Article
Chemistry, Organic
Anding Li, Ziru He, Bingyan Liu, Zhen Yang, Zichun Zhang
Summary: In this study, a concise and stereoselective total synthesis of (+/-)-cephanolide B was accomplished in 15 steps. The key steps in the synthesis included an intermolecular Diels-Alder reaction, a tandem reaction featuring intramolecular Pauson-Khand reaction, 6 pi-electrocyclization, and oxidative aromatization to construct the ABC-tricyclic rings (6-5-6), as well as a phthaloyl peroxide-mediated arene oxygenation to install the C-13 phenol group.
Article
Chemistry, Multidisciplinary
Annah E. Kalb, Mingxin Liu, Megan Bosso, Christopher Uyeda
Summary: A dinickel catalyst is used to promote the [2 + 2 + 1]-cycloaddition reaction of two aldehyde equivalents and a vinylidene, leading to the synthesis of unsymmetrical alkyl-substituted α-hydroxy ketones. Mechanistic studies show that migratory insertion of the aldehyde and C-O reductive elimination are crucial steps, and under dilute conditions, an enone side product is formed due to competing β-hydride elimination.
Article
Chemistry, Multidisciplinary
Deevi Basavaiah, Gangadhararao Golime, Shivalal Banoth, Saidulu Todeti
Summary: This study presents the first example of an umpolung strategy for intermolecular [2 + 2 + 1] cycloaddition between two aryl aldehydes and a nitrile, resulting in the formation of N-C, O-C, and C-C bonds and providing a straightforward synthetic protocol for obtaining 2,4,5-trisubstituted oxazoles.
Article
Chemistry, Multidisciplinary
Hui Wang, Yi Liu, Hongyuan Zhang, Baochao Yang, Haibing He, Shuanhu Gao
Summary: The asymmetric total syntheses of cephalotaxus C19 diterpenoids, which possess a unique cycloheptene A ring with a chiralmethyl group at C-12, were achieved using a universal strategy. Six members, including previously unreported compounds, were successfully synthesized. The concise approach involved a Nicholas/Hosomi-Sakurai cascade reaction to generate the cycloheptene ring with a chiral methyl group, followed by an intramolecular Pauson-Khand reaction for the construction of the target molecules' complete skeleton. This work provides a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related natural products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Zhen Yang
Summary: The total synthesis endeavors contribute to the discovery and invention of new synthetic reactions to advance organic synthesis. Bioactive compounds share common features, such as molecular complexity, protein-binding ability, structural rigidity, and three-dimensionality. Total synthesis offers an alternative solution for generating scarce natural products and their derivatives for studying their biological functions.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Ridge Michael P. Ylagan, Eric Jaewon Lee, Daniela E. Negru, Paolo Ricci, Bohyun Park, Haram Ryu, Mu-Hyun Baik, P. Andrew Evans
Summary: We report an enantioselective rhodium(I)-catalyzed Pauson-Khand reaction using 1,6-chloroenynes that contain challenging 1,1-disubstituted olefins. Unlike previous studies, this new approach allows for a wider range of substrates, including both carbon and heteroatom tethers with polar and non-polar substituents on the alkene. DFT calculations reveal the critical role of the halide, which pre-polarizes the alkyne and provides the appropriate steric profile for a favorable interaction with the chiral diphosphine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lisa-Catherine Rosenbaum, Maximilian Haefner, Tanja Gaich
Summary: A racemic and scalable enantioselective total synthesis of (+)-waihoensene was achieved, featuring an angular triquinane substructure with an all-cis-fused tetracyclic backbone and six contiguous stereocenters, four of which are quaternary. Enantioselectivity was introduced at an early stage, and key structural features were efficiently installed through several diastereoselective reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Paul Shaw, Storm J. Hassell-Hart, Gayle E. Douglas, Andrew G. Malcolm, Alan R. Kennedy, Gemma White, Laura C. Paterson, William J. Kerr
Summary: In this study, we applied silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers valuable oxygenated cyclopentenone products in high yields and allows for the incorporation of a variety of decorated structures.
Review
Chemistry, Multidisciplinary
Rosalie S. Doerksen, Tomas Hodik, Guanyu Hu, Nancy O. Huynh, William G. Shuler, Michael J. Krische
Summary: This article summarizes ruthenium-catalyzed cycloadditions to form five-, six-, and seven-membered rings, with a focus on applications in natural product total synthesis. The content is organized by ring size and reaction type, emphasizing processes that involve the formation of at least one C-C bond. Processes involving stoichiometric ruthenium, dehydrogenative condensation-reduction, s-bond activation-initiated annulations without net reduction of bond multiplicity, and photochemically promoted ruthenium-catalyzed cycloadditions are not covered.
Review
Chemistry, Organic
Sambasivarao Kotha, Ambareen Fatma
Summary: This article highlights various synthetic methodologies related to tetraquinane frameworks in crinipellin derivatives, including different synthetic strategies and emphasis on the core structure research.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Jorge Escorihuela
Summary: In this study, density functional theory calculations are used to clarify the mechanism and reactivity of enynes containing a vinyl fluoride moiety for the Co2(CO)(8)-mediated intramolecular Pauson-Khand reaction. The results show that alkene insertion is the rate-determining step for this reaction. The effect of substituents on the reaction has also been investigated, with fluorinated enynes having lower reactivity compared to malonate homologues.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
Article
Chemistry, Organic
Chong-Chong Chen, Zhiqiang Ren, Zhongliu Sun, Zezhong Sun, Xin Shu, Yunxia Wang, Xiangdong Hu
Summary: Cephalotaxus diterpenoids are attractive natural products with diverse chemical structures and valuable biological activities. This study developed a diastereoselective Pauson-Khand reaction as an effective strategy for synthesizing the core structure of these compounds, leading to the total synthesis of several compounds.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tianhao Ma, Hao Cheng, Mallesham Pitchakuntla, Weihao Ma, Yanxing Jia
Summary: We have achieved the first total synthesis of (-)-principinol C, which is a natural product with an intriguing and complex 5/7/6/5 tetracyclic skeleton and eight contiguous stereocenters. The key step in assembling the 5/7/6/5 tetracyclic skeleton was the intramolecular Pauson-Khand reaction. This synthetic route represents the first application of intramolecular Pauson-Khand reaction of enyne to construct the 7,5-bicyclic ring system in natural product synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yi Wang, Wei Liao, Yuanyuan Wang, Lei Jiao, Zhi-Xiang Yu
Summary: Through a 15-year investigation, we have delved into the mechanism of the [5 + 2 + 1] cycloaddition, identifying key steps in the catalytic cycle and elucidating the stereochemistry and chemical selectivity of the reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Pep Rojo, Antoni Riera, Xavier Verdaguer
Summary: The efficient electrophilic P-stereogenic transfer reagent BOM-tert-butylmethylphosphinite borane was used for the synthesis of bulky tertiary phosphines with high stereospecificity in a one-pot deprotection/substitution reaction. A wide range of tertiary phosphines in excellent enantiomeric excess was synthesized using this method, including a bulky P-stereogenic BisP* ligand analogue.
Review
Chemistry, Multidisciplinary
Albert Cabre, Xavier Verdaguer, Antoni Riera
Summary: This review provides an overview of the recent advances in the asymmetric hydrogenation (AH) synthesis of chiral amines reported from 2010 to 2020. Various types of chiral amines, including imines, enamides, enamines, allyl amines, and N-heteroaromatic compounds, are discussed.
Article
Chemistry, Multidisciplinary
Pep Rojo, Medea Molinari, Albert Cabre, Clara Garcia-Mateos, Antoni Riera, Xavier Verdaguer
Summary: Chiral compounds containing nitrogen heteroatoms are crucial for the chemical, pharmaceutical, and agrochemical industries. In this study, a series of P-stereogenic phosphinooxazoline iridium catalysts were synthesized and successfully used in the asymmetric hydrogenation of N-Boc-2,3-diarylallyl amines, achieving high enantioselectivity. The synthetic utility of the obtained 2,3-diarylpropyl amines was also demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Guillem Loren, Irene Espuny, Alicia Llorente, Craig Donoghue, Xavier Verdaguer, Roger R. Gomis, Antoni Riera
Summary: In the treatment of breast cancer, targeting the estrogen receptor signaling pathway has been a major strategy. However, resistance to hormone blockade is a common issue. This study designed and synthesized a series of proteolysis targeting chimeras (PROTACs) that can induce the degradation of estrogen receptor alpha in breast cancer cells. TVHL-1, a potent ERα degrader, was discovered and could serve as a valuable tool for biological study and potential therapeutics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Marina Bellido, Carlos Riego-Mejias, Alejandro Diaz-Moreno, Xavier Verdaguer, Antoni Riera
Summary: A novel method for preparing chiral methyl benzylic compounds is described, involving the preparation of terminal homoallyl sulfones from homoallyl alcohols through Lewis acid isomerization of oxetanes. Asymmetric hydrogenation of these homoallylic sulfones using an iridium catalyst yielded gamma-chiral sulfones with high enantioselectivities (up to 98% ee). The synthetic potential of this method was demonstrated through the total synthesis of (R)-(-)-curcumene.
Article
Chemistry, Physical
Maria Biosca, Pol de la Cruz-Sanchez, Jorge Faiges, Jessica Margalef, Ernest Salomo, Antoni Riera, Xavier Verdaguer, Joan Ferre, Feliu Maseras, Maria Besora, Oscar Pamies, Montserrat Dieguez
Summary: Ir-MaxPHOX-type catalysts exhibit high catalytic performance in the hydrogenation of a wide range of nonchelating olefins with different geometries, substitution patterns, and degrees of functionalization. These air-stable and readily available catalysts have been successfully used in the asymmetric hydrogenation of di-, tri-, and tetrasubstituted olefins (ee ' s up to 9996). The combination of theoretical calculations and deuterium labeling experiments has revealed the factors responsible for the observed enantioselectivity, allowing for the rationalization of suitable substrates for these Ircatalysts.
Review
Chemistry, Inorganic & Nuclear
Pep Rojo, Antoni Riera, Xavier Verdaguer
Summary: Since the development of BisP* ligand by Imamoto, P-stereogenic phosphines bearing a bulky tert-butyl group and a smaller alkyl group have shown remarkable performance in various asymmetric processes. Advances in this class of ligands include the introduction of more rigid backbones, the three-hindered quadrant concept, and the substitution of tert-butyl group with adamantyl. The industrial sector has also contributed by reporting successful P-stereogenic Buchwald-type monophosphines for asymmetric coupling reactions. This review focuses on the synthesis and applications of bulky P-stereogenic phosphines developed since the late 1990s, with a special emphasis on ligands successfully applied in asymmetric catalysis.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Enric Ros, Marina Bellido, Joan A. Matarin, Albert Gallen, Manuel Martinez, Laura Rodriguez, Xavier Verdaguer, Lluis Ribas de Pouplana, Antoni Riera
Summary: A set of 3-bromo-1,2,4,5-tetrazines with distinct substitutions have been used as reagents for late-stage functionalization. Spectroscopic studies showed that tetrazine ethers are intrinsically fluorescent and this fluorescence can be lost through iEDDA cycloaddition. Tetrazine-phenol ethers can undergo rapid iEDDA reactions with a second order rate constant compatible with bioorthogonal ligations. The coupling of 3-bromo-6-methyl-1,2,4,5-tetrazine with l-tyrosine and octreotide demonstrated the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo.
