9310
C. Alemany et al. / Tetrahedron 56 (2000) 9305±9312
0.5 mmol) and methyl iodide (50 mL, 0.8 mmol) were
added and the mixture was stirred at rt for 4 h. The reaction
was quenched by addition of water (1 mL) and extracted
with CH2Cl2. The organic layer was dried over MgSO4,
®ltered and carefully concentrated in vacuo. The residue
was puri®ed by ¯ash chromatography (CH2Cl2/MeOH
95:5) to yield methyl (3S,4S)-3-hydroxy-4-methylhexano-
ate, 16, (20 mg, 62%) as a very volatile liquid. Rf 0.50
(3S,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-5-phenyl-
pentanoic acid (5e). Mp 149±1508C [lit.35 148±148.58C];
Rf 0.40 (CH2Cl2/MeOH/AcOH 95:5:1); H NMR (CD3OD,
200 MHz) d 1.34 (s, 9H), 2.43 (m, 2H), 2.69 (dd, 1H, J9.0,
13.5 Hz), 2.86 (dd, 1H, J5.8, 14.0 Hz), 3.77 (m, 1H), 4.05
(m, 1H), 6.25 (broad d, J8.7 Hz, NH), 7.20±7.35 (m, 5H);
13C NMR (CD3OD, 50.3 MHz) d 28.7, 38.8, 40.1, 57.3,
69.9, 79.5, 127.2, 128.5, 129.3, 140.1, 158.2, 182.4; IR
(KBr) 3360, 2927, 1711, 1690. [a]2D0239.0 (c 1.4,
MeOH) [lit.35 237.0, lit.36 239.0].
1
1
(CH2Cl2/MeOH 95:5); H NMR d 0.91 (t, 3H, J6.8 Hz),
0.92 (d, 3H, J7.1 Hz), 1.15 (m, 1H), 1.40 (m, 2H), 2.46
(dd, 1H, J10.0, 16.3 Hz), 2.47 (dd, 1H, J2.2, 16.3 Hz),
3.01 (broad s, OH), 3.71 (s, 3H), 3.95 (m, 1H); 13C NMR d
11.7, 13.8, 25.9, 37.7, 39.8, 51.8, 71.6, 174.0; IR (neat)
3400±3000, 2980, 2920, 1740; [a]2D0232.8 (c 1.0,
CHCl3) [lit.26 233.0]; MS (NH3/CI) m/z (rel. int.) 178
(100, [M1NH14 ]).
(3R,4S)-5-Benzyloxy-3-hydroxy-4-methylpentanoic acid
(6b).37 Oil; Rf 0.13 (CH2Cl2/MeOH 95:5); 1H NMR d
0.93 (d, 3H, J6.9 Hz), 1.95 (m, 1H), 2.47 (dd, 1H,
J8.7, 15.9 Hz), 2.58 (dd, 1H, J3.3, 15.9 Hz), 3.51 (dd,
1H, J6.9, 9.3 Hz), 3.57 (dd, 1H, J5.1, 9.3 Hz), 4.00
(m, 1H), 4.52 (s, 2H), 6.40 (broad s, 2H, OH), 7.20±7.40
(m, 5H); 13C NMR d 13.6, 38.1, 39.2, 71.8, 73.4, 73.9,
127.6, 127.7, 128.4, 137.6, 175.4; IR (neat) 3400±3000,
1725, 1452; [a]2D0117.8 (c 1.1, CHCl3); MS (NH3/CI)
m/z (rel. int.) 256 (100, [M1NH14 ]). HRMS calcd for
C13H19O4 (M111) 239.1283, found 239.1288.
In a similar way, hydroboration of alcohol 13a with dicyclo-
hexylborane followed by treatment with saturated aq.
NaHCO3 and 30% H2O2 gave 82% yield of crude (3R,4S)-
3-hydroxy-4-methylhexanoic acid which was then trans-
formed without puri®cation into its methyl ester
(NaHCO3/MeI/DMF, 50%), methyl (3R,4S)-3-hydroxy-4-
methylhexanoate, 17:26 oil; Rf 0.50 (CH2Cl2/MeOH 95:5);
1H NMR d 0.89 (t, 3H, J7.1 Hz), 0.92 (d, 3H, J7.1 Hz),
1.20 (m, 1H), 1.50 (m, 2H), 2.41 (dd, 1H, J10.0, 16.3 Hz),
2.49 (dd, 1H, J2.2, 16.3 Hz), 3.01 (broad s, OH), 3.71
(s, 3H), 3.87 (m, 1H); 13C NMR d 11.4, 14.4, 24.9, 37.7,
39.8, 51.8, 71.6, 174.0; IR (neat) 3400±3000, 2980, 2920,
1740; [a]2D0134.8 (c 0.5, CHCl3) [lit.25 132.37]; MS
(NH3/CI) m/z (rel. int.) 178 (100, [M1NH14 ]).
(3R,4S)-4-Methoxy-5-phenylpentanoic acid (6c). Oil; Rf
0.10 (CH2Cl2/MeOH 95:5); 1H NMR d 2.59 (dd, 1H,
J8.7, 16.5 Hz), 2.69 (dd, 1H, J3.3, 16.5 Hz), 2.85 (d,
2H, J6.3 Hz), 3.31 (s, 3H), 3.44 (m, 1H), 4.00 (m, 1H),
7.15±7.30 (m, 5H); 13C NMR d 36.2, 36.7, 58.6, 69.0, 84.5,
126.4, 128.4, 129.4, 138.0, 178.0; IR (neat) 3400±3300,
1730; [a]2D019.1 (c 0.9, CHCl3); MS (NH3/CI) m/z (rel.
int.) 242 (100, [M1NH14 ]). HRMS calcd for C12H17O4
(M111) 225.1127, found 225.1122.
(3S,4S)-5-Benzyloxy-3-hydroxy-4-methylpentanoic acid
(5b). Oil; Rf 0.13 (CH2Cl2/MeOH 95:5); H NMR d 0.97
1
(3R,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-6-methyl-
heptanoic acid (6d). Mp 132±1348C [lit.34 135±1368C]; Rf
0.07 (CH2Cl2/MeOH 95:5); 1H NMR d 0.91 (d, 3H,
J6.6 Hz), 0.94 (d, 3H, J6.6 Hz), 1.32 (m, 2H), 1.45
(s, 9H), 1.66 (m, 1H), 2.59 (m, 2H), 3.70 (m, 1H), 4.01
(broad s, 1H), 4.72 (d, 1H, J8.1 Hz, NH), 5.90 (broad s,
1H, OH); 13C NMR d 21.5, 23.5, 24.7, 28.3, 37.2, 38.8, 53.0,
71.4, 80.1, 156.6, 175.8; IR (KBr) 3340, 1716, 1686;
[a]2D0225.3 (c 0.2, MeOH) [lit.34 227.6].
(d, 3H, J6.9 Hz), 1.99 (m, 1H), 2.46 (dd, 1H, J3.6,
16.2 Hz), 2.56 (dd, 1H, J9.6, 16.2 Hz), 3.50 (dd, 1H,
J6.9, 9.3 Hz), 3.56 (dd, 1H, J4.5, 9.3 Hz), 4.22
(m, 1H), 4.50 (d, 1H, J12.0 Hz), 4.54 (d, 1H,
J12.0 Hz), 7.20±7.40 (m, 5H); 13C NMR d 11.2, 37.6,
38.3, 70.3, 73.5, 73.7, 127.6, 127.8, 128.5, 137.6, 175.4;
IR (neat) 3400±3000, 1715, 1455, 1180; [a]2D028.8
(c 1.8, CHCl3); MS (NH3/CI) m/z (rel. int.) 256 (100,
[M1NH14 ]). HRMS calcd for C13H19O4 (M111)
239.1283, found 239.1278.
(3R,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-5-phenyl-
pentanoic acid (6e). Mp 183±1858C [lit.35 187.58C]; Rf
0.33 (CH2Cl2/MeOH/AcOH 95:5:1); 1H NMR (CD3OD,
200 MHz) d 1.18 (s, 9H), 2.36 (dd, 1H, J9.3, 15.6 Hz),
2.54 (m, 2H), 3.07 (dd, 1H, J3.3, 13.9 Hz), 3.61 (m, 1H),
3.90 (m, 1H), 6.40 (broad d, J10.9 Hz, NH), 7.10±7.25
(m, 5H); 13C NMR (CD3OD, 50.3 MHz) d 28.7, 37.7, 40.2,
58.0, 72.0, 79.9, 127.1, 129.2, 130.4, 140.2, 153.9, 175.7; IR
(KBr) 3355, 3000, 1700, 1680; [a]2D0217.2 (c 1.4, MeOH)
[lit.35 216.1]; HRMS calcd for C16H24NO5 (M111)
310.1654, found 310.1647.
(3S,4S)-4-Methoxy-5-phenylpentanoic acid (5c). Oil; Rf
0.10 (CH2Cl2/MeOH 95:5); 1H NMR d 2.53 (dd, 1H,
J4.2, 16.0 Hz), 2.65 (dd, 1H, J8.2, 16.0 Hz), 2.89 (m,
2H), 3.32 (s, 3H), 3.33 (m, 1H), 3.98 (m, 1H), 7.15±7.35 (m,
5H); 13C NMR d 36.1, 38.2, 58.6, 68.2, 84.3, 126.3, 128.4,
129.4, 137.9, 176.8; IR (neat) 3400±3300, 1730;
[a]2D013.2 (c 1.7, CHCl3); MS (NH3/CI) m/z (rel. int.)
242 (100, [M1NH14 ]). HRMS calcd for C12H17O4
(M111) 225.1127, found 225.1120.
(3S,4S)-4-(tert-Butoxycarbonylamino)-3-hydroxy-6-methyl-
heptanoic acid (5d). Mp 115±1168C [lit.34 117±1188C]; Rf
0.13 (CH2Cl2/AcOEt 9:1); 1H NMR d 0.92 (d, 6H,
J6.2 Hz), 1.25 (m, 2H), 1.46 (s, 9H), 1.72 (m, 1H), 2.53
(m, 2H), 3.65 (m, 1H), 4.01 (broad s, 1H), 4.83 (d, 1H,
J8.7 Hz, NH); 13C NMR d 22.1, 23.0, 24.7, 28.3, 39.7,
41.4, 52.1, 69.8, 79.6, 156.4, 177.8; IR (KBr) 3340, 1716,
1686; [a]2D0238.4 (c 1.0, MeOH) [lit.34 239.6].
Representative procedure for reduction of cobalt
complexes
Reduction of 14a with BH3:SMe2 catalysed by 15. To a
solution of of Co2(CO)8 (250 mg, 0.66 mmol) in anh. pen-
tane (2 mL) under Ar at rt, a solution of ketone 10a (115 mg,
0.63 mmol) in anh. pentane (1 mL) was added via cannula.
The dark red solution was stirred at rt After 2 h, TLC