Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles

Zhang, Lei; Xiang, Shao‐Hua; Wang, Jun; Xiao, Jian; Wang, Junqi; Tan, Bin

doi:10.1038/s41467-019-08447-z

Cited by 112 publications

(47 citation statements)

References 52 publications

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“…1a, Eq 1). On the other hand, while the activation of stable imines by chiral Brønsted acid catalysts has been extensively investigated in a variety of enantioselective Mannich reactions [25][26][27][28][29][30][31][32][33][34][35][36] , this electrophile-based activating protocol has not been applied to aminomethylation reactions with the in situ-generated formaldimines, probably owing to their generally unstable nature and the lack of steric environment on the carbon atom for efficient stereocontrols (Fig. 1a, Eq 2).…”

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confidence: 99%

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

et al. 2020

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Enantioselective α-aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules. However, current strategies rely on nucleophile-based enantioselective activation with inherently activated substrates only, and enantioselective protocol based on the activation of in situ-generated unstable formaldimines remains elusive, probably owing to their unstable nature and the lack of steric environment for efficient stereocontrols. Here, based on a rhodium/chiral phosphoric acid cooperative catalysis, we achieved an enantioselective three-component reaction of α-diazo ketones with alcohols and 1,3,5-triazines. A dual hydrogen bonding between the chiral phosphoric acid catalyst and two distinct active intermediates was proposed to be crucial for the efficient electrophile-based enantiocontrol. A series of chiral β-amino-α-hydroxy ketones including those derived from simple aliphatic alcohols, allylic alcohol, propargyl alcohol, complicated natural alcohols and water could all be prepared in high efficiency and enantioselectivity.

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confidence: 99%

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

et al. 2020

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“…It is worthwhile mentioning that product 9 if is an axially chiral pyrrole, with the free rotation through the C−N bond at room temperature being suppressed by the ortho ‐tolyl substituent. Axially chiral arylpyrroles can be found in bioactive natural products as well as in chiral ligands and catalysts …”

Section: Resultsmentioning

confidence: 99%

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

González-Soria

Alonso

2019

Adv Synth Catal

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It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate-driven synthesis of β-enaminones and N-aryl pyrroles from indolizines and nitrosoarenes; aryl-substituted indolizines lead to β-enaminones in a regio-and diastereoselective manner, whereas alkyl-substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the βenaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.

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“…The N‐arylcarbazole 10 served as an efficient ligand for palladium‐catalyzed enantioselective allylic alkylation of the racemic 14 with malonate nucleophiles ( 15 ). In the presence of a palladium catalyst (2 mol %) and 10 (4 mol %), these reactions proceeded efficiently, to furnish the desired products 16 a – c in excellent yields with commendable stereoselectivity (85–95 % ee ) . The absolute configuration of 8 was determined as ( aS ) by X‐ray crystallographic analysis (CCDC 1963374) and those of other products were assigned by analogy.…”

Section: Figurementioning

confidence: 99%

Chiral Phosphoric Acid Catalyzed Atroposelective C−H Amination of Arenes

et al. 2020

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N‐arylcarbazole structures are important because of their prevalence in natural products and functional OLED materials. C−H amination of arenes has been widely recognized as the most efficient approach to access these structures. Conventional strategies involving transition‐metal catalysts suffer from confined substrate generality and the requirement of exogenous oxidants. Organocatalytic enantioselective C–N chiral axis construction remains elusive. Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N‐arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N‐arylcarbazoles in good yields with excellent enantiocontrol. This approach not only offers an alternative to metal‐catalyzed C–N cross‐coupling, but also brings about opportunities for the exploitation of structurally diverse N‐aryl atropisomers and OLED materials.

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Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles

Cited by 112 publications

References 52 publications

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

Chiral Phosphoric Acid Catalyzed Atroposelective C−H Amination of Arenes

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