H‐Bonded Counterion‐Directed Catalysis: Enantioselective Gold(I)‐Catalyzed Addition to 2‐Alkynyl Enones as a Case Study

Abstract

H‐bonded counterion‐directed catalysis (HCDC) is a strategy wherein a chiral anion that is hydrogen‐bonded to the achiral ligand of a metal complex is responsible for enantioinduction. In this article we present the application of H‐bonded counterion‐directed catalysis to the Au(I)‐catalyzed enantioselective tandem cycloisomerization‐addition reaction of 2‐alkynyl enones. Following the addition of C‐, N‐ or O‐centered nucleophiles, bicyclic furans were obtained in moderate to excellent yield and enantioselectivity (28 examples, 59–96 % yield, 62 : 38 to 95 : 5 er). The optimal catalytic system, comprising a phosphinosquaramide Au(I) chloride complex and a BINOL‐derived phosphoramidate Ag(I) salt, was selected in a combinatorial fashion from a larger library with the help of high‐throughput screening. An enantioselectivity switch of ca. 120 Δee% was observed upon addition of the achiral Au(I) component to the Ag(I) salt.

Asymmetric gold catalysis enabled by specially designed ligands

“…Later, a similar transformation was achieved by Echavarren and Franchino by utilizing hydrogen bonded counterion-directed catalysis. 108,109 In the subsequent year, the same group demonstrated the application of their previously designed ligand L13A for the enantioselective dearomatization of 1-naphthols (13d) with allenamides (13e) to produce dearomatized naphthalenones (13f ) with good enantioselectivities (up to 92% ee) and moderate yields (up to 71%) (Scheme 13B). 110 The DFT calculations for the stereochemical outcome were found to be in good agreement with the experimental observations.…”

Microporous Polymeric Networks Containing a Long-Term Stable AuI Catalyst for Enyne Cyclization

“…Looking at a specific field of catalysis, in the last 2 decades, Au I complexes have emerged as exceptional catalytic materials − for the activation of alkynes , and, in particular, enynes, − which has permitted the obtainment of a wide variety of cyclic products used in synthetic chemistry as starting compounds . Au I complexes, of the [AuXL] type, are usually used for these reactions, which in the presence of a Ag salt, acting as a halide extractor, leads to the formation of a naked gold [AuL] + that acts as a very soft and active electrophile.…”

Enantioselective Au(i)-catalyzed tandem reactions between 2-alkynyl enones and naphthols by the tethered counterion-directed catalysis strategy

“…10 Interestingly, Echavarren also recently applied his H-bonded counterion-directed catalysis concept to the same reaction under Au( i ) catalysis using 1-naphthol and obtained exclusively the O -addition product. 11 Thus, intrigued by the divergent behavior of phenol and 1-naphthol under gold catalysis, with respect to 2-naphthol under silver catalysis ( O - vs. C -addition, Scheme 1, eqn (1) and (2)), and aiming at the improvement of these reactions in terms of enantioselectivity, we have investigated the use of naphthols in the tandem reactions above, using the TCDC approach (Scheme 1, eqn (3)).…”