Full Paper
(
m, 1H), 1.12–0.86 (m, 6H), 0.83 (d, J=7.3 Hz, 3H), 0.78 ppm (d, J=
31.6, 26.2, 23.42, 22.17, 21.1, 16.38 ppm; IR (ATR, neat): n˜ =2950,
1
3
6
1
1
3
.7 Hz, 3H); C NMR (75 MHz, CDCl ): d=major diastereoisomer:
2867, 1727, 1611, 1492, 1386, 1270, 1118, 1176, 1147, 1083,
3
À1
70.22, 150.2, 145.5, 128.0, 127.7, 127.25, 126.98, 126.94, 126.69,
26.46, 125.30, 124.18, 123.99, 74.6, 70.6, 60.7, 52.55, 47.2, 41.03,
7.9, 34.43, 31.6, 25.9, 23.42, 22.19, 21.0, 16.37 ppm; minor diaste-
1011 cm
;
HRMS (ESI): m/z calcd for C H N O : 479.2904
29
39
2
4
+
[M+H] ; found: 479.2904; HPLC (AD-H, hexane/iPrOH 80:20,
À1
0.5 mLmin , 258C, 5 mL): t =15.72 (major), 16.87 min (minor).
R
reoisomer: 170.18, 150.3, 145.5, 128.1, 127.8, 127.32, 127.02,
(
1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(2,8-dibromo-6,12-
dihydro-5,11-methanodibenzo[b,f][1,5]diazocin-13-yl)acetate
3k): Compounds 1e (0.11 g, 0.3 mmol, 1.0 equiv) and 2a (62 mg,
.3 mmol, 1.0 equiv) were treated according to the general proce-
1
5
1
1
26.90, 126.68, 126.52, 125.25, 124.21, 124.02, 74.7, 70.4, 60.6,
2.58, 47.3, 40.99, 37.7, 34.39, 31.6, 26.2, 23.38, 22.16, 21.1,
6.35 ppm; IR (ATR, neat): n˜ =2949, 2851, 2188, 2006, 1726, 1473,
(
0
À1
400, 1291, 1203, 1167, 1120 cm ; HRMS (ESI): m/z calcd for
dure. The crude product was purified by column chromatography
+
C H N O : 419.2693 [M+H] ; found: 419.2693; HPLC (AD-H,
hexane/iPrOH=80:20, 0.5 mLmin , 258C, 5 mL): t =9.07 (minor),
27
35
2
2
(R =(3:1) 0.24, pentane/Et O 95:5!3:1) after 6 days to afford 3k
f
2
À1
1
R
as a pale-yellow solid (96 mg, 56%, d.r.=55:45). H NMR (300 MHz,
9
.98 min (major).
CDCl ): d=7.33–7.21 (m, 2H), 7.05–7.01 (m, 2H), 7.02–6.88 (m, 2H),
3
4
.80–4.73 (m, 1H), 4.72–4.65 (m, 1H), 4.64–4.57 (m, 1H), 4.53 (d,
(
1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl
2-(2,8-diisopropyl-
J=17.4 Hz, 1H; minor), 4.52 (d, J=17.6 Hz, 1H; major), 4.11 (d, J=
1
2
6
,12-dihydro-5,11-methanodibenzo[b,f][1,5]diazocin-13-yl)ace-
tate (3i): Compounds 1c (0.15 g, 0.5 mmol, 1.0 equiv) and 2a
0.10 g, 0.5 mmol, 1.0 equiv) were treated according to the general
6.7 Hz, 1H), 4.00 (d, J=17.4 Hz, 1H), 2.67 (dd, J=15.0, 6.3 Hz, 1H),
.58 (ddd, J=14.9, 8.1, 1.5 Hz, 1H), 2.09–1.91 (m, 1H), 1.87 (heptd,
(
J=6.9, 2.7 Hz, 1H), 1.74–1.61 (m, 2H), 1.57–1.40 (m, 1H), 1.37–1.24
m, 2H), 1.15–0.95 (m, 1H), 0.96–0.87 (m, 6H), 0.82 (d, J=7.0 Hz,
procedure. The crude product was purified by column chromatog-
(
raphy (R =(3:1) 0.67, hexane/EtOAc 95:5!5:1) to afford 3i as
f
13
1
1H), 0.77 ppm (t, J=7.1 Hz, 3H); C NMR (75 MHz, CDCl ): d=
minor diastereoisomer: 169.77, 148.93, 144.27, 131.2, 130.7, 129.9,
3
a pale-yellow solid (0.22 g, 86%, d.r.=12:88). H NMR (300 MHz,
CDCl ): d=7.09–6.94 (m, 4H), 6.75 (s, 2H; minor), 6.72 (s, 2H;
3
1
5
1
1
7
2
1
29.82, 129.48, 128.7, 128.2, 126.88, 117.2, 117.00, 74.92, 70.3, 60.2,
2.23, 47.7, 40.97, 37.5, 34.3, 31.55, 26.2, 23.36, 22.16, 21.1,
6.3 ppm; major diastereosiomer: 169.78, 148.86, 144.26, 131.1,
30.6, 129.8, 129.80, 129.52, 128.8, 128.1, 126.92, 117.1, 116.97,
4.88, 70.5, 60.3, 52.21, 47.2, 41.01, 37.6, 34.4, 31.55, 26.0, 23.41,
2.18, 21.0, 16.4 ppm; IR (ATR, neat): n˜ =2948, 2851, 1727, 1489,
major), 4.83–4.66 (m, 2H), 4.66 (d, J=12.9 Hz, 1H; major), 4.64 (d,
J=14.6 Hz, 1H; minor), 4.56 (d, J=17.3, 1H; minor), 4.53 (d, J=
1
7.4, 1H; major), 4.16 (d, J=16.5 Hz, 1H), 4.05 (d, J=17.4 Hz, 1H;
major), 4.04 (d, J=17.4 Hz, 1H; minor), 2.79 (hept, J=6.5 Hz, 2H),
2
1
1
.71 (dd, J=14.4, 6.5 Hz, 1H), 2.62 (dd, J=14.7, 8.1 Hz, 1H), 2.11–
.99 (m, 1H), 1.93 (heptd, J=7.0, 2.8 Hz, 1H), 1.73–1.61 (m, 2H),
.58–1.43 (m, 1H), 1.38–1.26 (m, 1H), 1.18 (d, J=6.9 Hz, 12H;
À1
473, 1386, 1290, 1268, 1203, 1145, 1121 cm ; HRMS (ESI): m/z
+
calcd for C H Br N O : 575.0909 [M+H] ; found: 575.0901; HPLC
27
33
2
2
2
major), 1.17 (d, J=6.9 Hz, 12H; minor), 1.11–0.99 (m, 1H), 0.97–
À1
(
AD-H, hexane/iPrOH 90:10, 0.5 mLmin , 258C, 5 mL): t =15.67
R
0
.87 (m, 5H), 0.83 (d, J=7.0 Hz, 3H), 0.78 ppm (d, J=6.8 Hz, 3H);
1
3
(major), 27.72 min (minor).
C NMR (75 MHz, CDCl ): d=major diastereoisomer: 170.4, 148.05,
3
1
1
3
44.5, 144.28, 143.17, 127.7, 126.55, 126.2, 125.8, 125.3, 125.10,
24.58, 124.29, 74.55, 70.7, 60.6, 52.5, 47.3, 41.04, 37.9, 34.5, 33.7,
1.6, 25.9, 24.1, 23.42, 22.20, 21.0, 16.39 ppm; minor diastereoiso-
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(2,8-dichloro-6,12-
dihydro-5,11-methanodibenzo[b,f][1,5]diazocin-13-yl)acetate
(3l): Compounds 1g (84 mg, 0.3 mmol, 1.0 equiv) and 2a (62 mg,
0.3 mmol, 1.0 equiv) were treated according to the general proce-
dure. The crude product was purified by column chromatography
mer: 170.3, 148.12, 144.6, 144.32, 143.19, 127.8, 126.55, 126.3,
1
4
1
1
25.9, 125.4, 125.05, 124.64, 124.29, 74.58, 70.4, 60.5, 52.6, 47.4,
1.01, 37.8, 34.4, 33.6, 31.6, 26.1, 24.1, 23.38, 22.17, 21.1,
6.35 ppm; IR (ATR, neat): n˜ =2950, 2867, 1727, 1492, 1463, 1386,
(R
=(19:1) 0.24, pentane/Et
O 95:5!5:1) after 3 days to afford 3l
f
2
1
as a pale-yellow solid (35 mg, 24%, d.r.=54:46). H NMR (300 MHz,
À1
312, 1270, 1236, 1177, 1147, 1083, 1011 cm ; HRMS (ESI): m/z
CDCl ): d=7.17–7.09 (m, 2H), 7.03 (d, J=7.0 Hz, 1H; major), 7.00
3
+
calcd for C H N O : 503.3632 [M+H] ; found: 503.3630; HPLC
(d, J=7.0 Hz, 1H; minor), 6.99 (d, J=8.6 Hz, 1H; major), 6.99 (d, J=
8.6 Hz, 1H; minor), 7.08–6.94 (m, 2H), 6.95–6.86 (m, 2H), 4.76 (tt,
J=10.9, 4.0 Hz, 1H), 4.75–4.62 (m, 1H), 4.67–4.54 (m, 1H), 4.53 (d,
J=17.5 Hz, 1H; minor), 4.52 (d, J=17.5 Hz, 1H; major), 4.11 (d, J=
3
3
47
2
2
À1
(
(
AD-H, hexane/iPrOH 99.5:0.5, 0.5 mLmin , 258C, 5 mL): t =21.42
minor), 22.39 min (major).
R
(
6
1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl
H,12H-5,11-methanodibenzo[b,f][1,5]diazocin-13-yl)acetate (3j):
Compounds 1d (61 mg, 0.2 mmol, 1.0 equiv) and 2a (47 mg,
.2 mmol, 1.0 equiv) were treated according to the general proce-
dure. The crude product was purified by column chromatography
R =(3:1) 0.64, pentane/Et O 95:5!3:1) to afford 3j as a pale-
2-(2,8-dimethoxy-
1
2
6.7 Hz, 1H), 3.99 (d, J=17.6 Hz, 1H), 2.68 (dd, J=14.8, 6.4 Hz, 1H),
.58 (ddd, J=14.9, 8.1, 1.5 Hz, 1H), 2.07–1.94 (m, 1H), 1.88 (heptd,
J=7.0, 2.8 Hz, 1H), 1.73–1.61 (m, 2H), 1.55–1.41 (m, 1H), 1.37–1.23
m, 1H), 1.10–0.97 (m, 1H), 0.96–0.87 (m, 6H), 0.84–0.74 ppm (m,
0
(
13
5
1
1
3
H); C NMR (75 MHz, CDCl ): d=major diastereoisomer: 169.83,
3
(
f
2
48.36, 143.7, 129.42, 129.36, 129.27, 128.30, 128.22, 127.80,
27.75, 126.83, 126.55, 126.54, 74.87, 70.6, 60.4, 52.37, 47.2, 41.02,
7.7, 34.39, 26.0, 23.42, 22.2, 21.0, 16.4 ppm; minor diastereoiso-
1
yellow solid (92 mg, 85%, d.r.=62:38). M.p. 63.5–67.88C; H NMR
300 MHz, CDCl ): d=7.06–6.96 (m, 2H), 6.79–6.67 (m, 2H), 6.45–
(
3
6
(
.37 (m, 2H), 4.81–4.73 (m, 1H), 4.68 (dd, J=16.4, 3.2 Hz, 1H), 4.63
d, J=7.2 Hz, 1H; major), 4.63 (d, J=12.4 Hz, 1H; minor), 4.52 (d,
J=17.4 Hz, 1H; minor), 4.50 (d, J=17.4 Hz, 1H; major), 4.10 (d, J=
mer: 169.81, 148.43, 143.8, 129.46, 129.41, 129.30, 128.29, 128.22,
1
4
27.84, 127.74, 126.85, 126.58, 126.52, 74.92, 70.4, 60.3, 52.39, 47.3,
0.98, 37.5, 34.35, 26.2, 23.37, 22.2, 21.1, 16.3 ppm; IR (ATR, neat):
1
2
1
6
6.6 Hz, 1H), 3.98 (d, J=17.2 Hz, 1H), 3.70 (s, 6H), 2.77–2.53 (m,
H), 2.10–1.99 (m, 1H), 1.98–1.89 (m, 1H), 1.74–1.58 (m, 2H), 1.56–
.41 (m, 1H), 1.38–1.18 (m, 2H), 1.10–0.97 (m, 1H), 0.96–0.87 (m,
n˜ =2920, 2863, 1725, 1474, 1452, 1368, 1321, 1204, 1167,
À1
1
121 cm ; HRMS (ESI): m/z calcd for C H Cl N O : 487.1914 [M+
27
33
2
2
2
+
H] ; found: 487.1910; HPLC (AD-H, hexane/iPrOH 99.5:0.5,
.5 mLmin , 258C, 5 mL): t =14.76 (major), 28.10 min (minor).
13
H), 0.83 (d, J=7.0 Hz, 1H), 0.80–0.76 ppm (m, 3H); C NMR
À1
0
R
(
75 MHz, CDCl ): d=major diastereoisomer: 170.30, 156.2, 156.10,
3
1
7
2
1
43.18, 138.3, 128.75, 127.64, 127.36, 126.14, 114.5, 113.96, 110.6,
4.61, 71.0, 60.83, 55.5, 52.9, 47.2, 41.0, 38.0, 34.44, 31.6, 25.9,
3.42, 22.19, 21.0, 16.38 ppm; minor diastereoisomer: 170.25,
56.3, 156.13, 143.24, 138.3, 128.81, 127.59, 127.43, 126.09, 114.6,
Synthesis of model systems
2,5,8-Trimethyl-5,6,11,12-tetrahydrodibenzo[b,f][1,5]diazocine
[29]
114.04, 110.8, 74.63, 70.7, 60.75, 55.5, 52.9, 47.3, 41.0, 37.8, 34.40,
(6): Dimethyl sulfate (0.66 mL, 7.0 mmol, 4.5 equiv) was added to
Chem. Eur. J. 2016, 22, 390 – 403
401
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim