M. Amongero, T. S. Kaufman / Tetrahedron Letters 54 (2013) 1924–1927
1927
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In conclusion, a two-stage organocatalytic enantioselective ap-
proach to the synthesis of 1,2,3-trisubstituted azetidines, which
does not require protective groups, was developed; its scope and
limitations were studied. Overall chemical and optical yields were
highly satisfactory; however, the one-pot synthesis of the interme-
diate c-aminoalcohols was influenced by steric and electronic fac-
tors, sometimes resulting in unsuccessful transformations. Due to
its simplicity and effectiveness, the sequence may find use in syn-
thetic organic chemistry.
Acknowledgments
The authors are thankful to Agencia Nacional de Promoción
Científica
y Tecnológica, Consejo Nacional de Investigaciones
Científicas y Técnicas (CONICET), Fundación Josefina Prats and Sec-
retaría de Ciencia y Tecnología-UNR for the financial support.
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c
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microwave irradiation at 70 °C for 1 h. Then, brine (10 mL) was added and the
organic materials were extracted with EtOAc (4 ꢂ 20 mL). The organic phases
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methoxyphenyl)-3-methyl-2-(4-nitrophenyl)azetidine: IR (film,
m
): 2957, 2850,
1598, 1465, 1452, 1343, 1239, 1221, 1140, 1027, 849, 823 and 745 cmꢀ1
;
1H
NMR (300 MHz, CDCl3) d: 0.89 (d, J = 7.3, 3H), 2.95 (ddd, J = 3.0, 7.3 and 8.3,
1H), 3.61 (dd, J = 3.0 and 6.4, 1H), 3.75 (s, 3H), 3.79 (s, 3H), 3.92 (dd J = 6.4 and
7.3, 1H), 5.07 (d, J = 8.3, 1H), 5.86 (dd, J = 2.6 and 8.6, 1H), 6.03 (d, J = 2.6, 1H),
6.71 (d, J = 8.6, 1H), 7.52 (d, J = 8.7, 2H) and 8.23 (d, J = 8.7, 2H); 13C NMR d:
16.2, 29.9, 55.8, 56.7, 57.0, 68.6, 97.7, 103.5, 112.9, 123.6 (2C), 127.5 (2C),
142.2, 146.2, 147.2, 147.5 and 149.9. HRMS obsd.: m/z 329.1490; C18H21N2O4
requires m/z 329.1496. (2S,3R)-2-(3,4,5-Trimethoxyphenyl)-1-(3,4-dimetho-
10. (a) Kozikowski, A. P.; Tueckmantel, W.; Reynolds, I. J.; Wroblewski, J. T. J. Med.
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xyphenyl)-3-methylazetidine: IR (film,
m): 2955, 2849, 1680, 1588, 1501, 1140,
1349, 1209, 1033 and 795 cmꢀ1 1H NMR (300 MHz, CDCl3) d: 0.95 (d, J = 7.0,
;
3H), 2.81 (ddt, J = 2.9, 7.0 and 8.2, 1H), 3.54 (dd, J = 2.9 and 6.6, 1H), 3.75 (s, 3H),
3.79 (s, 3H), 3.84 (s, 6H), 3.85 (dd, J = 6.6 and 7.0), 3.87 (s, 3H), 4.89 (d, J = 8.2,
1H), 5.96 (dd, J = 2.6 and 8.7, 1H), 6.08 (d, J = 2.6, 1H), 6.57 (s, 2H), 6.72 (d,
J = 8.7, 1H); 13C NMR d: 15.9, 30.1, 55.8, 56.2 (2C), 56.7, 56.9, 60.9, 70.0, 98.0,
103.5 (2C), 103.8, 112.9, 135.5, 136.7, 141.9, 147.3, 149.7 and 153.2 (2C). HRMS
obsd.: m/z 396.1781; C21H27NNaO5 requires m/z 396.1781.