An Improved Process for the Enantioselective Synthesis of HCV NS5A Inhibitor Elbasvir (MK-8742) Chiral Amine Intermediate

2021 ◽  
Vol 91 (5) ◽  
pp. 932-938
Author(s):  
Vijaya Lakshmi Chapala ◽  
Naresh Kumar Katari ◽  
Giri Prasad Malavattu ◽  
Nagaraju Kerru ◽  
Pedavenkatagari Narayana Reddy ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Chiral Amine ◽  
Ns5a Inhibitor

Enantioselective Synthesis of Alcohols and Amines: The Kim Synthesis of (+)-Frontalin

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Imperial College ◽  
Enantioselective Synthesis ◽  
Heinrich Heine ◽  
Max Planck ◽  
Chiral Amine ◽  
P450 Monooxygenase ◽  
Cu Catalyst ◽  
Ready Availability ◽  
The University

Vlada B. Urlacher of the Heinrich-Heine University Düsseldorf showed (Chem. Commun. 2014, 50, 4089) that the P450 monooxygenase CYP154A8 from Nocardia farcinica could monohydroxylate n-octane 1 to 2 with high regioselectivity and ee. Fener Chen of Fudan University used (J. Org. Chem. 2014, 79, 2723) an organocatalyst to open the prochiral anhydride 3 to the monoester 4. Amir H. Hoveyda of Boston College added (Angew. Chem. Int. Ed. 2014, 53, 3387) (pinacolato)borane to the enone 5 to give 6, that was readily oxidized to the tertiary alcohol. Matthias Breuning of the University of Bayreuth designed (Chem. Commun. 2014, 50, 6623) a Cu catalyst for the enantioselective Henry addition of nitromethane to the aldehyde 7 to give 8. Benjamin List of the Max-Planck-Institute für Kohlenforschung optimized (Synlett 2014, 25, 932) the proline-catalyzed formation of the aldol prod­uct 10 from the aldehyde 9. Christian Wolf of Georgetown University devised (Chem. Commun. 2014, 50, 3151) the alkyne 12, that could be added to the aldehyde 11 to give 13 in high ee. Keiji Maruoka of Kyoto University developed (Org. Lett. 2014, 16, 1530) practical conditions for the organocatalyzed addition of an aldehyde 14 to an in situ- generated nitroso urethane, leading, after reduction, to the alcohol 15. Satoko Kezuka of Tokai University added (Tetrahedron Lett. 2014, 55, 2818) the benzyloxyamine 17 to the nitro alkene 16 to give the coupled product 18 in high ee. Xiaohua Liu and Xiaoming Feng of Sichuan University developed (Angew. Chem. Int. Ed. 2014, 53, 1636) a Pd catalyst for the preparation of 20 by the enantioselective amination of the diazo ester 19. Shou-Fei Zhu and Qi-Lin Zhou of Nankai University described (Angew. Chem. Int. Ed. 2014, 53, 2978) related work, not illustrated, on the enantioselective aryloxylation of an α-diazo ester. Alan Armstrong of Imperial College London, taking advantage (J. Org. Chem. 2014, 79, 3895) of the ready availability of enantiomerically secondary selenides such as 21, showed that it could be combined with 22 to give the α-chiral amine 23.

scholarly journals Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

2012 ◽  
Vol 8 ◽  
pp. 1668-1694 ◽  
Author(s):  
Chittaranjan Bhanja ◽  
Satyaban Jena ◽  
Sabita Nayak ◽  
Seetaram Mohapatra
Keyword(s):  
Enantioselective Synthesis ◽  
Synthetic Methods ◽  
Addition Reactions ◽  
Chiral Molecules ◽  
Cyclization Reactions ◽  
Central Importance ◽  
One Pot ◽  
Chiral Amine ◽  
Synthetic Compounds ◽  
Bioactive Natural Products

Enantioselective organocatalysis has become a field of central importance within asymmetric chemical synthesis and appears to be efficient approach toward the construction of complex chiral molecules from simple achiral materials in one-pot transformations under mild conditions with high stereocontrol. This review addresses the most significant synthetic methods reported on chiral-amine-catalyzed tandem Michael conjugate addition of heteroatom-centered nucleophiles to α,β-unsaturated compounds followed by cyclization reactions for the enantioselective construction of functionalized chiral chromenes, thiochromenes and 1,2-dihydroquinolines in optically enriched forms found in a myriad of bioactive natural products and synthetic compounds.

scholarly journals Modular synthesis of chiral 1,2-dihydropyridines via Mannich/Wittig/cycloisomerization sequence that internally reuses waste

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo-Shuai Mu ◽  
Xiao-Yuan Cui ◽  
Xing-Ping Zeng ◽  
Jin-Sheng Yu ◽  
Jian Zhou
Keyword(s):  
Enantioselective Synthesis ◽  
Side Reactions ◽  
Structural Components ◽  
Chiral Amine ◽  
Low Concentration ◽  
Unsaturated Ketones ◽  
Modular Synthesis ◽  
Enantioselective Addition ◽  
Product Water ◽  
Hydrolysis Of

Abstract1,2-Dihydropyridines are valuable and reactive synthons, and particularly useful precursors to synthesize piperidines and pyridines that are among the most common structural components of pharmaceuticals. However, the catalytic enantioselective synthesis of structurally diverse 1,2-dihydropyridines is limited to enantioselective addition of nucleophiles to activated pyridines. Here, we report a modular organocatalytic Mannich/Wittig/cycloisomerization sequence as a flexible strategy to access chiral 1,2-dihydropyridines from N-Boc aldimines, aldehydes, and phosphoranes, using a chiral amine catalyst. The key step in this protocol, cycloisomerization of chiral N-Boc δ-amino α,β-unsaturated ketones recycles the waste to improve the yield. Specifically, recycling by-product water from imine formation to gradually release the true catalyst HCl via hydrolysis of SiCl4, whilst maintaining a low concentration of HCl to suppress side reactions, and reusing waste Ph3PO from the Wittig step to modulate the acidity of HCl. This approach allows facile access to enantioenriched 2-substituted, 2,3- or 2,6-cis-disubstituted, and 2,3,6-cis-trisubstituted piperidines.

scholarly journals Organocatalytic atroposelective heterocycloaddition to access axially chiral 2-arylquinolines

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gongming Yang ◽  
Shaofa Sun ◽  
Zhipeng Li ◽  
Yuhan Liu ◽  
Jian Wang
Keyword(s):  
Drug Discovery ◽  
Asymmetric Synthesis ◽  
Vital Role ◽  
Optically Active ◽  
Enantioselective Synthesis ◽  
Chiral Amine ◽  
New Class ◽  
Axially Chiral ◽  
High Yields

AbstractAxially chiral heterobiaryls play a vital role in asymmetric synthesis and drug discovery. However, there are few reports on the synthesis of atropisomeric heterobiaryls compared with axially chiral biaryls. Thus, the rapid enantioselective construction of optically active heterobiaryls and their analogues remains an attractive challenge. Here, we report a concise chiral amine-catalyzed atroposelective heterocycloaddition reaction of alkynes with ortho-aminoarylaldehydes, and obtain a new class of axially chiral 2-arylquinoline skeletons with high yields and excellent enantioselectivities. In addition, the axially chiral 2-arylquinoline framework with different substituents is expected to be widely used in enantioselective synthesis.

New chiral amine ligands for enantioselective synthesis of certain (S)- and (R)-monobactams

2000 ◽  
Vol 23 (2) ◽  
pp. 125-136 ◽  
Author(s):  
M. Hussein ◽  
A. El-Shorbagi ◽  
N. Omar ◽  
Z. Farghaly ◽  
Kiyoshi Tomioka
Keyword(s):  
Enantioselective Synthesis ◽  
Chiral Amine ◽  
Amine Ligands

Catalytic enantioselective synthesis of indolizino[8,7-b]indole alkaloid derivatives based on the tandem reaction of tertiary enamides

2021 ◽  
Author(s):  
Xin-Ming Xu ◽  
Ming Xie ◽  
Jiazhu Li ◽  
Mei-Xiang Wang
Keyword(s):  
Indole Alkaloid ◽  
Enantioselective Synthesis ◽  
High Yield ◽  
Tandem Reaction ◽  
Indole Derivatives

An exquisite Pybox/Cu(OTf)2-catalyzed asymmetric tandem reaction of tertiary enamides was developed, which enabled the expeditious synthesis of indolizino[8,7-b]indole derivatives in high yield, excellent enantioselectivity and diastereoselectivity.

Enantioselective Synthesis of Azamerone

2018 ◽  
Author(s):  
Matthew L. Landry ◽  
Grace McKenna ◽  
Noah Burns
Keyword(s):  
Late Stage ◽  
Cross Coupling ◽  
Enantioselective Synthesis ◽  
Selective Synthesis

A concise and selective synthesis of the dichlorinated meroterpenoid azamerone is described. The paucity of tactics for the synthesis of chiral organochlorides motivated the development of unique strategies for accessing these motifs in enantioenriched forms. The route features a novel enantioselective chloroetherification reaction, a Pd-catalyzed cross-coupling between a quinone diazide and a boronic hemiester, and a late-stage tetrazine [4+2]-cycloaddition/oxidation cascade.

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

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