Asymmetric 1,4-addition of oxazolones to nitroalkenes by bifunctional cinchona alkaloid thiourea organocatalysts: synthesis of alpha,alpha-disubstituted alpha-amino acids.

An easy and simple synthetic approach to optically active alpha,alpha-quaternary alpha-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding alpha,alpha-quaternary alpha-amino acid derivatives with good yields, excellent diastereoselectivities (up to 98 % dr), and from moderate to good enantioselectivities (up to 92 % ee). The reaction can be performed on a large scale. The optically active oxazolone-nitroalkene addition products can be opened in a one-pot reaction to the corresponding ester-amide derivatives. Additional transformations are also presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones.

[1]  C. Zhao,et al.  Modularly designed organocatalytic assemblies for direct nitro-Michael addition reactions. , 2008, Angewandte Chemie.

[2]  Jin-gen Deng,et al.  Discovery of bifunctional thiourea/secondary-amine organocatalysts for the highly stereoselective nitro-Mannich reaction of alpha-substituted nitroacetates. , 2008, Chemistry.

[3]  A. Córdova,et al.  One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions. , 2008, Chemistry.

[4]  Tanmay Mandal Dr. and,et al.  Modularly Designed Organocatalytic Assemblies for Direct Nitro-Michael Addition Reactions† , 2008 .

[5]  A. Milelli,et al.  Organocatalytic asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids and derivatives. , 2008, Journal of the American Chemical Society.

[6]  A. Córdova,et al.  Organocatalytic Asymmetric Hydrophosphination of α,β-Unsaturated Aldehydes: Development, Mechanism and DFT Calculations , 2008 .

[7]  Paolo Melchiorre,et al.  Die asymmetrische Aminokatalyse – Goldrausch in der organischen Chemie , 2008 .

[8]  Armando Carlone,et al.  Asymmetric aminocatalysis--gold rush in organic chemistry. , 2008, Angewandte Chemie.

[9]  Y. Takemoto,et al.  Discovery and Application of Asymmetric Reaction by Multi-Functional Thioureas , 2008 .

[10]  T. Soós,et al.  Edge-to-face CH/pi aromatic interaction and molecular self-recognition in epi-cinchona-based bifunctional thiourea organocatalysis. , 2008, Chemistry.

[11]  S. Ley,et al.  A general organocatalytic enantioselective malonate addition to alpha,beta-unsaturated enones. , 2008, Chemistry.

[12]  R. Manzano,et al.  Novel bifunctional chiral urea and thiourea derivatives as organocatalysts: enantioselective nitro-Michael reaction of malonates and diketones. , 2008, Chemistry.

[13]  D. Du,et al.  Organocatalytic highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes. , 2008, Organic letters.

[14]  Xinhong Yu,et al.  Organocatalysis: asymmetric cascade reactions catalysed by chiral secondary amines. , 2008, Organic & biomolecular chemistry.

[15]  Jian Wang,et al.  A highly stereoselective hydrogen-bond-mediated Michael-Michael cascade process through dynamic kinetic resolution. , 2008, Angewandte Chemie.

[16]  S. Connon.  Asymmetric catalysis with bifunctional cinchona alkaloid-based urea and thiourea organocatalysts. , 2008, Chemical communications.

[17]  Scott E. Denmark,et al.  Lewis‐Base‐Katalyse in der organischen Synthese , 2008 .

[18]  Y. Gun’ko,et al.  Highly enantioselective desymmetrization of meso anhydrides by a bifunctional thiourea-based organocatalyst at low catalyst loadings and room temperature. , 2008, The Journal of organic chemistry.

[19]  S. Denmark,et al.  Lewis base catalysis in organic synthesis. , 2008, Angewandte Chemie.

[20]  Stephen J. Connon.  Die katalytische asymmetrische Strecker‐Reaktion: Fortschritte bei Ketiminen , 2008 .

[21]  S. Connon.  The catalytic asymmetric Strecker reaction: ketimines continue to join the fold. , 2008, Angewandte Chemie.

[22]  Keiji Maruoka,et al.  Recent development and application of chiral phase-transfer catalysts. , 2007, Chemical reviews.

[23]  D. MacMillan,et al.  Organocatalytic vinyl and Friedel-Crafts alkylations with trifluoroborate salts. , 2007, Journal of the American Chemical Society.

[24]  Y. Hayashi,et al.  Diphenylprolinol Silyl Ether as Catalyst of an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroalkanes with α,β-Unsaturated Aldehydes , 2007 .

[25]  K. Jørgensen,et al.  Organocatalytic Asymmetric Direct Phosphonylation of α,β-Unsaturated Aldehydes: Mechanism, Scope, and Application in Synthesis , 2007 .

[26]  J. Sansano,et al.  Catalytic Asymmetric Synthesis of α-Amino Acids , 2007 .

[27]  M. Nielsen,et al.  Enantioselective hydroxylation of nitroalkenes: an organocatalytic approach. , 2007, Chemical communications.

[28]  J. Tepe,et al.  The diverse chemistry of oxazol-5-(4H)-ones. , 2007, Chemical Society reviews.

[29]  J. Vicario,et al.  Organocatalytic Enantioselective Michael and Hetero‐Michael Reactions , 2007 .

[30]  B. List,et al.  Organocatalytic asymmetric transfer hydrogenation of nitroolefins. , 2007, Journal of the American Chemical Society.

[31]  Armando Carlone,et al.  Organocatalytic asymmetric hydrophosphination of α, β-unsaturated aldehydes , 2007 .

[32]  F. Himo,et al.  Enantioselective Organocatalytic Hydrophosphination of α,β-Unsaturated Aldehydes , 2007 .

[33]  Takashi Ooi,et al.  Fortschritte bei asymmetrischen Phasentransferkatalysen , 2007 .

[34]  K. Maruoka,et al.  Recent advances in asymmetric phase-transfer catalysis. , 2007, Angewandte Chemie.

[35]  S. Tsogoeva.  Recent Advances in Asymmetric Organocatalytic 1,4‐Conjugate Additions , 2007 .

[36]  M. Nielsen,et al.  Enantioselective organocatalytic conjugate addition of N heterocycles to alpha,beta-unsaturated aldehydes. , 2007, Angewandte Chemie.

[37]  Masakazu Tanaka.  Design and Synthesis of Chiral α,α-Disubstituted Amino Acids and Conformational Study of Their Oligopeptides , 2007 .

[38]  D. Alonso,et al.  Organocatalytic asymmetric conjugate additions , 2007 .

[39]  A. Córdova,et al.  Organocatalytic asymmetric 5-hydroxyisoxazolidine synthesis: a highly enantioselective route to beta-amino acids. , 2007, Chemical communications.

[40]  S. Bräse,et al.  Recent approaches towards the asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids. , 2007, Organic & biomolecular chemistry.

[41]  A. Córdova,et al.  Organocatalytic enantioselective aziridination of alpha,beta-unsaturated aldehydes. , 2007, Angewandte Chemie.

[42]  K. Jørgensen,et al.  Asymmetric organocatalytic beta-hydroxylation of alpha,beta-unsaturated aldehydes. , 2007, Journal of the American Chemical Society.

[43]  A. Córdova,et al.  Highly enantioselective synthesis of 2H-1-benzothiopyrans by a catalytic domino reaction , 2006 .

[44]  K. Jørgensen,et al.  Asymmetric synthesis of highly functionalized tetrahydrothiophenes by organocatalytic domino reactions. , 2006, Journal of the American Chemical Society.

[45]  H. Ogino,et al.  Enantioselective Ene Reaction of Cyclopentadiene and α,β‐Enals Catalyzed by a Diphenylprolinol Silyl Ether , 2006 .

[46]  E. Jacobsen,et al.  A Chiral Primary Amine Thiourea Catalyst for the Highly Enantioselective Direct Conjugate Addition of α,α‐Disubstituted Aldehydes to Nitroalkenes , 2006 .

[47]  Jung Woon Yang,et al.  The Organic Approach to Asymmetric Catalysis , 2006, Science.

[48]  Wei Wang,et al.  Enantioselective organocatalytic tandem Michael-Aldol reactions: one-pot synthesis of chiral thiochromenes. , 2006, Journal of the American Chemical Society.

[49]  S. Connon.  Organocatalysis mediated by (thio)urea derivatives. , 2006, Chemistry.

[50]  D. MacMillan,et al.  Enantioselective organocatalytic amine conjugate addition. , 2006, Journal of the American Chemical Society.

[51]  K. Jørgensen,et al.  Organocatalytic Conjugate Addition of Malonates to α,β‐Unsaturated Aldehydes: Asymmetric Formal Synthesis of (−)‐Paroxetine, Chiral Lactams, and Lactones , 2006 .

[52]  B. List,et al.  Asymmetrische Gegenanion‐vermittelte Katalyse , 2006 .

[53]  B. List,et al.  Asymmetric counteranion-directed catalysis. , 2006, Angewandte Chemie.

[54]  K. Scheidt,et al.  Direct nucleophilic acylation of nitroalkenes promoted by a fluoride anion/thiourea combination. , 2006, Journal of the American Chemical Society.

[55]  Eric N. Jacobsen,et al.  Asymmetrische Katalyse durch chirale Wasserstoffbrückendonoren , 2006 .

[56]  Mark S. Taylor,et al.  Asymmetric catalysis by chiral hydrogen-bond donors. , 2006, Angewandte Chemie.

[57]  B. List.  The ying and yang of asymmetric aminocatalysis. , 2006, Chemical communications.

[58]  Y. Takemoto,et al.  Enantioselective tandem michael reaction to nitroalkene catalyzed by bifunctional thiourea : total synthesis of (-)-epibatidine , 2006 .

[59]  T. Shinada,et al.  Enantio‐ and Diastereoselective Construction of α,α‐Disubstituted α‐Amino Acids for the Synthesis of Biologically Active Compounds , 2005 .

[60]  Raquel P. Herrera,et al.  Catalytic enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes by using a simple thiourea organocatalyst. , 2005, Angewandte Chemie.

[61]  S. Connon,et al.  Urea- and thiourea-substituted cinchona alkaloid derivatives as highly efficient bifunctional organocatalysts for the asymmetric addition of malonate to nitroalkenes: inversion of configuration at C9 dramatically improves catalyst performance. , 2005, Angewandte Chemie.

[62]  Yong Huang,et al.  Enantioselective organo-cascade catalysis. , 2005, Journal of the American Chemical Society.

[63]  Jian Wang,et al.  Organocatalytic asymmetric Michael addition of 2,4-pentandione to nitroolefins. , 2005, Organic letters.

[64]  T. Vilaivan,et al.  Recent Advances in Catalytic Asymmetric Addition to Imines and Related C=N Systems , 2005 .

[65]  Jinxing Ye,et al.  Enantioselective organocatalytic Michael addition of malonate esters to nitro olefins using bifunctional cinchonine derivatives. , 2005, Chemical communications.

[66]  A. Csámpai,et al.  Highly enantioselective conjugate addition of nitromethane to chalcones using bifunctional cinchona organocatalysts. , 2005, Organic letters.

[67]  J. Lex,et al.  Second-generation organocatalysts for the highly enantioselective dynamic kinetic resolution of azlactones. , 2005, Chemical communications.

[68]  Y. Takemoto,et al.  Bifunctional thiourea-catalyzed enantioselective double Michael reaction of γ,δ-unsaturated β-ketoester to nitroalkene: asymmetric synthesis of (−)-epibatidine , 2004 .

[69]  J. Frackenpohl,et al.  Recent Advances in Cinchona Alkaloid Chemistry , 2004 .

[70]  Peter I. Dalko,et al.  Im Goldenen Zeitalter der Organokatalyse , 2004 .

[71]  P. Dalko,et al.  In the golden age of organocatalysis. , 2004, Angewandte Chemie.

[72]  M. O'donnell,et al.  The enantioselective synthesis of alpha-amino acids by phase-transfer catalysis with achiral Schiff base esters. , 2004, Accounts of chemical research.

[73]  L. Tang,et al.  Asymmetric organic catalysis with modified cinchona alkaloids. , 2004, Accounts of chemical research.

[74]  S. O'connor,et al.  A Concise Synthesis of Sterically Hindered 3-Amino-2-Oxindoles , 2003 .

[75]  Scott J. Miller,et al.  Nucleophilic chiral amines as catalysts in asymmetric synthesis. , 2003, Chemical reviews.

[76]  H. Gröger.  Catalytic enantioselective Strecker reactions and analogous syntheses. , 2003, Chemical reviews.

[77]  B. Trost,et al.  Palladium-catalyzed asymmetric addition of pronucleophiles to allenes. , 2003, Journal of the American Chemical Society.

[78]  D. Enders,et al.  Asymmetric Michael Additions to Nitroalkenes , 2002 .

[79]  B. Trost,et al.  Synthesis of novel quaternary amino acids using molybdenum-catalyzed asymmetric allylic alkylation. , 2002, Journal of the American Chemical Society.

[80]  P. Balaram,et al.  Design of folded peptides. , 2001, Chemical reviews.

[81]  J. Gawroński,et al.  Cinchona Alkaloids and Their Derivatives: Versatile Catalysts and Ligands in Asymmetric Synthesis , 2001 .

[82]  N. Krause,et al.  Recent Advances in Catalytic Enantioselective Michael Additions , 2001 .

[83]  M. Sibi,et al.  Enantioselective Conjugate Additions , 2000 .

[84]  D. MacMillan,et al.  New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels−Alder Reaction , 2000 .

[85]  B. Trost,et al.  Enantioselective Allylations of Azlactones with Unsymmetrical Acyclic Allyl Esters , 1999 .

[86]  G. C. Fu,et al.  Enantioselective Construction of Quaternary Stereocenters: Rearrangements of O-Acylated Azlactones Catalyzed by a Planar-Chiral Derivative of 4-(Pyrrolidino)pyridine , 1998 .

[87]  C. Cativiela,et al.  Stereoselective synthesis of quaternary a-amino acids. Part 2: Cyclic compounds , 1998 .

[88]  H. Naganawa,et al.  Structure determination of altemicidin by nmr spectroscopic analysis , 1991 .

[89]  K. Lintner,et al.  Synthesis of [alpha-methyltyrosine-4]angiotensin II: studies of its conformation, pressor activity, and mode of enzymatic degradation. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[90]  Bennewitz.  Zur Entwicklung der physikalischen Chemie. Walther Nernst zum siebzigsten Geburtstag , 1934 .