D. Georgiadis et al. / Tetrahedron 57 '2001) 3471±3478
3475
1
calcd for C33H33NO6P -M1H)1 570.6, found 570.2; Anal.
Calcd for C33H32NO6P -569.6); C, 69.59; H, 5.66; N, 2.46.
Found: C, 69.31; H, 5.75; N, 2.67.
1444, 1021, 931, 846, 730, 702, 663, 620 cm21; H NMR
3
-200 MHz, CDCl3) d 0.84 -dd, JHH6.0 Hz, A3B3X,
3
JAB8.6 Hz, 6H, CH-CH3)2), 1.35 -dd, JHH6.7 Hz,
3JPH13.8 Hz, 3H, CH3), 1.36±1.50 -m, 2H, CHHCH-CH3)2,
CH-CH3)2), 1.52±1.69 -m, 1H, CHHCH-CH3)2), 1.77±1.96
-m, 1H, PCHH), 2.15±2.37 -m, 1H, PCHH), 2.86±3.01 -m,
1H, CHCOOBzl), 3.97±4.15 -m, 1H, PCH), 4.17±4.25 -m,
1H, CHCH2O), 4.33±4.48 -m, 2H, CHCH2O), 5.14 -s, 2H,
4.4.2. )R,R,S,S)-2-Methyl-3-))1-)N-)9-¯uorenylmethoxy-
carbonyl)amino)-2-phenylethyl)-hydroxyphosphinyl)
propanoic acid, benzyl ester )8b). White solid, mp 127±
1298C; TLC Rf-b) 0.72, Rf-c) 0.68; IR nmax -liquid ®lm)
3650±3120 -br), 3068, 3020, 2983, 1737, 1689, 1550,
3
OCH2Ph), 5.42 -d, JHH9.3 Hz, 1H, NH), 7.24±7.79 -m,
1503, 1444, 1021, 934, 849, 730, 702, 658, 622 cm21; H
13H, aryl); 13C NMR -50 MHz, CDCl3) d 13.9 -d,
2JPC12.6 Hz, CH3), 22.2 -d, ABX, JAB37.9, CH-CH3)2),
1
NMR -200 MHz, CDCl3) d 1.29 -d, 3JHH7.0 Hz, 3H, CH3),
1.78±1.95 -m, 1H, PCHH), 2.24±2.39 -m, 1H, PCHH),
2.74±3.11 -m, 2H, PhCHH, CHCOOBzl), 3.26±3.51 -m,
1H, PhCHH), 3.97±4.20 -m, 2H, CHCH2O), 4.22±4.39
-m, 2H, CHCH2O, PCH), 5.13 -s, 2H, OCH2Ph), 5.42 -d,
3JHH9.9 Hz, 1H, NH), 7.19±7.76 -m, 18H, aryl); 13C NMR
1
25.7 -CH-CH3)2), 28.6 -d, JPC91.2 Hz, PCH2, I), 29.0 -d,
1JPC91.2 Hz, PCH2, II), 37.2 -d, 2JPC3.9 Hz, CHCOOBzl,
2
I), 37.3 -d, JPC3.9 Hz, CHCOOBzl, II), 43.2 -d,
3JPC11.1 Hz, CH2CH-CH3)2), 45.1 -d, JPC105.2 Hz,
1
1
PCH, I), 45.9 -d, JPC105.2 Hz, PCH, II), 47.1
3
-50 MHz, CDCl3) d 19.0 -d, JPC9.5 Hz, CH3), 29.8 -d,
-CHCH2O), 66.7 -OCH2Ph), 67.2 -CHCH2O), 119.9, 125.0,
127.0, 127.4, 127.7, 128.1, 128.2, 128.4, 135.7, 141.2, 143.7
1
1JPC91.4 Hz, PCH2, I), 30.3 -d, JPC91.4 Hz, PCH2, II),
2
3
3
33.8 -CH2Ph), 34.7 -d, JPC42.7 Hz, CHCOOBzl), 46.9
-aryl), 156.0 -d, JPC6.8 Hz, OCONH), 175.2 -d, JPC
5.4 Hz, COOBzl); 31P NMR -81 MHz, CDCl3) d 53.01,
53.41; ESMS m/z calcd for C31H37NO6P -M1H)1 550.6,
found 550.3; Anal. Calcd for C31H36NO6P -549.6); C,
67.75; H, 6.60; N, 2.55. Found: C, 67.89; H, 6.26; N, 2.50.
-CHCH2O), 51.6 -d, 1JPC104.7 Hz, PCH), 66.8
-OCH2Ph), 67.2 -CHCH2O), 119.9, 125.0, 125.1, 126.9,
127.0, 127.6, 128.1, 128.2, 128.5, 129.1, 135.6, 136.3,
3
136.5, 141.1, 143.4, 143.8 -aryl), 156.0 -d, JPC5.9 Hz,
3
OCONH), 175.3 -d, JPC9.1 Hz, COOBzl); 31P NMR
-81 MHz, CDCl3) d 53.17, 53.23; ESMS m/z calcd for
C34H35NO6P -M1H)1 584.6, found 584.3; Anal. Calcd for
C34H34NO6P -583.6); C, 69.97; H, 5.87; N, 2.40. Found: C,
70.09; H, 5.74; N, 2.44.
4.5. General method for the synthesis of compounds of
type 9
Compound
8
-1 mmol) and 1-adamantyl bromide
4.4.3. )R,R,S,S)-2-Isobutyl-3-))1-)N-)9-¯uorenylmethoxy-
carbonyl)amino)-2-phenylethyl)-hydroxyphosphinyl)
propanoic acid, benzyl ester )8c). White solid, mp 131±
1338C; TLC Rf-b) 0.81, Rf-c) 0.77; IR nmax -liquid ®lm)
3640±3120 -br), 3065, 3020, 2983, 1742, 1689, 1543,
1503, 1445, 1362, 1023, 930, 847, 726, 704, 663,
-1.2 mmol) were dissolved in chloroform -10 ml), and the
reaction mixture was re¯uxed. To this re¯uxing mixture,
silver oxide -1.2 mmol) was added in ®ve equal portions
over 50 min. The reaction mixture was re¯uxed for two
additional hours. Then the solvents were removed in
vacuo and the residue was treated with diethylether. The
silver bromide and the excess of silver oxide were removed
by ®ltration through celite. The ®ltrates were concentrated
to dryness and the residue was puri®ed by column chroma-
tography using chloroform±2-propanol -98:2) as eluent.
621 cm21
;
1H NMR -200 MHz, CDCl3) d 0.78 -dd,
3JHH5.8 Hz, A3B3X, JAB11.6 Hz, 6H, CH-CH3)2),
1.22±1.48 -m, 2H, CHHCH-CH3)2, CH-CH3)2), 1.51±1.63
-m, 1H, CHHCH-CH3)2), 1.77±1.92 -m, 1H, PCHH), 2.02±
2.34 -m, 1H, PCHH), 2.75±3.01 -m, 2H, PhCHH,
CHCOOBzl), 3.27±3.36 -m, 1H, PhCHH), 3.96±4.09 -m,
2H, CHCH2O), 4.11±4.39 -m, 1H, PCH), 4.33±4.44 -m, 1H,
4.5.1. )R,S)-3-))1-)N-)9-Fluorenylmethoxycarbonyl)amino)-
2-phenylethyl)-adamantyloxyphosphinyl) propanoic acid,
benzyl ester )9a). White solid, mp 127±1298C; TLC Rf-d)
0.73, Rf-e) 0.84; IR nmax -liquid ®lm) 3650±3120 -br), 3071,
3010, 2978, 1740, 1693, 1551, 1504, 1445, 1016, 930, 841,
3
CHCH2O), 5.12 -s, 2H, OCH2Ph), 5.41 -d, JHH9.7 Hz,
1H, NH), 7.08±7.83 -m, 18H, aryl); 13C NMR -50 MHz,
CDCl3) d 22.2 -d, ABX, JAB35.6 Hz, CH-CH3)2), 25.7
1
1
-CH-CH3)2), 29.1 -d, JPC85.6 Hz, PCH2, I), 29.6 -d,
732, 700, 661, 620 cm21; H NMR -200 MHz, CDCl3) d
1JPC85.6 Hz, PCH2, II), 33.9 -CH2Ph), 37.3 -br,
1.53±1.71 -m, 6H, CHCH2CH of Ad group), 2.01±2.26
-m, 11H, CCH2 of Ad group, CH of Ad group, PCH2),
2.50±2.77 -m, 2H, CH2CO), 2.85±3.08 -m, 1H, PhCHH),
3.22±3.41 -m, 1H, PhCHH), 4.07±4.24 -m, 3H, CHCH2O,
PCH), 4.27±4.46 -m, 1H, CHCH2O), 5.12 -s, 2H, OCH2Ph),
5.58 -d, 3JHH10.1 Hz, 1H, NH), 7.17±7.78 -m, 18H, aryl);
13C NMR -50 MHz, CDCl3) d 23.8 -d, 1JPC91.4 Hz, PCH2,
I), 24.2 -d, 1JPC91.4 Hz, PCH2, II), 27.4 -d, 2JPC17.3 Hz,
CH2CO), 31.2 -CH of Ad group), 33.8 -CH2Ph), 35.6
3
CHCOOBzl), 43.2 -d, JPC10.8 Hz, CH2CH-CH3)2), 46.9
-CHCH2O), 51.7 -d, 1JPC102.5 Hz, PCH), 66.7 -OCH2Ph),
67.2 -CHCH2O), 119.9, 125.0, 125.2, 126.8, 127.0, 127.6,
128.2, 128.3, 128.4, 128.5, 129.2, 135.7, 136.4, 136.7,
3
141.1, 143.5, 143.8 -aryl), 156.0 -d, JPC6.1 Hz,
3
OCONH), 175.2 -d, JPC4.9 Hz, COOBzl); 31P NMR
-81 MHz, CDCl3) d 51.93, 52.40; ESMS m/z calcd for
C37H41NO6P -M1H)1 626.7, found 626.3; Anal. Calcd for
C37H40NO6P10.25H2O -629.8); C, 70.52; H, 6.48; N, 2.22.
Found: C, 70.47; H, 6.45; N, 2.37.
3
-CHCH2CH of Ad group), 44.5 -d, JPC4.8 Hz, CCH2 of
Ad group), 46.9 -CHCH2O), 50.5 -d, 1JPC111.3 Hz, PCH),
2
66.7 -OCH2Ph), 67.2 -CHCH2O), 83.8 -d, JPC10.3 Hz,
4.4.4. )R,R,S,S)-2-Isobutyl-3-))1-)N-)9-¯uorenylmethoxy-
carbonyl)amino)-ethyl)-hydroxyphosphinyl) propanoic
acid, benzyl ester )8d). White solid, mp 130±1328C;
TLC Rf-b) 0.77, Rf-c) 0.71; IR nmax -liquid ®lm) 3660±
3150 -br), 3074, 3014, 2986, 1734, 1692, 1551, 1506,
POC), 119.9, 125.0, 125.1, 126.7, 127.0, 127.6, 128.2,
128.5, 129.1, 135.5, 136.7, 141.2, 143.6, 143.8 -aryl),
3
3
156.1 -d, JPC6.0 Hz, OCONH), 172.1 -d, JPC17.2 Hz,
COOBzl); 31P NMR -81 MHz, CDCl3) d 49.16, 49.97;
ESMS m/z calcd for C43H47NO6P -M1H)1 704.8, found