Nickel-Catalyzed Asymmetric Addition of Aromatic Halides to Ketones: Highly Enantioselective Synthesis of Chiral 2,3-Dihydrobenzofurans Containing a Tertiary Alcohol

Abstract

A highly enantioselective and straightforward synthetic procedure to chiral 3-hydroxy-2,3-dihydrobenzofurans has been developed by nickel/bisoxazoline-catalyzed intramolecular asymmetric addition of aryl halides to unactivated ketones, giving 2,3-dihydrobenzofurans with a chiral tertiary alcohol at the C-3 position in good yields and excellent enantioselectivities (up to 92% yield and 98% ee). The gram-scale reaction also proceeded smoothly without a loss of yield and enantioselectivity.

Recent Advances Towards the Synthesis of Dihydrobenzofurans and Dihydroisobenzofurans

“…In 2020, Hui Lv and his research group disclosed a strategy towards enantioselective synthesis of 2,3‐dihydrobenzofurans containing tert ‐alcohol 60 by using Ni/bisoxazoline‐catalyzed intramolecular asymmetric addition of aryl halide to unactivated ketones 59 [100] . Typically, the products are isolated with high enantiomeric excesses and excellent yields (up to 99% ee and 92% yield).…”

“…In 2020, Hui Lv and his research group disclosed a strategy towards enantioselective synthesis of 2,3-dihydrobenzofurans containing tert-alcohol 60 by using Ni/bisoxazoline-catalyzed intramolecular asymmetric addition of aryl halide to unactivated ketones 59. [100] Typically, the products are isolated with high enantiomeric excesses and excellent yields (up to 99% ee and 92% yield). The Ni(PPh 3 ) 4 catalyst and bisoxazoline ligand L were identified as good catalysts and ligands for the asymmetric addition of aryl iodides to ketone due to their high yields and enantioselectivity.…”

Recent Advances in Nonprecious Metal Catalysis

“…Asymmetric addition of aromatic halides to carbonyl groups via nickel catalysis continues to target effective conditions with high enantioselectivity . Huang, Lv, and co-workers reported a highly enantioselective intramolecular addition of aryl iodides to ketones to provide chiral 2,3-dihydrobenzofurans in good to excellent yields with high enantioselectivity. A range of chiral ligands were evaluated, and Ni­(PPh 3 ) 4 and a bisoxazoline ligand (Scheme ) provided the best results (up to 92% yield and 98% ee).…”

Nickel-Catalyzed Intramolecular Nucleophilic Addition of Aryl Halides to Aryl Ketones for the Synthesis of Benzofuran Derivatives

“…The synthesis of benzofurans via nickel-catalyzed intramolecular nucleophilic addition has been less explored than other methods. Recently, Huang, Lv, and co-workers have described a highly enantioselective and straightforward nickel-catalyzed protocol to construct chiral 3-hydroxy-2,3-dihydrobenzofurans with high yield, good functional-group tolerance, and excellent enantio- Br strong base 10 However, the development of a simple and highly efficient nickel-catalyzed intramolecular nucleophilic addition reaction to synthesize benzofurans remains highly desirable. Herein, we report a simple and convenient protocol for the formation of benzofuran derivatives that is conducted through a nickel-catalyzed intramolecular nucleophilic addition process (Scheme 1).…”

“…3). 10 However, the development of a simple and highly efficient nickel-catalyzed intramolecular nucleophilic addition reaction to synthesize benzofurans remains highly desirable. Herein, we report a simple and convenient protocol for the formation of benzofuran derivatives that is conducted through a nickel-catalyzed intramolecular nucleophilic addition process (Scheme 1).…”