Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C-N Coupling with Chiral Bisphosphine Mono-oxides.

A novel approach to hemiaminal synthesis via palladium-catalyzed C-N coupling with chiral bisphosphine mono-oxides is described. This efficient new method exhibits a broad scope, provides a highly efficient synthesis of HCV drug candidate elbasvir, and has been applied to the synthesis of chiral N,N-acetals.

[1]  Jianguang Liu,et al.  Copper-catalyzed enantioselective intramolecular aryl C-N coupling: synthesis of enantioenriched 2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxamides via an asymmetric desymmetrization strategy. , 2015, Organic letters.

[2]  Shane W. Krska,et al.  Cobalt Precursors for High-Throughput Discovery of Base Metal Asymmetric Alkene Hydrogenation Catalysts , 2013, Science.

[3]  J. Caldwell,et al.  Putting chirality to work: the strategy of chiral switches , 2002, Nature Reviews Drug Discovery.

[4]  E. V. Van der Eycken,et al.  C-N bond forming cross-coupling reactions: an overview. , 2013, Chemical Society reviews.

[5]  Frank Glorius,et al.  Contemporary screening approaches to reaction discovery and development. , 2014, Nature chemistry.

[6]  S. Buchwald,et al.  Dialkylbiaryl Phosphines in Pd-Catalyzed Amination: A User's Guide. , 2010, Chemical science.

[7]  O. Kitagawa,et al.  Catalytic enantioselective synthesis of key intermediates for NET inhibitors using atropisomeric lactam chemistry , 2008 .

[8]  Yundong Wu,et al.  Pd-catalyzed asymmetric intramolecular aryl C-O bond formation with SDP(O) ligand: enantioselective synthesis of (2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanols. , 2015, Organic letters.

[9]  Inda,et al.  The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. , 1999, The New England journal of medicine.

[10]  D. Davies,et al.  The in vitro biological activities of synthetic 18-O-methyl mycalamide B, 10-epi-18-O-methyl mycalamide B and pederin. , 1997, Anti-cancer drug design.

[11]  J. Hartwig Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides. , 2008, Accounts of chemical research.

[12]  Melodie Christensen,et al.  Enantioselective synthesis of an HCV NS5a antagonist. , 2014, Organic letters.

[13]  T. Hashimoto,et al.  Axially chiral dicarboxylic acid catalyzed activation of quinone imine ketals: enantioselective arylation of enecarbamates. , 2013, Journal of the American Chemical Society.

[14]  B. Kasprzyk-Hordern Pharmacologically active compounds in the environment and their chirality. , 2010, Chemical Society reviews.

[15]  Bin Chen,et al.  Highly enantioselective synthesis of 2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-ones via catalytic asymmetric intramolecular cascade imidization-nucleophilic addition-lactamization. , 2014, Organic letters.

[16]  Qian Huang,et al.  Discovery of MK‐8742: An HCV NS5A Inhibitor with Broad Genotype Activity , 2013, ChemMedChem.

[17]  Robert J. Phipps,et al.  A doubly axially chiral phosphoric acid catalyst for the asymmetric tandem oxyfluorination of enamides. , 2012, Angewandte Chemie.

[18]  I. Agranat,et al.  The strategy of enantiomer patents of drugs. , 2010, Drug discovery today.

[19]  Guy R. Humphrey,et al.  Process Development of C−N Cross-Coupling and Enantioselective Biocatalytic Reactions for the Asymmetric Synthesis of Niraparib , 2014 .

[20]  Tian Li,et al.  Catalytic enantioselective addition of alcohols to isatin-derived N-Boc ketimines , 2013 .

[21]  W. Kim,et al.  Global epidemiology and burden of hepatitis C. , 2002 .

[22]  J. Antilla,et al.  Catalytic asymmetric addition of alcohols to imines: enantioselective preparation of chiral N,O-aminals. , 2008, Journal of the American Chemical Society.

[23]  Colin W Shepard,et al.  Global epidemiology of hepatitis C virus infection. , 2005, The Lancet. Infectious diseases.

[24]  Daisuke Imao,et al.  Optically active palladium-catalyzed asymmetric amination of aryl halide , 2005 .

[25]  V. Grushin Mixed phosphine--phosphine oxide ligands. , 2004, Chemical reviews.

[26]  Cheng-yi Chen,et al.  Enantioselective Synthesis of (1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic Acid Ethyl Ester (Vinyl-ACCA-OEt) by Asymmetric Phase-Transfer Catalyzed Cyclopropanation of (E)-N-Phenylmethyleneglycine Ethyl Ester , 2010 .

[27]  M. Reibarkh,et al.  Asymmetric synthesis of cyclic indole aminals via 1,3-stereoinduction. , 2014, The Journal of organic chemistry.

[28]  W. Marshall,et al.  Palladium(II) and Palladium(0) Complexes of BINAP(O) (2-(Diphenylphosphino)-2‘-(diphenylphosphinyl)-1,1‘-binaphthyl) , 2003 .

[29]  Kazuhiro Yoshida,et al.  An air-stable P-chiral phosphine ligand for highly enantioselective transition-metal-catalyzed reactions. , 2005, Journal of the American Chemical Society.

[30]  Qi‐Lin Zhou Privileged Chiral Ligands and Catalysts: ZHOU:PRIVILEGED CATALYSTS O-BK , 2011 .

[31]  A. Togni,et al.  A Novel Easily Accessible Chiral Ferrocenyldiphosphine for Highly Enantioselective Hydrogenation, Allylic Alkylation, and Hydroboration Reactions , 1994 .

[32]  B. List,et al.  N-phosphinyl phosphoramide--a chiral Brønsted acid motif for the direct asymmetric N,O-acetalization of aldehydes. , 2010, Angewandte Chemie.

[33]  V. Grushin Catalysis for Catalysis: Synthesis of Mixed Phosphine−Phosphine Oxide Ligands via Highly Selective, Pd-Catalyzed Monooxidation of Bidentate Phosphines , 1999 .

[34]  P. Murphy,et al.  The guanidine metabolites of Ptilocaulis spiculifer and related compounds; isolation and synthesis , 2000 .

[35]  M. Burk C2-symmetric bis(phospholanes) and their use in highly enantioselective hydrogenation reactions , 1991 .

[36]  Beat Ernst,et al.  Drug discovery today. , 2003, Current topics in medicinal chemistry.

[37]  John F. Hartwig,et al.  A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions , 2011, Science.

[38]  T. Imamoto,et al.  Recent Developments in Catalytic Asymmetric Hydrogenation Employing P‐Chirogenic Diphosphine Ligands , 2003 .

[39]  K. Rossen,et al.  Kinetic Resolution of rac-4,12-Dibromo[2.2]paracyclophane in a Palladium [2.2]PHANEPHOS Catalyzed Amination , 1997 .

[40]  Y. Rhee,et al.  Stereodefined N,O-acetals: Pd-catalyzed synthesis from homopropargylic amines and utility in the flexible synthesis of 2,6-substituted piperidines. , 2012, Journal of the American Chemical Society.