NHC-Catalyzed Organocatalytic Asymmetric Approach to 2,2-Disubstituted Benzofuran-3(2H)-ones Containing Fully Substituted Quaternary Stereogenic Center

Abstract

A highly efficient and enantioselective approach to the synthesis of functionalized benzofuran-3(2H)-ones is presented. It proceeds via an intramolecular Stetter reaction using β,β-disubstituted Michael acceptors in the construction of five-membered rings with fully-substituted quaternary stereogenic centers and is promoted by terpene-derived triazolium salts. As a result, a series of chiral 2,2-disubstituted benzofuran-3(2H)-one derivatives with linear, branched, and cyclic aliphatic substitutions on the quaternary stereogenic center were obtained in high yields and with excellent enantioselectivities of up to 99% ee.

Remote electronic effect on the N-heterocyclic carbene-catalyzed asymmetric intramolecular Stetter reaction and structural revision of products

“…Next, we investigated the reaction of β-disubstituted alkenoate 2b (Table 2) because the absence of an α-proton in the product excludes the possibility of decreasing the enantiomeric excess by the α-deprotonation. 31–34 The reaction of 2b was much slower than that of 2a and therefore was performed at 40 °C using 20 mol% catalysts. The reaction rate increased as the electron-withdrawing ability of the NHC substituent increased, giving 3b in 44%, 52%, 70%, and 77% yield when the substituent X was Me, H, Br, and NO 2 , respectively (entries 1–4).…”

Synthesis of Benzofuran Derivatives by Diphenylperhydroindolinol Silyl Ether-Catalyzed Asymmetric [3+3] Aza-cyclization ofα,β-Unsaturated Aldehydes

“…For example, Chen et al [10] exploited a chiral primary amine to construct chiral benzofuran derivatives and Şahin [11] brought whole-cell biocatalyst for green synthesis of enantiopure (S)-1-(benzofuran-2-yl)ethanol. Besides, Rafinski [12] reported N-heterocyclic carbene (NHC)-catalyzed organocatalytic asymmetric approach for the synthesis of functionalized benzofurans via an intramolecular Stetter reaction. Except for asymmetric desymmetrization, [3] lactonization, [4] bromoaminocyclization, [5] dearomatization, [6] and cascade [7] strategies for the synthesis of above chiral benzofurans, enantioselective [4＋2], [13] [4＋1], [14] [3＋ 3], [15] and [3＋2] [16] cyclization strategies were also applied.…”

Synthesis of 2-Substituted Benzo[b]furans/furo-Pyridines Catalyzed by NiCl2

“…Recently, York, Panli, and co-workers showed the coupling of unsaturated hydrocarbons with heteroaryl and aryl compounds using Pd catalysis [8,9]. Following their work, several methods were developed to synthesize 2-substituted benzo[b]furan/furo-pyridines [10][11][12][13]. However, to obtain these skeletons, noble metals (such as Pd and Rh), air sensitive phosphine ligands, or rigorous conditions usually seem to be necessary [14][15][16][17].…”