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.
A multicomponent reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and tertiary amine is discovered, which generates the unexpected H-pyrazolo5,1-aisoquinolines in good yields under mild ...conditions. In the reaction process, silver(I)-catalyzed intramolecular cyclization and copper(II)-catalyzed oxidation of an aliphatic C−H bond of tertiary amine in air are involved.
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.
From the viewpoint of synthetic accessibility and functional group compatibility, photoredox-catalyzed sulfur dioxide insertion strategy enables in situ generation of functionalized sulfonyl radicals ...from easily accessible starting materials under mild conditions, thereby conferring broader application potential. Here we present two complementary photoinduced sulfur dioxide insertion systems to trigger radical asymmetric Truce-Smiles rearrangements for preparing a variety of chiral sulfones that bear a quaternary carbon stereocenter. This protocol features broad substrate scope and excellent stereospecificity. Aside from scalability, the introduction of a quaternary carbon stereocenter at position β to bioactive molecule-derived sulfones further demonstrates the practicality and potential of this methodology.
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.
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.
The first copper-catalyzed atroposelective Michael-type addition between azonaphthalenes and arylboronic acids for the construction of biaryl atropisomers was established using a novel BINOL-derived ...phosphoramidite as a chiral ligand. A broad range of atropisomeric biaryls were obtained with good efficiency, and the practicality of this approach was verified by versatile transformations toward axially chiral ligands, catalysts, and other functional atropisomers. This set of catalytic systems successfully inhibited the routine 1,2-addition and promoted the formation of an aryl–aryl chiral axis. Meanwhile, this strategy bypassed the use of an oxidant as well as the harsh conditions normally necessary for transition-metal-mediated arene C–H coupling with arylboronic acids as an arylation counterpart, offering a straightforward alternative to access optically active biaryls.
Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein ...an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, 1H NMR, LC-MS, and control experiments.
Axially chiral 1,1′-spirobiindane-7,7′-diol (SPINOL) is the most fundamental and important privileged structure from which other chiral ligands containing a 1,1′-spirobiindane backbone are ...synthesized. Driven by the development of enantioselective syntheses of axially chiral SPINOL derivatives, we have successfully developed the first phosphoric acid-catalyzed asymmetric approach. This approach is highly convergent and functional group tolerant, efficiently providing SPINOLs in good yield with excellent enantioselectivity, thus delivering a practical and straightforward access to this privileged structure. It should be emphasized that the catalyst loading could be decreased to only 0.1 mol% for the preparative-scale synthesis. Furthermore, 4,4′-dimethyl-SPINOL-phosphoric acid was synthesized and applied to catalyze the model reaction for synthesis of enantioenriched SPINOL derivatives.
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.
