Article
Chemistry, Multidisciplinary
Oleg Grossmann, Rajat Maji, Miles H. Aukland, Sunggi Lee, Benjamin List
Summary: Strong and confined IDPi catalysts enable highly enantioselective substitutions of cyclic, aliphatic hemiaminal ethers with enol silanes, giving access to 2-substituted pyrrolidines, piperidines, and azepanes with high enantioselectivities. The method exhibits broad tolerance towards various enol silane nucleophiles. Mechanistic studies suggest the involvement of non-stabilized, cyclic N-(exo-acyl)iminium ions with the confined chiral counteranion as intermediates, while computational studies provide transition states that account for the observed enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Applied
I-Ting Chen, Ren-You Guan, Jeng-Liang Han
Summary: In this study, a catalytic asymmetric vinylogous Mannich/annulation/acylation reaction was developed for the synthesis of chiral spiro-oxindole piperidine derivatives with polyaromatic scaffolds. The reaction provided the desired products in good yields and high enantioselectivity. DFT computational calculations were used to explain the mechanism and origin of the observed enantioselectivity and O-acetylated products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Physical
Yusuke Tokuhiro, Kosuke Yoshikawa, Sei Murayama, Takeshi Nanjo, Yoshiji Takemoto
Summary: This article presents an alternative practical method for the asymmetric synthesis of beta-amino-alpha-ketoacid equivalents, utilizing a highly stereoselective organocatalyzed Mannich-type addition using glyoxylate cyanohydrin. The optimal aminothiourea catalyst provides a variety of adducts with excellent yield and stereoselectivity, and the reaction can be applied to a wider range of imine precursors. Experimental and computational studies reveal the factors contributing to the high diastereoselectivity and enantioselectivity of the reaction.
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
Polymer Science
Yanping Li, Ke Pan, Yougen Chen
Summary: A new type of degradable poly(beta-trimethylsilyloxy ester) was synthesized by the organocatalyzed Mukaiyama aldol polyaddition. These polyesters showed degradation behavior in the presence of nucleophiles, and the degradation mechanism was influenced by the nature of the catalyst used.
MACROMOLECULAR RAPID COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Jiahang Yan, Wenting Zhang, Qiaoqiao He, Jun Hou, Hongxin Zeng, Hongbo Wei, Weiqing Xie
Summary: This study presents a nickel-catalyzed asymmetric direct vinylogous Michael addition and a tandem catalytic asymmetric vinylogous Michael addition/intramolecular Michael addition, which provide efficient and selective routes to synthesize diverse organic compounds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Remi Andres, Qian Wang, Jieping Zhu
Summary: A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been achieved by several key steps, including a catalyst-controlled asymmetric Pictet-Spengler reaction, oxidative cleavage, and intramolecular nucleophilic addition. The synthesis confirmed the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Kazuki Ogura, Tsunayoshi Takehara, Takeyuki Suzuki, Shuichi Nakamuraa
Summary: A novel enantioselective vinylogous Mannich reaction was developed for the synthesis of acyclic delta-amino-alpha,beta-unsaturated carbonyl compounds, achieving excellent yields and enantioselectivities using a specific catalyst. This study provides an efficient route for the synthesis of compounds in this specific category.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
William R. R. Cassels, Evan T. T. Crawford, Jeffrey S. S. Johnson
Summary: We report a simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction for the synthesis of stereodefined alpha-monosubstituted-ss-ketoesters, dissymmetric ss-diesters, dissymmetric ss-diketones, and ss-keto amides. This method efficiently leverages product epimerization in solution. Mechanistic studies suggest that the initial enantioselective, diastereodivergent skeletal assembly is catalyzed by a chiral tertiary amine organocatalyst, followed by crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Review
Chemistry, Multidisciplinary
Huiting Lv, Yongli Du, Haibin Zhang, Yong Zheng, Zhijia Yan, Ning Dong
Summary: Mannich-type reactions utilize active alpha-H compounds, amines, and aldehydes to synthesize valuable beta-aminocarbonyl compounds. The yield, selectivity, and regioselectivity of the reaction are influenced by catalysts and the structural characteristics of the substrates. This article summarizes the developments in symmetric and asymmetric Mannich-type reactions according to the type of substrates and analyzes the factors affecting reaction outcomes.
Article
Chemistry, Multidisciplinary
Zhibing Weng, Ying Zhou, Xin Yue, Feng Jiang, Wengang Guo
Summary: In this study, catalytic asymmetric alpha-regioselective Michael additions of vinylogous alpha-ketoester enolates were conducted efficiently using a chiral bifunctional organocatalyst. The reactions yielded Rauhut-Currier type products with high yields and excellent regio- and enantioselectivities.
Article
Biochemistry & Molecular Biology
Marta Gil-Ordonez, Camille Aubry, Cristopher Nino, Alicia Maestro, Jose M. Andres
Summary: A series of N-Boc ketimines derived from pyrazolin-5-ones have been successfully used as electrophiles in enantioselective Mannich reactions with different 1,3-dicarbonyl compounds. The reaction enables the synthesis of 4-amino-5-pyrazolone derivatives with diverse structures, including the beta-diketone and pyrazolinone substructures. The use of a quinine-derived bifunctional squaramide as an organocatalyst with a very low loading proves to be highly effective in terms of yield and enantioselectivity. The obtained products can be further transformed into enantioenriched diheterocyclic systems, which show potential as drug candidates.
Article
Chemistry, Organic
Li Hui, Yin Liang
Summary: Vinylogous reaction is an efficient tool to introduce new functional groups at the gamma-position or more remote positions of the parent functional group. The resulting highly functionalized structures are widely present in natural products, biologically active compounds, and pharmaceuticals, and serve as important synthetic intermediates. The focus of our group is the development of efficient direct vinylogous reactions using copper catalysts, particularly in the catalytic asymmetric variants.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Remi Andres, Fenggang Sun, Qian Wang, Jieping Zhu
Summary: An asymmetric Pictet-Spengler reaction of alpha-ketoesters was developed, achieving high yields and ee values. The reaction mechanism was proposed to involve deprotonation of the pentahydro-beta-carbolinium ion as the rate- and enantioselectivity-determining step. This methodology was successfully applied in the enantioselective total synthesis of (+)-alstratine A, and the remeasurement of its [a](D) value revealed a correction in the initial report.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Patricia Cmelova, Peter Sramel, Barbora Zahradnikova, Viktoria Modrocka, Henrich Szabados, Maria Meciarova, Radovan Sebesta
Summary: This paper presents the synthesis and evaluation of a bifunctional organic catalyst that can efficiently catalyze the selective synthesis of polyfunctional molecules. The hybrid organocatalysts consist of Pro-Pro dipeptide and thiourea moiety connected via a 1,2-diaminocyclohexane unit.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Hao Chen, Arup Mondal, Philipp Wedi, Manuel van Gemmeren
Article
Chemistry, Organic
Kiron K. Ghosh, Alexander Uttry, Aylin Koldemir, Mike Ong, Manuel van Gemmeren
Review
Chemistry, Organic
Alexander Uttry, Manuel van Gemmeren
SYNTHESIS-STUTTGART
(2020)
Article
Chemistry, Multidisciplinary
Hao Chen, Mirxan Farizyan, Francesca Ghiringhelli, Manuel van Gemmeren
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Chemistry, Multidisciplinary
Kiron Kumar Ghosh, Alexander Uttry, Arup Mondal, Francesca Ghiringhelli, Philipp Wedi, Manuel van Gemmeren
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Review
Chemistry, Organic
Hao Chen, Mirxan Farizyan, Manuel van Gemmeren
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Review
Chemistry, Organic
Johannes E. Erchinger, Manuel van Gemmeren
Summary: This article discusses the combination of electrochemistry and Pd-catalyzed C-H activation/functionalization to achieve C-C, C-X, C-O, and C-P bond formation.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Arup Mondal, Manuel van Gemmeren
Summary: Alkynes are important motifs in organic synthesis due to their presence in natural products and bioactive molecules. The method of inserting alkynes into (hetero)arenes relies heavily on the regioselectivity of the halogenation step, and can achieve selective alkynylation of thiophenes. The developed palladium-catalyzed C-H activation/alkynylation of thiophenes allows for regiodivergent reactions and late-stage modifications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Francesca Ghiringhelli, Alexander Uttry, Kiron Kumar Ghosh, Manuel Van Gemmeren
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Editorial Material
Chemistry, Multidisciplinary
Sabine Bognar, Manuel van Gemmeren
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Sabine Bognar, Manuel van Gemmeren
Summary: A synthetically simple general one-step protocol was developed for the selective synthesis of a broad range of unsymmetrical dithioacetals consisting of one aromatic and one aliphatic thiol moiety. The mixed S,S-acetals were obtained in high yields, demonstrating excellent selectivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Philipp Wedi, Mirxan Farizyan, Klaus Bergander, Christian Mueck-Lichtenfeld, Manuel van Gemmeren
Summary: Recent discovery of palladium catalysts has enabled direct-group-free C-H activation of arenes without excess substrate, allowing for late-stage modification of complex organic molecules. The success lies in the use of two complementary ligands, N-acyl amino acid and N-heterocycle. Mechanistic studies have identified catalytically active species and a transition state model that explains the exceptional activity and selectivity of these catalysts, with potential for further method development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Alexander Uttry, Sourjya Mal, Manuel van Gemmeren
Summary: The study describes the late-stage deuteration of free carboxylic acids and enables the functionalization of non-activated methylene beta-C(sp(3))-H bonds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Carlos Santiago, Hao Chen, Arup Mondal, Manuel van Gemmeren
Summary: In this study, dual ligand-based palladium catalysts were used for late-stage olefination of arenes, successfully functionalizing complex arene substrates. The method utilizes the arene as a limiting reactant and controls the regioselectivity of the transformation by the steric and electronic properties of the substrate, providing a new pathway for preparing regioisomers.
Article
Chemistry, Organic
Manuel van Gemmeren, Benjamin List
Summary: This article details the development of Select Crowd Reviewing from the initial idea through a pilot phase to its current status as the default method for evaluating manuscripts at Synlett and SynOpen. The workflow for manuscript evaluation using Select Crowd Reviewing is described, along with a discussion of the advantages it offers compared to traditional peer review.