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Synlett 2012; 23(13): 1947-1949
DOI: 10.1055/s-0032-1316705
letter
© Georg Thieme Verlag Stuttgart · New York

Ti(Oi-Pr)4-Promoted Regio- and Stereoselective Aminolysis of 2,3-Epoxy Amides

Giuliana Righi*
a   CNR-Istituto di Chimica Biomolecolare- c/o Dip. Chimica, Sapienza Università di Roma, p.le A. Moro 5, 00185 Roma, Italy
,
Agnese Mantineo
b   Dip. Chimica, Sapienza Università di Roma, p.le A. Moro 5, 00185 Roma, Italy
,
Lorenza Suber
c   CNR-Istituto di Struttura della Materia, Via Salaria km 29, 300-00015 Monterotondo Scalo (Roma), Italy, Fax: +39(6)49913628   Email: giuliana.righi@cnr.it
,
Alessandra Mari*
b   Dip. Chimica, Sapienza Università di Roma, p.le A. Moro 5, 00185 Roma, Italy
› Author Affiliations
Further Information

Publication History

Received: 18 April 2012

Accepted after revision: 14 June 2012

Publication Date:
26 July 2012 (online)

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Abstract

A mild and inexpensive Ti(Oi-Pr)4-mediated aminolysis of 2,3-epoxy amides has been developed. The reaction proceeds with excellent regioselectivity, regardless of the steric hindrance of the substituents on the heterocyclic ring, providing vicinal amino alcohols that are very suitable for synthetic applications.

Key words

amides - diastereoselectivity - epoxides - regioselectivity - ring opening
 

  • References and Notes

    • 1a Padwa A, Murphree SS. ARKIVOC 2006; (iii): 6
    • 1b Bergmeier SC. Tetrahedron 2000; 56: 2561
      Crossref
    • 2a Connolly ME, Kersting F, Bollery CT. Prog. Cardio. Dis. 1976; 19: 203
    • 2b Bose DS, Narsaiah AV. Bioorg. Med. Chem. 2005; 3: 627
    • 2c Erhardt PW, Woo CW, Anderson WG, Gorczynski AR. J. Med. Chem. 1982; 25: 1408
      Crossref
    • 2d Zhu S, Meng L, Zhang Q, Wei L. Bioorg. Med. Chem. Lett. 2006; 16: 1854
      Crossref
    • 3a Schirok H. J. Org. Chem. 2006; 71: 5538
      Crossref
    • 3b Zhu S, Meng L, Zhang Q, Wei L. Bioorg. Med. Chem. Lett. 2006; 16: 1854
      Crossref
    • 3c Lindsay KB, Pyne SG. Tetrahedron 2004; 60: 4173
      Crossref
    • 3d Alikhani V, Beer D, Bentley D, Bruce I, Cuenoud BM, Fairhurst RA, Gedeck P, Haberthuer S, Hayden C, Janus D, Jordan L, Lewis C, Smithies K, Wissler E. Bioorg. Med. Chem. Lett. 2004; 14: 4705
      Crossref
    • 3e Ruediger E, Martel A, Meanwell N, Solomon C, Turmel B. Tetrahedron Lett. 2004; 45: 739
      Crossref
    • 3f Erdeen I. Comprehensive Heterocyclic Chemistry II . Vol. IA. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 97
      CrossrefGoogle Scholar
  • 4 Ager DJ, Prakash I, Schaad SR. Chem. Rev. 1996; 96: 835
    CrossrefPubMed
  • 5 Sello G, Orsini F, Bernasconi S, Di Gennaro P. Tetrahedron: Asymmetry 2006; 17: 372 ; and references cited therein
    Crossref
    • 6a Narsaiah AV, Wadavrao SB, Reddy AR, Yadav JS. Synthesis 2011; 485
      Article in Thieme Connect
    • 6b William DB, Cullen A. J. Org. Chem 2009; 74: 9509
      Crossref
    • 6c Chakraborti AK, Kondaskar A, Rudrawar S. Tetrahedron 2004; 60: 9085
      Crossref
    • 6d Kamble VT, Joshi NS. Green Chem. Lett. Rev. 2010; 3: 275
    • 6e Chimni SS, Bala N, Dixit VA, Bharatam V. Tetrahedron 2010; 66: 3042
      Crossref
    • 6f Duran PachonL, Gamez P, van Brussel JJ. M, Reedijk J. Tetrahedron Lett. 2003; 44: 6025
      Crossref
    • 6g Lindstrom UM, Olofsson B, Somfai P. Tetrahedron Lett. 1999; 40: 9273
      Crossref
    • 6h Chini M, Crotti P, Favero L, Macchia F, Pineschi M. Tetrahedron Lett. 1994; 35: 433
      Crossref
    • 7a Sarabia F, Sánchez-Ruiz A. J. Org. Chem. 2005; 70: 9514
      Crossref
    • 7b Pino-González MS, Assiego C. Tetrahedron: Asymmetry 2005; 16: 199
      Crossref
    • 7c Nikolai AK, Hesse M. Helv. Chim. Acta 2003; 86: 2028
      Crossref
    • 7d Prabhakaran EN, Nageswara Rao I, Boruah A, Iqbal J. J. Org. Chem. 2002; 67: 8247
      Crossref
    • 7e Valpuesta M, Durante P, Upez-Herrera FJ. Tetrahedron Lett. 1995; 36: 4681
      Crossref
  • 8 Azzena F, Calvani F, Crotti P, Gardelli C, Macchia F, Pineschi M. Tetrahedron 1995; 51: 10601
    Crossref
  • 9 Chong JM, Sharpless KB. J. Org. Chem. 1985; 50: 1560
    Crossref
    • 10a Righi G, Bonini C In Targets in Heterocyclic Systems . Attanasi O, Spinelli D. Società Chimica Italiana; Roma: 2000
      Google Scholar
    • 10b Righi G, Ciambrone S. Tetrahedron Lett. 2004; 45: 2103
      Crossref
    • 10c Righi G, Pietrantonio S, Bonini C. Tetrahedron 2001; 57: 10039
      Crossref
  • 11 The N-allyl group was chosen because of our specific interest in the preparation of optically active functionalized nanoparticles.
  • 12 Caron M, Sharpless KB. J. Org. Chem. 1985; 50: 1557
    Crossref
  • 13 HPLC analysis was performed with a VYDAC reverse-phase C18 column (25 cm by 4.6 mm); MeCN–H2O containing 0.1% TFA, 25:75 to 35:65; flow rate: 1.0 mL; UV detection: 254 nm
  • 14 General procedure: A mixture of 2,3-epoxy amide (1 mmol), amine (excess, 1 mL), and Ti(Oi-Pr)4 (1.5 mmol) was stirred at the required temperature for 12 h. After this time, EtOAc was added and the organic phase was washed with aqueous tartaric acid solution (0.5 M), dried over Na2SO4, and concentrated in vacuo. The crude product was purified by silica gel column chromatography (CH2Cl2–MeOH, 95:5, 0.2% NH4OH). Compound 3: 1H NMR (300 MHz, CDCl3): δ = 0.80–0.95 (m, 9 H), 1.15–1.65 (m, 12 H), 2.21–2.67 (m, 4 H), 2.74–2.85 (m, 1 H), 3.76–3.85 (m, 2 H), 3.89 (d, J = 7.1 Hz, 1 H), 4.59 (br s, 1 H), 5.04–5.20 (m, 2 H), 5.69–5.85 (m, 1 H), 7.80 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 20.5, 21.2, 27.5, 31.4, 41.5, 51.1, 63.6, 68.8, 116.5, 133.9, 173.4. Compound 8: 1H NMR (300 MHz, CDCl3): δ = 0.83 (t, J = 6.6 Hz, 3 H), 1.11–1.81 (m, 10 H), 2.34–2.51 (m, 2 H), 2.54–2.76 (m, 3 H), 3.76–3.84 (m, 2 H), 3.88 (d, J = 7.1 Hz, 1 H), 4.30 (br s, 1 H), 5.01–5.22 (m, 2 H), 5.67–5.86 (m, 1 H), 8.10 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 14.1, 21.2, 24.3, 26.5, 27.8, 41.3, 50.5, 67.4, 68.6, 116.1, 133.9, 173.48. Compound 9: 1H NMR (300 MHz, CDCl3): δ = 0.85 (t, J = 7.1 Hz, 3 H), 1.31–1.81 (m, 4 H), 2.53–2.63 (m, 2 H), 2.64–2.76 (m, 3 H), 3.57–3.76 (m, 5 H), 3.86–3.91 (m, 2 H), 4.11 (d, J = 7.15 Hz, 1 H), 5.10–5.23 (m, 2 H), 5.74–5.91 (m, 1 H), 7.65 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 14.2, 20.9, 27.8, 41.5, 50.0, 66.8, 67.4, 69.1, 116.5, 133.8, 173.4. Compound 10: 1H NMR (300 MHz, CDCl3): δ = 0.85–0.97 (m, 6 H), 1.21–1.65 (m, 12 H), 2.21–2.67 (m, 3 H), 2.91–3.05 (m, 1 H), 3.78–3.85 (m, 2 H), 4.01 (d, J = 7.2 Hz, 1 H), 4.21 (br s, 1 H), 5.04–5.20 (m, 2 H), 5.69–5.85 (m, 1 H), 7.69 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 17.9, 20.3, 21.2, 23.1, 27.5, 31.0, 41.2, 53.1, 56.8, 69.8, 116.3, 133.9, 172.4. Compound 11: 1H NMR (300 MHz, CDCl3): δ = 0.74–2.02 (m, 17 H), 2.41–2.56 (m, 1 H), 3.06–3.22 (m, 2 H), 3.79–3.98 (m, 2 H), 4.01–4.07 (m, 1 H), 5.06–5.24 (m, 2 H), 5.73–5.87 (m, 1 H), 7.21 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 19.1, 24.9, 25.0, 31.0, 33.5, 34.3, 41.0, 53.9, 56.4, 71.3, 116.1, 133.9, 172.1. Compound 12: 1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 7.1 Hz, 3 H), 1.24–1.57 (m, 4 H), 3.72–3.99 (m, 4 H), 4.28 (d, J = 1.6 Hz, 1 H), 5.04–5.27 (m, 2 H), 5.66–5.88 (m, 1 H), 6.57–6.78 (m, 3 H), 6.93–7.07 (br s, 1 H), 7.07–7.21 (m, 3 H). 13C NMR (75.4 MHz, CDCl3): δ = 14.2, 19.7, 31.6, 33.9, 41.3, 41.6, 55.5, 72.3, 113.8, 116.8, 117.5, 129.6, 133.9, 147.3, 172.7. Compound 13: 1H NMR (300 MHz, CDCl3): δ = 0.85–0.95 (m, 9 H), 1.21–1.65 (m, 12 H), 2.20–2.65 (m, 4 H), 2.79 (d, J = 2.1 Hz, 3 H), 2.81–2.95 (m, 2 H), 3.91 (d, J = 7.2 Hz, 1 H), 6.09 (br s, 1 H). 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 20.4, 21.1, 25.7, 27.4, 31.4, 41.5, 63.6, 68.8, 173.4. Compound 14: 1H NMR (300 MHz, CDCl3): δ = 0.82–0.95 (m, 9 H), 1.15–1.67 (m, 12 H), 2.23–2.65 (m, 4 H), 2.73–2.83 (m, 1 H), 3.91 (d, J = 7.1 Hz, 1 H), 4.39 (d, J = 14.5 Hz, 1 H), 4.42 (d, J = 14.5 Hz, 1 H), 4.62 (br s, 1 H), 6.39 (br s, 1 H), 7.05–7.37 (m, 5 H). 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 20.5, 21.2, 27.5, 31.4, 41.5, 55.4, 63.6, 68.8, 139.7, 128.5, 128.1, 126.8, 168.2. Compound 20: 1H NMR (300 MHz, CDCl3): δ = 0.84–1.97 (m, 13 H), 3.10–3.24 (m, 1 H), 3.76–4.12 (m, 4 H), 4.65 (d, J = 5.6 Hz, 1 H), 5.05–5.33 (m, 2 H), 5.76–5.94 (m, 1 H), 6.76 (br s, 1 H), 7.08–7.68 (m, 5 H). 13C NMR (75.4 MHz, CDCl3): δ = 26.0, 26.2, 28.4, 29.5, 30.2, 41.3, 47.1, 51.4, 63.9, 70.2, 116.3, 126.8, 128.1, 128.4, 130.6, 134.3, 175.0