T. Kawabata et al. / Tetrahedron 59 (2003) 965–974
971
Colorless oil: HPLC conditions: Daicel Chiralcpak AD,
hexane–2-propanol¼97:3, 0.6 mL/min, tR¼36, 49 (meso),
54 min. 1H NMR (400 MHz, CDCl3) d 7.30–7.20 (m, 10H),
7.10–7.02 (m, 4H), 4.87–4.55 (br m, 2H), 4.25–3.45 (br m,
8H), 3.24 (s, 6H), 3.00 (d, J¼13.6 Hz, 2H), 1.78–1.66 (m,
4H), 1.51, 1.48, 1.46 (three s, 24H). 1H NMR (400 MHz, d-
toluene, 1008C) d 7.06 (s, 10H), 5.04, 4.75 (br s and d,
J¼11.9 Hz, ratio¼1:3, 2H), 4.15–3.90 (m, 4H), 3.96 (d,
J¼11.9 Hz, 2H), 3.71, 3.37 (two d, J¼13.6, 13.6 Hz, 2H),
3.22 (s, 6H), 3.19, 3.12 (two d, J¼13.6, 13.6 Hz, 2H), 1.61,
1.51, 1.49 (three s, 10H), 1.42 (s, 18H). IR (neat) 2977,
1740, 1699, 1455, 1374, 1297, 1258, 1165, 1140, 1091,
757 cm21. MS m/z (rel intensity) 700 (Mþ, 0.1), 668 (1),
521 (2), 433 (20), 391 (20), 345 (100), 146 (60), 57 (60).
HRMS calcd for C38H56N2O10, Mþ 700.3935, found m/z
700.3923.
DnAB¼13.9 Hz, JAB¼6.8 Hz, 4H), 3.65 (d, J¼13.4 Hz, 2H),
3.31 (d, J¼13.4 Hz, 2H), 1.80–1.70 (m, 8H), 1.60–1.40 (m,
MS m/z (rel intensity) 634 (Mþ, 1), 543 (30), 513 (10), 422
(10), 266 (20), 238 (30), 105 (100). HRMS calcd for
C39H42N2O6, Mþ 634.3043, found m/z 634.3036.
4H). IR (neat) 2921, 2860, 1732, 1650, 1538, 1455 cm21
.
4.5.8. 2-(tert-Butoxycarbonyl-methoxymethylamino)-2-
methyl-3-phenylpropionic acid 2-{2-[2-(tert-butoxycar-
bonyl-methoxymethylamino)-2-methyl-3-phenyl-pro-
pionyloxy]-ethoxy}-ethyl ester (17). dl (68% ee): meso¼
2.2:1. Colorless oil. HPLC conditions: Daicel Chiralpak
AD, hexane–ethanol¼98:2, 0.8 mL/min, tR¼20, 26 (meso),
32 min. 1H NMR (400 MHz, CDCl3) d 7.30–7.20 (m, 6H),
7.11–7.04 (m, 4H), 5.15–4.20 (m, 4H), 4.27 (br t,
J¼4.7 Hz, 4H), 3.75–3.50 (m, 6H), 3.25 (s, 6H), 3.01 (d,
1
J¼13.3 Hz, 2H), 1.51, 1.49 (two s, 18H), 1.46 (s, 6H). H
4.5.5. 2-Benzyl-2-(tert-butoxycarbonyl-methoxymethyl-
amino)-pent-4-enoic acid 4-[2-benzyl-2-(tert-butoxycar-
bonyl-methoxymethylamino)-pent-4-enoyloxy]-butyl
ester (13). dl (52% ee): meso¼1.3:1. Colorless oil: HPLC
NMR (400 MHz, d-toluene, 1008C) d 7.06 (s, 10H), 4.76 (d,
J¼11.9 Hz, 2H), 4.25–4.10 (m, 4H), 3.96 (d, J¼11.9 Hz,
2H), 3.70 (d, J¼13.4 Hz, 4H), 3.50 (br t, J¼5.1 Hz, 8H),
3.23 (s, 6H), 3.12 (d, J¼13.4 Hz, 2H), 1.50 (s, 6H), 1.42 (s,
18H). IR (neat) 2978, 1740, 1698 cm21. MS m/z (rel
intensity) 716 (Mþ, 0.005), 656 (1.5), 593 (1.7), 537 (2.3),
361 (100), 349 (30), 146 (50). HRMS, m/z calcd for
C38H56N2O11: 716.3884, found: 716.3857.
conditions:
Daicel
Chiralpak
AD,
hexane–2-
propanol¼97:3, 1.0 mL/min, tR¼19, 27 (meso), 37 min.
1H NMR (400 MHz, CDCl3) d 7.30–7.20 (m, 6H), 7.10–
7.00 (m, 4H), 5.86–5.71 (m, 2H), 5.19, 5.18 (two d, J¼10.7,
17.2 Hz, 4H), 4.82–4.48 (br m, 2H), 4.20–3.95 (br m, 4H),
3.85–3.32 (br m, 4H), 3.27 (s, 6H), 3.14 (d, J¼13.6 Hz,
2H), 2.85–2.70 (br m, 2H), 2.61–2.50 (m, 2H), 1.71 (br s,
4H), 1.50 (s, 18H). 1H NMR (400 MHz, d-toluene, 1008C) d
7.06 (s, 10H), 5.92–5.80 (m, 2H), 5.09, 5.08 (two d, J¼19.6,
9.0 Hz, 4H), 4.70 (d, J¼12.1 Hz, 2H), 4.10–4.00 (m, 6H),
3.58 (d, J¼13.6 Hz, 2H), 3.28 (d, J¼13.6 Hz, 2H), 3.27 (s,
6H), 2.92 (dd, J¼7.0, 7.0 Hz, 2H), 2.70 (dd, J¼7.0, 7.0 Hz,
2H), 1.60 (s, 4H), 1.41 (s, 18H). IR (neat) 2978, 1741, 1698,
1454, 1405, 1373, 1295, 1218, 1175, 1136, 1082, 755,
705 cm21. MS m/z (rel intensity) 752 (Mþ, 0.1), 721 (0.5),
661 (1), 529 (10), 447 (10), 397 (30), 172 (30), 91 (30), 57
(100). HRMS calcd for C42H60N2O10, Mþ 752.4248, found
m/z 752.4263.
4.5.9. 2-Benzyl-2-(tert-butoxycarbonyl-methoxymethyl-
amino)-pent-4-enoic acid 2-{2-[2-benzyl-2-(tert-butoxy-
carbonyl-methoxymethylamino)-pent-4-enoyloxy]-
ethoxy}-ethyl ester (18). dl (76% ee): meso¼1.8:1. Color-
less oil. HPLC conditions: Daicel Chiralpak AD, hexane–
1
ethanol¼97:3, 0.8 mL/min, tR¼17, 20 (meso), 24 min. H
NMR (400 MHz, CDCl3, 208C) d 7.30–7.20 (m, 6H), 7.07–
7.05 (m, 4H), 5.85–5.75 (m, 2H), 5.20 (dd, J¼13.8, 2.0 Hz,
4H), 4.80–4.50 (m, 2H), 4.30–4.10 (m, 4H), 3.75–3.63 (m,
6H), 3.50–3.35 (m, 2H), 3.28 (s, 6H), 3.15 (d, J¼13.6 Hz,
2H), 2.85–2.74 (m, 2H), 2.57–2.52 (m, 2H), 1.51 (s, 18H).
1H NMR (400 MHz, d-toluene, 1008C) d 7.13–7.00 (m,
10H), 5.94–5.80 (m, 2H), 5.15–5.05 (m, 4H), 4.71 (d,
J¼11.8 Hz, 2H), 4.20–4.10 (m, 4H), 4.02 (d, J¼11.8 Hz,
2H), 3.58 (d, J¼13.8 Hz, 2H), 3.55–3.45 (m, 4H), 3.33–
3.24 (m, 8H), 2.94 (dd, J¼6.5, 6.5 Hz, 2H), 2.70 (dd, J¼6.5,
6.5 Hz, 2H), 1.41 (s, 18H). IR (neat) 2978, 1743,
1698 cm21. MS m/z (rel intensity) 768 (Mþ, 0.2) 737
(0.4), 645 (6), 557 (6), 463 (20), 413 (80), 172 (50), 57
(100). HRMS, m/z calcd for C42H60N2O11: 768.4197, found:
768.4175.
4.5.6. 2-(tert-Butoxycarbonyl-methoxymethylamino)-2-
methyl-3-phenylpropionic acid 5-[2-(tert-butoxycar-
bonyl-methoxymethylamino)-2-methyl-3-phenyl-pro-
pionyloxy]-pentyl ester (14). dl (74% ee): meso¼1.5:1.
Colorless oil. 1H NMR (400 MHz, CDCl3) d 7.30–7.20 (m,
6H), 7.08–7.04 (m, 4H), 4.85–4.55 (m, 2H), 4.20–4.00 (m,
4H), 3.75–3.50 (m, 4H), 3.25 (s, 6H), 3.00 (d, J¼13.6 Hz,
2H), 1.70–1.60 (m, 2H), 1.55–1.40 (m, 4H), 1.51 (s, 18H),
1.48 (s, 6H). IR (neat) 2977, 1739, 1699 cm21. MS m/z (rel
intensity) 714 (Mþ, 0.1) 682 (0.5), 591 (2.3), 503 (2.7), 359
(100), 267 (10), 178 (10), 146 (30). HRMS, m/z calcd for
C39H58N2O10: 714.4092, found: 714.4092. Determination
of the ratio of dl- to meso-isomers and ee of the dl-isomer
was performed with the corresponding benzoly derivative.
4.5.10. 2-(tert-Butoxycarbonyl-methoxymethylamino)-2-
methyl-3-phenylpropionic acid 2-({2-[2-(tert-butoxycar-
bonyl-methoxymethylamino)-2-methyl-3-phenyl-pro-
pionyloxy]-ethyl}-methylamino)-ethyl ester (19). dl (76%
ee): meso¼1.5:1. Colorless oil. 1H NMR (400 MHz, CDCl3,
208C) d 7.30–7.20 (m, 6H), 7.07–7.04 (m, 4H), 4.85–4.55
(m, 2H), 4.34–4.05 (m, 4H), 3.75–3.50 (m, 4H), 3.24 (s,
6H), 3.00 (d, J¼13.3 Hz, 2H), 2.71 (br t, J¼5.8 Hz, 4H),
2.34 (s, 3H), 1.51 (s, 18H), 1.48 (s, 6H). IR (neat) 2976,
1740, 1698 cm21. MS m/z (rel intensity) 729 (Mþ, 1) 698
(1), 638 (8), 393 (70), 247 (100), 215 (40), 146 (40). HRMS,
m/z calcd for C39H59N3O10: 729.4200, found: 729.4183.
Determination of the ratio of dl- to meso-isomers and ee of
the dl-isomer was performed with the corresponding
benzoly derivative.
4.5.7. 2-Benzoylamino-2-methyl-3-phenylpropionic acid
5-(2-benzoylamino-2-methyl-3-phenyl-propionyloxy)-
pentyl ester. Colorless oil. HPLC conditions: Daicel
Chiralcel OD, hexane–2-propanol¼85:15, 0.9 mL/min,
tR¼24, 28 (meso), 37 min. Colorless oil: 1H NMR
(400 MHz, CDCl3) d 7.67 (d, J¼7.0 Hz, 4H), 7.52–7.47
(m, 2H), 7.40 (t, J¼7.8 Hz, 4H), 7.30–7.20 (m, 4H), 7.10–
7.04 (m, 4H), 6.75 (s, 2H), 4.19 (ABX, JAB¼10.9 Hz,