Synlett 2011(9): 1212-1232  
DOI: 10.1055/s-0030-1260559
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Synthesis of 2-Thio-3-Chloroacrylamides and Investigation of their Reactivity

Marie Kissanea, Anita R. Maguire*b
a Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Ireland
b Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, University College Cork, Ireland
Fax: +353(21)4901770; e-Mail: a.maguire@ucc.ie;
Further Information

Publication History

Received 19 January 2011
Publication Date:
13 May 2011 (online)

Abstract

The stereoselective transformation of 2-thioamides to 2-thio-3-chloroacrylamides and the investigation of the scope of this transformation, including extension to ester and nitrile derivatives, is described. These highly functionalised acrylamide derivatives are synthetically versatile, and their reactivity has been investigated in a wide range of transformations, including chemoselective oxidation to the racemic sulfoxide or sulfone, and enantioselective and ­diastereoselective oxidation to the sulfoxides. The 2-thio-3-chloroacrylamides were found to be very effective Michael acceptors in nucleophilic addition/substitution reactions, dienophiles in Diels-Alder cycloadditions, and dipolarophiles in 1,3-dipolar cycloadditions. The level of oxidation at sulfur was found to strongly influence the reactivity. This account summarises synthetic and mechanistic aspects of the research programme focussed on the synthesis and reactivity of 2-thio-3-chloroacrylamides in our research group over the past decade.

1 Introduction - Discovery of 2-Thio-2-chloroacrylamides and Initial Observations

2 Synthesis of the β-Chloroacrylamides and Investigation of their Mechanistic Pathway

3 Extension of the Methodology to β-Haloacrylamides, β-Acrylates, and β-Acrylonitriles

4 Oxidation of the β-Chloroacrylamides

4.1 Chemoselective Sulfur Oxidation

4.2 Enantioselective Sulfur Oxidation

4.3 Diastereoselective Sulfur Oxidation

5 Nucleophilic Addition/Substitution Reactions of the β-­Chloroacrylamides

5.1 Addition of Carbon Nucleophiles

5.2 Addition of Nitrogen Nucleophiles

5.3 Addition of Oxygen Nucleophiles

5.4 Addition of Sulfur and Selenium Nucleophiles

5.5 Summary of Nucleophilic Additions

6 Reactivity of the β-Chloroacrylamides in Diels-Alder ­Cycloaddition Reactions

6.1 Cycloadditions with Cyclopentadiene

6.2 Cycloadditions with 2,3-Dimethyl-1,3-butadiene

6.3 Summary of Diels-Alder Cycloadditions

7 Reactivity of the β-Chloroacrylamides in 1,3-Dipolar ­Cycloaddition Reactions

7.1 Cycloadditions with Diazoalkanes

7.2 Cycloadditions with Nitrile Oxides and Nitrones

8 Conclusion

    References

  • 1 Maguire AR. Murphy ME. Schaeffer M. Ferguson G. Tetrahedron Lett.  1995,  36:  467 
  • 2 Murphy M. Lynch D. Schaeffer M. Kissane M. Chopra J. O’Brien E. Ford A. Ferguson G. Maguire AR. Org. Biomol. Chem.  2007,  5:  1228 
  • 3 Kissane M. Murphy M. Lynch D. Ford A. Maguire AR. Tetrahedron  2008,  64:  7639 
  • 4 Kissane M. Lynch D. Chopra J. Lawrence SE. Maguire AR. Org. Biomol. Chem.  2010,  8:  5602 
  • 5 Kissane M. Lawrence SE. Maguire AR. Org. Biomol. Chem.  2010,  8:  2735 
  • 6 Kissane M. Lawrence SE. Maguire AR. Tetrahedron  2010,  66:  4564 
  • 7 Kissane M. Maguire AR. Chem. Soc. Rev.  2010,  39:  845 
  • 8 Kissane M. Lawrence SE. Maguire AR. Tetrahedron: Asymmetry  2010,  21:  871 
  • 9 Kissane M. Lynch D. Chopra J. Lawrence SE. Maguire AR. Tetrahedron: Asymmetry  2008,  19:  1256 
  • 10 Kissane M. Murphy M. Lawrence SE. Maguire AR. Tetrahedron: Asymmetry  2010,  21:  2550 
  • 11 Kissane M. Murphy M. O’Brien E. Chopra J. Murphy L. Collins SG. Lawrence SE. Maguire AR. Org. Biomol. Chem.  2011,  9:  2452 
  • 12 Dilworth BM. McKervey MA. Tetrahedron  1986,  42:  3731 
  • 13 Geraghty NWA. Comprehensive Organic Functional Group Transformations   Kirby GW. Permgamon Press; Oxford: 1995.  p.4 
  • 15 Komatsu N. Hashizume M. Sugita T. Uemura S. J. Org. Chem.  1993,  58:  4529 
  • 16 Kelly P. Lawrence SE. Maguire AR. Synlett  2006,  1569 
  • 17 Kelly P. Lawrence SE. Maguire AR. Eur. J. Org. Chem.  2006,  4500 
  • 18 Collins SG. Maguire AR. Sci. Synth.  2007,  31a:  907 
  • 21 Ruano JLG. de la Plata BC. Organosulfur Chemistry I, In Topics in Current Chemistry   Vol. 204:  Springer; Berlin: 1999.  p.1 
  • 22 Garcia Ruano JL. Esteban Gamboa A. Martin Castro AM. Rodriguez JH. Lopez-Solera MI. J. Org. Chem.  1998,  63:  3324 
  • 23 Ruano JLG. Alemparte C. Castro AMM. Adams H. Ramos JHR. J. Org. Chem.  2000,  65:  7938 
  • 24 Ruano JLG. de la Plata BC. Top. Curr. Chem.  1999,  204:  1 
  • 25 Aggarwal VK. Anderson ES. Elfyn Jones D. Obierey KB. Giles R. Chem. Commun.  1998,  1985 
  • 26 Aggarwal VK. Jones DE. Martin-Castro AM. Eur. J. Org. Chem.  2000,  2939 
  • 27 Garcia Ruano JL. Alonso de Diego SA. Martin MR. Torrente E. Martin Castro AM. Org. Lett.  2004,  6:  4945 
  • 28 Garcia Ruano JL. Alonso de Diego SA. Blanco D. Martin Castro AM. Martin MR. Rodriguez Ramos JH. Org. Lett.  2001,  3:  3173 
  • 29 Ruano JLG. Fraile A. Martin MR. Tetrahedron: Asymmetry  1996,  7:  1943 
  • 30 Garcia Ruano JL. Bercial F. Gonzalez G. Martin Castro AM. Martin MR. Tetrahedron: Asymmetry  2002,  13:  1993 
  • 31 Ruano JLG. Fraile A. Gonzalez G. Martin MR. Clemente FR. Gordillo R. J. Org. Chem.  2003,  68:  6522 
  • 32 Ruano JLG. Peromingo MT. Alonso M. Fraile A. Martin MR. Tito A. J. Org. Chem.  2005,  70:  8942 
  • 33 Gilchrist TL. Storr RC. Organic Reactions and Orbital Symmetry   2nd ed.:  Cambridge University Press; Cambridge: 1979. 
  • 34 Fleming I. Frontier Orbitals and Organic Chemical Reactions   Wiley Interscience; London: 1976. 
  • 35 Engel PS. Chem. Rev.  1980,  80:  99 
  • 36 Martin-Vila M. Hanafi N. Jimenez JM. Alvarez-Larena A. Piniella JF. Branchadell V. Oliva A. Ortuno RM. J. Org. Chem.  1998,  63:  3581 
  • 37 Sasmal PK. Sridhar S. Iqbal J. Tetrahedron Lett.  2006,  47:  8661 
  • 38 Kauch M. Snieckus V. Hoppe D. J. Org. Chem.  2005,  70:  7149 
  • 39 Thomas EJ. Williams AC. J. Chem. Soc., Chem. Commun.  1987,  992 
  • 40 Vorbrueggen H. Ruh-Pohlenz C. Org. React.  2000,  55:  1 
  • 41 Wentrup C. Fischer S. Maquestiau A. Flammang R. Angew. Chem.  1985,  97:  74 
  • 42 Caramella P. Albini E. Bandiera T. Coda AC. Gruenanger P. Albini FM. Tetrahedron  1983,  39:  689 
  • 43 Ruano JLG. Fraile A. Martin MR. Tetrahedron  1999,  55:  14491 
  • 44 Torssell KBG. Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis   VCH Publishers; New York: 1988. 
  • 45 Louis C. Hootele C. Tetrahedron: Asymmetry  1997,  8:  109 
  • 46 Houk KN. Sims J. Watts CR. Luskus LJ. J. Am. Chem. Soc.  1973,  95:  7301 
14

Foley, D. A.; Doecke, C. W.; Buser, J. Y.; Koerner, A.; Merrit, J. M.; Murphy, L.; Kissane, M.; Collins, S. G.; Maguire, A. R. manuscript in preparation.

19

O’Mahony G. E., Kelly P., Lawrence S. E., Maguire A. R.; Arkivoc 2011, (i), 1.

20

Kissane, M.; Murphy, M.; Bateman, L. M.; McCarthy, D. G.; Maguire, A. R. Tetrahedron, in press.