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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
› Institutsangaben
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Publikationsverlauf

Received: 18. April 2012

Accepted after revision: 14. Juni 2012

Publikationsdatum:
26. Juli 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

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  • 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