UPDATES
1
1
1
27.5, 127.8, 128.7, 128.8, 129.5, 130.0, 130.4, 132.3, 136.7,
an additional 1 h. The reaction mixture was filtered through
celite pad, extracted with EtOAc, washed with brine, dried
over Na SO , and concentrated under reduced pressure. The
37.6, 159.1, 190.3, 207.5; IR (ATR): n=3055, 2929, 1758,
À1
687, 1625, 1511, 1451, 1304, 1243, 1172 cm ; HR-MS (ESI-
2
4
+
+
3
TOF): m/z=380.1257 [M+Na] , calcd. for C H NNaO :
3
crude residue was purified by flash chromatography on
silica gel (hexane/EtOAc, 2/8) to afford 10 as a white
powder; yield:10.8 mg (0.035 mmol, 82%); >95:5 d.r.; mp
2
3
19
80.1257.
10-Methyl-5,6-dihydro-7H-5,8-epiminobenzo[7]annulene-
1
7
1
1
1
,9(8H)-dione (8h): pale yellow oil; R =0.4 (hexane/EtOAc,
155–1568C; R =0.6 (EtOAc). H NMR (400 MHz, CDCl ):
f
f
3
1
/3); H NMR (400 MHz, CDCl ): d=2.41 (d, J=17.2 Hz,
d=1.68 (br s, 1H), 1.70 (dd, J=13.6, 2.4 Hz, 1H), 2.79 (ddd,
J=13.6, 8.4, 6.8 Hz, 1H), 3.65 (d, J=13.2 Hz, 1H), 3.68 (m,
3
H), 2.58 (s, 3H), 3.04 (dd, J=6.8, 17.2 Hz, 1H), 3.91 (s,
H), 4.54 (d, J=6.8 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.41
1
4
H), 3.77 (d, J=13.2 Hz, 1H), 3.79 (m, 1H), 3.80 (s, 3H),
.35 (br s, 1H), 4.97 (m, 1H), 5.21 (d, J=3.2 Hz, 1H), 6.84
(
dd, J=7.2, 8.0 Hz 1H), 7.61 (dd, J=7.2, 8.0 Hz, 1H), 7.93
13
(
d, J=8.0 Hz, 1H); C NMR (100 MHz, CDCl ): d=36.5,
3
(d, J=8.0 Hz, 2H), 6.94 (d, J=7.6 Hz, 1H), 7.19 (dd, J=7.6,
4
1
1
3.0, 62.5, 79.9, 126.46, 126.50, 128.5, 129.5, 135.6, 142.6,
7
7
.6 Hz, 1H), 7.20 (d, J=8.0 Hz, 2H), 7.28 (dd, J=7.6,
.6 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H); C NMR (100 MHz,
89.8, 208.0; IR (ATR): n=2950, 2852, 1759, 1690, 1601,
13
À1
457, 1278, 1250, 1109, 1020 cm ; HR-MS (ESI-TOF): m/
CDCl ): d=45.9, 53.1, 55.3, 61.4, 62.3, 70.4, 75.7, 113.7,
3
+
+
2
z=202.0868 [M+H] , calcd. for C H NO : 202.0863.
1
2
12
125.0, 126.9, 127.2, 127.4, 129.7, 130.7, 138.4, 140.5, 158.7; IR
8
-(4-Methoxybenzyl)-8-azabicyclo[3.2.1]octane-2,7-dione
À1
(
ATR): n=3381, 2939, 1510, 1245, 1034 cm ; HR-MS (ESI-
1
(
8i): pale yellow oil; R =(hexane/EtOAc, 1/3); H NMR
+
+
f
TOF): m/z=312.1606 [M+H] , calcd. for C H NNaO :
1
9
22
3
(400 MHz, CDCl ): d=1.96 (dd, J=8.4, 12 Hz, 1H), 2.39
3
3
12.1594. The relative configuration was confirmed by the
(
(
m, 2H), 2.53 (m, 2H), 2.88 (dd, J=7.2, 18.4 Hz, 1H), 3.51
s, 1H), 3.73 (m, 3H), 3.80 (s, 3H), 6.86 (d, J=7.6 Hz, 2H),
NOESY spectrum.
1
3
7
2
1
1
.22 (d, J=7.6 Hz, 2H); C NMR (100 MHz, CDCl ): d=
3
8.4, 35.3, 40.9, 53.7, 54.4, 55.3, 78.4, 114.0, 128.7, 129.8,
59.2, 201.7, 210.1; IR (ATR): n=2934, 2835, 1756, 1723,
À1
612, 1512, 1455, 1371, 1302, 1245 cm ; HR-MS (ESI-TOF):
+
+
3
m/z=282. 1112 [M+Na] , calcd for C H NNaO :
1
5
17
2
82.1101.
1-Methyl-6,7-dihydro-5,9-epiminobenzo[8]annulene-
,10(5H,9H)-dione (8k): pale yellow oil; R =0.4 (hexane/
1
8
f
1
EtOAc, 1/3); H NMR (400 MHz, CDCl ): d=2.13 (dd, J=
3
rac-(5R,7R,8R,9S)-9-Hydroxy-10-(4-methoxybenzyl)-
7
1
3
8
8
4
1
1
.6, 12.8 Hz, 1H), 2.27 (m, 1H), 2.37 (dd, J=6.0, 16.4 Hz,
H), 2.58 (s, 3H), 2.76 (m, 1H), 3.88 (s, 1H), 4.16 (d, J=
.6 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.45 (dd, J=7.2,
.0 Hz, 1H), 7.67 (dd, J=7.2, 7.6 Hz, 1H), 8.03 (d, J=
6
,7,8,9-tetrahydro-5H-5,8-epiminobenzo[7]annulen-7-yl iso-
butyrate (11): To stirred solution of 10 (134 mg,
0.43 mmol), DMAP (157 mg, 0.65 mmol) in CH Cl (15 mL)
was added (i-PrCO)
O (0.13 mL, 0.77 mmol) at À788C.
a
2
2
13
.0 Hz, 1H); C NMR (100 MHz, CDCl ): d=30.8, 34.4,
2
3
1.7, 57.8, 80.2, 126.21, 126.22, 127.3, 128.2, 129.8, 135.4,
After the mixture had been stirred at À788C for 5 h, H
O
2
92.1, 201.2; IR (ATR): n=3061, 2933, 2106, 1725, 1683,
was added and the reaction mixture was extracted with
EtOAc, washed with brine, dried over Na SO , and concen-
À1
600, 1495, 1452, 1292, 1155 cm ; HR-MS (ESI-TOF): m/
2
4
+
+
z=238.0842 [M+Na] , calcd. for C H NNaO : 238.0838.
trated under reduced pressure. The crude residue was puri-
1
3
13
2
3-[(4-Methoxybenzyl)oxy]-1,10b–dihydropyrido[2,1-a]iso-
fied by flash chromatography on silica gel (n-hexane/
indol-6(2H)-one (9): white powder; 111–1138C; R =0.3
EtOAc=17/3) to afford 11 as a colorless oil; yield: 131 mg
f
1
1
(
hexane/EtOAc, 1/1); H NMR (400 MHz, CDCl ): d=1.60
(0.34 mmol, 80%); R =0.7 (hexane/EtOAc, 3/2). H NMR
3
f
(
m, 1H), 2.49 (m, 2H), 2.62 (m, 1H), 3.82 (s, 3H), 4.50 (dd,
(400 MHz, CDCl ): d=0.91 (d, J=6.8 Hz, 3H), 1.00 (d, J=
3
J=3.2, 12.4 Hz, 1H), 4.78 (s, 2H), 6.68 (s, 1H), 6.92 (d, J=
6
6
.8 Hz, 3H), 1.59 (dd, J=14.0, 2.0 Hz, 1H), 2.36 (qq, J=6.8,
.8 Hz, 1H), 2.93 (m, 1H), 3.07 (d, J=11.6 Hz, 1H), 3.68 (d,
8
7
7
5
1
2
1
.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.47 (dd, J=7.2,
.2 Hz, 2H), 7.55 (dd, J=7.2, 7.2 Hz, 1H), 7.85 (d, J=
J=13.2 Hz, 1H), 3.76–3.86 (m, 2H), 3.80 (s, 3H), 3.80 (d,
J=13.2 Hz, 1H), 5.23 (dd, J=11.6, 4.8 Hz, 1H), 5.62 (m,
13
.2 Hz, 1H); C NMR (100 MHz, CDCl ): d=26.5, 26.6,
3
5.3, 57.5, 69.6, 99.2, 114.0, 121.7, 123.5, 128.47, 128.52,
29.6, 131.3, 132.9, 144.0, 146.6, 159.6, 164.4; IR (ATR): n=
925, 2852, 1687, 1655, 1613, 1515, 1403, 1343, 1244,
1
H), 6.85 (d, J=8.0 Hz, 2H), 6.92 (d, J=8.0 Hz, 1H), 7.17
(
dd, J=8.0, 8.0 Hz, 1H), 7.23 (d, J=8.0 Hz, 2H), 7.26 (dd,
13
J=8.0, 8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H); C NMR
100 MHz, CDCl ): d=18.5, 18.7, 33.9, 43.4, 53.9, 55.3, 61.4,
À1
+
153 cm ; HR-MS (ESI-TOF):m/z=344.1265 [M+Na] ,
(
+
3
calcd. for C H NNaO : 344.1257.
20
19
3
6
1
1
2.1, 70.9, 77.1, 113.8, 124.7, 126.4, 127.2, 127.4, 129.7, 130.5,
37.9, 140.5, 158.8, 175.6; IR (ATR): n=3067, 2973, 2945,
À1
731, 1611, 1510, 1456, 1244 cm ; HR-MS (ESI-TOF): m/
Derivatization Reactions
+
+
4
z=382.2010 [M+H] , calcd. for C H NO : 382.2013.
2
3
28
rac-tert-Butyl (5R,7R,8R,9S)-9-hydroxy-7-(isobutyryloxy)-
,7,8,9-tetrahydro-5H-5,8-epiminobenzo[7]annulene-10-car-
rac-(5R,7R,8S,9S)-10-(4-Methoxybenzyl)-6,7,8,9-tetrahydro-
6
5
H-5,8-epiminobenzo[7]annulene-7,9-diol (10): To a stirred
solution of 8a (13 mg, 0.042 mmol) in THF (1.0 mL) was
added 1.0M DIBAL-H in hexane (0.17 mL, 0.17 mmol) at
À788C. After the mixture had been stirred at À788C for
boxylate (12): To a stirred solution of 11 (50 mg, 0.13 mmol)
in EtOH (4.3 mL) was added (Boc) O (227 mg, 1.04 mmol),
and Pd(OH) (9.8 mg, 20%wt) at room temperature. After
being stirred for 2 h at room temperature under H atmos-
2
2
2
h, 0.2M potassium sodium (+)-tartrate (aqueous) was
2
added and stirring was continued at room temperature for
phere (1 atm), the reaction mixture was filtered through
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
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