Article
Chemistry, Organic
James C. Anderson, Eva Bouvier-Israel, Christopher D. Rundell, Xiangyu Zhang
Summary: The method synthetizes functionalized piperidines with 3 contiguous stereocentres using diastereoselective nitro-Mannich and reductive cyclization reactions, yielding stereochemically pure products in 19-57% yield.
Article
Chemistry, Physical
Helya J. Ghazvini, Hormoz Khosravi, Saber Mirzaei, Saeed Balalaie, Bernhard Breit
Summary: An innovative method for the selective formation of Z-vinyl-functionalized oxazoles via a rhodium-catalyzed nucleophilic addition of alpha-acidic isocyanoacetamides to allenes is described. By employing diverse isocyanoacetamides and allenes, a library of vinyl oxazoles can be efficiently synthesized in a stereo- and regiospecific manner. Mechanistic investigations reveal that the reaction proceeds through a concise rhodium-catalyzed ene reaction followed by reductive elimination.
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.
Article
Chemistry, Multidisciplinary
Aurelien Coelho, Mahasoa-Salina Souvenir Zafindrajaona, Alexis Vallee, Jean-Bernard Behr, Jean-Luc Vasse
Summary: The diastereoselective access to cyclopentanols and N,O-dimethylcyclopentylhydroxylamines from 4-pentenoic acid-derived Weinreb amides is described in this study, demonstrating a significant potential for future research.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Zhishuang Wang, Youwen Fei, Chongrong Tang, Lei Cui, Jie Shen, Kun Yin, Shanya Lu, Jian Li
Summary: The multicomponent protocol reported in this study allows for the assembly of several polycyclic dihydropyran-fused tetrahydroquinoline structures with excellent diastereoselectivity, using simple feedstocks to achieve a series of diverse structures that are difficult to attain by traditional sequences.
Article
Chemistry, Physical
Jeffrey S. Johnson, William R. Cassels, Evan T. Crawford
Summary: A simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction was disclosed for the synthesis of stereodefined alpha-monosubstituted-keto esters, dissymmetric diesters, dissymmetric diketones, and keto amides that productively leveraged product epimerization in solution. Mechanistic studies suggested that the initial enantioselective, diastereodivergent skeletal assembly was catalyzed by a chiral tertiary amine organocatalyst, which then facilitated second stage crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Article
Chemistry, Organic
Yuji Liu, Zhiwei Zeng, Wei Huang, Jean'ne M. Shreeve, Yongxing Tang
Summary: In this study, a mild and efficient method for synthesizing 5-nitro-1,2,4-triazol-3-one (TO) was reported. The synthesized compounds were fully characterized and one of them (Compound 2) showed promising properties as a high-performance insensitive energetic material.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Valentina Marras, P. Caboni, Francesco Secci, Regis Guillot, David J. Aitken, Angelo Frongia
Summary: A novel Bronsted acid catalyzed tandem reaction efficiently converts anilines and 2-alkylenecyclobutanones into highly functionalized cyclobuta-fused tetrahydroquinoline carboxylic esters with good to high yield. The reaction also achieves a dynamic diastereoselective cyclization, leading to the formation of three contiguous stereocenters with high stereoselectivity.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Applied
Benedetta Bassetti, Roberto Ballini, Marino Petrini, Alessandro Palmieri
Summary: In this study, a new and selective method for converting beta-nitro-beta,gamma-unsaturated ketones into conjugated dienones was reported. These dienones are electron-poor alkenes that are widely used in organic synthesis to obtain highly functionalized molecules. The method showed good yields and tolerance to various functional groups.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Xiaodong Gu, Qingwei Du, Weijian Song, Jun (Joelle) Wang
Summary: An efficient and practical method for synthesizing heterocyclic nucleosides is developed, employing a catalyst-free [3+2] annulation reaction between alpha-purine-substituted acrylates and nitrones. The reaction exhibits excellent tolerance towards functional groups and is conducted under mild conditions, using the green and sustainable solvent 2-methyltetrahydrofuran (2-MeTHF). Unlike other reactions with electron-deficient olefin dipolarophiles, different regioselective cycloaddition products were observed in this study. The resulting isoxazolidinyl nucleosides demonstrate good to excellent yields and hold promising applications in biochemistry and medicinal chemistry.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Taiwei Dong, Peifeng Wei, Min Li, Feng Gao, Yuan Qin
Summary: This study has successfully developed a highly efficient strategy for constructing tetrahydroquinoline derivatives using a [4+2] annulation reaction, achieving high yields, excellent diastereoselectivities, broad functional group tolerance, and the capacity for gram-scale production.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Organic
Jie Feng, Hui Liu, Yun Yao, Chong-Dao Lu
Summary: A series of alpha-mercapto-beta-amino acid derivatives were successfully synthesized through azaenolization of alpha-sulfanyl N-tert-butanesulfinylimidates and their nucleophilic addition to N-tosyl imines via a Mannich-type reaction. The resulting derivatives bearing a beta-sulfonylamino sulfide moiety participated in various inter- and intramolecular transformations.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jingdong Wang, Yuxin Liu, Zhonglin Wei, Jungang Cao, Dapeng Liang, Yingjie Lin, Hai-feng Duan
Summary: A series of chiral thiourea compounds with multiple H-bond donors derived from hydroquinine have been reported. The aza-Henry reaction of isatin-derived ketimines and long-chain nitro-alkanes catalyzed by these chiral thioureas shows high enantioselectivity and excellent diastereoselectivity. This work represents the first report on long-chain nitroalkanes as substrates with excellent diastereoselectivity in metal-free catalytic systems.
Article
Chemistry, Multidisciplinary
Andrew J. Tague, Quoc Hoang Pham, Christopher Richardson, Stephen G. Pyne, Christopher J. T. Hyland
Summary: A formal palladium-catalyzed decarboxylative (4+2) cycloaddition reaction has been developed to produce highly valuable tetrahydroquinolines in moderate to excellent yields with high diastereoselectivity. The reaction protocol can tolerate a range of substituted 2-nitro-1,3-enynes, which are an under-utilized class of dipolarophiles. The tetrahydroquinoline products obtained feature numerous pendant functionalities for further synthetic manipulations.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Philip J. Chevis, Chi Bong Eric Chao, Christopher Richardson, Christopher Hyland, Richmond Lee, Stephen G. Pyne
Summary: The crotylation reactions of chiral α-F, α-OBz and α-OH aldehydes were carried out under Petasis-borono-Mannich conditions using (E)- or (Z)-crotylboronates and primary amines. The reactions resulted in γ-addition products with high diastereoselectivity and enantioselectivity. The stereochemical outcomes of the reactions could be explained using transition state models and were supported by DFT calculations. Representative products were transformed into highly functionalized 1,2,3,6-tetrahydropyridines and 3H-oxazolo[3,4-a]pyridine-3-ones, which are valuable scaffolds in synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jasper L. Tyler, Adam Noble, Varinder K. Aggarwal
Summary: The strain-release-driven Friedel-Crafts spirocyclization of azabicyclo[1.1.0]butane-tethered (hetero)aryls has been developed to synthesize a unique library of azetidine spiro-tetralins with high complexity, showing great potential in drug discovery programs. This method highlights the rapid assembly of molecular complexity and the potential of the strain-release-driven spirocyclization strategy for the synthesis of medicinally relevant scaffolds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Mark J. Deeprose, Martin Lowe, Adam Noble, Kevin Booker-Milburn, Varinder K. Aggarwal
Summary: This study demonstrates a method for the synthesis of densely functionalized cyclobutanes with high regio- and diastereoselectivity, utilizing a sequential photocatalysis strategy to rapidly assemble structurally complex 3-azabicyclo[3.2.0] heptane scaffolds. The installation of all-carbon quaternary stereocenters is achieved through triplet sensitized [2 + 2] photocycloadditions followed by photoredox-catalyzed dechlorinative C-C bond forming reactions.
Article
Chemistry, Multidisciplinary
Hui Wang, Jingjing Wu, Adam Noble, Varinder K. Aggarwal
Summary: In this study, a coupling reaction is reported that enables the reversal of traditional selectivity for functionalization of primary boronic esters. This is achieved through the formation of a boronate complex with an electron-rich aryllithium, followed by reaction with an electron-deficient aryl nitrile to form an electron donor-acceptor complex. Visible-light photoinduced electron transfer generates a primary radical, which isomerizes to a more stable secondary radical and undergoes radical-radical coupling with the arene radical-anion, resulting in the formation of beta-aryl primary boronic ester products. Furthermore, this method allows for stereodivergent coupling, providing trans-substituted products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Molly E. Fairchild, Adam Noble, Varinder K. Aggarwal
Summary: This study reported the synthesis of cyclopentyl boronic esters bearing two contiguous, fully substituted stereocenters via electrophile-induced ring contractive 1,2-metallate rearrangement, with diastereodivergent construction achieved by simple variation of the reaction solvent. The utility of this methodology was demonstrated in the asymmetric total synthesis of (+)-herbertene-1,14-diol.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Daniele Fiorito, Selbi Keskin, Joseph M. Bateman, Malcolm George, Adam Noble, Varinder K. Aggarwal
Summary: This study presents a strategy for the stereocontrolled synthesis of 1,5-polyols using enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled with full control over the remote stereocenters.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Dominik Reich, Adam Noble, Varinder K. Aggarwal
Summary: Amino phosphonates are highly effective inhibitors in various biological processes due to their unique structural and electronic properties. They find numerous applications as enzyme inhibitors, herbicides, antiviral, antibacterial, and antifungal agents. This study presents a novel and convenient method utilizing visible-light organophotocatalysis to convert activated derivatives of alpha-amino acids directly into their respective alpha-amino phosphonate counterparts, demonstrating broad applicability, mild reaction conditions, and successful late-stage functionalization of drug molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Hui Wang, Wangyujing Han, Adam Noble, Varinder K. Aggarwal
Summary: This study reports a nickel/photoredox-catalyzed site-selective mono-deboronative arylation of 1,2-bis-boronic esters, which allows for selective coupling of the more sterically hindered secondary/tertiary positions. This is achieved by utilizing a 1,2-boron shift of primary β-boryl radicals to the thermodynamically favored secondary/tertiary radicals for arylation. The mild conditions of this method are suitable for a wide range of aryl halides, resulting in good yields and high regioselectivity. Additionally, this method allows for stereodivergent coupling of cyclic cis-1,2-bis-boronic esters to give trans-substituted products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Bernhard Wolfl, Nils Winter, Jiajing Li, Adam Noble, Varinder K. Aggarwal
Summary: The development of preparative methods for the synthesis of four-membered carbocycles is important for their utility in medicinal chemistry. A new methodology for producing spirocyclic epoxides and aziridines with a cyclobutane motif was developed. The reaction is efficient and can tolerate a broad variety of substrates. The products can be used as modular building blocks for introducing three-dimensional structures into target molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sheenagh G. Aiken, Joseph M. Bateman, Hsuan-Hung Liao, Alexander Fawcett, Teerawut Bootwicha, Paolo Vincetti, Eddie L. Myers, Adam Noble, Varinder K. Aggarwal
Summary: In this study, a highly efficient iterative strategy for the synthesis of polyacetates based on boronic ester homologation was reported. It does not require functional group manipulation between iterations. This methodology has been applied to the synthesis of bahamaolide A and has demonstrated versatility in various stereospecific transformations.
Article
Chemistry, Organic
Joseph C. Abell, Christian P. Bold, Laia Vicens, Tom Jentsch, Noelia Velasco Perez, Jasper L. Tyler, Robert N. Straker, Adam Noble, Varinder K. Aggarwal
Summary: Aza-spirocycles, highly rigid and three-dimensional structures, have been incorporated into pharmaceuticals due to their beneficial pharmacokinetic properties. We report a simple synthesis of spirocyclic dihydropyridines through an electrophile-induced dearomatization reaction, which offers the potential for rapid assembly of medicinally relevant spirocycles.
Article
Chemistry, Multidisciplinary
Jingjing Wu, Chao Shu, Zhihang Li, Adam Noble, Varinder K. Aggarwal
Summary: This article describes a visible-light photoredox-catalyzed decarboxylative halogenation reaction using inexpensive inorganic halide salts as halogenating agents. Bromination with lithium bromide can be achieved using an organic photoredox catalyst under simple conditions, while chlorination requires dual photoredox-copper catalysis. The reaction exhibits excellent functional group tolerance and can convert structurally complex natural products into alkyl bromides and chlorides. Additionally, the method is also applicable to thiocyanation reactions with potassium thiocyanide for the synthesis of alkyl thiocyanates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Kristian J. Chambers, Patthadon Sanghong, Daniel Carter Martos, Giorgia Casoni, Rory C. Mykura, Durga Prasad Hari, Adam Noble, Varinder K. Aggarwal
Summary: Enones are important functional groups in chemical synthesis and molecular biology. This study developed a one-pot strategy for the stereospecific conversion of boronic esters into enones using methoxyallene as a three-carbon building block. The methodology is versatile and has been successfully applied to the total synthesis of polyketide 10-deoxymethynolide.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ruocheng Sang, Wangyujing Han, Hanwen Zhang, Carla M. Saunders, Adam Noble, Varinder K. Aggarwal
Summary: Copper catalysts can promote the dehydrogenative borylation of alkanes with bis(catecholato)diboron under oxidant-free conditions. This is due to the unexpected dual role of the copper catalyst, which promotes the oxidation of the diboron reagent and generates an electrophilic bis-boryloxide that acts as an effective borylating agent in subsequent redox-neutral photocatalytic C-H borylations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Santosh K. K. Pagire, Chao Shu, Dominik Reich, Adam Noble, Varinder K. K. Aggarwal
Summary: Carbon-phosphorus bond formation is important in synthetic chemistry due to the essential biochemical roles of phosphorus-containing compounds. However, the synthesis of aliphatic phosphonates through phosphonylation of alkyl radicals is rarely used. In this study, a phosphorus radical trap called BecaP is introduced, which enables efficient phosphonylation of alkyl radicals under visible light photocatalytic conditions. The ambiphilic nature of BecaP allows redox neutral reactions with both nucleophilic and electrophilic alkyl radical precursors. This method is applicable for late-stage installation of phosphonate motifs into medicinal agents and natural products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hong-Cheng Shen, Mihai V. Popescu, Ze-Shu Wang, Louis de Lescure, Adam Noble, Robert S. Paton, Varinder K. Aggarwal
Summary: We report an iridium-catalyzed asymmetric alkylation-induced 1,2-metalate rearrangement of bicyclo[1.1.0]butyl boronate complexes enabled by strain release. This method allows for the asymmetric difunctionalization of C-C bonds, including dicarbonation and carboboration, providing a variety of enantioenriched three-dimensional cyclobutane products. The diastereoselectivity of the reaction has been rationalized based on experimental data and density functional theory calculations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Geeta Devi Yadav, Pooja Chaudhary, Balaram Pani, Surendra Singh
Summary: Chiral transition metal complexes with privileged ligands are efficient catalysts for various asymmetric organic transformations. Transition metal complexes of C1-symmetric pyrrolidine-based ligands have been widely used in asymmetric organic reactions. However, a comprehensive review article on the transition metal complexes of chiral C1-symmetric pyrrolidine-based ligands derived from (L)-proline has not been published.
TETRAHEDRON LETTERS
(2024)
