O. Paleta, B. Dolenský, J. Pale cˇ ek, J. Kví cˇ ala
FULL PAPER
CD
H, CH
or NH), 4.34 (d,
6.5 Hz, 1 H, CH
H, Ph-H), 6.92–7.02 (m, 2 H, Ph-H) ppm. C NMR (75.5 MHz,
CD COCD ): δ = 26.41 [(CH C], 39.29 (CH ), 42.69 (CH ), 43.39
C(CH ], 77.48 [CC(CH ], 76.63 (q, JCF = 30.6 Hz, CCF ),
26.18 (q, JCF = 283.6 Hz, CF ), 115.69, 116.89, 118.46, 127.98,
29.15, 144.88 (Ph), 171.43 (C=O) ppm. F NMR (376.6 MHz,
3
COCD
3
): δ = 1.06 (s, 9 H, CH
3
), 2.17 (d, 2JHH = 14.9 Hz, 1 The following new cyclization products were prepared and charac-
2
2
2
), 2.61 (d, JHH = 14.9 Hz, 1 H, CH ), 2.88 (br. s, 1 H, OH terized (for experimental details, see the Supporting Information).
2
2
J
HH = 16.5 Hz, 1 H, CH
2
), 5.14 (d, JHH =
Cyclization with Acetophenone (3d) to Give Products 8 and 18:
2R*,3aS*)-3a-Phenyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-tetra-
hydropyrrolo[2,1-b]quinazolin-1(2H)-one (8 ), (2R*,3aR*)-3a-
1
2
), 5.92 (br. s, 1 H, OH or NH), 6.55–6.65 (m, 2
(
13
c
3
3
3
)
3
2
2
phenyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-tetrahydropyrrolo[2,1-
2
[
1
1
3
)
3
3
)
3
3
t
b]quinazolin-1(2H)-one (8 ), (2S*,3aR*)-3a-phenyl-2-hydroxy-2-tri-
1
3
fluoromethyl-3,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-
19
c
one (18 ), and (2S*,3aS*)-3a-phenyl-2-hydroxy-2-trifluoromethyl-
–
1
CDCl
3
): δ = –80.32 (s, CF
3
) ppm. IR: ν˜ = 1702 (s) cm .
t
3
,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-one (18 ).
c
t
C H F N O (328.33): (mixture of 6 /6 = 95:5): calcd. C 58.22,
16 19 3 2 2
H 5.73, N 8.44; found C 58.53, H 5.83, N 8.53.
Cyclization with Propanal (3f) to Give Products 10, 20, and 33:
2R*,3S*,3aR*)-2-Hydroxy-3-methyl-2-trifluoromethyl-3,3a,4,9-
(
Cyclization with Hexan-2-one (3c)
tc
tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (10 ), (2R*,3R*,
aS*)-2-hydroxy-3-methyl-2-trifluoromethyl-3,3a,4,9-tetrahydro-
(
2R*,3aR*)-3a-Butyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-tetra-hy-
3
c
1
dropyrrolo[2,1-b]quinazolin-1(2H)-one (7 ): H NMR (300 MHz,
CDCl ): δ = 7.09 (t, J = 7.7 Hz, 1 H), 7.04 (d, J = 7.7 Hz, 1 H),
.86 (t, J = 7.7 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 5.09 (d, J =
7 Hz, 1 H), 4.21 (d, J = 17 Hz, 1 H), 4.10 (vbr. s, 1 H), 3.47 (br.
ct
pyrrolo[2,1-b]quinazolin-1(2H)-one (10 ), (2R*,3S*,3aS*)-2-hy-
droxy-3-methyl-2-trifluoromethyl-3,3a,4,9-tetrahydropyrrolo[2,1-b]-
quinazolin-1(2H)-one (10 ), (2R*,3R*,3aR*)-2-hydroxy-3-methyl-
3
6
1
tt
2
1
-trifluoromethyl-3,3a,4,9-tetrahydropyrrolo[2,1-b]quinazolin-
(2H)-one (10 ), (2R*,3S*,3aR*)-2-hydroxy-3-methyl-2-trifluoro-
s, 1 H), 2.61 (d, J = 14.8 Hz, 1 H), 2.18 (d, J = 14.8 Hz, 1 H), 1.98–
cc
1
7
.86 (m, 1 H), 1.76–1.64 (m, 1 H), 1.35–1.24 (m, 4 H), 0.89 (t, J =
methyl-3,3a,4,9-tetrahydropyrrolo[2,1-a]quinazolin-1(2H)-one
1
.1 Hz, 3 H) ppm. H NMR (300 MHz, CD
3
COCD
3
): δ = 7.08 (t,
tc
(
3
20 ), (2S*,3S*,3aR*)-2-hydroxy-3-methyl-2-trifluoromethyl-
J = 7.4 Hz, 1 H), 7.02 (d, J = 7.7 Hz, 1 H), 6.85 (t, J = 7.4 Hz, 1
H), 6.63 (d, J = 8.2 Hz, 1 H), 5.07 (d, J = 17 Hz, 1 H), 4.20 (d, J
ct
,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-one (20 ), and
(
2R*,3R*)-2-hydroxy-3-methyl-2-trifluoromethyl-3,9-dihydropyr-
=
17 Hz, 1 H), 3.84 (br. s, 2 H), 2.60 (d, J = 14.8 Hz, 1 H), 2.18
d, J = 14.8 Hz, 1 H), 1.98–1.85 (m, 1 H), 1.75–1.63 (m, 1 H), 1.35–
.25 (m, 4 H), 0.89 (t, J = 6.6 Hz, 3 H) ppm. 13C NMR (75.5 MHz,
CD COCD ): δ = 169.1, 143.5, 129.1, 128.1, 126.2 (q, J =
83.4 Hz), 119.8, 117.5, 117.5, 77.7 (q, J = 30.3 Hz), 72.7, 40.6 (br.
c
rolo[2,1-b]quinazolin-1(2H)-one (33 ).
(
1
Cyclization with 2-Methylpropanal (3g) to Give Products 11 and 21:
(
2R*,3aR*)-2-Hydroxy-3,3-dimethyl-2-trifluoromethyl-3,3a,4,9-
3
3
c
tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (11 ), (2R*,3aS*)-2-
2
19
hydroxy-3,3-dimethyl-2-trifluoromethyl-3,3a,4,9-tetrahydropyr-
s), 40.4, 37.9, 26.6, 24.0, 14.9 ppm. F NMR (75 MHz, CDCl
=
3
): δ
–80.7 (s) ppm. 1 F NMR (75 MHz, CD
3 3
COCD ): δ = –79.5
t
9
rolo[2,1-b]quinazolin-1(2H)-one (11 ), (2S*,3aS*)-2-hydroxy-3,3-
–1
dimethyl-2-trifluoromethyl-3,3a,4,5-tetrahydropyrrolo[1,2-a]quin-
(s) ppm. IR: ν˜ = 1677 (s) cm .
c
azolin-1(2H)-one (21 ), and (2S*,3aR*)-2-hydroxy-3,3-dimethyl-2-
(
2R*,3aS*)-3a-Butyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-tetra-
trifluoromethyl-3,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-
t
1
hydropyrrolo[2,1-b]quinazolin-1(2H)-one (7 ): H NMR (300 MHz,
CDCl ): δ = 7.06 (d, J = 7.7 Hz, 1 H), 7.02 (t, J = 7.3 Hz, 1 H),
.0 (t, J = 7.6 Hz, 1 H), 6.66 (d, J = 8.1 Hz, 1 H), 6.09 (br. s, 1 H),
t
one (21 ).
3
Cyclization with Phenylacetaldehyde (3h) to Give Products 12 and
6
5
1
1
2
2: (2R*,3S*,3aR*)-3-Phenyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-
.82 (br. s, 1 H), 4.88 (d, J = 17.2 Hz, 1 H), 4.28 (d, J = 17.2 Hz,
H), 2.50 (d, J = 14.8 Hz, 1 H), 2.43 (d, J = 14.8 Hz, 1 H), 1.98–
.78 (m, 2 H), 1.50–1.23 (m, 4 H), 0.88 (t, J = 7.1 Hz, 3 H) ppm.
tc
tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (12 ), (2R*,3R*,
aS*)-3-phenyl-2-hydroxy-2-trifluoromethyl-3,3a,4,9-tetrahydro-
3
ct
1
3
pyrrolo[2,1-b]quinazolin-1(2H)-one (12 ), (2S*,3S*,3aR*)-3-
C NMR (75.5 MHz, CDCl
3
): δ = 167.8, 143.4, 129.1, 128.23,
phenyl-2-hydroxy-2-trifluoromethyl-3,3a,4,5-tetrahydropyrrolo[1,2-
1
7
26.2 (q, J = 284 Hz), 119.7, 117.2, 117.1, 77.8 (q, J = 30.3 Hz),
ct
1
9
a]quinazolin-1(2H)-one (22 ), and (2S*,3S*,3aR*)-3-phenyl-2-hy-
2.6, 42.0 (br. s), 40.4, 38.5, 26.7, 23.9, 14.9 ppm. F NMR
): δ = –80.6 (s) ppm. 1 F NMR (75 MHz,
9
droxy-2-trifluoromethyl-3,3a,4,5-tetrahydropyrrolo[1,2-a]quinaz-
(
75 MHz, CDCl
3
tc
c
t
olin-1(2H)-one (22 ).
CD
3
COCD
3
19 3 2 2
): δ = –79.2 (s) ppm. C16H F N O (328.33) (7 /7 =
9
8
7:3): calcd. C 58.53, H 5.83, N 8.53; found C 58.15, H 5.96, N
.26.
Cyclization with Cyclohexanone (3k) to Give Products 14 and 24:
(
4aS*,5R*,13aR*)-5-Hydroxy-5-trifluoromethyl-1,2,3,4,4a,5,8,13-
tc
(
2S*,3aS*)-3a-Butyl-2-hydroxy-2-trifluoromethyl-3,3a,4,5-tetra- octahydroindolo[7a,1-b]quinazolin-6-one (14 ), (4aR*,5R*,13aS*)-
c
1
hydropyrrolo[1,2-a]quinazolin-1(2H)-one (17 ): H NMR (300 MHz, 5-hydroxy-5-trifluoromethyl-1,2,3,4,4a,5,8,13-octahydroindolo-
ct
CDCl
3
): δ = 8.02 (d, J = 8.1 Hz, 1 H), 7.26 (dd, J = 7.2, 2.6 Hz, 1
[7a,1-b]quinazolin-6-one (14 ), (2S*,2aS*,6aR*)-2-hydroxy-2-tri-
fluoromethyl-2,2a,3,4,5,6,7,8-octahydroindolo[1,7a-a]quinazolin-1-
H), 7.20–7.13 (m, 2 H), 5.99 (br. s, 1 H), 4.14 (d, J = 18.1 Hz, 1
H), 4.07 (d, J = 18.1 Hz, 1 H), 2.92 (d, J = 15.4 Hz, 1 H), 2.92 (br.
s, 1 H), 2.07 (dq, J = 15.4, J = 1.1 Hz, 1 H), 1.95 (td, J = 12, 2,2a,3,4,5,6,7,8-octahydroindolo[1,7a-a]quinazolin-1-one (24 ).
ct
one (24 ), and (2S*,2aR*,6aS*)-2-hydroxy-2-trifluoromethyl-
tc
3
.8 Hz, 1 H), 1.62–1.25 (m, 5 H), 0.88 (t, J = 7.2 Hz, 3 H) ppm.
C NMR (100 MHz, CD COCD ): δ = 166.5, 135.3, 128.1, 128.0,
3 3
Cyclization with Pentan-3-one (3l) to Give Products 25 and 28:
2R*,3S*,3aR*)-3a-Ethyl-2-hydroxy-3-methyl-2-trifluoromethyl-
13
(
1
7
27.5, 126.4, 126.2 (q, J = 284 Hz), 123.4, 77.4 (q, J = 30.7 Hz),
tc
3
,3a,4,9-tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (25 ),
5.4, 43.8, 41.5, 35.4, 26.9, 24.0, 14.9 ppm. 19F NMR (75 MHz,
(
3
2R*,3S*,3aS*)-3a-ethyl-2-hydroxy-3-methyl-2-trifluoromethyl-
,3a,4,9-tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (25 ),
CDCl
3
): δ = –78.8 (d, J = 0.9 Hz) ppm. C16
H
19
F
3
N
2
O
2
(328.33):
tt
calcd. C 58.53, H 5.83, N 8.53; found C 58.60, H 6.08, N 8.29.
(
2R*,3R*,3aS*)-3a-ethyl-2-hydroxy-3-methyl-2-trifluoromethyl-
ct
(
2S*,3aR*)-3a-Butyl-2-hydroxy-2-trifluoromethyl-3,3a,4,5-tetra-
3,3a,4,9-tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (25 ),
t
hydropyrrolo[1,2-a]quinazolin-1(2H)-one (17 ): Characteristic sig-
(2R*,3R*,3aR*)-3a-ethyl-2-hydroxy-3-methyl-2-trifluoromethyl-
1
cc
nals: H NMR (300 MHz, CDCl
.61 (d, J = 14.4 Hz, 1 H) ppm. 19F NMR (75 MHz, CD
δ = –78.9 (s) ppm.
3
): δ = 8.41 (d, J = 8.2 Hz, 1 H), 3,3a,4,9-tetrahydropyrrolo[2,1-b]quinazolin-1(2H)-one (25 ),
2
3
COCD
3
):
(2S*,3S*,3aS*)-3a-ethyl-2-hydroxy-3-methyl-2-trifluoromethyl-
cc
3,3a,4,5-tetrahydropyrrolo[1,2-a]quinazolin-1(2H)-one (28 ), and
1268
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1262–1270