Use of functionalized β-lactams as building blocks in heterocyclic chemistry

β-Lactams represent flexible building blocks suitable for the preparation of a large variety of nitrogen-containing target compounds. In the present study, the formerly neglected synthetic potential of 4-haloalkyl-β-lactams has been elaborated in detail with a focus on the preparation of different mono- and bicyclic heterocycles. A first approach involved ring transformations of these halogenated building blocks toward stereodefined aziridines, azetidines, pyrrolidines, and piperidines via intermediate aziridinium or azetidinium ions. In a second part, novel and stereoselective entries into 1,4- and 3,4-fused bicyclic β-lactams were developed through either a radical or an ionic cyclization protocol. Furthermore, the ring enlargement of halogenated β-lactams into functionalized mono- and bicyclic pyrrolidin-2-ones was established as the aza-analog of the cyclobutylmethylcarbenium ion to cyclopentylcarbenium ion rearrangement. Finally, chiral versions toward azetidin-2-ones and ring transformation products were elaborated, involving the synthesis of 3(S)-alkoxy-4(S)-[1(S)-chloroethyl]azetidin-2-ones and the preparation of bicyclic β-lactams annelated to piperazines, morpholines, and diazepanes.

[1]  K. Törnroos,et al.  Synthesis of 3,4-Fused Bicyclic β-Lactams and Their Transformation into Methyl cis-3-Aminotetrahydrofuran-2-carboxylates , 2010 .

[2]  Paula Pérez-Faginas,et al.  An Update on the Synthesis of β-Lactams , 2009 .

[3]  N. de Kimpe,et al.  Diastereoselective synthesis of bicyclic gamma-lactams via ring expansion of monocyclic beta-lactams. , 2009, The Journal of organic chemistry.

[4]  T. Tidwell,et al.  Preparation of β-lactams by [2+2] cycloaddition of ketenes and imines ☆ , 2008 .

[5]  A. Arrieta,et al.  The mechanism of the ketene-imine (staudinger) reaction in its centennial: still an unsolved problem? , 2008, Accounts of chemical research.

[6]  N. de Kimpe,et al.  Highly stereoselective synthesis of beta-lactams utilizing alpha-chloroimines as new and powerful chiral inductors. , 2008, Chemistry.

[7]  F. Fülöp,et al.  Stereoselective synthesis of hydroxylated β-aminocyclohexanecarboxylic acids , 2008 .

[8]  B. Alcaide,et al.  Stereoselective NaN3-catalyzed halonitroaldol-type reaction of azetidine-2,3-diones in aqueous media. , 2008, Organic & biomolecular chemistry.

[9]  T. Campo,et al.  Metal‐Catalyzed Regiodivergent Cyclization of γ‐Allenols: Tetrahydrofurans versus Oxepanes , 2007 .

[10]  B. Alcaide,et al.  β-Lactams: Versatile Building Blocks for the Stereoselective Synthesis of Non-β-Lactam Products , 2007 .

[11]  N. de Kimpe,et al.  Asymmetric synthesis of 1-(2- and 3-haloalkyl)azetidin-2-ones as precursors for novel piperazine, morpholine, and 1,4-diazepane annulated beta-lactams. , 2006, The Journal of organic chemistry.

[12]  Yong Liang,et al.  Origin of the relative stereoselectivity of the beta-lactam formation in the Staudinger reaction. , 2006, Journal of the American Chemical Society.

[13]  N. Kimpe,et al.  Ring transformation of 2-(haloalkyl)azetidines into 3,4-disubstituted pyrrolidines and piperidines , 2006 .

[14]  N. de Kimpe,et al.  Reduction of 4-(haloalkyl)azetidin-2-ones with LiAlH4 as a powerful method for the synthesis of stereodefined aziridines and azetidines. , 2006, Organic letters.

[15]  N. Kimpe,et al.  Electrophile-Induced Ring Expansions ofβ-Lactams toward γ-Lactams , 2005 .

[16]  M. Hahn,et al.  Alicyclic β-amino acids in Medicinal Chemistry , 2005, Amino Acids.

[17]  N. Kimpe,et al.  Diastereoselective ring expansion of beta-lactams toward gamma-lactams via N-acyliminium intermediates. , 2005 .

[18]  Samy O Meroueh,et al.  Bacterial resistance to beta-lactam antibiotics: compelling opportunism, compelling opportunity. , 2005, Chemical reviews.

[19]  N. de Kimpe,et al.  New reactions of functionalized β-lactams , 2005 .

[20]  S. Nguyen,et al.  The Enantioselective Synthesis of Conformationally Constrained Cyclic β- Amino Acids , 2005 .

[21]  Yan Yang,et al.  Synthesis of novel optically pure β-lactams , 2005 .

[22]  N. de Kimpe,et al.  Rearrangement of 4-(1-haloalkyl)- and 4-(2-haloalkyl)-2-azetidinones into methyl omega-alkylaminopentenoates via transient aziridines and azetidines. , 2004, The Journal of organic chemistry.

[23]  A. Deshmukh,et al.  Azetidin-2-ones, synthon for biologically important compounds. , 2004, Current medicinal chemistry.

[24]  J. Aizpurua,et al.  Asymmetric Synthesis of β-Lactams Through the Staudinger Reaction and Their Use as Building Blocks of Natural and Nonnatural Products , 2004 .

[25]  T. Lectka,et al.  Advances in the Catalytic, Asymmetric Synthesis of β-Lactams , 2004 .

[26]  F. Fülöp,et al.  Synthesis and transformation of novel cyclic β-amino acid derivatives from (+)-3-carene , 2003 .

[27]  G. S. Singh.  Recent Progress in the Synthesis and Chemistry of Azetidinones , 2003 .

[28]  B. Alcaide,et al.  Selective Bond Cleavage of the β-Lactam Nucleus: Application in Stereocontrolled Synthesis , 2002 .

[29]  B. Alcaide,et al.  4-Oxoazetidine-2-carbaldehydes as useful building blocks in stereocontrolled synthesis , 2002 .

[30]  T. Pilati,et al.  Stereoselective synthesis of a new enantiopure tricyclic β-lactam derivative via a tricarbonyl(η6-arene)chromium(0) complex , 2000 .

[31]  J. Aizpurua,et al.  Asymmetric Synthesis of β‐Lactams by Staudinger Ketene‐Imine Cycloaddition Reaction , 1999 .

[32]  J. Rodríguez‐López,et al.  Stereoselective Synthesis of Fused Bicyclic beta-Lactams through Radical Cyclization of Enyne-2-azetidinones(1). , 1999, The Journal of organic chemistry.

[33]  F. Evanics,et al.  Synthesis and ring—Chain tautomerism of angularly substituted cycloalkane-fused tetrahydro-1,3-oxazines , 1998 .

[34]  I. Ojima,et al.  Asymmetric synthesis of building-blocks for peptides and peptidomimetics by means of the β-lactam synthon method , 1997 .

[35]  Alan R. Katritzky,et al.  Comprehensive Heterocyclic Chemistry IV , 1996 .

[36]  I. Ojima.  Recent Advances in the .beta.-Lactam Synthon Method , 1995 .

[37]  J. Rodríguez‐López,et al.  Preparation of .alpha.-Methylene and .alpha.-Ethylidene .beta.-Lactams via the Ester Enolate-Imine Condensation Using .beta.-(Dialkylamino) Esters as Starting Materials: Scope and Synthetic Applications , 1994 .

[38]  R. Verhé,et al.  Synthesis of Secondary Allylic Amines , 1988 .

[39]  B. Tinant,et al.  Synthesis of azetidines from β-chloro imines , 1988 .

[40]  M. Ochiai,et al.  New methylseleno-promoted ketene-imine cycloaddition reaction. A simplified stereoselective synthesis of penam , 1986 .

[41]  T. T. Chou,et al.  Anodic Dimerization of 1,2,3,4-Tetrahydrocarbazole and Some of Its Derivatives. , 1986 .

[42]  L. Moens,et al.  The Favorskii rearrangement of .alpha.-chloro ketimines , 1986 .

[43]  R. Verhé,et al.  Synthesis of -Chloroimines , 1986 .

[44]  N. Kimpe,et al.  Regiospecific α‐Alkylation of α‐Haloalkylidenamines (“α‐Haloketimines”) , 1985 .

[45]  Norbert De Kimpe,et al.  Regiospezifische a-Alkylierung von a-Halogenalkylidenaminen (a-Halogenketiminen) , 1985 .

[46]  V. Hegde,et al.  Studies on lactams. Part 74. An approach to the total synthesis of amino sugars viaβ-lactams , 1985 .

[47]  R. Verhé,et al.  Reactivity of α-chloro-aldimines , 1976 .

[48]  A. Bose,et al.  beta-Lactams as Synthons. Synthesis of Heterocycles via beta-Lactam Cleavage , 1976 .

[49]  R. Verhé,et al.  A Facile Synthesis of 2,2-Dihalogenated Aliphatic Aldehydes , 1975 .

[50]  W. R. Vaughan,et al.  2,3-PYRROLIDINEDIONES. IV. FURTHER STUDIES ON TAUTOMERISM , 1955 .