Asymmetric Dearomative Fluorination of 2‐Naphthols with a Dicarboxylate Phase‐Transfer Catalyst

Abstract

A linked dicarboxylate phase-transfer catalyst enables smooth asymmetric dearomative fluorination of 2naphthols with Selectfluor under mild conditions to give the corresponding 1-fluoronaphthalenone derivatives in a highly enantioselective manner. This reaction, which is compatible with a range of functional groups, is the first example of catalytic asymmetric fluorination of 2-naphthols, and is expected to be useful in the synthesis of bioactive molecules. Scheme 1. Prior reactions and the present enantioselective dearomative fluorination of 2-naphthols.

Asymmetric Methods for Carbon‐Fluorine Bond Formation

“…The presence of a 3-substituent greatly decreased the enantioselectivity. [125] Another pathway of fluorinative dearomatization is intramolecular nucleophilic attack to the σ complex (fluorocyclization). Most of these reactions utilize 3-substituted indole derivatives as substrates.…”

Asymmetric Fluorination Reactions promoted by Chiral Hydrogen Bonding‐based Organocatalysts

“…Using the same dicarboxylic acid precatalysts 24a and more recently, Hamashima's group has developed two additional works. One of them is based on the development of an enantioselective 5‐ exo ‐fluorocyclization of ene‐oxime compounds [43] and the most recent one is an asymmetric dearomative fluorination of 2‐naphthols [44] . In all cases, the catalytic species is formed by a dicarboxylate dianion generated in situ by deprotonation of 24 and Selectfluor 1 , allowing the transfer of 1 from the solid phase to the liquid phase giving rise to a chiral Selectfluor species as described in Figure 5.…”

Asymmetric Dearomative Fluorination of 2‐Naphthols with a Dicarboxylate Phase‐Transfer Catalyst

“…X-ray structure of 4 a. [13] Angewandte Chemie Zuschriften by the derivatization of 4 a. Considering the potentially high reactivity of the ketone group with heteroatom-based nucleophiles within biomolecules, [1,15] we believe that the availability of chiral fluorinated naphthalenones and their derivatives will facilitate drug development.…”

“…The absolute configuration of the products was deduced to be S on the basis of an X-ray analysis of enantiopure 4 a (Figure 2). [13] To confirm the utility of the reaction, we examined the conversion of the fluorinated product 4 a, as shown in Scheme 2. When 4 a was treated with MeMgBr at À78 8C, tertiary alcohol 8 was obtained as a single diastereomer, the stereochemistry of which was determined by NMR analysis after methyl ether formation.…”

“…The stereochemistry of 9 was determined by X-ray analysis. [13] In contrast, treatment with m-chloroperbenzoic acid (mCPBA) predominantly provided Baeyer-Villiger product 10. When 10 was exposed to acidic conditions in MeOH, the ring-opening product 11 was obtained in good yield.…”