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

Abstract

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.

Heterovalent Metal Pair Sites on Metal–Organic Framework Ordered Macropores for Multimolecular Co-Activation

“…30−33 To date, the reported homogeneous Cu systems not only require ligands and bases but also bear high waste because of difficult recycling (Figure S30). 30,31,34,35 Despite several heterogeneous Cu catalysts such as Cu-MOFs, 36−38 Cu (oxides), 39−42 or Cu single atoms 43 have been utilized, the base or high reaction temperature is still necessary (Figure S30). Consequently, the design and synthesis of heterogeneous Cu-based catalysts for effective hydroboration of alkynes under mild and additive-free conditions are in great demand (Figure S30).…”

“…[34][35][36]39,44,45 And thus the activation of alkyne bonds on Cu sites will contribute to increasing the reaction activity. 35,46,47 However, in the absence of additives, the activation of B 2 Pin 2 to nucleophilic copper-boryl species is driven by the copper ethoxide (Cu-OEt) species generated from the dissociation of EtOH molecules on Cu coordination bonds, 43,48 with the result that the efficient ethanol dissociation proves to be another dominating step for lowering the reaction energy barrier. Therefore, if ethanol dissociation and alkyne activation are conducted in parallel within an ideal distance, the hydroboration reaction will be definitely promoted.…”

“…In addition, it is worth noting that the steric hindrance among styrene moiety, BPin moiety, and Cu-HMP on TSA4 (Figure S44) is responsible for the high regioselectivity of 3a product, in which the insertion of the alkyne into the Cu−B bond in a syn fashion providing a lower steric hindrance effect finally gives (E)-β-styrene boronate ester. 35,44 As is well known, during the heterogeneous catalytic process, the adsorption of substrates on active sites is crucial for subsequent activation and reactions. Based on this, the adsorption energies of EtOH/phenylacetylene on relevant sites are calculated to evaluate the corresponding adsorption effect (Table S5 and Figure S45).…”

Ag–NHC Complexes in the π-Activation of Alkynes

“…In 2022, we reported Ag(I)–thiazol-2-ylidene complexes and their application in the intramolecular cyclization to yield oxazolidines ( Scheme 5 ) [ 64 ]. The non-classical framework of thiazol-2-ylidene offers new opportunities in catalysis due to its differentiated half-umbrella-shaped ligand structure and enhanced p-electrophilicity [ 69 ]. We found that these Ag(I)–thiazol-2-ylidene complexes are highly active in the electrophilic cyclization of propargylic amides.…”

Wingtip‐Flexible N‐Heterocyclic Carbenes: Unsymmetrical Connection between IMes and IPr

“…[10,11] (3) The synthetic utility is further demonstrated in the late‐stage hydroboration of complex pharmaceuticals, enabling to introduce boron to drug molecules with excellent functional group tolerance [12] . (4) The most reactive Cu(I)‐NHC complex [9d,13] in this class has been commercialized in collaboration with MilliporeSigma to enable broad access of the synthetic chemistry community (no. 930873, NHC⋅HCl salts: no.…”