PAPER
New Route to Functionalized Cyclohexenes in Solvent-free Conditions
1115
(
m, CH CH N); 34.58 (q, CH COC ); 39.63 (m, C ); 42.47 (tq,
Hz); 2.47 (d, 1H, CH , J = 10.6 Hz); 3.54 (s, 3H, OCH ); 4.23 (d,
2
2
3
1
5
A’
3
CH N); 45.47 (dq, C ); 63.43 (dm, C ); 68.48 (s, C ); 103.23 (m,
1H, CH , J = 10.6 Hz); 7.30–7.60 (m, 5H arom.); 11.56 (s, 1H, NH).
2
1
2
6
X
C ); 126.48–146.24 (m, C H ); 158.11 (s, C ); 196.38 (q, COC );
13
3
6
5
4
3
C NMR (75 MHz, CDCl /TMS): d = 13.79 (qt, CH (CH ) ); 20.17
3
3
2 3
2
16.64 (m, COC1).
(tm, CH CH CH ); 28.42 (q, CH C ); 29.24 (q, CH CO); 31.90 (tm,
3 2 2 3 6 3
HRMS calc. 343.214 found 343.215
CH CH N); 39.23 (tm, C ); 42.47 (tq, CH N); 44.39 (dq, C ); 51.65
2 2 5 2 1
(
1
q, CO CH ); 59.23 (d, C ); 67.99 (s, C ); 102.35 (s, C ); 126.39–
46.32 (m, C H ); 158.10 (s, CHNH); 175.59 (m, CO CH ); 196.54
6 5 2 3
2 3 2 6 3
C H NO calc. C 73.44 H 8.51
N 4.07
3.81
2
1
29
3
found
73.15
8.40
(
q, COCH3).
HRMS calc. 359.209 found 359.208
C H NO calc. C 70.17 H 8.13
found 70.33 8.04
Methyl [(2,4 Diacetyl-5-hydroxy-5-methyl-3-phenylcyclohex-1-
enyl)amino]acetate (7d)
N 3.89
3.77
2
1
29
4
4
8h at r.t.; yield (65%); mp (MeOH/EtOH: 1/1) 177°C.
1
H NMR (300 MHz, CDCl /TMS): d = 1.25 (s, 3H, CH COH); 1.63
3
3
(
s, 3H, COCH ); 1.66 (s, 3H, COCH ); 2.41–2.50 (AB system, 2H,
Methyl 3-Acetyl-6-hydroxy-4-[(2-methoxy-2-oxoethyl)amino]-
6-methyl-2-phenylcyclohex-3-enecarboxylate (9d)
48h at r.t.; yield (65%); mp (EtOH) 178 °C.
3
3
J = 17.0 Hz); 2.78 (d, 1H, CH , J = 9.0 Hz); 3.80 (s, 3H,
A’
CH CO CH ); 4.60 (dm, 2H, CH CO Me, J = 5.9 Hz); 4.14 (d, 1H,
2
2
3
2
2
CH , J = 9 Hz); 7.10–7.35 (m, 5H arom.); 11.53 (t, 1H, NHCH , J
1
X
2
H NMR (300 MHz, CDCl /TMS): d = 1.26 (s, 3H, CH COH); 1.65
3
3
=
6.0 Hz).
(
s, 3H, COCH ); 2.42–2.56 (AB system, 2H, J = 17.3 Hz); 2.48 (d,
3
1
3
C NMR (75 MHz, CDCl /TMS): d = 28.21 (q, CH C ); 29.56 (q,
1H, CH , J = 10.5 Hz); 3.10 (s, 1H, OH); 3.54 (s, 3H, C CO CH );
3.79 (s, 3H, CH CO CH ); 4.07 (dm, 2H, CH CO Me, J = 6.2 Hz);
2 2 3 2 2
3
3
6
A
’
6
2
3
CH COC ); 34.59 (q, CH COC ); 39.41 (tm, C ); 44.26 (tq,
3
3
3
1
5
CH NH); 44.39 (dq, C ); 52.53 (q, CH CO CH ); 63.28 (dm, C );
4.25 (d, 1H, CH , J = 10,5 Hz); 7.30–7.70 (m, 5H arom.); 11.55 (t,
2
1
2
2
3
2
X
6
8.49 (m, C ); 156.49 (m, C ); 170.10 (m, CH CO CH ); 198.08 (q,
1H, NHCH , J = 6.0 Hz).
6
4
2
2
3
2
COC ); 216.49 (m, COC ).
13
3
1
C NMR (75 MHz, CDCl /TMS): d = 28.34 (q, C ); 29.41 (q,
3
6
HRMS calc. 359.1741 found 359.1732.
COCH ); 39.10 (tm, C ); 44.25 (td, CH NH); 44.32 (dq, C ); 51.69
3 5 2 1
(
q, C CO CH ); 52.52 (q, CH CO CH ); 59.10 (d, C ); 67.98 (m,
6 2 3 2 2 3 2
Methyl (3-Acetyl-6-hydroxy-6-methyl-4-methylamino-2-phe-
nylcyclohex-3-enyl)carboxylate (9a)
C ); 104.45 (s, C ); 126.55–145.78 (m, C H arom.); 156.45 (m,
C NH); 170.03 (m, CH CO CH ); 175.43 (m, C CO CH ); 198.17
(
6
3
6
5
4
2
2
3
6
2
3
4
8h at r.t.; yield (77%); mp (MeOH) 169 °C.
q, COCH3).
1
H NMR (300 MHz, CDCl /TMS): d = 1.27 (s, 3H, CH COH); 1.61
3
3
HRMS calc. 375.168 found 375.166
C H NO calc. C 63.74 H 6.73 N 3.75
(
s, 3H, COCH ); 2.40–2.69 (AB system, 2H, J = 18.0 Hz); 2.45 (d,
3
1
3
7
H, CHA’, J = 10.6 Hz); 2.93 (d, 3H, HNCH , J = 4.3 Hz); 3.53 (s,
3
20 25
6
H, OCH ); 3.70 (s, 1H, OH); 4.20 (d, 1H, CH , J = 10.6 Hz); 7.08–
3
X
found
63.98
6.71
3.73
.23 (m, 5H arom.); 11.39 (s, 1H, NH).
1
3
C NMR (75 MHz, CDCl /TMS): d = 28.42 (q, CH C ); 29.21 (q,
3
3
6
Dimethyl 6-Hydroxy-6-methyl-4-methylamino-2-phenylcyclo-
hex-3-ene-1,3-dicarboxylate (8)
HNCH ); 29.24 (q, CH CO); 39.14 (t, C ); 44.41 (d, C ); 51.64 (q,
CO CH ); 59.25 (d, C ); 67.93 (s, C ); 102.80 (s, C ); 126.44–
1
(
3
3
5
1
2
3
2
6
3
This compound (53% estimated by NMR) was obtained together
with the enamino ester 6 (47% NMR, characterized by a singlet at
4.45 ppm in the crude mixture) after 18h at r.t. After washing with
MeOH pure 8 was recovered in 38% yield: mp 171°C.
1
46.24 (m, C H ); 159.0 (s, C NH); 175.57 (m, CO CH ); 196.69
q, CH CO).
6 5 4 2 3
3
HRMS calc. 317.162 found 317.161
C H NO calc. C 68.12 H 7.30 N 4.41
7.28 4.24
H NMR (300 MHz, CDCl /TMS): d = 1.27 (s, 3H, CH C ); 2.37–
3
3
6
1
8
23
4
2
.67 (AB system, 2H, J = 17.5 Hz); 2.47 (d, 1H, C H , J =
1 A’
found
68.52
1
0.8 Hz); 2.91 (d, 3H, HNCH , J = 5.2 Hz); 3.23 (s, 3H,
3
Methyl (3-Acetyl-4-ethylamino-6-hydroxy-6-methyl-2-phenyl-
cyclohex-3-enyl)carboxylate (9b)
CH CO C ); 3.35 (s, 1H, OH); 3.51 (s, 3H, CH CO C );4.11 (d, 1H,
3 2 3 3 2 1
C H ); 7.06–7.27 (m, 5H arom.); 8.89 (m, 1H, NH).
2
X
3
6h at r.t.; yield (74%); mp (EtOH/Et 0: 1/1) 156 °C.
13
2
C NMR (75 MHz, CDCl /TMS): d = 28.44 (q, CH C ); 29.36 (qd,
3
3
6
1
H NMR (300 MHz, CDCl /TMS): d = 1.27 (s, 3H, CH COH); 1.28
HNCH ); 38.95 (m, C ); 43.27 (dq, C ); 49.76 (q, CH CO C );
51.59 (q, CH CO C ); 58.42 (dm, C ); 68.29 (m, C ); 91.47 (m,
3 2 1 2 6
3
3
3 5 1 3 2 3
(
t, 3H, CH CH , J = 7.2 Hz); 1.62 (s, 3H, COCH ); 2.41–2.71 (AB
2
3
3
system, 2H, J = 18.0 Hz); 2.46 (d, 1H, CH , J = 10.0 Hz); 3.30 (m,
C CO CH ); 125.73–146.84 (m, C H arom.); 157.07 (m, C4);
3 2 3 6 5
A’
2
H, CH CH ); 3.54 (s, 3H, OCH ); 4.23 (d, 1H, CH , J = 10 Hz);
170.25 (m, C CO CH ); 175.66 (m, C CO CH ).
3 2 3 1 2 3
2
3
3
X
7
.08–7.29 (m, 5H arom.); 11.45 (s, 1H, NH).
C H NO
5
HRMS calc. 333.1576 found 333.1571
1
8
23
1
3
C NMR (75 MHz, CDCl /TMS) d: 15.18 (qm, CH CH ); 28.43 (q,
3
3
2
CH C ); 29.30 (q, CH CO); 37.40 (tm, CH CH ); 39.24 (tm, C );
4
1
3
6
3
2
3
5
Acknowledgement
4.43 (dq, C ); 51.65 (q, CO CH ); 59.25 (d, C ); 68.01 (s, C );
1 2 3 2 6
03.32 (s, C ); 126.45–146.30 (m, C H ); 157.87 (s, C NH); 175.65
3
6
5
4
We thank PROLABO SA France for providing the Synthewave 402
and Dr J. Perrocheau for helpful discussions about NMR data. We
are grateful to one of the referees who brought the reference 14 to
our attention.
(m, CO CH ); 196.73 (sq, COCH ).
2
3
3
HRMS calc. 331.178 found 331.179
C H NO calc. C 68.85 H 7.60
68.41 7.60
N 4.22
4.05
1
9
25
4
found
References and Notes
Methyl (3-Acetyl-4-butylamino-6-hydroxy-6-methyl-2-phenyl-
cyclohex-3-enyl)carboxylate (9c)
(
1) Bram, G.; Loupy, A.; Villemin, D. Solid supports and
catalysts, in Organic Synthesis, ed. K. Smith Ellis Horwood
and Prentice Hall, 1992, vol 12 pp 302–325 and references
cited therein.
4
8h at r.t.; yield (78%); mp (EtOH) 169 °C.
1
H NMR (300 MHz, CDCl /TMS): d = 0.96 (t, 3H, CH (CH ) , J =
3
3
2 3
7
.3 Hz); 1.61 (s, 3H, COCH ); 2.41–2.71 (AB system, 2H, J = 17.5
3
Synthesis 1999, No. 7, 1112–1116 ISSN 0039-7881 © Thieme Stuttgart · New York