N-(β,β-Difluorovinyl)oxazolidin-2-ones: First Synthesis and Application in [3+2]- and [4+2]-Cycloaddition-Type Reactions

Abstract

N-(β,β-Difluorovinyl)oxazolidin-2-ones were conveniently prepared in good yields in two steps from the parent oxazolidin-2-ones. The [3+2]- and [4+2]-cycloaddition-type reactions with electron-deficient partners were investigated as first application of these new enamides. TMSOTf was efficient in promoting these two reactions, and the corresponding heterocyclic difluoro adducts were obtained in high yields.

Key words

N-(β,β-difluorovinyl)oxazolidin-2-ones - trimethylsilyl trifluoromethanesulfonate - 1,3-dipolar cycloaddition - Diels-Alder reaction - dipolarophile - nitrone - heterodiene

References and Notes

• 1a Thayer AM. Chem. Eng. News  2006,  84 (23):  15 
• 1b Thayer AM. Chem. Eng. News  2006,  84 (23):  27 
• 2a Purser S. Moore PR. Swallow S. Gouverneur V. Chem. Soc. Rev.  2008,  37:  320 
• 2b Kirk KL. Org. Process Res. Dev.  2008,  12:  305 
• 2c O’Hagan D. Chem. Soc. Rev.  2008,  37:  308 
• 2d Müller K. Faeh C. Diederich F. Science  2007,  317:  1881 
• 2e Sun S. Adejare A. Curr. Top. Med. Chem.  2006,  6:  1457 
• 2f Iseki K. Tetrahedron  1998,  54:  13887 
• 2g Welch JT. Eswarakrishnan S. Fluorine in Bioorganic Chemistry   Wiley; New York: 1991. 
• 2h Tozer MJ. Herpin TF. Tetrahedron  1996,  52:  8219 
• 2i Welch JT. Tetrahedron  1987,  43:  3123 
• 3 Singh RP. Schreeve JM. Synthesis  2002,  2561 
• 4 Percy JM. Top. Curr. Chem.  1997,  193:  131 
• 5a Arany A. Crowley PJ. Fawcett J. Hursthouse MB. Kariuki BM. Light ME. Moralee AC. Percy JM. Salafia V. Org. Biomol. Chem.  2004,  2:  455 
• 5b Okano T. Nakajima A. Eguchi S. Synlett  2001,  1449 
• 5c Purrington SZ. Thomas HN. J. Fluorine Chem.  1998,  90:  47 
• 5d Howarth JA. Owton WM. Percy JM. Tetrahedron  1995,  51:  10289 
• 5e Bennette AJ. Percy JM. Synlett  1992,  483 
• 5f Percy JM. Rock MH. Tetrahedron Lett.  1992,  33:  6177 
• 6a Gogsig TM. Sobjerg LS. Lindhardt AT. Jensen KL. Skrydstrup T. J. Org. Chem.  2008,  73:  3404 
• 6b Fang X. Wu YM. Deng J. Wang SW. Tetrahedron  2004,  60:  5487 
• 6c Ichikawa J. Wada Y. Fujiwara M. Sakoda K. Synthesis  2002,  1917 
• 6d Ichikawa J.
  J. Fluorine Chem.  2000,  105:  257 
• 6e Ichikawa J. Fujiwara M. Nawata H. Okauchi T. Manami T. Tetrahedron Lett.  1996,  37:  8799 
• 6f Ichikawa J. Ikeura C. Minami T. Synlett  1992,  739 
• 6g Ichikawa J. Hamada S. Sonoda T. Kobayashi H. Tetrahedron Lett.  1992,  33:  337 
• 6h Ichikawa J. Moriya T. Sonoda T. Kobayashi H. Chem. Lett.  1991,  20:  961 
• 6i Ichikawa J. Sonoda T. Kobayashi H. Tetrahedron Lett.  1989,  30:  1641 
• 6j Ichikawa J. Sonoda T. Kobayashi H. Tetrahedron Lett.  1989,  30:  5437 
• 6k Ichikawa J. Sonoda T. Kobayashi H. Tetrahedron Lett.  1989,  30:  6379 
• 6l Tanaka K. Nakai T. Ishikawa N. Tetrahedron Lett.  1978,  4809 
• 6m Percy JM. Tetrahedron Lett.  1990,  31:  3931 
• 7a Fustero S. Sanz-Cervera JF. Aceña JL. Sánchez-Roselló M. Synlett  2009,  525 
• 7b Zhi L, Van Oeveren CA, Chen J.-H, and Higuchi RI. inventors; PCT Int. Appl., WO 2002066475,  A220020829. 
• 7c Kudo Y, Katsumata A, Maeda K, Akiyama S, Yaosaka M, Morimoto K, Nakahira K, Ohki T, Hamada N,
  Yano T, Noguchi J, and Watanabe S. inventors; PCT Int. Appl., WO 2001068613,  A120010920. 
• 7d Okamoto H, and Kato S. inventors; Jpn. Kokai Tokkyo Koho, JP 02178259,  A19900711. 
• 7e Haszeldine RN. Tipping AE.
  J. Chem. Soc. C  1968,  4:  398 
• 8a Nguyen TB. Vuong TMH. Martel A. Dhal R. Dujardin G. Tetrahedron: Asymmetry  2008,  19:  2084 
• 8b Nguyen TB. Martel A. Dhal R. Dujardin G. Synlett  2008,  2041 
• 8c Nguyen TB. Martel A. Dhal R. Dujardin G. J. Org. Chem.  2008,  73:  2621 
• 8d Nguyen TB. Gaulon C. Chapin T. Tardy S. Tatibouet A. Rollin P. Dhal R. Martel A. Dujardin G. Synlett  2006,  3255 
• 9a Gohier F. Bouhadjera K. Faye D. Gaulon C. Maisonneuve V. Dujardin G. Dhal R. Org. Lett.  2007,  9:  211 
• 9b Gaulon C. Dhal R. Chapin T. Maisonneuve V. Dujardin G. J. Org. Chem.  2004,  69:  4192 
• 9c Gaulon C. Gizecki P. Dhal R. Dujardin G. Synthesis  2003,  2269 
• 9d Gaulon C. Gizecki P. Dhal R. Dujardin G. Synlett  2002,  952 
• 10a Feiring AE. Wonchoba ER. J. Org. Chem.  1992,  57:  7014 
• 10b Dlouba I. Kvicala J. Paleta O. J. Fluorine Chem.  2002,  117:  149 
• 12 Dhavale DD. Trombini C. J. Chem. Soc., Chem. Commun.  1992,  1268 
• 14 Amiii H. Kobayashi T. Terasawa H. Uneyama K. Org. Lett.  2001,  3:  3103 

11

Procedures and compounds are described in the Supplementary Information.

13

Only minor adduct 9b, of cis configuration, could be separated from the adduct mixture by column chroma-tography.

15

From the NMR study on adduct 11b, the cis/trans distribution (cis I/cis II/trans I/trans II = 52:22:18:8) was deduced.