Atroposelective Synthesis of 1,1′‐Bipyrroles Bearing a Chiral N−N Axis: Chiral Phosphoric Acid Catalysis with Lewis Acid Induced Enantiodivergence

Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially chiral biaryl amino alcohols are far less developed. Herein, we have rationally designed a versatile C 1symmetric biaryl amino alcohol scaffold 1-(1-aminopyrrol-2-yl)naphthalen-2-ol (NPNOL) on the basis of axially chiral C2-arylpyrrole framework. For its enantioselective synthesis, the chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3dicarbonyl compounds and azoalkenes had been established. By using this practical method, a wide range of NPNOLs were readily prepared in high yields and excellent atroposelectivities (38 examples, up to 89 % yield and 99 % ee). DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity. The easy transformations of NPNOL-derived products into organocatalysts/ligands and their preliminary applications in asymmetric catalytic reactions demonstrated the promising utility of NPNOL.

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The Rational Design and Atroposelective Synthesis of Axially Chiral C2‐Arylpyrrole‐Derived Amino Alcohols

Han

Zhang

Wang

et al. 2022

Angewandte Chemie

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Synthesis of Atropisomeric Hydrazides by One‐Pot Sequential Enantio‐ and Diastereoselective Catalysis

et al. 2022

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The first catalytic enantioselective and diastereoselective synthesis of atropisomeric hydrazides was achieved using a sequential catalysis protocol. This strategy is based on a one‐pot sequence of two organocatalytic cycles featuring the enamine amination of branched aldehydes followed by nitrogen alkylation under phase‐transfer conditions. The resulting axially chiral hydrazides were obtained directly from commercially available reagents in high yields and with good stereocontrol. The permutation of organocatalysts allowed easy access to all stereoisomers, enabling a stereodivergent approach to enantioenriched atropisomeric hydrazides.

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Enantioselective Synthesis of N−N Bisindole Atropisomers

Zhang

Wang

et al. 2022

Angewandte Chemie

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NÀ N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of NÀ N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of NÀ N bisindole atropisomers via the palladium-catalyzed de novo construction of one indole skeleton is presented. A wide variety of NÀ N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indolecarbazole, and non-biaryl-indole atropisomers possessing a chiral NÀ N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol.

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Atroposelective Synthesis of 1,1′‐Bipyrroles Bearing a Chiral N−N Axis: Chiral Phosphoric Acid Catalysis with Lewis Acid Induced Enantiodivergence

Cited by 11 publications

References 80 publications

The Rational Design and Atroposelective Synthesis of Axially Chiral C2‐Arylpyrrole‐Derived Amino Alcohols

The Rational Design and Atroposelective Synthesis of Axially Chiral C2‐Arylpyrrole‐Derived Amino Alcohols

Synthesis of Atropisomeric Hydrazides by One‐Pot Sequential Enantio‐ and Diastereoselective Catalysis

Enantioselective Synthesis of N−N Bisindole Atropisomers

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