Article
Chemistry, Organic
Mengzhu Guo, Fengying Dong, Xiangcong Yin, Lubin Xu, Liang Wang, Shuai-Shuai Li
Summary: In this study, medicinally significant 3-monosubstituted tetrahydroquinolines and 1,2-dihydroquinolines were controllably constructed via a redox-neutral vinylogous cascade condensation/[1,5]-hydride transfer/cyclization process in ethanol, showcasing novel features such as green solvent and metal-free conditions. Additionally, the electrophilicity and nucleophilicity of alpha,alpha-dicyanoalkenes were effectively utilized as hydride acceptors and gamma-exclusive nucleophiles.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Qingdong Hu, Chang Guo
Summary: The synthesis of structurally diverse multiligated platinum complexes, characterized by X-ray crystallography, opens up new reaction space and enables faster screening. The Pt/Cu dual catalytic system shows new cooperative reactivity, leading to the asymmetric synthesis of valuable functionalized indoles with good yields and excellent enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Daniel Moock, Tobias Wagener, Tianjiao Hu, Timothy Gallagher, Frank Glorius
Summary: This study presents a method for enantio- and diastereoselective hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis, allowing controlled installation of up to six new defined stereocenters to produce complex octahydrobenzofurans prevalent in bioactive molecules. The unique combination of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor enables the process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Jen-Yu Kuan, I-Ting Chen, Hsuan Lin, Jeng-Liang Han
Summary: We have developed a substrate-dependent, regio- and stereocontrolled diversity-oriented organocatalytic vinylogous Michael addition/cyclization cascade of 2-alkylidene indane-1,3-diones with enals, using secondary amines as the catalyst. This method allows for the selective synthesis of spiroindane-1,3-diones, tetrahydrofluoren-9-one derivatives, and benzofused oxabicyclo[3.3.1]nonanes. Plausible catalytic pathways have been proposed, and DFT calculations have clarified the mechanisms involved.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Xinxin Lv, Ya-Nan Qi, Jiahao Wang, Xiaowei Zhao, Zhiyong Jiang
Summary: The first vinylogous dearomatization reaction is reported, which utilizes a photoinduced platform. Various benzothiophenes functionalized by ketones at the 3-position could efficiently react with 3-methylenechroman-4-ones, leading to the formation of valuable products that contain pharmaceutically significant chromones and 2,3-dihydrobenzo[b]thiophenes simultaneously. The reaction involves hydrogen-atom transfer, dearomatization, olefin migration, and radical cross coupling.
Review
Chemistry, Organic
Zhen-Hua Wang, Yong You, Jian-Qiang Zhao, Yan-Ping Zhang, Jun-Qing Yin, Wei-Cheng Yuan
Summary: In conjugated pi systems, suitable strategies can generate pi-extended enolates from pronucleophiles and these tend to undergo stereoselective vinylogous reactions for remote functionalization. However, bench-stable unsaturated pronucleophiles have historically lacked proximal functionalization. Recent development of synthetic methods and catalytic systems have addressed this issue. This review highlights the achievements, mechanism insights, and challenges in the proximal functionalization of unsaturated pronucleophiles.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Yadi Niu, Laiping Yao, Hongli Zhao, Xue Tang, Qian Zhao, Yuling Wu, Bo Han, Wei Huang, Gu Zhan
Summary: This study presents a new method for the asymmetric synthesis of spiroxindole cyclopentanes containing five stereocenters. The strategy demonstrated a broad substrate scope and high selectivity.
Article
Chemistry, Multidisciplinary
Jianfeng Jiang, Xia Wang, Shengping Liu, Sichen Zhang, Binmiao Yang, Yu Zhao, Shenci Lu
Summary: We report an unprecedented gold and oxidative NHC relay catalysis for highly enantioselective cascade annulation between readily available alpha-amino-ynones with enals. This method utilizes in situ-generated pyrrolin-4-ones as a novel and versatile synthon, reacting with alpha,beta-unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole-fused lactones in high yield and excellent enantioselectivity. The utility of the lactone products is demonstrated by their facile conversion to densely functionalized pyrroles and pyrrolin-4-ones with high yields and excellent stereopurity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jingwen Wei, Yangyang Xing, Xiaohan Ye, Bao Nguyen, Lukasz Wojtas, Xin Hong, Xiaodong Shi
Summary: In this study, a new synthetic strategy for enantioselective 1,2-dihydropyridine synthesis was reported. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, the synthesis was achieved through a formal [3+2+1] fashion with up to 95% yield and up to 99% enantiomeric excess (e.e.).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Yun-Jie Tsou, Nadaraj Sathishkumar, I-Ting Chen, Ting-An Lee, Hsin-Tsung Chen, Jeng-Liang Han
Summary: This study reports a new method for a hydrogen-bond-donor-directed enantiodivergent vinylogous aldol-cyclization cascade reaction using thiourea or squaramide cinchona alkaloid catalysts. The results also reveal the kinetic mechanism of the reaction and the enantioselectivity determined by the geometry of the pronucleophile.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kazuhiko Semba, Naoki Ohta, Fritz Paulus, Masaki Ohata, Yoshiaki Nakao
Summary: This new method allows for allylarylation of electron-deficient alkenes using aryl boronates and allylic carbonates as starting materials, leading to a variety of carbon skeletons. Mechanistic studies reveal that the reaction is facilitated by a cooperative catalysis involving Pd-0/Pd-II redox and Pd-II/Pd-II non-redox catalytic cycles.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Organic
Bei Zhang, Gongming Yang, Donghui Guo, Jian Wang
Summary: The dual catalytic strategy provides an effective and convenient solution for the synthesis of complex or hard-integrated frameworks. The cooperation of NHCs and other catalysts has greatly broadened the extension of NHC catalysis. This article briefly reviews the early investigations of NHC cooperation with other catalysts under the relay catalytic mode, and the latest progress in the use of synergism to achieve dual catalysis, and highlights the breakthroughs and limitations of these methods. In addition, the prospect of NHC-driven dual catalytic models is also forecast here.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Applied
Laiyu An, Linghong Chen, Hongzhou Yang, Ling Ye, Hongjun Yang, Xinying Li, Zhigang Zhao, Xuefeng Li
Summary: A convenient and functionalized vinylogous nucleophile has been used to synthesize bridged bicyclic compounds via cascade Michael/Henry reaction. The reaction showed high reactivity without the need for a catalyst under mild conditions. Various structurally distinctive bicyclo[3.2.1]octanes were obtained in isolated yields of 40-96% with excellent diastereoselectivities (& GE;10:1 dr). The gram-scale synthesis was also demonstrated.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Chaitanya Ittamalla, Saikrishna Chintha, Nagaraju Medishetti, Jagadeesh Babu Nanubolu, Krishnaiah Atmakur
Summary: The title compounds were synthesized through a reaction between vinyl malononitriles and arylidene pyrazolones catalyzed by base. The reaction involves Michael addition followed by intramolecular cyclization, resulting in the formation of two new C-C bonds. Furthermore, the same reaction with alpha,alpha-dicyano olefins and vinyl malononitriles produces 1,6-dihydro biphenyl compounds. The advantages of this protocol include simple reaction conditions, high yields, and compatibility.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Hao-Dong Qian, Zhi-Heng Li, Shuang Deng, Chaochao Yao, Hua-Ming Xiang, Guang Xu, Zi-Qi Geng, Zihao Wang, Linfeng Chen, Chunrong Liu, Cuiju Zhu, Xiaotian Qi, Hao Xu
Summary: Distinct regio- and enantioselectivity control has been achieved in copper-catalyzed vinylogous and bisvinylogous propargylic substitution using a novel chiral N,N,P ligand. The developed method provides an efficient and selective approach to the synthesis of enantioenriched alkynyl unsaturated carbonyl compounds, with excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is demonstrated by gram-scale synthesis and application to the enantioselective synthesis of challenging compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Sandeep Pimparkar, Trisha Bhattacharya, Arun Maji, Argha Saha, Ramasamy Jayarajan, Uttam Dutta, Gang Lu, David W. Lupton, Debabrata Maiti
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Chemistry, Physical
Jing Cao, Rachel Gillard, Azar Jahanbakhsh, Martin Breugst, David W. Lupton
Article
Chemistry, Physical
Nicholas E. S. Tay, Wei Chen, Alison Levens, Vincent A. Pistritto, Zeng Huang, Zhanhong Wu, Zibo Li, David A. Nicewicz
Article
Chemistry, Multidisciplinary
Jeremy T. Maddigan-Wyatt, Mitchell T. Blyth, Jhi Ametovski, Michelle L. Coote, Joel F. Hooper, David W. Lupton
Summary: A phosphine-catalyzed approach to pyrrolines has been developed, involving two mechanistically unlinked catalytic processes, and successfully synthesizing various pyrrolines. The reaction shows high sensitivity to the selection of catalysts.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Venkatachalam Pitchumani, Martin Breugst, David W. Lupton
Summary: This study demonstrates the enantioselective conversion of beta-substituted acrylamides to enantioenriched quinolones using electron-withdrawing protection and moderate nucleophilicity N-heterocyclic carbenes. The reaction shows complete diastereoselectivity, good yield, and modest enantioselectivity. Computational studies support the concept of decreased amide bond character with electron-withdrawing protection of the nitrogen.
Article
Chemistry, Organic
Jose A. Forni, Milena L. Czyz, David W. Lupton, Anastasios Polyzos
Summary: A regioselective C(sp(3))-C(sp(2)) cross coupling reaction between inert gamma-C(sp(3))-H bonds in aliphatic amines and cyanoarenes under electrochemical conditions in flow is reported. The reaction utilizes a removable redox active auxiliary to trigger selective 1,7-hydrogen atom transfer for functionalization of a gamma-position aliphatic C-H bond. The cyanoarene radical anion acts both as a selective arylating reagent and a redox active mediator, enabling controlled one-electron reduction of the redox active auxiliary. This strategy provides a new approach for gamma-C(sp(3))-H bond functionalization to generate sterically crowded carbon centers under mild reaction conditions and without additional catalysts or radical initiators.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Organic
Jeremy T. Maddigan-Wyatt, Jing Cao, Jhi Ametovski, Joel F. Hooper, David W. Lupton
Summary: Here, an enantioselective catalytic annulation of electron-poor allenes with aminocrotonates is reported. The reaction proceeds via umpolung gamma-amination and beta-umpolung intramolecular conjugate addition. The reaction provides ready access to chiral compounds with high yields and high enantiomeric ratios, and an assisted tandem-catalytic variant is also proposed.
Article
Chemistry, Multidisciplinary
Simon Cromwell, Randy Sutio, Changhe Zhang, Georgina K. Such, David W. Lupton
Summary: In this study, a reaction cascade involving the addition of C1-pyridinium enolate to thiocarbonyl compounds was reported, leading to the synthesis of a range of dihydrothiophenes and dihydrothiopyrans. Mechanistic investigations and experimental evidence supported the involvement of an activated acid intermediate and turnover limiting cyclization in the reaction pathway, with subsequent formation of β-thiolactone regenerating the catalyst.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Microbiology
Laura Perlaza-Jimenez, Kher-Shing Tan, Sarah J. Piper, Rachel M. Johnson, Rebecca S. Bamert, Christopher J. Stubenrauch, Alexander Wright, David Lupton, Trevor Lithgow, Matthew J. Belousoff
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, and its treatment often requires the use of last-line antibiotics like linezolid. This study identified linezolid-resistant mutants in MRSA strains and found that mutations in the ribosomal protein uL3 were responsible for the resistance. Cryo-electron microscopic analysis revealed structural rearrangements in the ribosome caused by these mutations.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Suk Woo Kang, James Antoney, David W. Lupton, Robert Speight, Colin Scott, Colin J. Jackson
Summary: The stereoselective reduction of alkenes conjugated to electron-withdrawing groups has been extensively studied for the commercial production of fine chemicals. The old yellow enzyme (OYE) family and a subset of flavin/deazaflavin oxidoreductases (FDOR) have been shown to exhibit complementary enantioselectivity. This study explores several enzymes of the FDOR-A subgroup and identifies two enzymes (MSMEG_2027 and MSMEG_2850) that can selectively reduce a wide range of compounds. Protein crystallography and computational docking provide mechanistic insights into the observed stereoselectivity. These findings highlight the potential of FDOR and OYE families in asymmetric ene-reduction.
Article
Chemistry, Medicinal
Biljana Vujcic, Jessica Wyllie, Tania, Jed Burns, Keith F. White, Simon Cromwell, David W. Lupton, Jason L. Dutton, Tatiana P. Soares da Costa, Sevan D. Houston
Summary: The threat of a post-antibiotic era is caused by the rise of antibacterial resistance and depletion of effective antibiotic agents. One solution is to reengineer existing antibiotic drugs by covalently linking two pharmacophores using cage hydrocarbons like cubane, BCO, adamantane, and BCP as linkers. This report demonstrates the successful construction of dimers based on trimethoprim and tedizolid antibiotics using these hydrocarbons. The design strategy presented highlights the potential of this group as a platform for the rapid and modular construction of novel antibiotics.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Suk Woo Kang, James Antoney, David W. Lupton, Robert Speight, Colin Scott, Colin J. Jackson
Summary: Asymmetric reduction by ene-reductases has been extensively studied, with the Old Yellow Enzyme (OYE) family being the most researched. However, the limited substrate range and stereocomplementary pairs of current ene-reductases necessitate the development of a complementary class. Flavin/deazaflavin oxidoreductases (FDORs) that use F-420 as a cofactor have gained attention due to their stereocomplementarity with OYEs. In this study, the activity of eight FDOR-B enzymes was investigated, comparing their specific activity, kinetic properties, and stereoselectivity with FDOR-A enzymes and OYE family.
Editorial Material
Multidisciplinary Sciences
Yuji Nakano, David W. Lupton
Review
Chemistry, Multidisciplinary
Yuji Nakano, Jeremy T. Maddigan-Wyatt, David W. Lupton
Summary: Conjugate acceptors are commonly used electrophilic functional groups in organic synthesis. Our research focuses on their ability to undergo polarity inversion through the conjugate addition of Lewis base catalysts. We have achieved cycloisomerizations and annulation reactions using simple conjugate acceptors and those embedded within more complicated substrates. However, significant challenges remain to be addressed before a universal approach to polarity inversion of all conjugate acceptors can be achieved.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Jing Cao, Antonia Seitz, Jose A. Forni, Anastasios Polyzos, David W. Lupton
Summary: This article reports on a reaction design that avoids the facile oxidation of phosphine organocatalyst and combines traditional nucleophilic phosphine organocatalysis with photoredox catalysis to enable Giese coupling with ynoates. The approach exhibits good generality, and its mechanism is supported by cyclic voltametric, Stern-Volmer quenching, and interception studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)