2640
M. D. Groaning et al. / Tetrahedron 57 (2001) 2635±2642
over 4 h. The reaction was monitored via TLC (4:1 Hex/
EtOAc) then treated with sat. aq. NH4Cl, resulting in a
colorless mixture. The layers were separated and the
aqueous layer was washed with CH2Cl2. The organic layers
were combined, dried (Na2SO4), ®ltered, and concentrated
under reduced pressure to afford the crude products 20 and
21. The crude products were puri®ed by ¯ash chroma-
tography on SiO2 eluting with EtOAc/Hex (1:1). 21 (a±c)
were not characterized due to the rather small quantities that
were formed.
131.9, 138.0, 142.2, 165.8, 176.1; IR (neat) 1748,
1716 cm21
.
1.2. General procedure for the oxidative removal of
silicon from 20
To a solution of the silylcyclobutane 20 (0.47 mmol) in
10 mL of THF at 08C, was added tetrabutylammonium
hydroxide (0.94 mL, 1.0 M in MeOH). Hydrogen peroxide
(1.40 mL, 30% solution in water) was added and the reac-
tion was stirred vigorously for 24 h, and then diluted with
CH2Cl2 and water. The layers were separated and the
aqueous layer was washed with CH2Cl2. The combined
layers were dried over Na2SO4, ®ltered, and concentrated
in vacuo to yield a crude oil. The crude products were
puri®ed by ¯ash chromoatography eluting with EtOAc/
Hex (1:1) to yield the hydroxymethylcyclobutanes 27.
1.1.1. Bicyclic lactam 20a. Colorless solid (0.59 g, 68%
yield), mp 1808C (EtOAc/Hex). 1H NMR (CDCl3,
300 MHz) d0.11 (s, 3H), 0.14 (s, 3H), 0.83 (app t, J
14.1 Hz, 1H), 1.10 (dd, J13.9, 3.0 Hz, 1H), 1.19 (s, 9H),
1.68 (ddd, J12.6, 9.0, 3.5 Hz, 1H), 2.55±2.65 (m, 1H),
2.74±2.82 (m, 1H), 3.23 (dd, J8.8, 7.3 Hz, 1H), 3.95
(app t, J9.1 Hz, 1H), 4.73 (dd, J8.8, 7.7 Hz, 1H), 5.12
(app t, J8.3 Hz, 1H), 6.95±7.34 (m, 25H); 13C NMR
(CDCl3, 75 MHz) d20.4, 1.3, 19.9, 25.0, 27.8, 37.9,
44.5, 53.8, 59.5, 64.4, 75.2, 81.8, 100.1, 125.5, 127.2,
1.2.1. Bicyclic lactam 27a. Viscous oil/foam (50 mg, 63%
1
yield). H NMR (CDCl3, D2O wash, 300 MHz) d1.40 (s,
9H), 2.03 (ddd, J13.2, 9.3, 4.1 Hz, 1H), 2.58 (ddd, J12.9,
9.4, 6.8 Hz, 1H), 2.80 (m, 1H), 3.27 (dd, J9.3, 6.9 Hz, 1H),
3.72 (dd, J12.1, 6.0 Hz, 1H), 3.85 (dd, J12.0, 3.8 Hz,
1H), 3.96 (app t, J9.0 Hz, 1H), 4.73 (br, s, HOD), 4.78
(dd, J9.0, 7.8 Hz, 1H), 5.17 (app t, J8.1 Hz, 1H), 7.09±
7.41 (m, 10H); 13C NMR (CDCl3, 75 MHz) d19.8, 27.8,
41.7, 47.5, 59.1, 62.0, 63.0, 74.7, 83.3, 100.6, 125.8, 126.9,
127.6, 128.3, 128.5, 138.0, 141.9, 168.1, 176.6; IR (neat)
1731 cm21. HRMS: (FAB), (M1H) Calcd for C26H29NO5:
127.6, 128.0, 128.2, 128.4, 129.9, 138.0, 142.2, 165.8,
176.1; IR (neat) 1736, 1717 cm21
23
[a]D 211.5
.
(c0.80, CH2Cl2).
1.1.2. Bicyclic lactam 20b. Colorless solid (0.15 g, 75%
yield), mp 140±1438C (EtOAc/Hex). 1H NMR (CDCl3,
300 MHz) d0.13 (s, 6H), 0.81 (app t, J14.2 Hz, 1H),
1.22±1.26 (m, 1H), 1.30 (s, 9H), 1.48 (s, 3H), 1.49±1.60
(m, 1H), 2.28±2.38 (m, 1H), 2.64±2.71 (m, 1H), 3.23 (app t,
J8.2 Hz, 1H), 4.18 (dd, J8.7, 7.8 Hz, 1H), 4.74 (app t,
J8.7 Hz, 1H), 5.13 (app t, J7.8 Hz, 1H), 6.98±7.35 (m,
20H); 13C NMR (CDCl3, 75 MHz) d20.4, 1.5, 19.8, 24.0,
24.8, 28.0, 37.7, 43.5, 54.0, 57.6, 65.1, 75.2, 82.0, 98.1,
125.6, 125.7, 127.6, 128.1, 128.8, 130.0, 139.4, 146.3,
166.7, 174.5; IR (neat) 1735, 1712 cm21; Anal. Calcd for
C39H53NO4Si: C 76.67, H 7.20, found C 76.70, H 7.24;
23
436.2124, found: 436.2130; [a]D 119.1 (c0.68, CH2Cl2).
1.2.2. Bicyclic lactam 27b. Viscous oil/foam (33 mg, 53%
1
yield). H NMR (CDCl3, D2O wash, 300 MHz) d1.48 (s,
3H), 1.51 (s, 9H), 1.80 (ddd, J13.0, 9.3, 3.6 Hz, 1H), 2.33
(ddd, J13.1, 9.5, 7.2 Hz, 1H), 2.70 (m, 1H), 3.20 (dd, J
9.2, 7.4 Hz, 1H), 3.78 (dd, J11.8, 6.3 Hz, 1H), 3.88 (dd,
J11.7, 3.8 Hz, 1H), 4.22 (dd, J8.8, 7.3 Hz, 1H), 4.76 (br.
s, HOD), 4.81 (app t, J8.7 Hz, 1H), 5.18 (app t, J7.6 Hz,
1H), 7.20±7.35 (m, 5H); 13C NMR (CDCl3, 75 MHz) d
19.0, 24.6, 28.0, 41.1, 46.6, 56.9, 62.5, 63.4, 75.3, 83.1, 98.4,
125.3, 127.5, 128.7, 168.6, 174.4; IR (®lm) 3478, 1734,
1710 cm21. HRMS: (FAB), (M1H) Calcd for C21H27NO5:
23
[a]D 132.3 (c0.86, CH2Cl2).
1.1.3. Bicyclic lactam 20c. Colorless solid (100 mg, 50%
yield), mp 82±858C (EtOAc/Hex). 1H NMR (CDCl3,
300 MHz) d0.11 (s, 3H), 0.14, (s, 3H), 0.83 (app t, J
14.1 Hz, 1H), 1.30 (s, 9H), 1.40 (dd, J14.2, 2.7 Hz, 1H),
2.00±2.18 (m, 2H), 2.74±2.83 (m, 1H), 3.18 (dd, J9.9,
4.5 Hz, 1H), 3.78 (dd, J8.6, 7.1 Hz, 1H), 4.47 (app t, J
8.3 Hz, 1H), 4.92 (s, 1H), 5.14 (app t, J7.5 Hz, 1H), 6.96±
7.36 (m, 20H); 13C NMR (CDCl3, 75 MHz) d20.3, 1.2,
21.7, 28.0, 30.4 35.7, 40.6, 53.7, 58.9, 60.8, 73.0, 82.0, 96.1,
125.6, 126.1, 127.7, 128.0, 128.8, 129.9, 139.8, 146.1,
166.4, 177.9; IR (neat) 1744, 1712 cm21; Anal. Calcd for
C41H45NO4Si: C 76.48, H 7.04, found: C 76.30, H 7.09;
23
374.1967, found: 374.1969; [a]D 1103.1 (c1.3, CH2Cl2).
1.2.3. Lactone 29. To a ¯ame-dried round bottom ¯ask was
added bicyclic lactam 27b (400 mg, 1.07 mmol) followed
by 5 mL of dichloromethane. PTSA (5 mg) was added at
room temperature and the reaction was stirred under an
argon atmosphere for 2 h. The reaction mixture was concen-
trated under reduced pressure to afford a pale yellow
residue. The crude mixture was puri®ed via chromatography
(SiO2, 4:1 Hex/EtOAc) to give a colorless solid (291 mg,
91%), mp112±1148C (EtOAc/Hex), [a]D23248 (c1.1,
CHCl3); 1H NMR (CDCl3, 300 MHz) d1.42 (s, 3H), 2.07
(ddd, J3, 8, 11 Hz, 1H), 2.83 (ddd, J6, 8, 12 Hz, 1H),
3.1723.28 (m, 2H), 4.24 (dd, J7, 9 Hz, 1H), 4.36 (J5,
10 Hz, 1H), 4.70 (app. t, J8 Hz, 1H), 4.83 (app. t, J8Hz,
1H), 5.26 (app. t, J8 Hz, 1H), 7.23±7.38 (m, 5H); 13C
NMR (CDCl3, 75MHz) d23.2, 25.4, 36.5, 44.5, 56.7,
57.6, 74.1, 74.3, 97.9, 125.2, 127.5, 128.7, 139.0, 172.4,
23
[a]D 190.6 (c0.64, CH2Cl2).
1.1.4. Bicyclic lactam 23a,23b. Colorless oil (50 mg, 21%
yield) as an inseparable mixture of diastereomers. Major
diastereomer: 1H NMR (CDCl3, 300 MHz) d0.13 (s,
6H), 0.79±0.88 (m, 1H), 1.28 (s, 3H), 1.39±1.50 (m, 1H),
1.89 (dd, J9.3 Hz, 1H), 2.28±2.38 (m, 1H), 2.41±2.48 (m,
1H), 2.83 (d, J8.2 Hz, 1H), 3.9 (dd, J8.7, 7.8 Hz, 1H),
4.24 (app t, J8.7 Hz, 1H), 4.73 (app t, J7.8 Hz, 1H), 5.1
(s, 2H), 6.98±7.35 (m, 25H); 13C NMR (CDCl3, 75 MHz)
d20.4, 1.3, 19.9, 25.0, 27.8, 37.9, 44.5, 53.8, 59.5, 64.4,
75.2, 81.8, 100.1, 126.5, 127.2, 127.6, 128.0, 128.2, 128.4,
172.9; IR (®lm) 1769, 1708 cm21
.
1.2.4. Lactam 30b. To a dichloromethane solution of 27b