Page 228 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

216 hydrolysis, oxidation and reduction

Ethyl (3R,4R)-4-(acetamido)-3-hydroxy-5-phenylpentanoate (2)
1 H NMR (270 MHz, CDCl 3 ): d 1.28 (3H, t, J ˆ 6.9 Hz), 1.99 (3H, s), 2.38 (2H,
ABX, J ˆ 3.0, 17.3 Hz), 2.57 (1H, ABX, J ˆ 10.3, 17.3 Hz), 2.91 (2H, d, J ˆ
7.6 Hz), 3.60±4.05 (2H, m), 4.15 (2H, q, J ˆ 6.9 Hz), 5.83±5.87 (1H, m), 7.19±7.49
(5H, m, aromatic).
13 C NMR (67.5 MHz, CDCl 3 ). d 173.5, 170.0, 137.9, 129.3, 128.6, 126.5,
66.8, 60.9, 53.9, 38.6, 38.2, 23.4, 14.1.
ÿ1
IR(CHCl 3 ) 3350, 2922, 1729, 1647, 1537, 1372, 1295 cm ; MS (EI, 70 eV)
279 (M , 11 %), 220 (9), 192 (14), 167 (19), 149 (68), 135 (49).
‡
HRMS (EI, 70 eV) calculated for C 14 H 15 NO 4 279.1471 (M ), found
‡
279.1434.
HPLC (Silica gel 60±5 mm, 7.5 o.d.x 300 mm, elution with 12 % 2-propanol in
hexane, 3.0 mL/min) Rt 29±33 min; [a] D 25 ˆ ‡69:08 (c ˆ 0.116, MeOH) (>95 %
ee).
‡
Use of [Rh(cod)(S, S)-diop] CiO ÿ [8] instead of [Rh(cod)(S)-BINAP] CiO ÿ
‡
4 4
gave its diastereomer 3 with 72 % stereoselectivity and >95 % ee.
Ethyl (3R,4S)-4-(acetamido)-3-hydroxy-5-phenylpentanoate (3)
1
H NMR (270 MHz, CDCl 3 ): d 1.28 (3H, t, J ˆ 6.9 Hz), 1.88 (3H, s), 2.53 (3H,
m), 2.87 (1H, ABX, J ˆ 8.6, 14.0 Hz), 2.99 (1H, ABX, J ˆ 4.6, 14.0 Hz), 3.76±
4.15 (2H, m), 4.20 (2H, q, J ˆ 6.9 Hz), 5.53±5.49 (1H, m), 7.19±7.53 (5H, m,
aromatic).
13 C NMR (67.5 MHz, CDCl 3 ): d 172.9, 169.1, 141.5, 129.3, 128.6, 126.7,
68.9, 60.9, 54.2, 38.2, 35.1, 23.3, 14.1.
ÿ1
IR (CHCl 3 ) 3350, 2922, 1729, 1647, 1537, 1372, 1295 cm .
MS (EI, 70 eV) 279 (M ), 220, 192, 174, 163, 135.
‡
HRMS (EI, 70 eV) calculated for C 14 H 15 NO 4 261.1471 (M ), found 261.1495.
‡
HPLC (Silica gel 60±5 mm, 7.5 o.d.x 300 mm, elution with 12 % 2-propanol in
hexane, 3.0 mL/min) Rt 34±40 min; [a] 25 ˆ ÿ55:58 (c ˆ 0.072, MeOH) (>95 %
D
ee).
Conclusion
A direct method for the respective preparation of the core units of statin
analogues (3R,4R)-2, (3S,4S)-2, (3R,4S)-3, and (3S,4R)-3 in enantiomerically
pure form is described. These analogues are prepared from the same molecule
1 in a one-pot, sequential asymmetric hydrogenation process utilizing Rh(I)-
and Ru(II)-chiral phosphine complexes. Some other examples are depicted in
Table 13.1.