ꢀ
P. Szczesniak et al. / Tetrahedron 72 (2016) 3032e3039
3037
4.4. General procedure for radical cyclization
110.3, 108.3, 107.5, 106.1, 60.4, 56.1, 56.0, 55.6, 54.0, 46.3, 44.1;
HRMS (ESI-TOF) m/z calcd for C18H19NO4 [Mþ] 313.1312 found
313.1325; IR (film, CH2Cl2) nmax 1712, 1505, 1465, 1366, 1320, 1217,
To a solution of enaminone 2ael (0.1 mmol) in benzene (15 ml)
tributyltin hydride (Bu3SnH) (32 ul, 0.12 mmol 1.2 equiv) and AIBN
(3.2 mg, 0.02 mmol, 20 mol %) were added under argon. The re-
action mixture was stirred at 80 ꢀC for 16 h (TLC monitoring). After
the substrate was consumed, the reaction mixture was evaporated
under reduced pressure. The crude product was diluted with ace-
tonitrile (10 ml), and washed three times with hexanes. The ace-
tonitrile phase was concentrated under reduced pressure to give
a residue, which was purified by silica gel column chromatography
to give the corresponding adducts (3ael).
1188, 1112, 1018, 747 cmꢁ1
.
4.4.5. (4R*,10bR*)-Ethyl 8,9-dimethoxy-2-oxo-1,2,3,4,6,10b-hexahy-
dropyrido[2,1-a]isoindole-4-carboxylate (3e). Yellow oil; isolated
yield 24 mg (38%) for anionic cyclization, 12 mg (38%) for radical
cyclization; Rf 0.29 (50% AcOEt in hexanes); chromatography (40%
AcOEt in hexanes); 1H NMR (500 MHz, C6D6)
d: 6.50 (s, 1H), 6.34 (s,
1H), 4.64 (dd, J¼11.4, 2.6 Hz, 1H), 4.27 (dd, J¼11.5, 2.5 Hz, 1H),
3.94e3.88 (m, 3H), 3.74 (dd, J¼6.8, 3.6 Hz, 1H), 3.43 (s, 3H), 3.41 (s,
3H), 2.70 (dd, J¼14.2, 3.1 Hz, 1H), 2.63 (dd, J¼15.2, 3.5 Hz, 1H); 2.39
(dd, J¼15.2, 6.8 Hz, 1H); 2.21 (dd, J¼14.2, 11.5 Hz, 1H), 0.58 (t,
4.4.1. (4R
*
,10bR )-8,9-Dimethoxy-4-phenyl-1,3,4,10b-tetrahydropyr-
*
ido[2,1-a]isoindol-2(6H)-one (3a). Yellow solid; mp 101e103 ꢀC;
isolated yield 47 mg (72%) for anionic cyclization, 17 mg (53%) for
radical cyclization; Rf 0.24 (50% AcOEt in hexanes); chromatogra-
J¼7.2 Hz, 3H); 13C NMR (125 MHz, C6D6)
d: 204.2, 170.9, 150.2, 150.1,
134.9, 131.0, 107.4, 106.0, 61.0, 60.6, 58.8, 55.9, 55.7, 46.3, 45.0, 42.0,
14.3; HRMS (ESI-TOF) m/z calcd for C17H21NO5 [Mþ] 319.142 found
319.141; IR (film, CH2Cl2) nmax 1726, 1689, 1499, 1292, 1198, 1122,
phy (40% AcOEt in hexanes); 1H NMR (500 MHz, C6D6)
d: 7.30e7.14
(m, 5H), 6.39 (s, 1H), 6.34 (s, 1H), 4.62e4.56 (m, 1H), 4.00 (d,
J¼12.7 Hz, 1H), 3.87 (dd, J¼11.2, 3.5 Hz, 1H), 3.58e3.53 (m, 1H), 3.41
(m, 6H), 2.58 (dd, J¼16.7, 11.2 Hz, 1H), 2.50e2.44 (m, 2H), 2.34 (dd,
1027 cmꢁ1
.
4.4.6. (4R*,10bR*)-4-Isopropyl-8,9-dimethoxy-1,3,4,10b-tetrahy-
dropyrido[2,1-a]isoindol-2(6H)-one (3f). Yellow oil; isolated yield
36 mg (63%) for anionic cyclization, 9 mg (32%) for radical cycli-
zation; Rf 0.33 (50% AcOEt in hexanes); chromatography (40% AcOEt
J¼16,1, 12.4 Hz, 1H); 13C NMR (125 MHz, C6D6)
d 207.0, 150.3, 150.0,
143.4, 134.2, 130.7, 128.9, 128.8, 107.1, 106.4, 96.4, 62.8, 61.7, 58.7,
56.0, 55.9, 48.1, 44.8; HRMS (ESI-TOF) m/z calcd for C20H21NO3 [Mþ]
323.1523 found 323.1511; IR (film, CH2Cl2) nmax 1718, 1507, 1454,
in hexanes); 1H NMR (500 MHz, C6D6)
d: 6.54 (s, 1H), 6.38 (s, 1H),
1356, 1224, 1190, 1111, 756, 702 cmꢁ1
.
4.46 (dt, J¼11.9, 3.4 Hz, 1H), 4.14 (d, J¼12.1 Hz, 1H), 3.72 (ddd,
J¼12.1, 3.4, 0.7 Hz, 1H), 3.49 (s, 3H), 3.47 (s, 3H), 2.71e2.68 (m, 1H),
2.35 (dd, J¼15.5, 3.5 Hz, 1H), 2.28 (d, J¼2.4 Hz, 2H), 2.13 (dd, J¼15.5,
11.9 Hz, 1H), 1.74 (m, 1H), 0.92 (d, J¼6.8 Hz, 3H), 0.86 (d, J¼6.8 Hz,
4.4.2. (4R ,10bR*)-4-(4-Bromophenyl)-8,9-dimethoxy-1,3,4,10b-tet-
*
rahydropyrido[2,1-a]isoindol-2(6H)-one (3b). Yellow solid; mp
136e137 ꢀC; isolated yield 27 mg (34%) for anionic cyclization,
14 mg (34%) for radical cyclization; Rf 0.28 (50% AcOEt in hexanes);
chromatography (40% AcOEt in hexanes); 1H NMR (500 MHz, C6D6)
3H); 13C NMR (125 MHz, C6D6)
d: 208.0, 150.1, 149.9, 135.5, 130.6,
107.3, 106.4, 64.3, 62.2, 58.2, 56.1, 56.0, 45.2, 39.1, 30.8, 19.4, 17.2;
HRMS (ESI-TOF) m/z calcd for C17H23NO3 [Mþ] 289.168 found
289.168; IR (film, CH2Cl2) nmax 1716, 1506, 1351, 1322, 1222, 1190,
d
7.34 (d, J¼8.4 Hz, 2H), 7.16e7.13 (s, 2H), 6.94 (d, J¼8.3 Hz, 2H), 6.42
(s, 1H), 6.34 (s, 1H), 4.44 (t, J¼5.0 Hz, 1H), 3.92 (m, 1H), 3.47e3.43
1113, 1002 cmꢁ1
.
(m, 1H), 3.45 (s, 3H), 3.41 (s, 3H), 2.48e2.38 (m, 2H), 2.35e2.25 (m,
2H); 13C NMR (125 MHz, C6D6)
d
206.6, 150.4, 150.1, 142.4, 134.0,
4.4.7. (4R*,11bR*)-9,10-Dimethoxy-4-phenyl-3,4,6,7-tetrahydro-1H-
pyrido[2,1-a]isoquinolin-2(11bH)-one (3g). Colorless solid; mp
139e141 ꢀC; isolated yield 48 mg (71%) for anionic cyclization,
25 mg (75%) for radical cyclization; Rf 0.36 (50% AcOEt in hexanes);
chromatography (40% AcOEt in hexanes); 1H NMR (500 MHz,
132.0, 130.5, 129.0, 121.4, 107.0, 106.4, 62.2, 61.7, 58.6, 56.0, 55.9,
47.8, 44.7; HRMS (ESI-TOF) m/z calcd for C20H20NO379Br [Mþ]
401.0634 found 401.0623; IR (film, CH2Cl2) nmax 1719, 1508, 1325,
1224, 1191, 1112, 1009, 839 cmꢁ1
.
CDCl3) d: 7.35e7.29 (m, 5H), 6.60 (s, 1H), 6.47 (s, 1H), 4.54 (t,
4.4.3. (4R
*
,10bR*)-8,9-Dimethoxy-4-(4-methoxyphenyl)-1,3,4,10b-
J¼5.1 Hz, 1H), 4.07 (dd, J¼8.9, 4.9 Hz, 1H), 3.84 (s, 3H), 3.80 (s, 3H),
tetrahydropyrido[2,1-a]isoindol-2(6H)-one (3c). Orange solid; mp
122e124 ꢀC; isolated yield 49 mg (69%) for anionic cyclization,
15 mg (42%) for radical cyclization; Rf 0.32 (50% AcOEt in hexanes);
chromatography (40% AcOEt in hexanes); 1H NMR (500 MHz, C6D6)
3.28e3.24 (m, 1H), 2.95e2.80 (m, 5H), 2.78 (ddd, J¼15.0, 4.1, 1.1 Hz,
1H), 2.71 (dd, J¼14.8, 9.8 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d:
208.0,152.3,147.4,139.5,128.7,128.3,128.1,127.5,126.0,111.5,108.9,
96.9 63.9, 55.9, 54.2, 46.9, 46.5, 43.6, 29.7 28.7; HRMS (ESI-TOF) m/z
calcd for C21H23NO3 [Mþ] 337.1678 found 337.1695; IR (film,
CH2Cl2) nmax 1706,1610, 1517, 1451, 1357,1256,1232,1129, 1021, 769,
d
: 7.34 (d, J¼8.6 Hz, 2H), 6.92 (d, J¼8.6 Hz, 2H), 6.73e6.66 (m, 2H),
4.48 (t, J¼5.0 Hz, 1H), 3.88e3.80 (m, 1H), 3.49e3.45 (m, 1H), 3.45 (s,
3H), 3.42e3.39 (m, 6H), 3.32 (dd, J¼12.3, 3.2 Hz, 1H), 2.99 (d,
J¼13.6 Hz, 1H), 2.75e2.58 (m, 4H); 13C NMR (125 MHz, C6D6)
702 cmꢁ1
.
d
205.1, 154.7, 152.7, 147.7, 132.1, 131.9, 129.8, 128.8, 114.7, 108.4,
4.4.8. (4R*,11bR*)-4-(4-Bromophenyl)-9,10-dimethoxy-3,4,6,7-
tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one (3h). Colorless
solid; mp 128e129 ꢀC; isolated yield 21 mg (25%) for anionic cy-
clization, 8 mg (20%) for radical cyclization; Rf 0.31 (50% AcOEt in
hexanes); chromatography (40% AcOEt in hexanes); 1H NMR
105.1, 67.6, 65.2, 59.7, 55.1, 52.3, 52.7, 48.0, 42.7; HRMS (ESI-TOF) m/
z calcd for C21H23NO4 [Mþ] 353.1632 found 353.1621; IR (film,
CH2Cl2) nmax 1715, 1511, 1464, 1306, 1247, 1224, 1175, 1112, 1033,
839 cmꢁ1
.
(200 MHz, CDCl3)
d (ppm): 7.48e7.44 (m, 2H), 7.28e7.24 (m, 2H),
4.4.4. (4R*,10bR*)-4-(Furan-2-yl)-8,9-dimethoxy-1,3,4,10b-tetrahy-
dropyrido[2,1-a]isoindol-2(6H)-one (3d). Dark brown oil; isolated
yield 39 mg (63%) for anionic cyclization, 17 mg (53%) for radical
cyclization; Rf 0.35 (50% AcOEt in hexanes); chromatography (40%
6.60 (s, 1H), 6.45 (s, 1H), 4.14 (t, J¼5.0 Hz, 1H), 4.08 (dd, J¼14.6,
7.1 Hz, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 3.30e3.24 (m, 1H), 2.89e2.84
(m, 4H), 2.75e2.61 (m, 3H); 13C NMR (50 MHz, CDCl3)
d: 206.1,
150.4,149.6,142.6,135.5, 133.2,128.7,128.2,122.3,110.2,108.9, 63.9,
AcOEt in hexanes); 1H NMR (500 MHz, C6D6)
d: 7.06 (dd, J¼1.8,
58.9, 55.9, 52.2, 46.9, 45.1, 41.5, 30.2; HRMS (ESI-TOF) m/z calcd for
0.8 Hz, 1H), 6.48 (s, 1H), 6.30 (s, 1H), 6.12 (m, 1H), 6.05 (dd, J¼3.2,
1.8 Hz,1H), 4.23e4.18 (m, 2H), 4.09 (dd, J¼11.8, 2.2 Hz,1H), 3.89 (dd,
J¼11.8, 2.2 Hz, 1H), 3.43 (s, 3H), 3.42 (s, 3H), 2.68e2.63 (m, 2H), 2.58
(dd, J¼15.3, 6.2 Hz, 1H), 2.29 (dd, J¼14.4, 11.6 Hz, 1H); 13C NMR
C
21H2279BrNO3 [Mþ] 415,0785 found 415,0742; IR (film, CH2Cl2)
nmax 1716, 1510, 1337, 1256, 1232, 1189, 1131, 851 cmꢁ1
.
4.4.9. (4R*,11bR*)-9,10-Dimethoxy-4-(4-methoxyphenyl)-3,4,6,7-
tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one (3i). Colorless
(125 MHz, C6D6)
d
: 205.5, 154.6, 150.0, 149.9, 142.2, 134.8, 131.3,