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. 2023 Sep 7;13(17):5131-5139.
doi: 10.1039/d3cy00717k. Epub 2023 Jul 26.

[Au(Np#)Cl]: Highly Reactive and Broadly Applicable Au(I)─NHC Catalysts for Alkyne π-Activation Reactions

Mahbubur Rahman  1 , Pengcheng Gao  1 , Qun Zhao  1 , Roger Lalancette  1 , Roman Szostak  2 , Michal Szostak  1
Affiliations

[Au(Np#)Cl]: Highly Reactive and Broadly Applicable Au(I)─NHC Catalysts for Alkyne π-Activation Reactions

Mahbubur Rahman et al. Catal Sci Technol. .

Abstract

Cationic Au(I)─NHC (NHC = N-heterocyclic carbene) complexes have become an important class of catalysts for alkyne π-activation reactions in organic synthesis. In particular, these complexes are characterized by high stability of catalytic species engendered by strong σ-donation and metal backbonding. Herein, we report the synthesis and characterization of well-defined [Au(NHC)Cl] complexes featuring recently discovered IPr# family of ligands that hinge upon modular peralkylation of aniline. These ligands have been commercialized in collaboration with MilliporeSigma (IPr#: 915653; Np#: 915912; BIAN-IPr#: 916420). Evaluation of the [Au(NHC)Cl] complexes in a series of Au(I)─NHC-catalyzed π-functionalizations of alkynes, such as hydrocarboxylation, hydroamination and hydration, resulted in the identification of wingtip-flexible [Au(Np#)Cl] as a highly reactive and broadly applicable catalyst with the re-activity outperforming the classical [Au(IPr)Cl] and [Au(IPr*)Cl] complexes. The utility of this catalyst has been demonstrated in the direct late-stage derivatization of complex pharmaceuticals. Structural and computational studies were conducted to determine steric effects, frontier molecular orbitals and bond orders of this class of catalysts. Considering the attractive features of well-defined Au(I)─NHC complexes, we anticipate that this class of bulky and wingtip-flexible Au(I)─NHCs based on the modular peralkylated naphthylamine scaffold will find broad application in π-functionalization of alkynes in various areas of organic synthesis and catalysis.

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Conflict of interest statement

Conflicts of interest The authors declare the following competing financial interest(s): Rutgers University has filed patent(s) on ligands and precatalysts described in this manuscript (US 63/155,492, Mar 2, 2021).

Figures

Fig. 1.
Fig. 1.
Structures of well-defined and air-stable [Au(NHC)Cl] complexes.
Fig. 2.
Fig. 2.
(A) X-ray crystal structure of complex [Au(Np#)Cl] (2) (50% ellip-soids). Selected bond lengths [Å] and bond angles [°]: Au1─Cl1, 2.2823(7); Au1─C1, 1.983(2); C1─N1, 1.358(3); C1─N2, 1.353(2); N1─C4, 1.443(2); N2─C54, 1.440(3); Cl1─Au1─C1, 174.31(6); Au1─C1─N1, 125.3(1); Au1─C1─N2, 129.5(1); Au1─C1─N1─C4, 11.4(3); Au1─C1─N2─C54, 19.0(3). (B) Topographical steric map of [Au(Np#)Cl] (2) showing %Vbur per quadrant. Anti C2-symmetric (rac) conformation. Hydrogen atoms have been omitted for clarity. See, SI. CCDC 2260430.
Fig. 3.
Fig. 3.
Topographical steric maps of [Au(Np#)Cl]; (A) anti; (B) syn; showing %Vbur per quadrant (B3LYP 6-311++g(d,p)). (C), (D) The corresponding C2-symmetric (rac) anti and Cs-symmetric (meso) syn conformations of [Au(Np#)Cl].
Fig. 4.
Fig. 4.
HOMO and LUMO energy levels of [Au(Np#)Cl] (2), [Au(IPr*)Cl] (4) and [Au(IPr)Cl] (5) at (B3LYP 6-311++g(d,p)).
Scheme 1.
Scheme 1.
Hydrocarboxylation of Alkynes using [Au(NHC)Cl] Complexes. Conditions: 1-Octyne (6b) (1.0 equiv), benzoic acid (7a) (1.2 equiv), [Au(NHC)Cl] (1–5) (2.0 mol%), NaBArF4 (4.0 mol%), toluene (0.2 mL), 80 °C, 15 h.
Scheme 2.
Scheme 2.
Kinetic Profile of Hydrocarboxylation of 1-Octyne with Benzoic Acid using [Au(NHC)Cl]. Conditions: 1-Octyne (6b) (1.0 equiv), benzoic acid (7a) (1.2 equiv), [Au(NHC)Cl] (1–5) (2.0 mol%), NaBArF4 (4.0 mol%), toluene (0.2 mL), 80 °C. [Au(IPr#)Cl] (1); [Au(Np#)Cl] (2); [Au(BIAN-IPr#)Cl] (3); [Au(IPr*)Cl] (4); [Au(IPr)Cl] (5).
Scheme 3.
Scheme 3.
Substrate Scope of Hydrocarboxylation of Alkynes Catalyzed by [Au(Np#)Cl]. Conditions: Alkyne (6) (1.0 equiv), carboxylic acid (7) (1.2 equiv), [Au(Np#)Cl] (2) (2.0 mol%), NaBArF4 (4.0 mol%), toluene (0.2 mL), 80 °C. Isolated yields.
Scheme 4.
Scheme 4.
Hydrocarboxylation of Alkynes using [Au(NHC)Cl] Complexes. Conditions: Alkyne (6) (1.0 equiv), aniline (9a) (1.2 equiv), [Au(NHC)Cl] (1-5) (0.05 mol%), NaBArF4 (0.1 mol%), 50 °C, 15 h.
Scheme 5.
Scheme 5.
Kinetic Profile of Hydrocarboxylation of 1-Octyne with Benzoic Acid using [Au(NHC)Cl]. Conditions: Phenylacetylene (6g) (1.0 equiv), aniline (9a) (1.2 equiv), [Au(NHC)Cl] (1–5) (0.05 mol%), NaBArF4 (0.1 mol%), 50 °C. [Au(IPr#)Cl] (1); [Au(Np#)Cl] (2); [Au(BIAN-IPr#)Cl] (3); [Au(IPr*)Cl] (4); [Au(IPr)Cl] (5).
Scheme 6.
Scheme 6.
Substrate Scope of Hydrocarboxylation of Alkynes Catalyzed by [Au(Np#)Cl].a aConditions: Alkyne (6) (1.0 equiv), amines (9) (1.2 equiv), [Au(Np#)Cl] (2) (1.5 mol%), NaBArF4 (3.0 mol%), 50 °C, 15 h. b[Au(Np#)Cl] (2) (0.05 mol%). Isolated yields.
Scheme 7.
Scheme 7.
Hydrocarboxylation of Alkynes using [Au(NHC)Cl] Complexes. Conditions: Phenylacetylene (6g) (1.0 equiv), [Au(NHC)Cl] (1–5) (50 ppm), AgSbF6, MeOH (1.0 mL), water (0.2 mL), 80 °C, 15 h.
Scheme 8.
Scheme 8.
Substrate Scope of Hydrocarboxylation of Alkynes Catalyzed by [Au(Np#)Cl].a aConditions: Alkyne (6) (1.0 equiv), [Au(Np#)Cl] (2) (50 ppm), AgSbF6, MeOH (1.0 mL), H2O (0.2 mL), 80 °C, 15 h. b[Au(Np#)Cl] (2) (0.1 mol%), 1,4-dioxane (1.0 mL), 120 °C. Isolated yields.
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