Article
Chemistry, Applied
Romain Melot, Sandra Olivero, Veronique Michelet
Summary: A synthetic route for alkynylated saturated N-heterocycles was developed via a sequential combination of Shono oxidation and gold(I)-catalyzed alkynylation reaction. The electrochemical Shono oxidation enabled efficient access to various N,O-acetals through direct C-H bond functionalization of cyclic amines. The gold-catalyzed process allowed the introduction of aryl acetylene partners with different electron properties. Promising initial results on asymmetric version were obtained.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Zhenwei Lv, Yan Li, Erik V. Van der Eycken, Lingchao Cai, Liangliang Song
Summary: Here, we report a metal-free cascade cyclization reaction that constructs structurally novel polyheterocycles by utilizing a hypervalent iodine(III) reagent. Under ambient conditions, alkyne-tethered N-alkoxybenzamides undergo a 6-exo-dig cyclization/dearomatization process to generate diverse N-O fused spiro polyheterocycles in good to high yields. This method features short reaction times, broad substrate scope, easy handling, and shows promising antifungal activity against crop and forest pathogenic fungi.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Zhenwei Lv, Yan Li, Erik V. Van der Eycken, Lingchao Cai, Liangliang Song
Summary: In this study, a metal-free cascade cyclization method was developed for the construction of structurally novel polyheterocycles. The approach involves the use of a hypervalent iodine(iii) reagent and generates diverse N-O fused spiro polyheterocycles in high yields. The synthesized compounds exhibit good antifungal activity against crop and forest pathogenic fungi, with one compound showing superior performance compared to the positive control.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Rupkumar Khuntia, Sanat Kumar Mahapatra, Lisa Roy, Subhas Chandra Pan
Summary: In this study, a new method has been developed to rapidly synthesize structurally diverse and complex molecules from easily available starting materials through catalytic reactions. Through the analysis of the mechanistic intricacies, the roles of chiral and Lewis base catalysts in the reaction have been investigated.
Article
Chemistry, Multidisciplinary
Rupkumar Khuntia, Sanat Kumar Mahapatra, Lisa Roy, Subhas Chandra Pan
Summary: An important goal in organic synthesis and medicinal chemistry is to efficiently and affordably synthesize structurally diverse and complex molecules from readily available starting materials. In this study, a protocol for the synthesis of benzofuran fused azocine derivatives and spiro-cyclopentanone benzofurans has been developed. The method involves sequential catalysis with chiral H-bonding catalyst and Lewis base catalyst. The products exhibit high yields and high stereo- and enantioselectivities.
Article
Chemistry, Multidisciplinary
Ndidi U. N. Iwumene, Daniel F. Moseley, Robert D. C. Pullin, Michael C. Willis
Summary: Rhodium-catalyzed hydroacylation reactions can be used to synthesize linear α,β-unsaturated enone intermediates, which can be used to construct diverse substituted saturated O-, N-, and S-heterocycles in a one-pot process. The reaction conditions can be adjusted to selectively form O-heterocycles with high levels of diastereoselectivity.
Article
Chemistry, Organic
Suven Das
Summary: This review focuses on the recent (2015-2021) applications of 1,3-indanedione in organic transformations, particularly in the construction of fused and spiro scaffolds. The synthesis of nitrogen- and oxygen-containing fused heterocyclic systems is illustrated, as well as the formation of complex spiro-heterocycles/carbocycles. The described reactions generally involve readily available starting materials, cheap catalysts, one-pot under mild conditions, and environmentally friendly processes.
Article
Chemistry, Organic
Charis Amber Roberts, Bohyun Park, Li-Ping Xu, Jose B. Roque, Charles S. Yeung, Djamaladdin G. Musaev, Richmond Sarpong, Rebecca Lyn LaLonde
Summary: Methods focusing on functionalizing the periphery of azacyclic scaffolds have become increasingly popular. Experimental observations show that the regioselectivity of C-C cleavage can be altered by changing the ligand set used in the coupling chemistry.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Kota Koshino, Kenji M. Kojima, Iain McKenzie, Shigekazu Ito
Summary: This study investigated the radical reactivity of 10-mesityl-1,8-bis(trifluoromethyl)-9-phosphaanthracene using muon spin rotation/resonance (muSR) techniques, identifying a paramagnetic species generated by regioselective addition. Density functional theory calculations revealed two possible isomers for the P-muonium product, with the metastable planar pi-conjugated structure showing experimentally determined hyperfine coupling constants. The promotion of this metastable structure is attributed to the larger zero-point energy due to the light muon, one ninth of the proton mass.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Bita Manavi, Hossein Zahedian Tejeneki, Frank Rominger, Mahsa Armaghan, Walter Frank, Hamid Reza Bijanzadeh, Saeed Balalaie
Summary: This report discusses two distinctive intramolecular cyclizations of o-propargyloxy diketopiperazines achieved via a copper(I)-catalyzed reaction, offering an opportunity for the synthesis of challenging Diazabicyclics and Spiro-Diketopiperazinochromanes with high yields and exclusive diastereoselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Lian Xue, Xia Song, Xinying Zhang, Xuesen Fan
Summary: An effective and sustainable synthesis of O-heterocycle spiro-fused cyclopentaquinolinone and cyclopentaindene derivatives has been presented through light-driven cascade reactions. The reactions are initiated by visible light-induced radical formation from O-heterocycle, followed by regioselective addition onto acrylamide or acrylate moiety and cascade radical annulation. The newly developed protocol has advantages including broad substrate scope, mild reaction conditions, excellent atom-economy, high efficiency, and good compatibility with diverse functional groups.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Takuya Suga, Masaharu Nakamura, Ryusei Takada, Yutaka Ukaji
Summary: A new method involving low-valent titanium-mediated homolytic C-O bond cleavage for the generation of benzyl radicals from acetals is presented. The developed titanium reagent, which is low cost and easily accessible, enables efficient access to alpha-alkoxy carbon radical species via the reaction.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2021)
Article
Chemistry, Applied
Christian H. Schiwek, Simone Stegbauer, Thomas Pickl, Thorsten Bach
Summary: In this study, a diastereoselective arene hydrogenation reaction was reported and applied to benzo-fused N-heterocycles. A total of 48 saturated heterocycles were obtained by hydrogenation with yields of 72-98% and moderate to high diastereoselectivities.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Chemistry, Organic
Shuyan Yu, Zeyu Liu, Hongbing Lan, Kun Qian, Xiaohua Ding, Zhigang Yin
Summary: This mini-review provides a summary of the synthetic progress of fused bicyclic N,O-acetals. Different reaction types, including hetero-Diels-Alder cycloaddition, step-by-step reactions, [3+2] cycloaddition, and other novel strategies, are elaborated. The catalytic systems and reaction mechanisms are also described in detail.
CURRENT ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Organic
Suven Das
Summary: 3-nitrochromenes, as an important class of organic compounds, have been attracting attention due to their easy availability and versatile reactivity for constructing complex molecular architectures. This review highlights recent advances (2017-2021) in the synthesis of various fused- and spiro scaffolds involving 3-nitrochromene derivatives, focusing on their reaction mechanisms and promising biological activities.
SYNTHETIC COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Nicole Hauser, Michael A. Imhof, Sarah S. Eichenberger, Tomas Kundig, Erick M. Carreira
Summary: The first total syntheses of the indole diterpenoids (+)-shearinine G and D were achieved through late-stage coupling, diastereoselective intramolecular cyclopropanation, Sharpless dihydroxylation/Achmatowicz reaction, and Prins cyclization. Tuning of the substituents on the parent arylcarboxaldehyde led to divergent products, further transformed into shearinines G and D, with unexpected stereochemical outcomes in the Riley-type oxidation of a bicyclic enone.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Nicolas Muller, Benedikt S. Schreib, Sebastian U. Leutenegger, Erick M. Carreira
Summary: In this study, the palladium-catalyzed aminoalkynylation of electronically unbiased olefins with iodoalkynes was reported. Using the picolinamide auxiliary, the syn-selective aminoalkynylation of mono-, di-, and trisubstituted alkenes was achieved, leading to the formation of corresponding pyrrolidines in high yield and single diastereomers. The picolinamide also allowed for the rapid synthesis of functionalized olefins and subsequent Pictet-Spengler reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Moritz E. Hansen, Samuel O. Yasmin, Susanne Wolfrum, Erick M. Carreira
Summary: The first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome, were reported. These natural products were rapidly delivered through a cascade of cyclization reactions using a solid-phase peptide synthesis (SPPS) based route. This versatile process was also used for a streamlined synthesis of mutanobactin D. Additionally, an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block, was provided.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Nils Trapp, Michael Worle, Bernd Kuhn, Paul Gerber, Raffael Vorberg, Erick M. M. Carreira, Klaus Mueller
Summary: The molecular and crystal structures of 19 N-alkyl-substituted pipecolamide derivatives, including partial fluorination patterns, were presented. The different fluorination patterns in the N-alkyl group resulted in diastereomeric compounds with distinct crystal and molecular structures. The study also revealed an extraordinary conformational diversity in the various N-alkylpiperidine units, and provided insight into consistent conformational patterns and their modulation factors.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Supratim Ghosh, Avtar Changotra, David A. Petrone, Mayuko Isomura, Erick M. Carreira, Raghavan B. Sunoj
Summary: In this study, the mechanism of a chiral Ir-phosphoramidite-catalyzed asymmetric reductive deoxygenation reaction was investigated using density functional theory. It was found that Bi(OTf)3 promotes ionic and noncovalent interactions, which play a crucial role in nucleophile selectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: Intermolecular cyclopropanation of mono-, di-, and trisubstituted olefins with alpha-bromo-beta-ketoesters and alpha-bromomalonates under organophotocatalysis is reported. The transformation exhibits broad functional group tolerance, producing highly substituted cyclopropanes. Mechanistic investigations, including Stern-Volmer quenching, quantum yield determination, and deuteration experiments, provide insights into the catalytic cycle.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Marlene Fadel, Erick M. Carreira
Summary: The first total synthesis of (+)-pedrolide, a tigliane-derived diterpenoid featuring an unprecedented 5-5-6-6-3 carbon skeleton, was achieved. A key step in the synthesis involved the construction of the bicyclo[2.2.1]heptane core via an intramolecular cyclopentadiene-Diels-Alder cycloaddition. A norbornadiene was used as a surrogate for cyclopentadiene, and the unmasking of the cyclopentadiene was achieved through a complex Diels-Alder reaction cascade. This synthesis also provided a novel approach to a densely functionalized carane in an efficient and enantioselective manner.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sven M. Papidocha, Hendrik H. Bulthaupt, Erick M. Carreira
Summary: The first total synthesis of heavily oxidized cassane-type diterpenoids, neocaesalpin A, AA, and nominal neocaesalpin K, was achieved using a redox-flexible platform as a key intermediate. The synthesis involved an intermolecular Diels-Alder reaction and a novel late-stage oxidation method for furfuryl acetate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: In this study, unactivated olefins are converted into alkyl azides using bench-stable NaN3 in the presence of FeCl3·6H2O under blue-light irradiation. The reaction exhibits anti-Markovnikov selectivity and can be conducted under mild ambient conditions in the presence of air and moisture.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hendrik H. Bulthaupt, Fabian Glatz, Sven M. Papidocha, Chunyan Wu, Shawn Teh, Susanne Wolfrum, Lucia Balazova, Christian Wolfrum, Erick M. Carreira
Summary: This study reports the synthesis and enantioselectivity of a series of compounds, and reveals the stimulating effect of one of the compounds on the respiration of brown adipocytes, which has potential applications in obesity treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Manuel Freis, Willi M. Amberg, Henry Lindner, Erick M. Carreira
Summary: We have developed a method for difunctionalization of unactivated, terminal olefins using intermolecular addition of alpha-bromoketones, -esters, and -nitriles followed by formation of 4- to 6-membered heterocycles with pendant nucleophiles. The reaction can be conducted with alcohols, acids, and sulfonamides as nucleophiles, yielding products with 1,4 functional group relationships that can be further manipulated. The reaction employs a benzothiazinoquinoxaline organophotoredox catalyst at a low catalyst loading and is tolerant to air and moisture.
Article
Chemistry, Multidisciplinary
Monica Guberman, Miroslav Kosar, Anahid Omran, Erick M. Carreira, Marc Nazare, Uwe Grether
Summary: Labeled chemical probes are crucial for the development and commercialization of drugs. They play a significant role in various research phases and provide valuable tools for specific application needs. The reverse-design approach enables the generation of high-quality probes based on previously optimized small molecules, fostering collaborations between academia and industry.
Article
Chemistry, Multidisciplinary
David M. Fischer, Moritz Balkenhohl, Erick M. Carreira
Summary: The cycloisomerization of beta-, gamma-, and delta-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates using a CoIII(salen) catalyst with t-BuOOH or air as the oxidant is reported in this study. The method exhibits good functional group tolerance and provides a new class of cyclic building blocks. The strong solvent dependence of the transformation and the synthetic versatility of the N-sulfonyl imidate product class are highlighted.