Beyond esoteric interest, organocatalysis has now become one major pillar of asymmetric catalysis. Here, we discuss how new activation modes are conquering challenging stereoselective transformations ...and the recent integration of organocatalysis with emerging photo- and electrocatalysis, as well as artificial intelligence.Organocatalysis has become a major pillar of (asymmetric) catalysis. Here, the authors discuss recent trends in organocatalytic activation modes for challenging stereoselective transformations and the emerging integration with other fields, such as photoredox catalysis and electrosynthesis.
Atropisomerism is a stereochemical behavior portrayed by three-dimensional molecules that bear rotationally restricted σ bond. Akin to the well-represented point-chiral molecules, atropisomerically ...chiral compounds are finding increasing utilities in many disciplines where molecular asymmetry is influential. This provides steady demand on atroposelective synthesis, where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods while expanding the structural diversity of atropisomers. This review summarizes key achievements in stereoselective preparation of biaryl, heterobiaryl, and nonbiaryl atropisomers documented between 2015 and 2020. Emphasis is placed on the synthetic strategies for each structural class, while examples are cited to illustrate the potential applications of the accessed atropochiral targets.
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.
In the frame: 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 offers opportunities for the exploitation of structurally diverse N‐aryl atropisomers and OLED materials. CPA=chiral phosphoric acid.
The Ugi reaction constructs α-acylaminoamide compounds by combining an aldehyde or ketone, an amine, a carboxylic acid, and an isocyanide in a single flask. Its appealing features include inherent ...atom and step economy together with the potential to generate products of broad structural diversity. However, control of the stereochemistry in this reaction has proven to be a formidable challenge. We describe an efficient enantioselective four-component Ugi reaction catalyzed by a chiral phosphoric acid derivative that delivers more than 80 α-acylaminoamides in good to excellent enantiomeric excess. Experimental and computational studies establish the reaction mechanism and origins of stereoselectivity.
The well‐defined conformational properties of axially chiral compounds bring extraordinary values to an assortment of bioactive molecules, advanced materials, organocatalysts as well as chiral ...ligands in asymmetric transformations. The demonstrated usefulness and untapped potential of axially chiral structural motifs stimulate increasing efforts to develop novel and efficient approaches for their preparation. In this regard, the chiral phosphoric acids broadly used in asymmetric Brønsted acid catalysis have shown high relevance for atroposelective synthesis as well. Our strong interest in reaction chemistry of atropisomers has established a rewarding research programme in our group. The course of studies will be recounted in this Account, with discussion focused on the use of chiral phosphoric acids to catalyze construction of several key axially chiral structures such as BINAM, BINOL, NOBIN, arylquinones, SPINOL, arylpyrrole analogues and axially chiral alkenes.
What is the most favorite and original chemistry developed in your research group?
Organocatalytic asymmetric arene C—H functionalization.
What is the most important personality for scientific research?
Persistence, smart thinking.
What are your hobbies?
Playing basketball, playing card.
What's your favorite book(s)?
The Ordinary World by the famous Chinese writer Yao Lu.
Who influences you mostly in your life?
My parents and my supervisors Prof. Guofu Zhong and Carlos F. Barbas III.
How do you supervise your students?
I advise my students to work smartly and work hard.
The well‐defined conformational properties of axially chiral compounds bring extraordinary values to an assortment of bioactive molecules, advanced materials, organocatalysts as well as chiral ligands in asymmetric transformations. The demonstrated usefulness and untapped potential of axially chiral structural motifs stimulate increasing efforts to develop novel and efficient approaches for their preparation. In this regard, the chiral phosphoric acids broadly used in asymmetric Brønsted acid catalysis have shown high relevance for atroposelective synthesis as well. Our strong interest in reaction chemistry of atropisomers has established a rewarding research programme in our group. The course of studies will be recounted in this account, with discussion focused on the use of chiral phosphoric acids to catalyze construction of several key axially chiral structures such as BINAM, BINOL, NOBIN, arylquinones, SPINOL, arylpyrrole analogues and axially chiral alkenes.
Presented here is a class of novel axially chiral aryl‐p‐quinones as platform molecules for the preparation of non‐C2 symmetric biaryldiols. Two sets of aryl‐p‐quinone frameworks were synthesized ...with remarkable enantiocontrol by means of chiral phosphoric acid catalyzed enantioselective arylation of p‐quinones by central‐to‐axial chirality conversion. These aryl‐p‐quinones were then used to access a wide spectrum of highly functionalized non‐C2 symmetric biaryldiols with excellent retention of the enantiopurity.
A class of atropisomeric aryl‐p‐quinones were efficiently assembled by means of chiral phosphoric acid catalyzed enantioselective arylation of p‐quinones through a central‐to‐axial chirality transfer process. This novel axially chiral framework served as a platform for diversity‐oriented synthesis of a wide range of highly functionalized non‐C2 symmetric biaryldiols with preservation of the chirality.
Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective ...construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.
In recent years, visible light driven enantioselective chemical transformations have emerged as new additions to the toolkit of synthetic chemists to accomplish more efficient assembly of chiral ...molecules. Nonetheless, implementing precise stereocontrol on photoinduced intermolecular radical coupling process remains arduous. Recent studies unveil the underexplored competence of chiral phosphoric acid for this class of asymmetric photoredox reactions, endowed by its capability as a bifunctional H‐bonding catalyst for synchronous interaction with radical intermediate and substrate while channeling the cross‐coupling in a highly enantioselective manner. This paper highlights the recent advances, future outlook as well as the prospective challenges in this research area.
In recent years, visible light driven enantioselective chemical transformations have emerged as new additions to the toolkit of synthetic chemists to accomplish more efficient assembly of chiral molecules. Nonetheless, implementing precise stereocontrol on photoinduced intermolecular radical coupling process remains arduous. Recent studies unveil the underexplored competence of chiral phosphoric acid for this class of asymmetric photoredox reactions, endowed by its capability as a bifunctional H‐bonding catalyst for synchronous interaction with radical intermediate and substrate while channeling the cross‐coupling in a highly enantioselective manner. This paper highlights the recent advances, future outlook as well as the prospective challenges in this research area.
Atropisomeric biaryl motifs are ubiquitous in chiral catalysts and ligands. Numerous efficient strategies have been developed for the synthesis of axially chiral biaryls. In contrast, the asymmetric ...construction of o-quinone-aryl atropisomers has yet to be realized. Inspired by the rapid progress of the chemistry of biaryls, here we present our initial investigations about the atroposelective construction of axially chiral arylquinones by a bifunctional chiral phosphoric acid-catalyzed asymmetric conjugate addition and central-to-axial chirality conversion. With o-naphthoquinone as both the electrophile and the oxidant, three types of arylation counterparts, namely 2-naphthylamines, 2-naphthols and indoles, are utilized to assemble a series of atropisomeric scaffolds in good yields and excellent enantioselectivities. This approach not only expands the axially chiral library but also offers a route to a class of potential, chiral biomimetic catalysts.
Axially chiral 2‐arylpyrrole frameworks are efficiently accessed through a direct chirality transfer strategy by rapid cyclization of enantioenriched atropisomeric alkenes, which are generated by ...organocatalytic asymmetric N‐alkylation reactions. This approach accommodates a broad scope of substrates with remarkably high chirality transfer efficiency, affording novel atropisomers with a fully substituted pyrrole moiety and high enantiopurities. Given the enantioenriched atropisomeric alkenes, novel heterocyclic 2‐arylazepine atropisomers were realized through a rationally designed ene reaction.
Axially chiral 2‐arylpyrrole frameworks are efficiently accessed through a direct chirality transfer strategy by rapid cyclization of enantioenriched atropisomeric alkenes, generated by organocatalytic asymmetric N‐alkylation reactions. This approach accommodates a broad scope of substrates with remarkably high chirality transfer efficiency. Given the enantioenriched atropisomeric alkenes, novel heterocyclic 2‐arylazepine atropisomers were realized through a rationally designed ene reaction.
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