Ring size and nothing else matters: unusual regioselectivity of alkyne hydration by NHC gold(i) complexes

Abstract

We have found that expanded-ring NHC gold(i) complexes efficiently and regioselectively catalyze the hydration of alkylarylacetylenes in an anti-Markovnikov fashion due to steric repulsion build-up in the transition state, giving benzylalkyl ketones.

Confinement‐Induced Selectivities in Gold(I) Catalysis—The Benefit of Using Bulky Tri‐(ortho‐biaryl)phosphine Ligands

“…A reaction via 37 β would be more favourable since, in this case, the phenyl group would be pointing away from the coordination sphere. Similar levels of regioselectivity were recently reported for the hydration of alkylarylacetylenes using a 7‐membered NHC as the ligand [44] …”

Efforts Towards Control of Regioselectivity in the Gold(I) Catalyzed Hydration of Internal Alkynes. Effects of Solvent, Temperature and Substrate on Regioselectivity

“…Hydration of diarylacetylenes with C1 shows a preference for Markovnikov‐type products, consistent with the selectivity seen by Asachenko and coworkers with [(6‐Dipp)Au(η 2 ‐MeCCPh)]+ ( C4 ; Table 3). [1] For alkylarylalkynes, anti‐Markovnikov selectivity is observed with C1 , with product ratios dependent on solvent. The selectivity is under kinetic control, since the two possible ketone products have nearly identical Gibbs reaction energies (ΔG) [52] .…”

“…But internal alkyne regioselectivity is substrate specific and sensitive to conditions, [19,20] and finding a hydration method for internal alkynes can be challenging, especially alkylarylacetylenes. The hydration product ratio depends on the preferred pathway of nucleophilic attack by water (Figure 1), and understanding the factors controlling this preference remains an area of significant interest [1] . Catalysis with Nolan's [(IPr)AuCl]/AgSbF 6 and its variants [11,13,21,22] are among the most selective for Anti‐Markovnikov hydration of alkylarylacetylenes, apparently by favoring water attack at the alkyl‐substituted carbon [11,23] .…”

“…The gold-catalyzed hydration of alkynes [1][2][3][4][5][6][7][8] allows access to alkyl and aryl ketones. [9,10,[11][12][13][14][15][16][17]18] For terminal alkynes, Au hydration typically yields Markovnikov selectivity, generating a methyl ketone.…”

“…The hydration product ratio depends on the preferred pathway of nucleophilic attack by water (Figure 1), and understanding the factors controlling this preference remains an area of significant interest. [1] Catalysis with Nolan's [(IPr)AuCl]/ AgSbF 6 and its variants [11,13,21,22] are among the most selective for Anti-Markovnikov hydration of alkylarylacetylenes, apparently by favoring water attack at the alkyl-substituted carbon. [11,23] Other ligands have shown promise, including a weakly coordinating anionic variant of IPr [24] that yielded us [17] improved selectivity in internal alkyne hydration reactions.…”