xin chang

Scopus Publications

Asymmetric Relay Catalysis Enables Unreactive Allylic Alcohols to Participate in 1,3-Dipolar Cycloaddition of Azomethine Ylides
Xiang Cheng, Cong Fu, Bo-Bin Chen, Xin Chang, Xiu-Qin Dong, and Chun-Jiang Wang
American Chemical Society (ACS)
Current synthetic transformations occur readily with starting materials that possess both innate reactivity and steric accessibility or functional-group-oriented reactivity. However, achieving reactions with inactive feedstock substrates remains significantly challenging and normally requires cumbersome prior functional group manipulations. Herein, we report an unprecedented example of catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with nonactivated alkenes enabled by copper/ruthenium relay catalysis. Key to the success is the temporary activation strategy initiated by oxidative dehydrogenation of inert allylic alcohols into electron-demanding reversed highly reactive enones, which triggers the ensuing Cu-catalyzed asymmetric 1,3-dipolar cycloaddition followed by reductive hydrogenation to deliver highly functionalized chiral pyrrolidines with the construction of two C-C bonds and four well-defined stereogenic centers in an atom-/step-economical and redox-neutral manner. This method features mild reaction conditions, operational simplicity, and broad substrate scope and is also characterized by formal dynamic kinetic resolution. Mechanistic studies and control experiments supported a typical borrowing-hydrogen cascade orthogonally merged with 1,3-dipolar cycloaddition and revealed that the superiority and reliability of relay catalysis are enabled by the controlled release of highly reactive but unstable enones to impede the undesired polymerization. It should be noted that up to four stereoisomers of the challenging and otherwise inaccessible pyrrolidines and cyclobutanes could be readily prepared through concise late-stage elaborations.


Dual Cu/Ir Catalyzed Asymmetric Allylation and Pictet-Spengler Cyclization: Stereodivergent Access to Chiral Indole Fused 9-Azabicyclo[4.2.1]nonanes^†
Xin‐Lian Liu, Lu Xiao, Yi Liu, Yan Li, Zuo‐Fei Wang, Xin Chang, Xiu‐Qin Dong, and Chun‐Jiang Wang
Wiley
Comprehensive SummaryNitrogen‐containing bridged‐heterocycles and indoles are key subunits of many natural products and pharmacologically active molecules. We herein present a bimetallic Cu/Ir catalyzed asymmetric allylation of ketimine esters and (E)‐4‐indolyl allyl carbonates followed by acid‐promoted Pictet‐Spengler cyclization sequences, enabling stereodivergent synthesis of chiral indole fused 9‐azabicyclo[4.2.1]nonanes containing an eight‐membered ring with one tertiary and two quaternary stereogenic centers. This one‐pot sequential protocol features step economy, good substrate tolerance, and excellent stereoselective control.







Rational Design and Stereodivergent Construction of Enantioenriched Tetrahydro-β-Carbolines Containing Multistereogenic Centers
Taotao Chen, Qi Xiong, Hui Xu, Lu Xiao, Zuo-Fei Wang, Xin Chang, Yanfeng Dang, Xiu-Qin Dong, and Chun-Jiang Wang
American Chemical Society (ACS)
Chiral tetrahydro-β-carbolines, as one of the most intriguing subtypes of indole alkaloids, have emerged as the privileged units in plenty of natural products and biologically active molecules with an impressive range of bioactive properties. However, the stereodivergent construction of these valuable skeletons containing multistereogenic centers from readily available starting materials remains very challenging, especially, in view of the introduction of an axial chirality. Herein, we developed an efficient method toward enantioenriched tetrahydro-β-carbolines with readily available tryptophan-derived aldimine esters and allylic carbonates under mild reaction conditions. The reaction proceeds in a sequential fashion involving synergistic Cu/Ir-catalyzed stereodivergent allylation and the Brønsted acid-promoted stereospecific Pictet-Spengler reaction, affording a wide range of chiral tetrahydro-β-carbolines bearing up to four stereogenic centers in good yields with excellent stereoselectivity control. When N-aryl-substituted tryptophan-derived aldimine esters were utilized, notably, a unique C-N heterobiaryl axis could be simultaneously constructed with the formation of the third point stereogenic center in the last cyclization step through dynamic kinetic resolution (DKR). Computational mechanistic studies established a plausible synergistic mechanism for dual Cu/Ir-catalyzed asymmetric allylation and the succeeding protonation-assisted Pictet-Spengler cyclization to complete the annulation. Structure-activity relationship analyses unveil the origins of stereochemistry for the building of one axis and three point stereogenic centers.


Iridium-Catalyzed Asymmetric Cascade Allylation/[1,4]-Phospha-Brook Rearrangement Reaction
Zhi-Yuan Yi, Hui Xu, Xin Chang, Yanfeng Dang, Xiu-Qin Dong, and Chun-Jiang Wang
American Chemical Society (ACS)



Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence
Hao-Ran Yang, Xiang Cheng, Xin Chang, Zuo-Fei Wang, Xiu-Qin Dong, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol.


Visible-light-enabled stereoselective synthesis of functionalized cyclohexylamine derivatives via [4 + 2] cycloadditions
Yi-Nan Lu, Chao Che, Guangjin Zhen, Xin Chang, Xiu-Qin Dong, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
Photocatalyzed [4 + 2] cycloaddition of benzocyclobutylamines with α-substituted vinylketones afforded benzocyclohexylamines in moderate to good yields with excellent diastereoselectivities. An asymmetric version of this was preliminarily investigated.


Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ-Hydroxy α-Amino Acids and Small Peptides
Cong Fu, Ling He, Xin Chang, Xiang Cheng, Zuo‐Fei Wang, Zongpeng Zhang, Vladimir A. Larionov, Xiu‐Qin Dong, and Chun‐Jiang Wang
Wiley
AbstractAn atom‐ and step‐economical and redox‐neutral cascade reaction enabled by asymmetric bimetallic relay catalysis by merging a ruthenium‐catalyzed asymmetric borrowing‐hydrogen reaction with copper‐catalyzed asymmetric Michael addition has been realized. A variety of highly functionalized 2‐amino‐5‐hydroxyvaleric acid esters or peptides bearing 1,4‐non‐adjacent stereogenic centers have been prepared in high yields with excellent enantio‐ and diastereoselectivity. Judicious selection and rational modification of the Ru catalysts with careful tuning of the reaction conditions played a pivotal role in stereoselectivity control as well as attenuating undesired α‐epimerization, thus enabling a full complement of all four stereoisomers that were otherwise inaccessible in previous work. Concise asymmetric stereodivergent synthesis of the key intermediates for biologically important chiral molecules further showcases the synthetic utility of this methodology.


Stereodivergent assembly of δ-valerolactones with an azaarene-containing quaternary stereocenter enabled by Cu/Ru relay catalysis
Kui Tian, Zhuan Jin, Xin-Lian Liu, Ling He, Hong-Fu Liu, Pin-Ke Yu, Xin Chang, Xiu-Qin Dong, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
Stereodivergent synthesis of chiral δ-valerolactones bearing a unique azaarene-containing α-quaternary and a tertiary stereocenter was enabled by Cu/Ru relay catalysis via cascade borrowing hydrogen/Michael addition/lactonization protocol.


Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones via cooperative copper and iridium catalysis
Kui Tian, Xin Chang, Lu Xiao, Xiu-Qin Dong, and Chun-Jiang Wang
Elsevier BV



Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes
Xiang Cheng, Xin Chang, Yuhong Yang, Zongpeng Zhang, Jing Li, Yipu Li, Wenxiao Zhao, Lung Wa Chung, Huailong Teng, Xiu-Qin Dong,et al.
Springer Science and Business Media LLC



Electron-rich benzofulvenes as effective dipolarophiles in copper(i)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides
Xin Chang, Xue-Tao Liu, Fangfang Li, Yuhong Yang, Lung Wa Chung, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
Electron-rich benzofulvenes serve as 2π-components in Cu-catalyzed asymmetric 1,3-DC reactions of azomethine ylides, affording chiral spiro-pyrrolidines in high yields with exclusive chemo-/regioselectivity and moderate to excellent stereoselectivity.


Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis
Bing-Ke Zhu, Hui Xu, Lu Xiao, Xin Chang, Liang Wei, Huailong Teng, Yanfeng Dang, Xiu-Qin Dong, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
Highly selective assembly of 2,3-fused indolizines was achieved via a cascade allylation/Friedel–Crafts type reaction with Cu/Ir catalysis. This protocol furnishes a stereodivergent synthesis of chiral indolizines bearing three stereogenic centers with excellent results.


Stereodivergent synthesis of enantioenriched unnatural α-amino acids enabled by synergistic dual metal catalysis
Liang Wei, Xin Chang, Zongpeng Zhang, Zuo-Fei Wang, and Chun-Jiang Wang
Science China Press., Co. Ltd.



Cooperative Catalyst-Enabled Regio- and Stereodivergent Synthesis of α-Quaternary α-Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols
Lu Xiao, Xin Chang, Hui Xu, Qi Xiong, Yanfeng Dang, and Chun‐Jiang Wang
Wiley
We describe c ooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et 3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir- p-allyl species in the presence of achiral Pd or chiral Ir complexes, respectively. The less or more substituted allylic termini of the metal-p-allyl species are amenable to nucleophilic attack by the chiral Cu-azomethine ylide , the formation of which is simultaneously facilitated by Et 3 B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. The use of readily available allylic alcohols as electrophilic precursors represents an improvement from an environmental and atom/step economy perspective . Computational mechanistic studies reveal the crucial role of the Et 3 B additive and the origins of stereo- and regioselectivities by analyzing steric effects, dispersion interactions, and frontier orbital population.


Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction
Zhi-Yuan Yi, Lu Xiao, Xin Chang, Xiu-Qin Dong, and Chun-Jiang Wang
American Chemical Society (ACS)
An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available β-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the β-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.


Recent Advances in Catalytic Asymmetric 1,3-Dipolar Cycloaddition Reactions with Kinetic Resolution
Huachao Liu, Chong Shen, Xin Chang, and Chunjiang Wang
Shanghai Institute of Organic Chemistry



Stereodivergent Construction of 1,4-Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis
Xin Chang, Xiang Cheng, Xue‐Tao Liu, Cong Fu, Wei‐Yi Wang, and Chun‐Jiang Wang
Wiley
An unprecedented hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with copper-catalyzed asymmetric Michael addition in a one-pot procedure. The current method enables the efficient preparation of highly functionalized δ-hydroxyesters bearing 1,4-nonadjacent stereocenters in good yields with high levels of diastereoselectivity and excellent enantioselectivity under mild reaction conditions. The full complement of the four stereoisomers of hydroalkylation products could be readily accessed by orthogonal permutations of two chiral metal catalysts. The current work highlights the power of relay catalysis for the stereodivergent construction of 1,4-nonadjacent stereocenters that were otherwise inaccessible.


Stereodivergent Synthesis of Enantioenriched α-Deuterated α-Amino Acids via Cascade Cu(I)-Catalyzed H-D Exchange and Dual Cu- and Ir-Catalyzed Allylation
Cong Fu, Xin Chang, Lu Xiao, and Chun-Jiang Wang
American Chemical Society (ACS)
A one-pot Cu-mediated H-D exchange with inexpensive heavy water as the deuterium source, followed by Cu- and Ir-catalyzed stereodivergent allylic alkylation, has been developed, providing efficient access to enantioenriched α-deuterium-labeled α-amino acids from readily available glycine imine esters in a high yield with excellent stereoselectivity. High deuterium enrichment, exquisite regioselectivity, precise stereoselectivity control, and operationally convenient procedures make this protocol appealing for the preparation of highly synthetically useful α-deuterated α-amino acids.


Catalytic Asymmetric Benzylation of Azomethine Ylides Enabled by Synergistic Lewis Acid/Palladium Catalysis
Xin Chang, Jing-Di Ran, Xue-Tao Liu, and Chun-Jiang Wang
American Chemical Society (ACS)
The synergistic chiral Lewis acid/achiral Pd catalyst system was successfully applied in the enantioselective benzylation of various imine esters, giving a range of α-benzyl-substituted α-amino acid derivatives in satisfactory yield with excellent enantioselectivity. It is worth noting that this strategy exhibits good tolerance for bicyclic and monocyclic benzylic electrophiles. Furthermore, the utility of this synthetic protocol was demonstrated by the expedient preparation of enantioenriched antihypertensive drug α-methyl-l-dopa.


Palladium-Catalyzed Asymmetric Allylic Alkylation/α-Iminol Rearrangement: A Facile Access to 2-Spirocyclic-Indoline Derivatives
Xin Chang, Chao Che, Zuo-Fei Wang, and Chun-Jiang Wang
Chinese Chemical Society
An unprecedented Pd-catalyzed asymmetric allylic alkylation of 1-(indol-2-yl)cyclobutanols followed by an α-iminol rearrangement was reported. High yields with excellent chemo-, regio-, diastereo-,...


Catalytic asymmetric synthesis of enantioenriched α-deuterated pyrrolidine derivatives
Xin Chang, Xiang Cheng, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
A strategy of combining H/D-Ex and azomethine ylide-involved 1,3-DC was developed for the construction of α-deuterated pyrrolidine derivatives in good yields with excellent stereoselectivities and uniformly high levels of deuterium incorporation.


Cu-catalyzed endo-selective asymmetric 1,3-dipolar cycloaddition of azomethine ylides with ethenesulfonyl fluorides: Efficient access to chiral pyrrolidine-3-sulfonyl fluorides
Yi-Nan Li, Xin Chang, Qi Xiong, Xiu-Qin Dong, and Chun-Jiang Wang
Elsevier BV



Palladium catalyzed cascade umpolung allylation/acetalation for the construction of quaternary 3-amino oxindoles
Xi-Shang Sun, Xin Chang, Li-Min Shi, Zuo-Fei Wang, Liang Wei, and Chun-Jiang Wang
Royal Society of Chemistry (RSC)
A highly diastereoselective synthesis of quaternary 3-amino oxindoles via a palladium catalyzed three-component cascade umpolung allylation/acetalation process has been developed. The current method could be extended to cascade umpolung allenylation/acetalation.


β-Substituted Alkenyl Heteroarenes as Dipolarophiles in the Cu(I)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides Empowered by a Dual Activation Strategy: Stereoselectivity and Mechanistic Insight
Xin Chang, Yuhong Yang, Chong Shen, Kun-Shan Xue, Zuo-Fei Wang, Hengjiang Cong, Hai-Yan Tao, Lung Wa Chung, and Chun-Jiang Wang
American Chemical Society (ACS)
The catalytic asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides with various electron-deficient alkenes provide the most straightforward protocol for the preparation of enantioenriched pyrrolidines in organic synthesis. However, the employment of conjugated alkenyl heteroarenes as dipolarophiles in such protocols to afford a class of particularly important molecules in medicinal chemistry is still a great challenge. Herein, we report that various β-substituted alkenyl heteroarenes, challenging internal alkene substrates without a strong electron-withdrawing substituent, were successfully employed as dipolarophiles for the first time in the Cu(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides. This reaction furnishes a large array of multistereogenic heterocycles incorporating both the biologically important pyrrolidine and heteroarene skeletons in good yields with exclusive diastereoselectivity and excellent enantioselectivity. Our extensive density functional theory (DFT) calculations proposed a working model to explain the origin of the stereochemical outcome and elucidated uncommon dual activation/coordination of both the dipole and dipolarophile substrates by the metal, in which a sterically bulky, rigid, and monodentate phosphoramidite ligand with triple-homoaxial chirality plays a pivotal role in providing an effective chiral pocket around the metal center, resulting in high enantioselectivity. The additional coordination of the heteroatom in the dipolarophile substrate to Cu is also critical for the exclusive diastereoselectivity and enhanced reactivity. Our calculations also predicted the reverse and high enantioinduction for the corresponding substrates with monocyclic heteroarenes as well as regiospecific cycloaddition to the less reactive internal C═C bond of one related dipolarophile diene substrate. Such unique steric effect-directed enantioswitching and coordination-directed regioselectivity were verified experimentally.