β-Cyclodextrin–NHC–Gold(I) Complex (β-ICyD)AuCl: A Chiral Nanoreactor for Enantioselective and Substrate-Selective Alkoxycyclization Reactions

Abstract

NHC-capped β-cyclodextrin (β-ICyD) was used as a ligand for gold-catalyzed alkoxycyclization reactions. The cavity was found to be responsible for a triple selectivity: (i) the asymmetric shape of the cavity of β-ICyD induced highly stereoselective cyclizations, (ii) the shape of the interior favored the formation of a six-membered ring in the absence of a nucleophile, and finally, (iii) the encapsulation of the metal inside the cavity disfavored the addition of sterically hindered alcohols. Highly enantioselective and substrate-selective alkoxycyclizations of enynes are therefore promoted by the cavity-based molecular reactor (β-ICyD)AuCl.

Permethylated NHC‐Capped α‐ and β‐Cyclodextrins (ICyDMe) Regioselective and Enantioselective Gold‐Catalysis in Pure Water

“…The hydroxycyclization reaction of enyne 30 was also tested with both ( ICyD Me )AuCl catalysts in pure water (Scheme 7). [64] In a first set of reactions performed in the presence AgSbF 6 , both α‐CD and β‐CD‐derived catalysts 5α and 5β were found to be efficient in forming the expected cyclized alcohol 31 , which was isolated in 74 and 63 % yield, respectively (Table 6, entries 1, 2). In addition, the β‐CD‐derived catalyst 5β was also found to induce a high control of enantioselectivity, leading to the formation of 31 with 95 % ee (entry 2).…”

Recent Advances in the Development of Chiral Gold Complexes for Catalytic Asymmetric Catalysis

“…In 2020, Sollogoub, Fensterbank and Mouriès‐Mansuy [54] reported enantioselective alkoxycyclization reactions catalyzed NHC‐capped β‐cyclodextrin (β‐ICyD) gold(I) catalyst. (Scheme 37) The cyclodextrin moiety assisted the construction of a size‐exclusive chiral cavity, allowing only small‐sized nucleophiles to enter and participate in gold(I)‐catalyzed enantioselective alkoxycyclization with high enantioselectivity (up to 94% ee).…”

Synthetic Application of Cyclodextrins in Combination with Metal Ions, Complexes, and Metal Particles

“…[162] In a recent contribution, they reported a related comparative study utilizing gold complexes (71, 77βa, 77βb) performing alkoxycyclizations of enynes using alcohols (methanol, isopropyl alcohol, benzyl alcohol) and, in comparison, water. [163] Under standard reaction conditions, the precatalyst was first activated by AgSbF 6 followed by adding the substrate. In general, high enantio-and substrate selectivities were observed.…”

“…Namely, the reagent is complexed via the triple bond to Au with the gem-dimethyl group positioned in the middle of the cavity forming cyclopropane intermediate complex 80 (Scheme 41). [163] Since the access of large alcohols is Yield [a] [%]…”

“…Namely, the reagent is complexed via the triple bond to Au with the gem‐dimethyl group positioned in the middle of the cavity forming cyclopropane intermediate complex 80 (Scheme 41). [163] Since the access of large alcohols is restricted, 1,6‐enynes undergo a cyclopropane‐carbene rearrangement to diene products. In the case of small and good nucleophiles, such as methanol, the favored alkoxycyclization pathway prevails.…”