C. E. Hoesl et al. / Tetrahedron 58 (2002) 6757–6770
6765
0.73, CH Cl ). IR (KBr): n (cm21)¼1727, 1681, 1605,
CH2CH2), 2.36–2.48 (m, 1H, CH2CH2), 2.87–2.99 (m, 1H,
CH2CH2), 3.53 (s, 3H, COOCH3), 3.74–3.83 (m, 2H,
OCH2CH2O), 3.86–3.92 (m, 2H, OCH2CH2O), 4.00 (d,
J¼10.9 Hz, 1H, OCH2), 4.23 (d, J¼10.9 Hz, 1H, OCH2),
4.87–4.91 (m, 1H, OCHO), 5.32–5.39 (m, 1H, NCHCH2),
6.22 (d, J¼5.7 Hz, 1H, NCHCH ), 7.27–7.37 (m, 3H,
Harom.), 7.59–7.66 (m, 2H, Harom.), 8.06 (s, 1H, NCHvC).
MS (CI, CHþ5 ); m/z (%): 568 [Mþþ1] (50), 466 (13), 372
(110), 195 (91), 167 (192), 139 (77). C31H41NO7Si
(567.65): calcd C 65.59, H 7.28, N 2.47; found C 65.46,
H 7.42, N 2.47.
~
2
2
1562, 1219, 816, 699. 1H NMR (nitrobenzene-d5, 1408C): d
(ppm)¼0.54 (s, 3H, SiCH3), 0.55 (s, 3H, SiCH3), 0.89 (s,
6H, 2£CH3), 1.34 (s, 3H, CH3), 1.85–1.94 (m, 2H,
CH2CH2), 2.37–2.48 (m, 1H, CH2CH2), 2.70–2.83 (m,
1H, CH2CH2), 3.56 (s, 3H, COOCH3), 3.98 (d, J¼10.9 Hz,
1H, OCH2), 4.22 (d, J¼10.9 Hz, 1H, OCH2), 6.31 (d,
J¼5.7 Hz, 1H, HCPh), 6.35 (d, J¼5.7 Hz, 1H, NCHPhCH ),
7.15–7.35 (m, 6H, Harom.), 7.54–7.63 (m, 4H, Harom.),
8.19 (s, 1H, NCHvC). MS (CI, CHþ5 ); m/z (%): 544
[Mþþ1] (2), 512 (1), 466 (14), 195 (1). C32H37NO5Si
(543.73): calcd C 70.69, H 6.86, N 2.58; found C 70.44, H
7.07, N 2.62.
4.4.7. (1S,5R )-1-[(2R )-2,4-Diphenyl-1,2-dihydropyridyl-
carbonyl]-5,8,8-trimethyl-3-oxabicyclo[3.2.1]octan-2-
one (10a) and (1S,5R )-1-[(2S )-2,4-diphenyl-1,2-dihydro-
pyridylcarbonyl]-5,8,8-trimethyl-3-oxabicyclo[3.2.1]-
octan-2-one (11a). The reaction was performed according
to GP2. Generation of 5c as described for the preparation of
8a and 9a with 78 mg (0.50 mmol, 1.0 equiv.) of 3c. The
solvent and TMSCl were removed in vacuo. The residue
was dissolved in 5 ml of CH2Cl2. Arylation with 1.5 ml
(1.50 mmol, 3.0 equiv.) of phenylmagnesium bromide
(1.0 M in THF); arylation temperature 2788C; arylation
time 1 h; quenching at 2788C with phosphate buffer
(pH¼7, c¼1.0 M). The reaction mixture was extracted
with CH2Cl2. The combined organic layers were dried
(MgSO4) and concentrated in vacuo. Purification by CC
(n-heptane/EtOAc¼75:25) afforded 177 mg (83%) of a
mixture of 10a and 11a. Separation of the diastereomers by
preparative HPLC (n-heptane/EtOAc¼85:15; 15.0 ml/min).
Analytical HPLC (n-heptane/EtOAc¼80:20; 1.0 ml/min):
d.s. (10a/11a)¼38.3/61.7; 10a: tR¼15.8 min; 11a: tR¼
19.7 min.
4.4.6. Methyl (S )-4-(dimethylphenylsilyl)-6-(2-[1,3]di-
oxolan-2-ylethyl)-1-[(1S,5R )-5,8,8-trimethyl-2-oxo-3-
oxabicyclo[3.2.1]octylcarbonyl]-1,6-dihydropyridine-3-
carboxylate (8b) and methyl (R )-4-(dimethylphenyl-
silyl)-6-(2-[1,3]dioxolan-2-ylethyl)-1-[(1S,5R )-5,8,8-tri-
methyl-2-oxo-3-oxabicyclo[3.2.1]octylcarbonyl]-1,6-
dihydropyridine-3-carboxylate (9b). The reaction was
performed according to GP2. Preparation of 2 from 408 mg
(1.50 mmol) of 16b in 7.5 ml of CH2Cl2, 135 ml (203 mg,
1.60 mmol, 1.06 equiv.) of oxalyl chloride and 2 ml of
DMF. Generation of 5b from 2 in 7.5 ml of CH2Cl2, 318 mg
(1.50 mmol, 1.0 equiv.) of 3b in 7.5 ml of CH2Cl2, 272 ml
(335 mg, 1.50 mmol, 1.0 equiv.) of TMSOTf. Alkylation
with 4.5 ml (4.50 mmol, 3.0 equiv.) of 2-([1,3]dioxolan-2-
yl)ethylmagnesium bromide (1.0 M in THF); alkylation
temperature 2788C; alkylation time 3 h; quenching at
2788C with phosphate buffer (pH¼7, c¼1.0 M). Work up
as described for the preparation of 8a and 9a. Purification
by CC (n-heptane/EtOAc¼50:50) afforded 350 mg (41%)
of a mixture of 8b and 9b. Separation of the dia-
stereomers by preparative HPLC (n-heptane/EtOAc¼70:30;
12.0 ml/min) yielded 315 mg (37%) of 8b and 35 mg
(4%) of 9b. Analytical HPLC (n-heptane/EtOAc¼70:30;
1.5 ml/min): d.s. (8b/9b)¼87.2/12.8; 8b: tR¼11.1 min; 9b:
tR¼16.2 min.
Compound 10a. Colorless crystals, mp 198–2028C. TLC:
Rf¼0.34 (n-heptane/EtOAc¼60:40). [a]2D0¼þ615.88 (c¼
0.5, CH Cl ). IR (KBr): n (cm21)¼2957, 1730, 1634, 759,
~
2
2
730, 701. 1H NMR (C2D2Cl4, 1208C): d (ppm)¼0.93 (s, 6H,
CH3), 1.37 (s, 3H, CH3), 1.81–2.06 (m, 3H, CH2CH2),
2.29–2.62 (m, 1H, CH2CH2), 3.98 (d, J¼11.0 Hz, 1H,
OCH2), 4.17 (dd, J¼11.0, 1.9 Hz, 1H, OCH2), 5.76 (d, J¼
7.8 Hz, 1H, NCHvCH ), 6.21 (dbr, J¼6.1 Hz, 1H, NCH Ph),
6.26 (d, J¼6.1 Hz, 1H, NCHPhCH ), 6.86 (d, J¼7.8 Hz, 1H,
NCHvCH), 7.22–7.40 (m, 6H, Harom.), 7.43–7.48 (m, 2H,
Harom.), 7.50–7.55 (m, 2H, Harom.). MS (70 eV); m/z (%):
427 (2) [Mþ], 350 (8), 232 (100), 195 (32), 167 (16), 139
(16). C28H29NO3 (427.54): calcd C 78.66, H 6.84, N 3.28;
found C 78.49, H 7.07, N 3.22.
Compound 8b. Colorless crystals, mp 1508C. TLC: Rf¼0.28
(n-heptane/EtOAc¼50:50). [a ]2D0¼þ496.78 (c¼0.39,
CH Cl ). IR (KBr): n (cm21)¼1728, 1677, 1601, 1556,
~
2
2
1221, 815, 702. 1H NMR (nitrobenzene-d5, 1408C): d
(ppm)¼0.56 (s, 6H, 2£SiCH3), 0.90 (s, 3H, CH3), 1.06 (s,
3H, CH3), 1.43 (s, 3H, CH3), 1.83–2.01 (m, 6H, CH2CH2,
CH2CH2), 2.36–2.48 (m, 2H, CH2CH2), 3.56 (s, 3H,
COOCH3), 3.73–3.82 (m, 2H, OCH2CH2O), 3.84–3.94
(m, 2H, OCH2CH2O), 3.99 (d, J¼10.9 Hz, 1H, OCH2), 4.19
(d, J¼10.9 Hz, 1H, OCH2), 4.87–4.91 (m, 1H, OCHO),
5.10–5.16 (m, 1H, NCHCH), 6.31 (d, J¼5.8 Hz, 1H,
NCHCH ), 7.29–7.37 (m, 3H, Harom.), 7.61–7.66 (m, 2H,
Harom.), 8.03 (s, 1H, NCHvC). MS (70 eV); m/z (%): 567
[Mþ] (149), 552 (43), 466 (69), 372 (108), 195 (113).
C31H41NO7Si (567.65): calcd C 65.59, H 7.28, N 2.47;
found C 65.32, H 7.54, N 2.44.
Compound 11a. Colorless crystals, mp 87–908C. TLC:
Rf¼0.29 (n-heptane/EtOAc¼60:40). [a ]2D0¼2300.08
(c¼0.05, CH Cl ). IR (KBr): n (cm21)¼2965, 1728, 1651.
~
2
2
1H NMR (C2D2Cl4, 1408C): d (ppm)¼0.86 (s, 3H, CH3),
0.92 (s, 3H, CH3), 1.28 (s, 3H, CH3), 1.79–1.97 (m, 2H,
CH2CH2), 2.17–2.35 (m, 1H, CH2CH2), 2.58–3.10 (m, 1H,
CH2CH2), 3.97 (d, J¼11.1 Hz, 1H, OCH2), 4.20 (d, J¼
11.1 Hz, 1H, OCH2), 5.65 (d, J¼7.4 Hz, 1H, NCHvCH ),
6.05–6.15 (m, 1H, NCH Ph), 6.43 (d, J¼5.2 Hz, 1H,
NCHPhCH ), 6.86 (d, J¼7.4 Hz, 1H, NCHvCH), 7.20–
7.55 (m, 10H, Harom.). MS (70 eV); m/z (%): 427 (5) [Mþ],
350 (14), 232 (100), 195 (33), 167 (15). C28H29NO3
(427.54): calcd C 78.66, H 6.84, N 3.28; found C 78.89,
H 6.92, N 2.98.
Compound 9b. Colorless crystals, mp 688C. TLC: Rf¼0.28
(n-heptane/EtOAc¼50:50). [a ]2D0¼2342.68 (c¼0.31,
CH Cl ). IR (KBr): n (cm21)¼1726, 1672, 1602, 1556,
~
2
2
1231, 816, 704. 1H NMR (nitrobenzene-d5, 1408C): d
(ppm)¼0.55 (s, 6H, 2£SiCH3), 0.92 (s, 3H, CH3), 1.01 (s,
3H, CH3), 1.32 (s, 3H, CH3), 1.78–1.99 (m, 6H, CH2CH2,