Novel Microwave-Assisted One-Pot Synthesis of Isoxazoles by a Three-Component Coupling-Cycloaddition Sequence

Abstract

The consecutive Sonogashira coupling of acid chlorides with terminal alkynes, followed by 1,3-dipolar cycloaddition under dielectric heating of in situ generated nitrile oxides from hydroximinoyl chlorides furnishes isoxazoles in moderate to good yields in the sense of a one-pot three-component reaction.

alkynes - cross-couplings - cycloaddition - isoxazole - microwave reaction

References

<A NAME="RT14107SS-1">1</A> For a review, see: Carlsen L. Döpp D. Döpp H. Duus F. Hartmann H. Lang-Fugmann S. Schulze B. Smalley RK. Wakefield BJ. In Houben-Weyl, Methods in Organic Chemistry   Vol. E8a:  Schaumann E. Georg Thieme Verlag; Stuttgart, Germany: 1992.  p.45-204  

<A NAME="RT14107SS-2">2</A> Rowley M. Broughton HB. Collins I. Baker R. Emms F. Marwood R. Patel S. Ragan CI. J. Med. Chem.  1996,  39:  1943 

<A NAME="RT14107SS-3">3</A> Frolund B. Jorgensen AT. Tagmose L. Stensbol TB. Vestergaard HT. Engblom C. Kristiansen U. Sanchez C. Krogsgaard-Larsen P. Liljefors T. J. Med. Chem.  2002,  45:  2454 

<A NAME="RT14107SS-4">4</A> Daidone G. Raffa D. Maggio B. Plescia F. Cutuli VMC. Mangano NG. Caruso A. Arch. Pharm. Pharm. Med. Chem.  1999,  332:  50 

<A NAME="RT14107SS-5A">5a</A> Talley JJ. Prog. Med. Chem.  1999,  13:  201 

<A NAME="RT14107SS-5B">5b</A> Talley JJ. Brown DL. Carter JS. Graneto MJ. Koboldt CM. Masferrer JL. Perkins WE. Rogers RS. Shaffer AF. Zhang YY. Zweifel BS. Seibert K. J. Med. Chem.  2000,  43:  775 

<A NAME="RT14107SS-6">6</A> Giovannoni MP. Vergelli C. Ghelardini C. Galeotti N. Bartolini A. Kal Piaz V. J. Med. Chem.  2003,  46:  1055 

<A NAME="RT14107SS-7">7</A> Li W.-T. Hwang D.-R. Chen C.-P. Shen C.-W. Huang C.-L. Chen T.-W. Lin C.-H. Chang Y.-L. Chang Y.-Y. Lo Y.-K. Tseng H.-Y. Lin C.-C. Song J.-S. Chen H.-C. Chen S.-J. Wu S.-H. Chen C.-T. J. Med. Chem.  2003,  46:  1706 

<A NAME="RT14107SS-8">8</A> For a recent review, see: Wakefield BJ. In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations   Vol. 11:  Schaumann E. Georg Thieme Verlag; Stuttgart, Germany: 2001.  p.229 

<A NAME="RT14107SS-9">9</A> Bandiera T. Grünanger P. Albini FM. J. Heterocycl. Chem.  1992,  29:  1423 

<A NAME="RT14107SS-10">10</A> Cuadrado P. Gonzalez-Nogal AM. Valero R. Tetrahedron  2002,  58:  4975 

<A NAME="RT14107SS-11">11</A> Vicentini CB. Verones AC. Poli T. Guarneri M. Giori P. Ferretti V. J. Heterocycl. Chem.  1990,  27:  1481 

<A NAME="RT14107SS-12">12</A> He Y. Lin N.-H. Synthesis  1994,  989 

<A NAME="RT14107SS-13A">13a</A> Barber GN. Olofson RA. J. Org. Chem.  1978,  43:  3015 

<A NAME="RT14107SS-13B">13b</A> Nitz TJ. Volkots DL. Aldous DJ. Oglesby RC. J. Org. Chem.  1994,  59:  5828 

<A NAME="RT14107SS-14A">14a</A> Denmark SE. Kallemeyn JM. J. Org. Chem.  2005,  70:  2839 

<A NAME="RT14107SS-14B">14b</A> Jaeger V. Colinas PA. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products, In Chemistry of Heterocyclic Compounds   Vol. 59:  Padwa A. Pearson WH. Wiley; Hoboken: 2002.  p.361 

<A NAME="RT14107SS-15A">15a</A> Müller TJJ. In Targets in Heterocyclic Systems   Vol. 10:  Attanasi OA. Spinelli D. Società Chimica Italiana; Rome: 2006.  p.54 

<A NAME="RT14107SS-15B">15b</A> Müller TJJ. Chimica Oggi/Chemistry Today  2007,  25:  70 

<A NAME="RT14107SS-16">16</A> For a recent review on multi-component synthesis of heterocycles by transition-metal catalysis, see: D’Souza DM. Müller TJJ. Chem. Soc. Rev.   2007.  36:  p.1095 

<A NAME="RT14107SS-17">17</A> Rotaru AV. Druta ID. Oeser T. Müller TJJ. Helv. Chim. Acta  2005,  88:  1798 

<A NAME="RT14107SS-18">18</A> Toda Y. Sonogashira K. Hagihara N. Synthesis  1977,  777 

<A NAME="RT14107SS-19A">19a</A> Karpov AS. Müller TJJ. Org. Lett.  2003,  5:  3451 

<A NAME="RT14107SS-19B">19b</A> Karpov AS. Müller TJJ. Synthesis  2003,  2815 

<A NAME="RT14107SS-19C">19c</A> Karpov AS. Merkul E. Rominger F. Müller TJJ. Angew. Chem. Int. Ed.  2005,  44:  6951 

<A NAME="RT14107SS-19D">19d</A> Karpov AS. Merkul E. Rominger F. Müller TJJ. Eur. J. Org. Chem.  2006,  2991 

For important reviews on 1,3-dipolar cycloadditions, see:

<A NAME="RT14107SS-20A">20a</A> Huisgen R. Angew. Chem., Int. Ed. Engl.  1963,  2:  565 

<A NAME="RT14107SS-20B">20b</A> Padwa A. 1,3-Dipolar Cycloaddition Chemistry   John Wiley & Sons; New York: 1984. 

<A NAME="RT14107SS-21">21</A>

Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC-661680 (5w), and CCDC-661681 (6a). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: [phone]; E-mail: [e-mail]].

<A NAME="RT14107SS-22">22</A> Becker HGO. Beckert R. Domschke G. Fanghänel E. Habicher WD. Metz P. Pavel D. Schwetlick K. Organikum   Wiley-VCH; Weinheim, New York, Chichester, Brisbane, Singapore, Toronto: 2001.  21st ed.

<A NAME="RT14107SS-23A">23a</A> Liu K.-C.. Shelton RB. Howe RK. J. Org. Chem.  1980,  45:  3916 

<A NAME="RT14107SS-23B">23b</A> Shaw FKN. McMillan A. Gudmundson AG. Armstrong MD. J. Org. Chem.  1958,  23:  1171