Regioselective Synthesis of 3‐Carbo‐5‐phosphonylpyrazoles through a One‐Pot Claisen–Schmidt/1,3‐Dipolar Cycloaddition/Oxidation Sequence

A one-pot reaction involving an aldehyde, a methyl ketone, and the Bestmann-Ohira reagent has been developed for the synthesis of variously substituted 3-carbo-5-phosphonylpyrazoles. Our synthetic methodology features a domino Claisen- Schmidt/1,3-dipolar cycloaddition/oxidation sequence,which leads to the target compounds in excellent yields. We further demonstrated that this unprecedented sequence could also be combined with a copper-catalyzed azide- alkyne cycloaddition in a one-pot, four-step cascade process generating five new bonds and two heterocyclic rings.

[1]  D. Habrant,et al.  Conversion of carbonyl compounds to alkynes: general overview and recent developments. , 2010, Chemical Society reviews.

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

[3]  B. Shi,et al.  Rhodium carbene routes to oxazoles and thiazoles. Catalyst effects in the synthesis of oxazole and thiazole carboxylates, phosphonates, and sulfones. , 2010, The Journal of organic chemistry.

[4]  M. Smietana,et al.  Expanding the borononucleotide family: synthesis of borono-analogues of dCMP, dGMP and dAMP. , 2009, Organic & biomolecular chemistry.

[5]  S. Fustero,et al.  Recent Advances in the Synthesis of Pyrazoles. A Review , 2009 .

[6]  Chao-Jun Li,et al.  Green chemistry for chemical synthesis , 2008, Proceedings of the National Academy of Sciences.

[7]  M. Smietana,et al.  Borononucleotides: synthesis, and formation of a new reversible boronate internucleosidic linkage. , 2008, Chemical communications.

[8]  C. Lamberth.  Pyrazole chemistry in crop protection , 2007 .

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

[10]  D. Chatfield,et al.  1,3-dipolar cycloadditions of trimethylsilyldiazomethane revisited: steric demand of the dipolarophile and the influence on product distribution. , 2007, The Journal of organic chemistry.

[11]  M. Chiacchio,et al.  Synthesis and biological activity of phosphonated nucleosides: part 1. Furanose, carbocyclic and heterocyclic analogues. , 2006, Current medicinal chemistry.

[12]  E. Quesada,et al.  One-pot conversion of activated alcohols into 1,1-dibromoalkenes and terminal alkynes using tandem oxidation processes with manganese dioxide , 2006 .

[13]  M. Drysdale,et al.  Discovery and development of pyrazole-scaffold Hsp90 inhibitors. , 2006, Current topics in medicinal chemistry.

[14]  F. Palacios,et al.  Synthesis of β-Aminophosphonates and -Phosphinates , 2005 .

[15]  K. Houk,et al.  Synthesis and relative stability of 3,5-diacyl-4,5-dihydro-1H-pyrazoles prepared by dipolar cycloaddition of enones and alpha-diazoketones. , 2004, The Journal of organic chemistry.

[16]  C. Stevens,et al.  Synthetic methods for azaheterocyclic phosphonates and their biological activity. , 2004, Chemical reviews.

[17]  K. Hinkle,et al.  A convenient scalable one-pot conversion of esters and Weinreb amides to terminal alkynes , 2004 .

[18]  R. Benhida,et al.  Ultrasound-accelerated aromatisation of trans- and cis-pyrazolines under heterogeneous conditions using claycop , 2004 .

[19]  Ling Zhang,et al.  A Facile Synthesis of 4‐(O,O‐Dialkylphosphoryl)‐1,3‐oxazole by Rhodium‐Catalyzed Heterocycloaddition , 2004 .

[20]  H. Bestmann,et al.  Further Improvements of the Synthesis of Alkynes from Aldehydes , 2003 .

[21]  G. Giacomelli,et al.  Microwave‐Assisted Solution‐Phase Synthesis of 1,4,5‐Trisubstituted Pyrazoles , 2003 .

[22]  M. Hayashi,et al.  Oxidative aromatization of 1,3,5-trisubstituted pyrazolines and Hantzsch 1,4-dihydropyridines by Pd/C in acetic acid. , 2002, Organic letters.

[23]  P. Durand,et al.  Practical one-step synthesis of ethynylglycine synthon from Garner's aldehyde , 2002 .

[24]  Morten Meldal,et al.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. , 2002, The Journal of organic chemistry.

[25]  F. Clerici,et al.  Isothiazoles. Part 12: Isothiazolylphosphonates, a new class of isothiazole dioxides , 2001 .

[26]  Yuxiu Liu,et al.  New Strategy for the Synthesis of Phosphonyl Pyrazoles , 1999 .

[27]  Hua-zheng Yang,et al.  A novel approach to phosphonyl-substituted heterocyclic system(I) , 1997 .

[28]  H. Bestmann,et al.  An Improved One-pot Procedure for the Synthesis of Alkynes from Aldehydes , 1996 .

[29]  Jianhua Zheng,et al.  Synthesis of perfluoroalkylated heterocyclic phosphonates , 1995 .

[30]  R. Neidlein,et al.  Synthesis and Reactions of Dialkyl (1-R-5-Amino-3-methylsulfanyl-1H-pyrazol-4-yl)-phosphonates , 1995 .

[31]  S. Ohira.  Methanolysis of Dimethyl (1-Diazo-2-oxopropyl) Phosphonate: Generation of Dimethyl (Diazomethyl) Phosphonate and Reaction with Carbonyl Compounds , 1989 .

[32]  K. Bhattacharyya,et al.  Photochemical transformations of (E)-1-(2'-arylidene-1'-phenylhydrazinyl)-1,2-dibenzoylalkenes , 1986 .

[33]  J. Gilbert,et al.  Diazoethenes: their attempted synthesis from aldehydes and aromatic ketones by way of the Horner-Emmons modification of the Wittig reaction. A facile synthesis of alkynes , 1982 .

[34]  J. Gilbert,et al.  Elaboration of aldehydes and ketones to alkynes: improved methodology , 1979 .

[35]  J. Shah,et al.  Oxidative dehydrogenation of pyrazolines with cobalt(II) and oxygen , 1978 .

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

[37]  E. W. Colvin,et al.  One-step conversion of carbonyl compounds into acetylenes , 1973 .

[38]  E. Corey,et al.  A synthetic method for formyl→ethynyl conversion (RCHO→RCCH or RCCR′) , 1972 .

[39]  D. Seyferth,et al.  Reactions of dimethylphosphono-substituted diazoalkanes. (MeO)2P(O)CR transfer to olefins and 1,3-dipolar additions of (MeO)2P(O)C(N2)R , 1971 .