Organocatalytic Enantioselective Regiodivergent C−H Bond Functionalization of 1‐Naphthols with 1‐Azadienes

Abstract

An organocatalyst‐controlled site‐selectivity switchable enantioselective Friedel‐Crafts reaction of unprotected 1‐naphthols has been established for the first time via the conjugate addition of 1‐azadienes. By two chiral complementary squaramide and phosphoric acid, both ortho‐ and para‐selective Friedel‐Crafts alkylations of 1‐naphthols were independently achieved with high efficiency and enantioselectivity. With this strategy, a wide range of optically active triarylmethanes have been achieved in high yields with good to excellent enantioselectivities.

Asymmetric Catalytic Approaches Employing α,β‐Unsaturated Imines

“…Benefitting from the advancement in asymmetric catalysis, Li and Li et al proposed a switchable enantioselective Friedel-Crafts reaction, employing two complementary site-selective organocatalysts for example chiral squaramide 143 and phosphoric acid 145 catalysts respectively (Scheme 42). [51] By the combination of chiral squaramide and phosphoric acid as catalysts, both ortho-and para-selective Friedel-Crafts alkylations of 1-naphthols 141 could be achieved respectively with high enantioselectivity. A wide range of optically active triarylmethanes was independently developed from BDAs 44 via Michael addition.…”

Regiodivergent Organocatalytic Reactions

“…According the proposed mechanism (Scheme 51), the enamine of the α-enaminones (26-2) initially acts as a nucleophile to attack the Re face of the quinone ( 26 Recently, in 2020, the group of Li and Li reported orthoand para-selective regiodivergent C-H functionalization between 1-naphthols (27-1) and 1-azadienes (27-2) via a Michael addition reaction (Scheme 52) [157]. The chiral squaramide catalyst afforded a product in which an ortho-selective C-H bond was constructed, whereas para-selective C-H bond formation occurred in the case of chiral phosphoric acid catalysts.…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…The desired product 22 was obtained in very high chemical yield (95%), and with an excellent enantiomeric ratio (97:3), when the urea-analog of system 19 (19a) was applied as catalyst (Scheme 8) [28]. The same reaction was investigated using thiourea bifunctional catalyst 19 which led to the appropriate chiral product with a moderate yield (72%) and enantioselectivity (62% of ee) [29]. It should be stressed that chiral triarylmethanes are the structural skeleton of many systems that exhibit antiviral and antibacterial effects, as well as a drug for tuberculosis or skin diseases.…”