene) ligands, these studies
have been almost exclusively limited to the derivatives of imidazol-2-ylidenes.
However, the molecular properties of N-aryl-imidazol-2-ylidenes,
such as IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene),
are limited by (1) the high degree of heteroatom stabilization and
(2) symmetrical substitution of the nitrogen atoms. Herein, we report
a study on Cu(I)–thiazol-2-ylidenes, thiazole analogues of
imidazol-2-ylidenes, which (1) feature a distinct half-umbrella shape
of the coordinating ligand and (2) exhibit lower heteroatom stabilization
of the ancillary ligand through reduced π-donation from sulfur.
We present the development of a family of stable Cu(I)–thiazol-2-ylidenes,
where the combined sterics of thiazol-2-ylidenes lead to monomers
[Cu(NHC)X] or bridged-halo dimers [Cu(NHC) (μ-X)]2, their crystallographic characteristics, and application to the
hydroboration of alkynes to afford trisubstituted vinylboronates by
β-hydroboration of internal alkynes or terminal vinylboronates
by β-hydroboration of terminal alkynes. Application to the late-stage
modification and detailed mechanistic studies on the catalyst structure
and activation are presented. Most crucially, Cu(I)–thiazol-2-ylidenes
show a much higher β-selectivity in the hydroboration of alkynes
than that of classical imidazol-2-ylidenes, affording vinylborons
in excellent yields at ambient conditions. The unique “half-umbrella”
shape of thiazol-2-ylidenes reverses the α/β regioselectivity
observed with imidazol-2-ylidenes in the hydroboration of terminal
alkynes. Kinetic studies demonstrate that Cu(I)–thiazol-2-ylidenes
supersede imidazol-2-ylidenes. Considering the significant utility
of borylative transformations of π-systems, we anticipate that
Cu(I)–thiazol-2-ylidenes will advance the synthetic transformations
of boryl–copper in organic synthesis and catalysis.