K. Knepper et al. / Tetrahedron 60 (2004) 8591–8603
8601
(q, CH2CAr), 143.5 (q, C-3a), 167.9 (q, CON). IR (CH2Cl2):
n¼1693 (CON), 1615 (arene), 918 (arene) cm21. MS (EI),
m/z (%)¼328 (Mþ, 15), 237 (15), 222 (95), 193 (10), 132
(10), 106 (30), 91 (100). HRMS (C22H20N2O): Calcd
328.1576, found 328.1569.
C-7a), 133.6 (þ, CHvCH2), 136.7 (þ, CHvCH2), 136.7
(q, C-3a), 147.2 (q, C-7), 153.4 (q, C-6), 167.7 (q, CON). IR
(CH2Cl2): n¼3373 (NH), 1694 (CON), 1599 (arene), 1045
(CH2vCH) cm21. MS (EI), m/z (%)¼288 (Mþ, 15), 247
(10), 232 (100), 205 (5), 190 (10). HRMS (C16H20N2O3):
Calcd 288.1474, found 288.1475.
2.5.7. (S,S)-2-(1-Phenyl-ethyl)-3-(1-phenyl-ethylamino)-
2,3-dihydro-isoindol-1-one (20g). Colorless oil, 22%, 1:1-
mixture of diastereomers. 1H NMR (300 MHz, CDCl3):
2.5.10. 2-Cyclopropyl-3-cyclopropylamino-6,7-
dimethoxy-2,3-dihydro-isoindol-1-one (21d). Colorless
3
1
d¼0.81, 1.08 (, J¼6.59, 6.59 Hz, 3H, NHCHCH3), 1.79,
oil, 17%. H NMR (400 MHz, CDCl3): d¼0.15–0.42 (ca,
3
1.83 (d, J¼7.16, 7.16 Hz, 3H, NCHCH3), 3.61, 3.72 (q,
4H, 2£CH2), 0.68–1.05 (ca, 5H, 2£CH2 and NH), 2.08 (dd,
3J¼9.35, 4.92 Hz, 1H, CHNH), 2.64 (dd, 3J¼6.95, 4.04 Hz,
1H, CHN), 3.85 (s, 3H, OCH3), 4.05 (s, 6H, OCH3), 5.12 (s,
1H, 3-H), 7.02 (d, 3J¼8.08 Hz, 1H, 4-H), 7.11 (d,
3J¼8.08 Hz, 1H, 5-H). 13C NMR (100 MHz, CDCl3):
d¼5.1, 5.5, 7.2, 8.0 (2, 4£CH2), 23.1, 24.7 (þ, 2£CH),
56.9, 62.6 (þ, 2£OCH3), 73.6 (þ, C-3), 116.3 (þ, C-4),
118.9 (þ, C-5), 125.0 (q, C-7a), 136.5 (q, C-3a), 147.0 (q,
C-7), 153.3 (q, C-6), 167.2 (q, CON). IR (CH2Cl2): n¼3357
(NH), 1694 (CON), 1600 (arene) cm21. MS (EI), m/z
(%)¼232 (M2C3H6Nþ, 100), 190 (10), 84 (30).
C16H20N2O3.
3J¼6.59, 6.59 Hz, 3H, NHCHCH3), 5.02, 5.28 (s, 1H, 3-H),
5.33, 5.62 (q, 3J¼7.16, 7.16 Hz, 1H, NCHCH3), 6.93–7.47,
7.67–7.77 (ca, 14H, Ar-H). 13C NMR (75 MHz, CDCl3):
d¼18.1, 18.4 (þ, NCHCH3), 23.8, 24.6 (þ, NHCHCH3),
50.5, 50.7 (þ, NCH), 52.5, 55.2 (þ, NHCH), 71.5, 72.0 (þ,
C-3), 123.0–131.8 (þ, CHAr), 132.1, 132.6, 141.1, 142.3,
144.0, 145.7, 146.0, 146.1 (q, CAr), 167.6 and 168.2 (q,
CON). IR (CH2Cl2): n¼2923 (aliphatic), 1686 (CON), 1602
(arene) cm21. MS (EI), m/z (%)¼356 (Mþ, 15), 341 (15),
236 (20), 225 (15), 172 (100), 132 (25), 105 (20), 77 (10).
HRMS (C24H24N2O): Calcd 356.1889, found 356.1886.
2.5.8. 6,7-Dimethoxy-2-propyl-3-propylamino-2,3-di-
1
2.5.11. 3-Diethylamino-2-propyl-2,3-dihydro-isoindol-1-
one (25b). Colorless oil, 10%. 1H NMR (400 MHz, CDCl3):
d¼0.94 (t, 3J¼7.46 Hz, 3H, CH3), 1.01–1.12 (ca, 6H,
2£CH3), 1.57 (m, 2H, CH3CH2CH2NH), 2.56 (m, 4H,
hydro-isoindol-1-one (21b). Yellow oil, 40%. H NMR
(300 MHz, CDCl3): d¼0.80 (t, 3J¼7.44 Hz, 3H, CH3), 0.94
3
(t, J¼7.44 Hz, 3H, CH3), 1.33 (m, 2H, CH3CH2CH2NH),
3
2
1.61 (m, 2H, CH3CH2CH2N), 1.80 (bs, 1H, NH), 2.01 (ddd,
3J¼14.32, 7.22 Hz, 2J¼4.34 Hz, NHCHH), 2.23 (ddd,
N(CH2CH3)2), 3.21 (ddd, J¼12.88, 7.07 Hz, J¼6.44 Hz,
3
2
1H, NCHH), 3.78 (ddd, J¼13.13, 7.90 Hz, J¼6.44 Hz,
1H, NCHH), 5.34 (s, 1H, 3-H), 7.40–7.51 (ca, 3H, Ar-H),
7.80 (d, 3J¼6.94 Hz, 1H, 7-H). 13C NMR (100 MHz,
CDCl3): d¼11.7 (þ, CH2CH2CH3), 15.0 (þ, N(CH2CH3)2),
21.9 (2, CH2CH2CH3), 38.4, 41.4, 43.7 (2, 3£NCH2), 76.1
(þ, C-3), 123.4 (þ, C-4), 123.5 (þ, C-7), 128.9 (þ, C-5),
131.2 (þ, C-6), 133.5 (q, C-7a), 143.9 (q, C-3a), 167.7 (q,
CON). IR (CH2Cl2): n¼2925 (aliphatic), 1686 (CON), 1615
(arene) cm21. MS (EI), m/z (%)¼246 (Mþ, 10), 174 (100),
146 (10), 132 (30), 104 (5), 77 (5). C15H22N2O, HRMS:
Calcd 246.1732, found 246.1740.
2
3J¼14.04, 7.07 Hz, J¼4.43 Hz, 1H, NHCHH), 3.05 (ddd,
2
3J¼13.85, 8.29 Hz, J¼5.56 Hz, 1H, NCHH), 3.73 (ddd,
2
3J¼13.85, 8.56 Hz, J¼5.18 Hz, 1H, NCHH), 3.86 (s, 3H,
OCH3), 4.05 (s, 3H, OCH3), 5.23 (s, 1H, 3-H), 7.04 (d,
3
3J¼8.10 Hz, 1H, 4-H), 7.13 (d, J¼8.10 Hz, 1H, 5-H). 13C
NMR (75 MHz, CDCl3): d¼11.7, 11.9 (þ, 2£CH2CH3),
21.8, 23.7 (2, 2£CH2CH3), 40.8 (2, NCH2), 42.9 (2,
NHCH2), 56.8, 62.6 (þ, 2£OCH3), 71.7 (þ, C-3), 116.1 (þ,
C-4), 118.2 (þ, C-5), 125.1 (q, C-7a), 137.1 (q, C-3a), 147.1
(q, C-7), 153.2 (q, C-6), 16708 (q, CON). IR (CH2Cl2):
n¼2926 (aliphatic), 1687 (CON). 1613 (arene) cm21. MS
(EI), m/z (%)¼292 (Mþ, 5), 234 (10), 220 (25), 205 (100),
145 (5). HRMS (C16H24N2O3): Calcd 292.1787, found
292.1793.
2.5.12. 2-Allyl-3-diethylamino-2,3-dihydro-isoindol-1-
one (25c). Colorless oil, 12%. 1H NMR (400 MHz,
CDCl3): d¼0.90–1.10 (ca, 6H, 2£CH2CH3), 2.45–2.60
2
3
(ca, 4H, 2£CH2CH3), 3.75 (dd, J¼13.90 Hz, J¼6.82 Hz,
2
2.5.9. 2-Allyl-3-allylamino-6,7-dimethoxy-2,3-dihydro-
isoindol-1-one (21c). Colorless oil, 49%. 1H NMR
(400 MHz, CDCl3): d¼1.95 (bs, 1H, NH), 2.77 (ddt,
2J¼14.15 Hz, 3J¼5.43 Hz, 4J¼3.16 Hz, 1H, NHCHH),
2.90 (ddt, 2J¼14.15 Hz, 3J¼6.44 Hz, 4J¼2.59 Hz, 1H,
NHCHH), 3.73 (ddt, 2J¼15.60 Hz, 3J¼7.14 Hz,
4J¼2.02 Hz, 1H, NCHH), 3.86 (s, 3H, OCH3), 4.05 (s,
6H, OCH3), 4.45 (ddt, 2J¼15.60 Hz, 3J¼5.00 Hz,
4J¼3.07 Hz, 1H, NCHH), 4.99 (ddd, 3J¼10.24 Hz,
4J¼4.30 Hz, 2J¼1.59 Hz, 1H, CHvCHH), 5.08 (ddd,
1H, NCHH), 4.50 (d, J¼13.90 Hz, 1H, NCHH), 5.30 (s,
3
1H, 3-H), 5.13 (m, 2H, CHvCH2), 5.77 (dddd, J¼17.37,
10.42, 7.32, 6.82 Hz, 1H, CHvCH2), 7.35–7.49 (ca, 3H,
Ar-H), 7.77 (d, 3J¼7.07 Hz, 1H, 7-H). 13C NMR (100 MHz,
CDCl3): d¼15.1 (þ, 2£CH3), 42.3 (2, NCH2CH), 43.8 (2,
2£CH2CH3), 75.9 (þ, C-3), 117.3 (2, CHvCH2), 123.5
(þ, C-4), 123.6 (þ, C-7), 128.9 (þ, C-5), 131.4 (q, C-7a),
133.2 (þ, C-6), 133.8 (þ, CHvCH2), 143.5 (q, C-3a), 170.0
(q, CON). IR (CH2Cl2): n¼2922 (aliphatic), 1693 (CON),
1615 (arene) cm21. MS (EI), m/z (%)¼244 (Mþ, 10), 172
(100), 152 (15), 132 (15), 77 (5). HRMS (C15H20N2O):
Calcd 244.1576, found 244.1579.
4
2
3J¼17.18 Hz, J¼4.93 Hz, J¼1.59 Hz, 1H, CHvCHH),
5.16 (ddd, 3J¼10.17 Hz, 4J¼3.79 Hz, 2J¼1.40 Hz, 1H,
CHvCHH), 5.21 (ddd, 3J¼17.18 Hz, 4J¼4.43 Hz,
2J¼1.40 Hz, 1H, CHvCHH), 5.27 (s, 1H, 3-H), 5.67–
2.5.13. 3-Methoxy-2-propenyl-2,3-dihydro-isoindol-1-
1
3
5.89 (ca, 2H, 2£CH2CHvCH2), 7.05 (d, J¼8.08 Hz, 1H,
one ((E)-26). Colorless solid, 25%. H NMR (400 MHz,
CDCl3): d¼1.78 (dd, 3J¼6.75 Hz, 4J¼1.67 Hz, 2H,
4-H), 7.16 (d, 3J¼8.08 Hz, 1H, 5-H). 13C NMR (100 MHz,
CDCl3): d¼42.1 (2, NCH2), 44.0 (2, NHCH2), 56.8, 62.6
(þ, 2£OCH3), 71.3 (þ, C-3), 116.0 (2, CHvCH2), 116.4
(þ, C-4), 117.8 (2, CHvCH2), 118.5 (þ, C-5), 124.8 (q,
3
CHvCHCH2), 2.84 (s, 1H, OCH3), 5.66 (dt, J¼14.65,
6.75 Hz, 1H, CHvCHtransCH2), 6.09 (s, 1H, 3-H), 6.92 (dd,
3J¼14.65 Hz, 4J¼1.67 Hz, 1H, NCHvCH), 7.53 (d,