Gold(I) Complexes in Ionic Liquids: An Efficient Catalytic System for the C‐H Functionalization of Arenes and Heteroarenes under Mild Conditions

Abstract

Use of ionic liquids bearing the proper counteranion as reaction solvents allows to boost the reactivity of gold(I) complexes as catalysts in the hydroarylation of alkynes with arenes and heteroarenes. Several commercial complexes of general structure LAuX have been tested as catalysts, with L=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene standing out as the one delivering the best performance. Beside high activity, enabling the use of <1 mol‐% catalyst under mild conditions (low temperature, no need for an acid cocatalyst), gold‐based catalytic systems in ionic liquids also exhibit tunable chemo‐ and regioselectivity in these reactions and turn out to be recyclable, which renders them quite attractive for synthetic applications.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C−H Bond Functionalization

“…From 1 H NMR kinetics, it was confirmed that IPrAuNTf 2 promotes the in situ σ,π‐acetylide formation from terminal alkynes, which enables the reversibility of protons to favor the crucial second hydroarylation. Biffis and Baron recently unraveled a similar sort of double C−H activation of heteroarenes towards alkynes by gold(I) catalysis in ionic liquid ([BMIM][NTf 2 ]) [250] . This chemistry is site‐selective with respect to heteroarenes and regioselective with respect to alkynes.…”

“…Biffis and Baron recently unraveled a similar sort of double CÀ H activation of heteroarenes towards alkynes by gold(I) catalysis in ionic liquid ([BMIM][NTf 2 ]). [250] This chemistry is site-selective with respect to heteroarenes and regioselective with respect to alkynes. Likewise, it is relevant that AuBr 3 also catalyzes the regioselective hydroarylation of phenylacetylene with 2,4,5-trisubstituted furan to afford sequential Markovnikovselective hydrofurylated product.…”

Gold-Catalyzed Intermolecular Alkyne Hydrofunctionalizations—Mechanistic Insights

“…In comparison, the same group reported that AuCl 3 -catalyzed hydroarylation of the same alkyne by mesitylene requires days and the addition of a silver(I) salt. In our hands [111], Au(I)-catalyzed hydroarylation of ethyl propiolate by heteroarenes in ionic liquids achieves similar conversion at room temperature instead of 60 • C, under otherwise identical conditions. Furthermore, in contrast with hydroarylation with regular arenes (see Section 6.1), hydroarylation of both electron-rich phenylacetylene and electron-deficient ethyl propriolate can be effectively catalyzed by Au(I)-NHC and Au(I)-phosphine complexes.…”

“…In our most recent contributions to this topic, [110,111] ionic liquids (IL) are adopted as the solvent system in Au(I) catalysis of Reaction 2. Under neutral conditions in an IL, IPrAuCl catalyzed Reaction 2 at low catalyst loading to achieve full conversion of the alkyne within one hour, a significant improvement over the same system in dichloroethane.…”

Selectivity Control in Gold-Catalyzed Hydroarylation of Alkynes with Indoles: Application to Unsymmetrical Bis(indolyl)methanes

“…Since the turn of the century, homogeneous gold catalysis has become increasingly popular for facilitating chemoselective nucleophilic additions to unsaturated carbon–carbon bonds . For example, the hydroarylation of alkynes with indoles has been studied extensively using gold catalysis due to the products’ relevance in medicinal and natural products. , The intermolecular version of this reaction with unactivated alkynes has previously been reported to occur via double addition of the indole to form symmetrical 3,3′-bis­(indolyl)­methanes (BIMs) 3 (Scheme A). ,, It is usually not possible to isolate the single addition vinylindole intermediates 4 , , as 4 reacts further under these conditions to form BIMs 3 . The BIM motif appears in many natural and pharmaceutically active compounds, such as echinosulfonic acids A–D and mucronatins A and B (Figure ), and synthetic methods toward these motifs have therefore been widely investigated .…”