(2R, 3S)-3-Hydroxy-2-methyl-1-morpholino-5-phenylpentan-1-one

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 (2R, 3S)-3-Hydroxy-2-methyl-1-morpholino-5-phenylpentan-1-one (4), 97% ee , as white solid, mp 76-78 °C










 (S)-MTPA ester of (-)-4:  

¹⁹F (CDCl₃) δ: -70.88; ¹H (400 MHz, CDCl₃) δ: 1.14 (d, J = 6.9 Hz, 3H), 1.96 (m, 2H), 2.49 (t, J = 8.0 Hz, 2H), 2.91 (quint, J = 6.8 Hz, 1H), 3.32 (m, 2H), 5.42 (m, 1H).

Partial data for the (R)-MTPA ester of (-)-4: ¹⁹F (CDCl₃) δ: -70.81; ¹H (400 MHz, CDCl₃) δ: 1.06 (d, J = 6.9 Hz, 3 H), 2.00 (m, 2 H), 2.61 (m, 2 H), 2.89 (quint, J = 6.9 Hz, 1 H), 3.29 (m, 2H), 5.46 (m, 1 H).



  Syn-4 exhibits the following properties: white solid; mp 76-78 °C; [∝]_D^22.8 = -10.7 (c = 0.25, CHCl₃);  

¹H NMR pdf(400 MHz, CDCl₃) δ: 1.15 (d, J = 7.2 Hz, 3 H), 1.51-1.62 (m, 1 H), 1.92 (dtd, J = 5.4, 9.3, 13.6 Hz, 1 H), 2.52 (dq, J = 2.1, 7.2 Hz, 1 H), 2.68 (ddd, J = 7.1, 9.2, 13.8 Hz, 1 H), 2.88 (ddd, J = 5.2, 9.4, 14.3 Hz, 1 H), 3.43 (br t, J = 4.8 Hz, 2 H), 3.51-3.71 (m, 6 H), 3.93 (ddd, J = 2.1, 3.8, 9.4 Hz, 1 H), 4.39 (s, 1 H), 7.16-7.24 (m, 3 H), 7.26-7.31 (m, 2 H);  

¹³C NMR pdf(100 MHz, CDCl₃) δ: 10.2, 32.5, 35.7, 39.0, 41.9, 46.2, 66.8, 66.9, 70.5, 126.0, 128.5 (2C), 128.7 (2C), 142.2, 176.3; IR (neat) 3428, 2921, 2857, 1616, 1454, 1434, 1224, 1114, 1025 cm^-1;

HRMS (ESI) calcd for C₁₆H₂₃NNaO₃ [M+Na]⁺ 300.1570. Found 300.1572; Anal. calcd for C₁₆H₂₃NO₃: C, 69.29; H, 8.36; N, 5.05. Found: C, 69.15; H, 8.41; N, 5.07.

The diastereomer ratio (syn-4/anti-4) was determined to be >20:1 from the ratio of resonance integrations at 1.13-1.17 ppm (methyl substituent of syn isomer) and 1.17-1.21 ppm (methyl substituent of anti isomer-see Note 11). Both isomers co-elute by TLC analysis.

The anti-4 diastereomer was prepared in low yield (with d.r. ca. 8:1 ) from syn-4 by Mitsunobu reaction and exhibits the following properties: colorless oil; [∝]_D^26.4 = -9.4 (c = 0.54, CHCl₃);

¹H NMR (400 MHz, CDCl₃) δ: 1.20 (d, J = 7.1 Hz, 3 H), 1.70-1.85 (m, 2 H), 2.59-2.73 (m, 2 H), 2.92 (ddd, J = 5.4, 9.4, 13.7 Hz, 1 H), 3.44-3.49 (m, 2 H), 3.56-3.71 (m, 7 H), 3.94 (d, J = 6.4 Hz, 1 H), 7.16-7.23 (m, 3 H), 7.26-7.31 (m, 2 H);

¹³C NMR (100 MHz, CDCl₃) δ: 15.3, 32.3, 37.2, 40.2, 41.8, 46.1, 66.7, 66.9, 73.4, 125.8, 128.4 (2C), 128.5 (2C), 142.2, 175.1;


 IR (neat) 3426, 3026, 2922, 2857, 1614, 1496, 1454, 1435, 1361, 1301, 1268, 1220, 1113, 1069, 1026, 934, 846 cm^-1.

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