Organocatalytic Atroposelective Arylation of 2‐Naphthylamines as a Practical Approach to Axially Chiral Biaryl Amino Alcohols

Abstract

The first phosphoric acid catalyzed direct arylation of 2-naphthylamines with iminoquinones for the atroposelective synthesis of axially chiral biaryl amino alcohols has been developed. This reaction constitutes a highly functional-group-tolerant route for the rapid construction of enantioenriched axially chiral biaryl amino alcohols, and is a rare example of 2-naphthylamines acting as nucleophiles in an organocatalytic enantioselective transformation. Furthermore, the products, which feature various halogen atoms, provide access to structurally diverse axially chiral amino alcohols through further transformations.

Direct Construction of NOBINsvia Domino Arylation and Sigmatropic Rearrangement Reactions

“…To this end, several challenges will be encountered: (1) selection of suitable nucleophilic naphthyl reagent; (2) efficient formation of the transient intermediate before rearrangement; (3) regioselectivity control in [3,3]-sigmatropic rearrangement; (4) mild reaction conditions to accommodate wide-scope functional groups. In accordance with our continuous efforts on biaryl syntheses, [7] we herein present our recent findings in diversified synthesis of NOBINs via an arylation and [3,3]-sigmatropic rearrangement sequence under mild conditions in the absence of transition metal catalyst. A group of diarylhalonium salts were effectively utilized and both N-/O-naphthylhydroxylamines were verified competent nucleophiles for this transformation (Figure 2c).…”

“…13 C NMR (100 MHz, CDCl 3 ) δ: 153. 7,152.5,141.0,140.3,135.9,135.7,133.5,132.9,131.0,130.9,130.5,129.1,128.7,128.6,128.6,128.4,128.3,127.5,127.5,127.5,127.4,125.3,125.1,123.9,122.0,119.9,118.0,116.8,113.0,67.2. HRMS (ESI) calcd for [M+H] C 34 H 26 NO 3 , m/z: 496.1907NO 3 , m/z: 496. , found: 496.1904.…”

Highly atroposelective synthesis of nonbiaryl naphthalene-1,2-diamine N-C atropisomers through direct enantioselective C-H amination

“…It should be mentioned, while chiral 2-naphthylamine derivatives such as BINAP and NOBIN 39–41 are widely used as enantioselective catalysts in various reactions, the enantioselective construction of 2-naphthylamine derivatives is still rare 42–47 . Recently, Tan 48 reported the organocatalytic arylations of 2-naphthylamine to successfully form biaryl atropisomers. However, the more challenging chiral nonbiaryl N-C atropisomers of 2-naphthylamine derivatives have not been discovered.

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Catalytic Kinetic Resolution by Enantioselective Aromatization: Conversion of Racemic Intermediates of the Barton–Zard Reaction into Enantioenriched 3‐Arylpyrroles

“…Although the feasibility of this approach was demonstrated in 1984 by Myers, examples of such a self‐immolative process remained rare. Stimulated by the seminal work of Tan and co‐workers,– and Bonne, Rodriguez and co‐workers,– we have been interested in the asymmetric synthesis of atropisomers bearing a five‐membered heterocycle, structures which are among the less exploited classes of axially chiral biaryls, and have recently reported a catalytic enantioselective synthesis of 3‐arylpyrroles by heteroannulation of isocyanoacetates with aryl‐substituted alkynyl ketones . As a continuation of this research project, we sought to develop an alternative asymmetric synthesis involving enantioselective aromatization of racemates under kinetic resolution conditions .…”