Symmetry in Cascade Chirality-Transfer Processes: A Catalytic Atroposelective Direct Arylation Approach to BINOL Derivatives

Abstract

Herein we disclose a scalable organo-catalytic direct arylation approach for the regio- and atroposelective synthesis of non-C2-symmetric 2,2′-dihydroxy-1,1′-binaphthalenes (BINOLs). In the presence of catalytic amounts of axially chiral phosphoric acids, phenols and naphthols are coupled with iminoquinones via a cascade process that involves sequential aminal formation, sigmatropic rearrangement, and rearomatization to afford enantiomerically enriched BINOL derivatives in good to excellent yields. Our studies suggest that the (local) symmetry of the initially formed aminal intermediate has a dramatic impact on the level of enantioinduction in the final product. Aminals with a plane of symmetry give rise to BINOL derivatives with significantly lower enantiomeric excess than unsymmetrical ones featuring a stereogenic center. Presumably asymmetric induction in the sigmatropic rearrangement step is significantly more challenging than during aminal formation. Sigmatropic rearrangement of the enantiomerically enriched aminal and subsequent rearomatization transfers the central chirality into axial chirality with high fidelity.

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

“…In the following step, aromatization with central‐to‐axial chirality conversion affords the axially chiral biaryl amino alcohol ,. However, a cascade process that involves sequential aminal formation, sigmatropic rearrangement, and aromatization cannot be ruled out at this stage …”

Design and Enantioselective Construction of Axially Chiral Naphthyl‐Indole Skeletons

“…In spite of these elegant achievements in enantioselective construction of chiral biaryl backbones, there are still some challenges to be overcome in this field of research (Scheme ). For instance, most of these enantioselective methods are enabled by chiral metal/ligand catalysts, and only a small number of transformations can be promoted by chiral organocatalysts,––, which have significant advantages, such as easy operation and mild reaction conditions, and are superior for synthesizing chiral bioactive compounds . More importantly, the accessible chiral biaryl backbones are mainly restricted to binaphthyl, phenyl‐naphthyl, and biphenyl frameworks .…”

Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach

“…[1b-d, 3] Nevertheless,r esolution-free,e nantioselective electrophilic aromatic nitration processes (even with chiral auxiliaries) have yet to be reported. While enantioselective Friedel-Crafts-type reactions [4] and enantioselective aromatic brominations [5] have been studied extensively,o nly the enantioselective nitration of crotylsilanes, [6] but not of aromatic substrates,h as been described.To advance the growing field of chirality-assisted synthesis [7] (CAS), we now describe an enantioselective nitration strategy which makes use of chiral diester auxiliaries with remote stereocenters to induce axial chirality upon trifold nitration. We employ our chiral auxiliaries to achieve the first enantioselective synthesis of a C 3v -symmetric tribenzotriqui-nacene (TBTQ) [8] derivative,w hich is not based on either ak inetic, [9] crystallization-based, [10] or chromatographic [11] resolution.…”

“…[1b-d, 3] Nevertheless,r esolution-free,e nantioselective electrophilic aromatic nitration processes (even with chiral auxiliaries) have yet to be reported. While enantioselective Friedel-Crafts-type reactions [4] and enantioselective aromatic brominations [5] have been studied extensively,o nly the enantioselective nitration of crotylsilanes, [6] but not of aromatic substrates,h as been described.…”