Total Synthesis and Characterization of 7-Hypoquinuclidonium Tetrafluoroborate and 7-Hypoquinuclidone BF3 Complex.

Derivatives of the fully twisted bicyclic amide 7-hypoquinuclidone are synthesized using a Schmidt-Aubé reaction. Their structures were unambiguously confirmed by X-ray diffraction analysis and extensive spectroscopic characterization. Furthermore, the stability and chemical reactivity of these anti-Bredt amides are investigated. 7-Hypoquinuclidonium tetrafluoroborate is shown to decompose to a unique nitrogen bound amide-BF3 complex of 7-hypoquinuclidone under anhydrous conditions and to react instantaneously with water making it one of the most reactive amides known to date.

[1]  R. Szostak,et al.  Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon-Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C-N Rotational Pathway. , 2015, The Journal of organic chemistry.

[2]  R. Gonnade,et al.  Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction , 2015, Beilstein journal of organic chemistry.

[3]  R. Szostak,et al.  An efficient computational model to predict protonation at the amide nitrogen and reactivity along the C-N rotational pathway. , 2015, Chemical communications.

[4]  J. Goodman,et al.  The most reactive amide as a transition-state mimic for cis-trans interconversion. , 2015, Journal of the American Chemical Society.

[5]  A. Greenberg,et al.  Novel bridgehead bicyclic lactams: (a) Molecules predicted to have O-protonated and N-protonated tautomers of comparable stability; (b) hyperstable lactams and their O-protonated tautomers , 2014 .

[6]  J. Aubé,et al.  Chemistry of bridged lactams and related heterocycles. , 2013, Chemical reviews.

[7]  J. Aubé.  A new twist on amide solvolysis. , 2012, Angewandte Chemie.

[8]  J. Clayden.  Organic chemistry: Stabilizers cause instability , 2012, Nature.

[9]  J. Aubé,et al.  Mechanism of the acid-promoted intramolecular schmidt reaction: theoretical assessment of the importance of lone pair-cation, cation-π, and steric effects in controlling regioselectivity. , 2012, The Journal of organic chemistry.

[10]  J. Aubé,et al.  Medium-bridged lactams: a new class of non-planar amides. , 2011, Organic & biomolecular chemistry.

[11]  J. Aubé,et al.  Cation-pi control of regiochemistry of intramolecular schmidt reactions en route to bridged bicyclic lactams. , 2007, Journal of the American Chemical Society.

[12]  T. Ly,et al.  Synthesis of 2-quinuclidonium by eliminating water: experimental quantification of the high basicity of extremely twisted amides. , 2007, Journal of the American Chemical Society.

[13]  S. Marsden,et al.  Concise access to indolizidine and pyrroloazepine skeleta via intramolecular Schmidt reactions of azido 1,3-diketones. , 2006, Organic & biomolecular chemistry.

[14]  Brian M. Stoltz,et al.  Synthesis and structural analysis of 2-quinuclidonium tetrafluoroborate , 2006, Nature.

[15]  R. L. Funk,et al.  Total synthesis of (+/-)-perophoramidine. , 2004, Journal of the American Chemical Society.

[16]  S. Buchwald,et al.  Palladium-catalyzed intramolecular C-O bond formation. , 2001, Journal of the American Chemical Society.

[17]  J. Aubé,et al.  Reactions of Alkyl Azides and Ketones as Mediated by Lewis Acids: Schmidt and Mannich Reactions Using Azide Precursors , 2000 .

[18]  J. Aubé,et al.  Regiochemical studies of the ring expansion reactions of hydroxy azides with cyclic ketones. , 2000, The Journal of organic chemistry.

[19]  J. Aubé,et al.  Hydrolysis of Iminium Ethers Derived from the Reaction of Ketones with Hydroxy Azides: Synthesis of Macrocyclic Lactams and Lactones , 1999 .

[20]  J. Aubé,et al.  Ring expansion by in situ tethering of hydroxy azides to ketones: The boyer reaction , 1997 .

[21]  S. Masuda,et al.  Synthesis of Lactones by Baeyer-Villiger Oxidation with Magnesium Monoperphthalate Hexahydrate. , 1997, The Journal of organic chemistry.

[22]  A. Greenberg,et al.  Structures and energetics of two bridgehead lactams and their N- and O-protonated forms: an ab initio molecular orbital study , 1993 .

[23]  J. Aubé,et al.  Intramolecular Schmidt Reaction of Alkyl Azides , 1991 .

[24]  Kenneth B. Wiberg,et al.  Barriers to rotation adjacent to double bonds. 3. The carbon-oxygen barrier in formic acid, methyl formate, acetic acid, and methyl acetate. The origin of ester and amide resonance , 1987 .

[25]  P. Hofmann,et al.  Bond Angles in Lactones and Lactams , 1985 .

[26]  H. Hall,et al.  Anti-Bredt bridgehead nitrogen compounds in ring-opening polymerization , 1983 .

[27]  D. Fiat,et al.  Oxygen-17 and nitrogen-14 NMR studies of amide systems , 1981 .

[28]  R. Seeber,et al.  Electroanalytical evidences for the instability of hydrogen tetrafluoroborate in acetonitrile , 1976 .

[29]  F. Winkler,et al.  Amide group deformation in medium‐ring lactams , 1975 .

[30]  P. H. Clippard,et al.  Nuclear magnetic resonance spectra of several trimethylamine-boron trihalide complexes , 1969 .

[31]  J. Lehn,et al.  Nuclear Spin—Spin Interactions. V. 1H–14N Spin—Spin Coupling and Quadrupolar Relaxation in Quaternary Ammonium Salts , 1965 .

[32]  H. Hall.  Polymerization and Ring Strain in Bridged Bicyclic Compounds , 1958 .

[33]  L. Pauling,et al.  Fundamental dimensions of polypeptide chains , 1953, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[34]  L. Pauling,et al.  THE PLANARITY OF THE AMIDE GROUP IN POLYPEPTIDES , 1952 .

[35]  L. Pauling,et al.  The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. , 1951, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Jeffrey Aubé,et al.  Efficient Nitrogen Ring-Expansion Process Facilitated by in Situ Hemiketal Formation. An Asymmetric Schmidt Reaction , 1995 .