Formal aminocyanation of α,β-unsaturated cyclic enones for the efficient synthesis of α-amino ketones.

Installation of amino functionality on organic molecules through direct CN bond formation is an important research objective. To achieve this goal, a 1,2-aminocyanation reaction was developed. The reaction occurs through the formation of pyrazolines by means of a formal dipolar cycloaddition of cyclic α,β-unsaturated ketones with lithium trimethylsilyldiazomethane followed by novel protonolytic N-N bond cleavage under mild conditions. This two-step process provides a diverse array of structurally complex free and mono-alkylated α-amino ketones in excellent yields.

[1]  G. Frey,et al.  Praktische Titan(III)‐katalysierte Synthese von cyclischen Aminoketonen und Pyrrolidinonen – Entwicklung einer formalen [4+1]‐Cycloaddition , 2013 .

[2]  Jan Streuff,et al.  Convenient titanium(III)-catalyzed synthesis of cyclic aminoketones and pyrrolidinones--development of a formal [4+1] cycloaddition. , 2013, Angewandte Chemie.

[3]  G. Roth,et al.  Synthesis of oxindolyl pyrazolines and 3-amino oxindole building blocks via a nitrile imine [3 + 2] cycloaddition strategy. , 2012, Organic letters.

[4]  J. Malinowski,et al.  α-Amination of keto-nitrones via multihetero-Cope rearrangement employing an imidoyl chloride reagent. , 2012, Chemical communications.

[5]  J. Kemsley.  FIRM FINED FOR CHEMIST’S DEATH: SAFETY: Sepracor Canada admits lack of lab ventilation in worker fatality case , 2011 .

[6]  K. K. Hii,et al.  Transition metal catalyzed enantioselective α-heterofunctionalization of carbonyl compounds. , 2011, Chemical reviews.

[7]  M. Smietana,et al.  Three-component reaction using the Bestmann-Ohira reagent: a regioselective synthesis of phosphonyl pyrazole rings. , 2010, Angewandte Chemie.

[8]  I. Namboothiri,et al.  Phosphonylpyrazoles from Bestmann-Ohira reagent and nitroalkenes: synthesis and dynamic NMR studies. , 2010, The Journal of organic chemistry.

[9]  T. Vilaivan,et al.  Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds , 2010, Molecules.

[10]  C. Drăghici,et al.  Preparation of tethered aldehyde ynoates and ynones by ring fragmentation of cyclic gamma-oxy-beta-hydroxy-alpha-diazo carbonyls. , 2010, The Journal of organic chemistry.

[11]  P. Magnus,et al.  Synthesis of carbamates from diethoxycarbonyl hydrazine derivatives by E1cB eliminative cleavage of the N-N'-bond rather than reduction. , 2009, Organic letters.

[12]  D. Taber,et al.  Convenient access to bicyclic and tricyclic diazenes. , 2008, The Journal of organic chemistry.

[13]  C. Drăghici,et al.  Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy-alpha-diazoesters. , 2008, Journal of the American Chemical Society.

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

[15]  T. Soeta,et al.  Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron-deficient olefins. , 2007, Organic letters.

[16]  S. Mobin,et al.  Base-mediated reaction of the Bestmann-Ohira reagent with nitroalkenes for the regioselective synthesis of phosphonylpyrazoles. , 2007, Organic letters.

[17]  P. Knochel,et al.  Preparation of aryl-alkylamines via electrophilic amination of functionalized arylazo tosylates with alkylzinc reagents. , 2006, Organic letters.

[18]  T. Hashimoto,et al.  Enantioselective 1,3-dipolar cycloaddition reaction between diazoacetates and alpha-substituted acroleins: total synthesis of manzacidin A. , 2006, Journal of the American Chemical Society.

[19]  Jacob M. Janey.  Fortschritte bei katalytischen enantioselektiven α‐Aminierungen und α‐Oxygenierungen von Carbonylverbindungen , 2005 .

[20]  J. Janey.  Recent Advances in Catalytic, Enantioselective α Aminations and α Oxygenations of Carbonyl Compounds , 2005 .

[21]  D. Hall,et al.  Design of a nonreductive method for chemoselective cleavage of hydrazines in the presence of unsaturations: application to a stereoconvergent three-component synthesis of (-)-methyl palustramate. , 2004, The Journal of organic chemistry.

[22]  E. Erdik.  Electrophilic α-amination of carbonyl compounds , 2004 .

[23]  Gregory K Friestad,et al.  Trifluoroacetyl-activated nitrogen-nitrogen bond cleavage of hydrazines by samarium(II) iodide. , 2004, Organic letters.

[24]  J. Sansano,et al.  Azomethine Ylides in Organic Synthesis , 2003 .

[25]  H. Takayama,et al.  Structure reinvestigation of gelsemoxonine, a constituent of Gelsemium elegans, reveals a novel, azetidine-containing indole alkaloid. , 2003, Organic letters.

[26]  S. Kanemasa.  Metal-Assisted Stereocontrol of 1,3-Dipolar Cycloaddition Reactions , 2002 .

[27]  H. Wasserman,et al.  β-Lactams as building blocks in the synthesis of macrocyclic spermine and spermidine alkaloids , 2002 .

[28]  S. Gougeon,et al.  Enantioselective desymmetrization of meso bicyclic hydrazines: a novel approach to the asymmetric synthesis of polysubstituted amino cyclopentanic cores. , 2002, The Journal of organic chemistry.

[29]  A. Padwa,et al.  Synthetic applications of 1,3-dipolar cycloaddition chemistry toward heterocycles and natural products , 2002 .

[30]  C. Che,et al.  Amidation of silyl enol ethers and cholesteryl acetates with chiral ruthenium(II) schiff-base catalysts: catalytic and enantioselective studies. , 2002, Chemical communications.

[31]  G. Friestad,et al.  Asymmetric Allylsilane Additions to EnantiopureN-Acylhydrazones with Dual Activation by Fluoride and In(OTf)3 , 2001 .

[32]  G. Friestad,et al.  Asymmetric Allylsilane Additions to Enantiopure N-Acylhydrazones with Dual Activation by Fluoride and In(OTf)(3) We thank the National Science Foundation (Vermont EPSCoR) and the University of Vermont for generous support. , 2001, Angewandte Chemie.

[33]  D. Enders,et al.  Efficient asymmetric synthesis of alpha-trifluoromethyl-substituted primary amines via nucleophilic 1,2-addition to trifluoroacetaldehyde SAMP- or RAMP-hydrazone. , 2001, Organic letters.

[34]  J. Zhang,et al.  Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives. , 2001, The Journal of organic chemistry.

[35]  Linhua Wang,et al.  Acylimine mediated N N bond cleavage of pyrazolidinediones and subsequent conversion to dihydropyrimidinediones and malonamides , 2001 .

[36]  Carreira,et al.  Versatile, diastereoselective additions of silyl ketene acetals, allyl tributylstannane, and Me(3)SiCN to N-acyl pyrazolines: asymmetric synthesis of densely functionalized pyrazolidines , 2000, Organic letters.

[37]  Toshio Kanai,et al.  Lewis Acid-Catalyzed Enantioselective 1,3-Dipolar Cycloadditions of Diazoalkane: Chiral Ligand/Achiral Auxiliary Cooperative Chirality Control , 2000 .

[38]  M. Jung,et al.  Use of optically active cyclic N,N-dialkyl aminals in asymmetric induction. , 2000, Organic letters.

[39]  Wirth,et al.  Direct amination of olefins through sequential triazolinedione ene reaction and carbanion-assisted cleavage of the N-N urazole bond , 2000, Organic letters.

[40]  Corey L. Stanchina,et al.  Regio- and stereoselective synthesis of N-H aziridines N-N bond reduction ofN-quinazolinylaziridines , 1999 .

[41]  J. Podlech.  Trimethylsilyldiazomethane (TMS‐CHN2) and lithiated trimethylsilydiazomethane – versatile substitutes for diazomethane , 1998 .

[42]  Davidr . Evans,et al.  Chiral Magnesium Bis(sulfonamide) Complexes as Catalysts for the Merged Enolization and Enantioselective Amination of N-Acyloxazolidinones. A Catalytic Approach to the Synthesis of Arylglycines , 1997 .

[43]  M. Botta,et al.  Reactivity of lithium trimethylsilyldiazomethane and diazomethane toward the 5,6-double bond of uracil and uridine derivatives , 1997 .

[44]  T. Shioiri,et al.  Trimethylsilyldiazomethane : A Useful Reagent for Generating Alkylidene Carbenes and Its Application to Organic Synthesis , 1996 .

[45]  Richard E. Moore,et al.  Welwitindolinones, Unusual Alkaloids from the Blue-Green Algae Hapalosiphon welwitschii and Westiella intricata. Relationship to Fischerindoles and Hapalinodoles , 1994 .

[46]  Kazuhiro Miwa,et al.  Extension of the Colvin Rearrangement Using Trimethylsilyldiazomethane. A New Synthesis of Alkynes , 1994 .

[47]  G. Himbert.  Advances in the Use of Synthons in Organic Chemistry , 1994 .

[48]  J. Lohrenz,et al.  Lithio-diazomethane and lithio-(trimethylsilyl)diazomethane: Theoretical and experimental studies of their structures, reactions and reaction products , 1994 .

[49]  M. Brimble,et al.  Allylic amination by the Lewis acid-mediated ene reactions of diethyl azodicarboxylate with alkenes , 1993 .

[50]  K. Hatano,et al.  Reaction of lithium trimethylsilyldiazomethane with β-amino-α,β-unsaturated ketones , 1993 .

[51]  Keiichi Ito,et al.  Photoreactions of 4- and 3-Azidocoumarins in the Presence of Nucleophiles , 1993 .

[52]  W. Oppolzer,et al.  Asymmetric Synthesis of α‐Amino Acids and α‐N‐Hydroxyamino Acids from N‐Acylbornane‐10,2‐sultams: 1‐chloro‐1‐nitrosocyclohexane as a practical [NH] equivalent , 1992 .

[53]  M. Burk,et al.  Enantioselective hydrogenation of the C=N group : a catalytic asymmetric reductive amination procedure , 1992 .

[54]  W. Oppolzer,et al.  Asymmetric .alpha.-amination of ketone enolates by chiral .alpha.-chloro-.alpha.-nitroso reagents: a new approach to optically pure erythro-.beta.-amino alcohols , 1992 .

[55]  U. Brinker,et al.  Carbene rearrangements. Part 36. Intramolecular reactions of diazocyclobutanes. Synthesis of trans-tricyclo[5.1.0.01,4]octane [[3.5.4]fenestrane]. , 1990 .

[56]  Davidr . Evans,et al.  Electrophilic azide transfer to chiral enolates. A general approach to the asymmetric synthesis of .alpha.-amino acids , 1987 .

[57]  H. Davies,et al.  Synthesis of fused 1,2-diazetidinones via an intramolecular Horner-Emmons reaction , 1986 .

[58]  Tadashi. Sasaki,et al.  Synthesis of β-N-Phenylamino Alcohols and α-N-Phenylamino Acids via Reduction of the Adducts of Silyl Enol Ethers and Bis-silyl Ketene Acetals with Nitrosobenzene , 1985 .

[59]  Tadashi. Sasaki,et al.  Synthesis of α-Aroyl-N-phenylnitrones by Silver Oxide Oxidation of the Adducts of Silyl Enol Ethers to Nitrosobenzene , 1985 .

[60]  J. M. Mellor,et al.  Reductive cleavage of the nitrogen–nitrogen bond in hydrazine derivatives , 1984 .

[61]  A. K. Forrest,et al.  De novo-synthesis of carbohydrates preparation of 4-amino-4-deoxy-d,l-ribose derivatives , 1984 .

[62]  Tadashi. Sasaki,et al.  UNEQUIVOCAL SYNTHESIS OF PHENACYLIDENEANILINE FROM SILYL ENOL ETHERS AND NITROSOBENZENE AND ONE-POT CYCLOADDITION REACTIONS OF THE RELATED ANILS , 1983 .

[63]  A. Padwa,et al.  Intramolecular cycloaddition reactions of olefinic tosylhydrazones , 1980 .

[64]  E. W. Colvin,et al.  A simple procedure for the elaboration of carbonyl compounds into homologous alkynes , 1977 .

[65]  R. Hinman.  Hydrogenolysis of the Nitrogen—Nitrogen Bond of Acylhydrazines with Raney Nickel , 1957 .