Highly regioselective lithiation of pyridines bearing an oxetane unit by n-butyllithium.

The first regioselective ortho-lithiation at the 4-position of simple pyridine derivatives containing a 3-oxetane unit has been achieved using n-butyllithium as base. Electrophilic quenching of the resulting lithio species provides a rapid access to a broad range of new functionalized pyridine oxetane building blocks.

[1]  K. F. Morgan,et al.  2-(Aryl-sulfonyl)oxetanes as designer 3-dimensional fragments for fragment screening: synthesis and strategies for functionalisation. , 2014, Chemical communications.

[2]  C. Espiritu,et al.  Use of 2'-spirocyclic ethers in HCV nucleoside design. , 2014, Journal of medicinal chemistry.

[3]  Richard D. Taylor,et al.  Rings in drugs. , 2014, Journal of medicinal chemistry.

[4]  Stefan A. Ruider,et al.  Ring expansion of 3-oxetanone-derived spirocycles: facile synthesis of saturated nitrogen heterocycles. , 2013, Angewandte Chemie.

[5]  G. Clarkson,et al.  Asymmetric Synthesis of 2-Substituted Oxetan-3-ones via Metalated SAMP/RAMP Hydrazones , 2013, The Journal of organic chemistry.

[6]  A. Fekri,et al.  Control of Site of Lithiation of 3-(Aminomethyl)pyridine Derivatives , 2013 .

[7]  Adam E. Goetz,et al.  Regioselective Reactions of 3,4-Pyridynes Enabled by the Aryne Distortion Model , 2012, Nature chemistry.

[8]  F. Perna,et al.  Exploiting the lithiation-directing ability of oxetane for the regioselective preparation of functionalized 2-aryloxetane scaffolds under mild conditions. , 2012, Angewandte Chemie.

[9]  Jianwei Sun,et al.  Synthesis of eight-membered lactones: intermolecular [6+2] cyclization of amphoteric molecules with siloxy alkynes. , 2012, Angewandte Chemie.

[10]  J. T. Njardarson,et al.  Catalytic ring expansion of vinyl oxetanes: asymmetric synthesis of dihydropyrans using chiral counterion catalysis. , 2012, Angewandte Chemie.

[11]  L. Pustilnik,et al.  Metabolism-directed design of oxetane-containing arylsulfonamide derivatives as γ-secretase inhibitors. , 2011, Journal of medicinal chemistry.

[12]  V. Blair,et al.  Alkali-metal mediated zincation of N-heterocyclic substrates using the lithium zincate complex, (THF)Li(TMP)Zn(tBu)(2) and applications in in situ cross coupling reactions , 2011 .

[13]  F. Perna,et al.  2-Lithiated-2-phenyloxetane: a new attractive synthon for the preparation of oxetane derivatives. , 2011, Chemical communications.

[14]  E. Carreira,et al.  Oxetanes as versatile elements in drug discovery and synthesis. , 2010, Angewandte Chemie.

[15]  M. D. Hill,et al.  Recent strategies for the synthesis of pyridine derivatives. , 2010, Chemistry.

[16]  Franz Schuler,et al.  Oxetanes in drug discovery: structural and synthetic insights. , 2010, Journal of medicinal chemistry.

[17]  D. Hertel,et al.  Synthesis and Characterization of Oxetane-Functionalized Phosphorescent Ir(III)-Complexes , 2009 .

[18]  E. Carreira,et al.  Spirocyclic oxetanes: synthesis and properties. , 2008, Angewandte Chemie.

[19]  M. Yamashita,et al.  Carbonylative polymerization of oxetanes initiated by acetyl cobalt complexes. , 2008, Chemistry, an Asian journal.

[20]  A. J. Amass,et al.  Cationic Ring-Opening Polymerization of Oxetane via a Non-Steady-State Controlled Polymerization Process: A Comparison of Initiators Yielding Living and Nonliving Polymers , 2008 .

[21]  N. Hoffmann,et al.  Photochemical reactions as key steps in organic synthesis. , 2008, Chemical reviews.

[22]  J. Crivello.  Hybrid free radical/cationic frontal photopolymerizations , 2007 .

[23]  E. Carreira,et al.  Oxetanes as promising modules in drug discovery. , 2006, Angewandte Chemie.

[24]  P. Gros,et al.  TMSCH2Li-induced regioselective lithiation of (S)-nicotine. , 2006, Organic & biomolecular chemistry.

[25]  F. Mongin,et al.  Advances in the directed metallation of azines and diazines (pyridines, pyrimidines, pyrazines, pyridazines, quinolines, benzodiazines and carbolines). Part 1: Metallation of pyridines, quinolines and carbolines , 2001 .

[26]  K. Nicolaou,et al.  The Conquest of Taxol , 1995 .

[27]  D. B. Collum,et al.  Is N,N,N',N'-tetramethylethylenediamine a good ligand for lithium? , 1992 .

[28]  Victor Snieckus,et al.  Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics , 1990 .

[29]  D. Norbeck,et al.  Synthesis of (-)-oxetanocin , 1988 .

[30]  S. Ōmura,et al.  Synthesis of a new amino acid-antibiotic, oxetin and its three stereoisomers. , 1986, Chemical & pharmaceutical bulletin.

[31]  K. Okuma,et al.  Reaction of dimethyloxosulfonium methylide with epoxides. Preparation of oxetanes , 1983 .

[32]  J. A. Turner.  Regiospecific electrophilic substitution of aminopyridines: ortho lithiation of 2-, 3-, and 4-(pivaloylamino)pyridines , 1983 .

[33]  T. Güngör,et al.  ortho-Functionalization of Aminopyridines; Regioselective Lithiation of 3-Pivaloylaminopyridines , 1982 .

[34]  F. Marsais,et al.  Regioselective o-Lithiation of 3-Alkoxypyridines; A Convenient Route to New o-Disubstituted Pyridines , 1982 .

[35]  R. Ronald,et al.  Regioselective metalation reactions of some substituted (methoxymethoxy)arenes , 1982 .

[36]  G. Holan.  Rational Design of Degradable Insecticides , 1971, Nature.

[37]  J. Clayden.  Organolithiums: Selectivity for Synthesis , 2002 .

[38]  A. Nelson,et al.  Stereospecific conversion of (1R*,3S*)- and (1R*,3R*)-3-cyclohexyl-1-phenylpropane-1,3-diol into the corresponding 2,4-disubstituted oxetanes , 2000 .

[39]  D. Comins,et al.  Lithiation of methoxypyridines directed by .alpha.-amino alkoxides , 1990 .

[40]  V. Snieckus,et al.  The 2-(trimethylsilyl)ethoxymethoxy (OSEM) directed ortho metalation group. New regiospecific synthetic routes to substituted benzenes and pyridines , 1990 .

[41]  M. Chen,et al.  Regioselective alkylation of 3-trimethylsilyl-3-sulfolene: route to stereospecific 2-silylated butadiene derivatives , 1988 .

[42]  D. Comins,et al.  Ortho lithiation of 2-, 3-, and 4-methoxypyridines , 1988 .

[43]  F. Marsais,et al.  Review on the metallation of π -deficient heteroaromatic compounds , 1983 .