R. Warmuth et al. / Tetrahedron 57 )2001) 6383±6397
6395
CH2Cl2); dH 1400 MHz, CDCl3) 7.38±7.29 15H, m), 7.22±
7.18 13H, m), 7.15±7.13 11H, m), 4.49 11H, ABX, J10.8,
4.4 Hz), 4.31 11H, ABX, J10.8, 10.8 Hz), 4.00 11H, ABX,
J10.8, 4.4 Hz), 3.22 11H, t, J13.7 Hz), 2.77±2.72 11H,
m), 2.48±2.40 11H, m), 2.30±2.26 12H, m), 2.05±1.93 13H,
m), 1.57±1.48 11H, m); dC 150 MHz, CDCl3) 172.12,
141.87, 139.76, 138.68, 132.36, 129.39, 129.09, 128.58,
128.13, 127.04, 126.23, 17.12, 68.87, 51.57, 37.89, 36.82,
28.14, 25.32; MALDI HRMS m/z 330.1465 1M1Na1)
1calcd for C20H21NNaO2, 330.1475).
dH 1400 MHz, CDCl3) 7.39±7.30 15H, m), 7.09 11H, dd,
J8.1, 6.1 Hz, 6-H), 6.95 11H, dd, J10.5, 2.6 Hz, 9-H),
6.89 11H, ddd, J8.1, 8.1, 2.6 Hz, 7-H), 4.54 11H, dd, J
10.8, 4.2 Hz, 50-H), 4.34 11H, dd, J10.8, 10.8 Hz, 60-Ha),
4.02 11H, dd, J10.8, 4.2 Hz, 60-He), 3.14 11H, br t, J
13.7 Hz), 2.76±2.72 11H, m), 2.48±2.24 13H, m), 2.03±
1.93 13H, m), 1.49±1.45 11H, m); dC 150 MHz, CDCl3)
171.48 1s, C-20), 160.96 1d, JCF245 Hz, C-8), 141.92 1d,
JCF5.7 Hz, C-15a), 138.34 1s, Ph), 137.51 1d, JCF3.4 Hz,
C-11a), 133.60 1dd, JCF7.6 Hz, C-6), 129.13 1d, Ph),
128.67 1d, Ph), 126.96 1d, Ph), 116.85 1dd, JCF23.3 Hz,
C-7 or C-9), 114.32 1dd, JCF20.2 Hz, C-7 or C-9), 75.39
1t, C-60), 68.56 1s, C-1,30), 51.67 1d, C-50), 37.84 1t, C-2 or
C-5), 36.07 1t, C-2 or C-5), 28.13 1t, C-3 or C-4), 25.22 1t,
C-3 or C-4); MALDI HRMS m/z 348.1370 1M1Na1) 1calcd
for C20H20FNNaO2, 348.138).
4.7.20. .1,30S)-Indan-1-spiro-30-[.50R)-50-phenyl-20,30,50,60-
tetrahydro-10,40-oxazin-20-one] ..1,30S,50R)-16c). Oil;
[a]24D1128.08 1c 0.77 CH2Cl2); dH 1400 MHz, CDCl3)
7.50±7.44 13H, m), 7.38±7.32 13H, m), 7.30±7.23 13H,
m), 4.54±4.49 11H, m), 4.53±4.42 12H, m), 3.22±3.14
11H, m), 3.06±2.98 12H, m), 2.20±2.13 11H, m), 1.95
11H, br s); dC 150 MHz, CDCl3) 171.36 1s), 144.70 1s),
144.15 1s), 137.83 1s), 129.13 1d), 129.06 1d), 128.86 1d),
127.25 1d), 127.10 1d), 125.05 1d), 124.45 1d), 75.90 1t),
72.37 1s), 54.35 1d), 42.441t), 30.631t); Anal. Calcd for
C18H17NO2: C, 77.40; H, 6.13; N, 5.01. Found: C, 77.57;
H, 6.06; N, 5.12.
4.7.24. Synthesis of N-[.R)-20-hydroxy-10-phenylethyl]-
.S)-1-amino-benzocyclopentane-1-carboxamide ..1S,10R)-
15c) via aminolysis of .1S,10R)-16c. A solution of 16c
126.5 mg, 0.095 mmol) in 2 mL methanol is cooled to 08C
and is purged with dry ammonia for 10 min and left standing
for 24 h at room temperature. Evaporation off the solvent
yields quantitatively 15c as a colorless oil. [a]24 127.48
D
4.7.21. .1,30S)-7-Fluoro-1,2,3,4-tetrahydronaphthalene-
1-spiro-30-[.50R)-50-phenyl-20,30,50,60-tetrahydro-10,40-
oxazin-20-one] ..1,30S,50R)-16d). Colorless solid; mp
1618C; [a]24D199.08 1c 0.31 CH2Cl2); dH 1400 MHz,
CDCl3) 7.49±7.47 12H, m), 7.42±7.34 13H, m), 7.29 11H,
dd, J9.9, 2.7 Hz), 7.09 11H, dd, J8.4, 5.9 Hz), 6.94 11H,
ddd, J8.4, 8.4, 2.7 Hz), 4.60±4.55 11H, m), 4.53±4.48
12H, m), 2.90±2.73 12H, m), 2.56±2.50 11H, ddd, J13.5,
10.4, 3.1 Hz), 2.29±2.22 11H, m), 2.10±1.99 12H, m), 1.87±
1.79 11H, m); dC 150 MHz, CDCl3) 172.11 1s, C-20), 161.34
1d, JCF244 Hz, C-7), 140.12 1d, JCF6.5 Hz, C-14a),
137.47 1s, Ph), 133.29 1d, JCF3.4 Hz, C-16a), 130.76 1dd,
JCF7.6 Hz, C-5), 129.12 1d, Ph), 128.96 1d, Ph), 127.33 1d,
Ph), 115.47 1dd, JCF21.4 Hz, C-6 and C-8), 76.09 1t, C-60),
63.12 1s, C-1,30), 52.58 1d, C-50), 34.02 1t, C-4), 28.70 1t,
C-2), 18.80 1t, C-3); MALDI HRMS m/z 334.1231 1M1
Na1) 1calcd for C19H18FNNaO2, 334.1219).
1c 1.26CH2Cl2); dH 1400 MHz, CDCl3) 8.00 11H, br s),
7.30±7.10 18H, m), 7.06 11H, dt, J8.5, 1.6 Hz), 6.49
11H, br s), 4.43 11H, br s), 3.85 11H, dd, J9.6, 4.0 Hz),
3.51 11H, dd, J11.2, 4.0 Hz), 3.33 11H, dd, J9.6,
11.2 Hz), 2.95±2.80 11H, m), 2.75±2.60 11H, m), 2.62±
2.52 11H, m), 2.2 11H, br s), 1.85 11H, m); dC 1100.56
MHz, CDCl3) 179.09 1s), 145.28 1s), 144.24 1s), 143.05
1s), 128.67 1d), 128.611d), 127.441d), 126.971d), 126.681d),
125.051d), 123.631d), 74.39 1s), 67.68 1t), 61.68 1d), 35.27
1t), 31.24 1t); MALDI HRMS m/z 319.146 1M1Na1) 1calcd
for C18H20N2NaO2, 319.142).
4.7.25. Synthesis of methyl ester 17a .Procedure F). The
crude TMSCN addition adduct 14a 1prepared from
0.20 mmol 8a via Procedure C) was stirred in dry CH2Cl2
15 mL at 2188C); HCl gas was purged into the solution for
15 min. Then methanol 11 mL) was added to the solution,
HCl gas was further bubbled for 20 min. The cold bath was
removed, and the resulting solution was stirred at room
temperature for 12 h. The excess HCl gas and CH2Cl2
were evaporated off to dryness, and the residue was
dissolved in ethyl acetate 15 mL). The solution was washed
with sat. NaHCO3 15 mL), the aqueous solution was
extracted with ethyl acetate twice 12£5 mL). The combined
organic layers were dried over MgSO4 and concentrated in
vacuo. Flash chromatography of the residue on silica gel
1elution with 15% ethyl acetate in n-hexane) gave
11S,10R)-17a, a colorless oil 197% yield based on 14a).
4.7.22. .1,30S)-8-Fluorobenzocycloheptan-1-spiro-30-[.50R)-
50-phenyl-20,30,50,60-tetrahydro-10,40-oxazin-20-one] ..1,30S,
50R)-16e). Colorless solid; mp 1268C; [a]24D155.48 1c 0.54
CH2Cl2); dH 1400 MHz, CDCl3) 7.37±7.29 15H, m), 7.16
11H, dd, J10.7, 2.6 Hz, 9-H), 7.14 11H, dd, J8.2,
6.1 Hz, 6-H), 6.90 11H, ddd, J10.8, 8.2, 2.6 Hz, 7-H),
4.53±4.46 11H, m), 4.36±4.26 12H, m), 3.43±3.37 11H,
m), 2.93±2.88 11H, m), 2.37±2.34 12H, m), 2.20 11H, br
s), 1.90±1.82 13H, m), 1.58±1.53 11H, m); dC 150 MHz,
CDCl3) 172.60, 161.42 1JCF244 Hz, C-8), 143.98 1JCF
5.7 Hz, C-15a), 138.76, 138.64 1JCF3.1 Hz, C-11a),
133.12 1JCF7.6 Hz, C-6), 129.04, 128.61, 127.32, 114.90
1JCF14.1 Hz, C-7 or 9), 114.47 1JCF11.1 Hz, C-9 or 7),
72.95, 67.21, 54.97, 35.67, 34.15, 27.66, 23.72; MALDI
HRMS m/z 348.1391 1M1Na1) 1calcd for C20H20FNNaO2,
348.1376). Anal. Calcd for C20H20FNO2: C, 73.83; H, 6.20;
N, 4.30. Found: C, 73.72; H, 6.23; N, 4.46.
[a]24 12.468 1c 0.53, THF); dH 1400 MHz, CDCl3)
D
7.29±7.17 17H, m), 7.11 12H, t, J6.4 Hz), 4.03 11H, br
s), 3.90 11H, dd, J4.4, 10 Hz), 3.71 13H, s), 3.64 11H,
dd, J4.4, 10.8 Hz), 3.43 11H, dd, J10, 10.8 Hz), 2.72
12H, dd, J4.8, 7.6 Hz), 2.38 11H, br s), 2.16 11H, ddd,
J3.2, 11.2, 14.4 Hz), 1.87 11H, ddd, J2.8, 6.0, 9.2 Hz),
1.64±1.53 11H, m), 1.49±1.40 11H, m); dC 150.28 MHz,
CDCl3) 178.16, 143.21, 137.27, 136.84, 129.83, 128.41,
127.98, 127.24, 127.20, 126.86, 126.54, 68.18, 65.64,
61.59, 53.03, 30.86, 29.86, 18.44; HR-FABMS m/z
1M1H1) 326.178 1calcd for C20H23NO3, 326.176).
4.7.23. .1,30R)-8-Fluorobenzocycloheptan-1-spiro-30-[.50R)-
50-phenyl-20,30,50,60-tetrahydro-10,40-oxazin-20-one] ..1,30R,
50R)-16e). Colorless oil; [a]24 279.28 1c 0.77 CH2Cl2);
D