PAPER
[16]Metacyclophanes
1987
[m, (CH3)2CH], 1372 [w, (CH3)2CH], 1222 (s, C–N), 1106 (s,
COC), 1032 (m), 1005 (m), 914 (m, RCH=CH2), 836 (m), 776
cm–1 (m).
1.13–1.38 [m, 16 H, CH2, CH(CH3)2], 0.87 [s, 9 H, SiC(CH3)3],
0.00 [s, 3 H, Si(CH3)2], –0.04 [s, 3 H, Si(CH3)2].
13C NMR (90.6 MHz, CDCl3): d (major isomer) = 167.9 (C=O),
147.3 (CarO), 144.8 (CarO), 138.9 (Colef), 138.2 (CarO), 136.9
(ColefH), 133.8 (Colef), 129.4 [=C(CO)CH3], 129.1 (Car), 127.5
(ColefH), 125.8 (ColefH), 125.1 (ColefH), 104.3 (CarH), 80.5 (OCH),
76.8 [OCH(CH3)2], 71.1 [OCH(CH3)2], 61.1 (OCH3), 37.4 (CH2),
30.0 (CH2), 30.2 (CH2), 28.3 (CH2), 27.9 (CH2), 27.5 (CH2), 26.1
[SiC(CH3)3], 23.7 (CH2), 23.3 (CH2), 22.6 [OCH(CH3)2], 18.4
[SiC(CH3)3], 13.1 [=C(CO)CH3], 11.4 (CH3), –4.3 [Si(CH3)2], –4.7
[Si(CH3)2]; d (minor isomer) = 168.4 (C=O), 147.5 (CarO), 144.9
(CarO), 139.3 (Colef), 138.1 (CarO), 136.8 (ColefH), 134.4 (Colef),
129.2 [=C(CO)CH3], 128.6 (Car), 127.2 (ColefH), 126.9 (ColefH),
125.3 (ColefH), 104.1 (CarH), 81.4 (OCH), 77.6 [OCH(CH3)2], 71.1
[OCH(CH3)2], 61.0 (OCH3), 36.6 (CH2), 30.0 (CH2), 28.9 (CH2),
27.8 (CH2), 27.4 (CH2), 26.3 (CH2), 26.2 [SiC(CH3)3], 23.5 (CH2),
23.2 (CH2), 22.6 [OCH(CH3)2], 18.6 [SiC(CH3)3], 13.1
[=C(CO)CH3], 10.1 (CH3), –4.4 [Si(CH3)2], –4.6 [Si(CH3)2].
1H NMR (360 MHz, CDCl3): d = 8.21 (s, 1 H, NH), 8.18 (s, 1 H,
CarH), 7.03 [d, 3J = 10.2 Hz, 1 H, CH2=CHCH=C(CO)], 6.67 (ddd,
3
3J = 17.0 Hz, 3J = 10.2 Hz, J = 10.2 Hz, 1 H, CH2=CHCH=C),
5.76–5.68 (m, 1 H, CH2=CHR), 5.56 (d, 3J = 16.8 Hz, 1 H,
HtransCH=CHCH=C), 5.47–5.42 (m, 2 H, HcisCH=CHCH=C,
CH2CH=CCH3R), 5.01–4.94 (m, 2 H, CH2=CHR), 4.61–4.54 [m,
3 H, CarCH2O, OCH(CH3)2], 4.42 [sept, 3J = 6.1 Hz, 1 H,
OCH(CH3)2], 4.04–3.98 (m, 3 H, CHOTBDMS, C=CHCH2O), 3.85
(s, 3 H, OCH3), 3.69–3.66 (m, 2 H, CH2O), 3.57–3.55 (m, 2 H,
CH2O), 2.28–2.14 (m, 2 H, CH2), 2.08 [d, 4J = 0.9 Hz,
3
3 H, =C(CO)CH3], 1.57 (s, 3 H, CH3), 1.36 [d, 6 H, J = 6.2 Hz,
OCH(CH3)2], 1.29 [d, 6 H, 3J = 6.1 Hz, OCH(CH3)2], 0.85 [s, 9 H,
SiC(CH3)3], 0.01 [s, 3 H, Si(CH3)2], –0.04 [s, 3 H, Si(CH3)2].
13C NMR (90.6 MHz, CDCl3): d = 166.3 (C=O), 147.0 (CarO),
145.9 (CarO), 140.9 (CarO), 139.7 (HRC=CR¢CH3), 135.5
(HRC=CH2), 134.8 (ColefH), 132.1 (ColefH), 131.3 [=C(CO)CH3],
128.5 (Car), 125.0 (Car), 123.6 (=CHCH=CH2), 122.4
(HRC=CR¢CH3), 116.5 (HRC=CH2), 107.8 (CarH), 78.4 (TBDM-
SOCH), 77.8 [OCH(CH3)2], 71.2 [OCH(CH3)2], 69.9 (CH2O), 69.3
(CH2O), 67.4 (CH2O), 63.3 (CH2O), 61.5 (OCH3), 41.2 (CH2), 25.9
[SiC(CH3)3], 22.8 [OCH(CH3)2], 22.3 [OCH(CH3)2], 18.3
[SiC(CH3)3], 13.1 [=C(CO)CH3], 11.8 (CH3), –4.6 [Si(CH3)2], –4.9
[Si(CH3)2].
MS (EI): m/z (%) = 613 (100, [M+]), 570 (10), 505 (5), 396 (10),
306 (5), 167 (5), 73 (46), 43 (8).
HRMS: m/z calcd for C36H59NO5Si: 613.4157; found: 613.4163.
(9R,10E)-9-(tert-Butyldimethylsilyloxy)-20,22-diisopropoxy-19-
methoxy-4,10-dimethyl-13,16-dioxa-2-azabicyclo[16.3.1]doco-
sa-1(22),4,6,10,18,20-hexaen-3-one (3b)
The procedure used for the synthesis of 3a was performed with 4b
(40 mg, 62 mmol) using Grubbs catalyst25 (7.5 mg, 9.1 mmol) in re-
fluxing CH2Cl2 (125 mL). After flash chromatography (P–EA,
90:10), the product (30 mg, 79%) was obtained as an 80:20 mixture
of two isomers. Minor isomer; Rf 0.18 (P–EA, 90:10), [CAM, UV];
major isomer; Rf 0.16 (P–EA, 90:10); [CAM, UV]; [a]D20 –1.16
(c = 0.48, CH2Cl2).
MS (EI): m/z (%) = 645 (44, [M+]), 613 (24), 604 (6), 346 (24), 304
(33), 303 (100), 261 (34), 239 (20), 166 (6), 141 (5), 95 (100), 73
(39).
Anal. Calcd for C36H59NO7Si (645.9): C, 69.34; H, 9.21; N, 2.17.
Found: C, 66.94; H, 9.28; N, 1.98.
(9R,10E)-9-(tert-Butyldimethylsilyloxy)-20,22-diisopropoxy-19-
methoxy-4,10-dimethyl-2-azabicyclo[16.3.1]docosa-
1(21),4,6,10,18(22),19-hexaen-3-one (3a)
1H NMR (360 MHz, CDCl3): d = 8.51 (s, 1 H, NH), 8.13 (s, 1 H,
CarH), 7.01 (d, 3J = 11.4 Hz, 1 H, C3-H), 6.43 (v. t, 3J = ~10.9 Hz,
1 H, C4-H), 6.09–6.01 (m, 1 H, C5-H), 5.44 (v. t, 3J = 5.7 Hz, 1 H,
C9-H), 4.84 (d, 3J = 12.0 Hz, 1 H, C10-H), 4.60–4.55 [m, 2 H, C10-
H, OCH(CH3)2], 4.28–4.21 [m, 2 H, C7-H, OCH(CH3)2], 4.12–3.99
(m, 2 H, C15-H), 3.80 (br s, 3 H, OCH3), 3.67–3.51 (m, 4 H, C12-
H, C11-H), 2.48–2.44 (m, 2 H, C6-H), 2.05 (br s, 3 H, C2-CH3),
1.63 (br s, 3 H, C8-CH3), 1.37–1.35 [m, 9 H, CH(CH3)2], 1.27 [d,
3J = 6.2 Hz, 3 H, CH(CH3)2], 0.85 [s, 9 H, SiC(CH3)3], –0.04 [s,
3 H, Si(CH3)2], –0.08 [s, 3 H, Si(CH3)2].
13C NMR (90.6 MHz, CDCl3): d = 167.5 (C=O), 146.9 (CarO),
144.7 (CarO), 140.6 (Colef), 138.7 (Colef), 136.4 (Colef), 133.6
(ColefH), 129.3 (ColefH), 126.9 (ColefH), 125.4 (ColefH), 124.5 (Colef),
123.5 (ColefH), 106.1 (CarH), 80.3 (OCH), 75.4 [OCH(CH3)2], 71.2
[OCH(CH3)2], 69.1 (OCH2), 69.0 (OCH2), 67.5 (OCH2), 63.3
(OCH2), 61.4 (OCH3), 36.9 (CH2), 25.9 [SiC(CH3)3], 23.1
[OCH(CH3)2], 22.5 [OCH(CH3)2], 22.3 [OCH(CH3)2], 22.2
[OCH(CH3)2], 18.3 [SiC(CH3)3], 12.7 [=C(CO)CH3], 11.0 (CH3),
–4.6 [Si(CH3)2], –4.9 [Si(CH3)2].
A solution of Grubbs catalyst25 (5 mg, 6.2 mmol) in CH2Cl2 (1.0 mL)
was added to refluxing CH2Cl2 (120 mL) under argon. After stirring
for 5 min, a solution of 4a (40 mg, 62.4 mmol) in CH2Cl2 (4.0 mL)
was added. The solution was refluxed until the completion of the re-
action (TLC), and the solvent was then removed in vacuo. After
flash chromatography (P–EA, 95:05), the product (36 mg, 79%)
was obtained as a 60:40 mixture of two isomers which were not sep-
arated; Rf 0.71 (P–EA, 90:10) [CAM, UV]; [a]D20 +110.3 (c = 0.43,
CH2Cl2).
IR(film): 3434 (m, NH), 2928 (vs, CH2), 2855 (s, CH2), 1672 (s,
C=O), 1601 (m, C=C), 1510 (s), 1469 (m), 1434 (m), 1418 (s), 1382
[m, (CH3)2CH], 1372 [w, (CH3)2CH], 1222 (s, C–N), 1106 (s,
COC), 1032 (m), 1005 (m), 914 (m, RCH=CH2), 836 (m), 776
cm–1 (m).
1H NMR (360 MHz, CDCl3): d (major isomer) = 8.41 (s, 1 H, NH),
3
7.97 (s, 1 H, CarH), 6.97 (d, J = 11.1 Hz, 1 H, C3-H), 6.41 (v. t,
3J = ~11.1 Hz, 1 H, C4-H), 6.09–6.03 (m, 1 H, C5-H), 5.21 (v. t,
3J = 6.3 Hz, 1 H, C9-H), 4.61–4.54 [m, 1 H, OCH(CH3)2], 4.14–
4.10 [m, 1 H, OCH(CH3)2], 4.05–4.01 (m, 1 H, C7-H), 3.79 (s, 3 H,
OCH3), 2.80–2.73 (m, 2 H, C6-H), 2.48–2.44 (m, 2 H, C15-H), 2.02
(br s, 3 H, C2-CH3), 1.96–1.94 (m, 2 H, CH2), 1.69–1.66 (m, 2 H,
C11-H), 1.64 (s, 3 H, C8-CH3), 1.13–1.38 [m, 16 H, CH2,
CH(CH3)2], 0.86 [s, 9 H, SiC(CH3)3], –0.03 [s, 3 H, Si(CH3)2],
–0.07 [s, 3 H, Si(CH3)2]; d (minor isomer) = 8.21 (s, 1 H, NH), 7.93
(s, 1 H, CarH), 6.97 (d, 3J = J = 11.1 Hz, 1 H, C3-H), 6.41 (v. t, 3J =
~11.1 Hz, 1 H, C4-H), 6.09–6.03 (m, 1 H, C5-H), 5.55–5.43 (m,
1 H, C9-H), 4.61–4.54 [m, 1 H, OCH(CH3)2], 4.16–4.10 [m, 2 H,
C7-H, OCH(CH3)2], 3.82 (s, 3 H, OCH3), 2.70–2.55 (m, 2 H, C6-
H), 2.40–2.36 (m, 2 H, C15-H), 2.03 (s, 3 H, C2-CH3), 1.92–1.88
(m, 2 H, CH2), 1.69–1.66 (m, 2 H, CH2), 1.64 (s, 3 H, C8-CH3),
MS (EI): m/z (%) = 617 (100, [M+]), 575 (10), 513 (8), 359 (20),
316 (30), 274 (20), 220 (10), 209 (32), 152 (37), 127 (42), 108 (14),
73 (70, [C4H9O+]), 55 (10).
HRMS: m/z calcd for C35H55NO7Si: 617.3748; found: 617.3756.
(9R,10E)-9-Hydroxy-20,22-diisopropoxy-19-methoxy-4,10-
dimethyl-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-
hexaen-3-one (19a)
To a solution of silyl ether 3a (66 mg, 107 mmol) in THF (2 mL),
was added TBAF (1.0 M in THF, 0.15 mL, 0.15 mmol) slowly at r.t.
The mixture was stirred overnight at r.t. Then, Et2O (5 mL) and H2O
(5 mL) were added. The aqueous layer was extracted with Et2O
(2 × 10 mL). The combined organic layers were washed once with
brine, dried (Na2SO4), filtered and concentrated in vacuo. After
Synthesis 2005, No. 12, 1977–1990 © Thieme Stuttgart · New York