Synthesis of some substituted 5,6,11,12-tetrahydro-dibenzo[a,e]cyclooctene derivatives through the intermediacy of tricarbonyl(η6 -arene)chromium complexes

Article abstract of DOI:10.1016/j.tetlet.2004.02.050

5,6,11,12-Tetrahydrodibenzo[a,e]cyclooctene derivatives with α- and β-substituents are readily accessible from [Cr(CO)₃(5,6,11,12- tetrahydrodibenzo[a,e]cyclooctene)] 2 via a two-step sequence, which involves addition of a nucleophile and oxidation of the intermediate anionic cyclohexadienyl complex. Nucleophiles used included LiCMe₂CN (A), LiCH₂CN (B), and (C). The results show that the primary carbanion LiCH₂CN and the S-stabilized carbanion give mixtures of α- and β-substituted products and in both cases α-isomers were major, whereas the opposite regioselectivity was obtained with the tertiary carbanion LiCMe₂CN.

Full text of DOI:10.1016/j.tetlet.2004.02.050

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2967–2971
Synthesis of some substituted 5,6,11,12-tetrahydro-
dibenzo[a,e]cyclooctene derivatives through the intermediacy
of tricarbonyl(g6-arene)chromium complexes
A. Moshtaghi Zenouzꢀ
Chemistry Department, Faculty of Science, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran
Received 30 October 2003; revised 27 January 2004; accepted 5 February 2004
Abstract—5,6,11,12-Tetrahydrodibenzo[a,e]cyclooctene derivatives with a- and b-substituents are readily accessible from
[Cr(CO)3(5,6,11,12-tetrahydrodibenzo[a,e]cyclooctene)] 2 via a two-step sequence, which involves addition of a nucleophile and
oxidation of the intermediate anionic cyclohexadienyl complex. Nucleophiles used included LiCMe2CN (A), LiCH2CN (B), and
(C). The results show that the primary carbanion LiCH CN and the S-stabilized carbanion
2
mixtures of a- and b-substituted products and in both cases a-isomers were major, whereas the opposite regioselectivity was
obtained with the tertiary carbanion LiCMe2CN.
give
LiCHS(CH2)3S
LiCHS(CH2)3S
ꢀ 2004 Elsevier Ltd. All rights reserved.
Tricarbonyl(g6-arene)chromium
complexes
have
5,6,11,12-Tetrahydrodibenzo[a,e]cyclooctene
1
was
emerged as important intermediates in organic synthe-
sis, the presence of the transition metal facilitating regio-
and stereo-selective substitution of positions on or
adjacent to the aromatic ring.1
prepared by the Wurtz reaction between a,a0-dibromo-
o-xylene and sodium in dioxane.3 Mono(tricarbonyl-
chromium)complex 2 was synthesized by treating 1
with hexacarbonylchromium in di-n-butyl ether and
tetrahydrofuran (9:1 v/v) at reflux temperature4
(Scheme 1).
Aromatic substitution under mild conditions can be
achieved via complexation of the arene to the electron-
withdrawing Cr(CO)3 fragment, followed by the addi-
tion of a C-nucleophile and oxidative decomplexation.
Nucleophilic addition reactions of C-nucleophiles at low
temperature, followed by oxidative decomplexation
gave a- and b-substituted derivatives of 1. With the
Substituted arenes when complexed to the Cr(CO)3
fragment, often react with carbon nucleophiles with high
regioselectivity, and the addition/oxidation sequence
has been developed into a useful synthetic methodol-
ogy.2
nucleophiles LiCH2CN and
addition to
LiCHS(CH2)3S
the site a to the ring junction predominated over that to
the b-site. Normally, in Cr(CO)3-mediated reactions, the
kinetically preferred site of attack is a to the ring junc-
tion, but the bulk of the arene substituent and the
carbanion can bring about changes in regioselectivity.
This paper describes the synthesis of some substituted
5,6,11,12-tetrahydrodibenzo[a,e]cyclooctene derivatives
through the intermediacy of [Cr(CO)3(5,6,11,12-tetra-
hydrodibenzo[a,e]cyclooctene)] 2 and the results of a
study of regioselectivity in nucleophilic addition to 2.
S-Stabilized carbanion
added selectively
LiCHS(CH2)3S
to the C-atom a to the ring junction, a result, which did
not vary with time or temperature, showing that 1,3-
dithiane-Li adds irreversibly (Table 1). The primary
carbanion LiCH2CN also added selectively to the a-
position. In all these cases, product distribution reflects
kinetic control, and the observed regioselectivity can be
rationalized by assuming either charge or orbital control
of addition.5–7 The opposite b regioselectivity was
obtained with the tertiary carbanion LiC(Me)2CN. The
Keywords: Tricarbonylchromium complexes; Regioselectivity; C-Nu-
cleophiles 5,6,11,12-tetrahydrodibenzo[a,e]cyclooctene.
ꢀ
E-mail: adelehmz@yahoo.com
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.050

2968
A. Moshtaghi Zenouz / Tetrahedron Letters 45 (2004) 2967–2971
(1.1 eq.)
Cr(CO)6
b
a
n-
Bu2O - THF(9:1)
60 h
Cr(CO)3
M
1
2:
M = absent (72%)
M = Cr(CO)3 (14%)
Scheme 1.
Table 1. Substituted 5,6,11,12-tetrahydrodibenzo[a,e]cyclooctenes via addition of C-nucleophiles
R
R
+
1) LiR
2) I2
Cr(CO)3
3a-5a
3b-5b
Nucleophile LiR
Conditionsa [ꢁC, h]
Product distributionb
Yield [%]
LiC(Me)2CN
LiC(Me)2CN
LiCH2CN
)30/1.3
)55/0.7
)20/1
100 (3b)
65 (3b)
39 (4b)
62
65
23
35 (3a)
61 (4a)
LiCHS(CH2)3S
LiCHS(CH2)3S
)10/1
75 (5a)
75 (5a)
25 (5b)
25 (5b)
96
96
)25/2.5
LiCHS(CH2)3S
)50/2.5
75 (5a)
25 (5b)
96
a All reactions conducted in THF/HMPA 10:1.
b Ratio determined by 1H NMR.
1
substitution patterns were deduced by inspection of H
NMR and (H,H-COSY) spectra.
1. Experimental
1.1. [Cr(CO)3(5,6,11,12-tetrahydrodibenzo[a,e]cyclooc-
tene)] 2
Hydrolysis of the isomeric dithiane derivatives 5a,b gave
a- and b-carbaldehyde derivatives 6a,b (Scheme 2).
Reaction of 6a with MeLi gave alcohol 7, dehydration
of which in the presence of p-toluenesulfonic acid in
refluxing benzene is presumed to give 5,6,11,12-tetra-
hydrodibenzo[a,e]cycloocten-1-ylethene, which dimer-
ized under the reaction conditions giving 8 (Scheme 3).
The GC-mass analysis indicated the presence of only a
Mp 186 ꢁC; IR (KBr): m ¼ 3022 (w), 3068 (w), 2950–
2850 (w), 1945 (s), 1850 (br, s), 760 (m), 669 (s), 630 (s),
531 (m) cmꢁ1; IR (THF): m ¼ 1960 and 1885 cmꢁ1 (CO);
1H NMR (400 MHz, DMSO-d6): d 2.64–2.74 (m, 2H),
2.78–2.83 (m, 2H), 2.97–3.08 (m, 2H), 3.22–3.31 (m,
2H), 5.4–5.45 (m, 2H, ArHa), 5.47–5.52 (m, 2H, ArHa),
7 (s, 4H, ArHb); 13C NMR (50 MHz, DMSO-d6): d 32.6
(2 · CH2), 33.2 (2 · CH), 93.5 (2 · CH), 96.6 (2 · CH),
113.1 (2 · C), 126.2 (2 · CH), 129.6 (2 · CH), 139 (2 · C),
234.3 (3 · CO); MS (EI): m=z ð%Þ ¼ 344 (10) [Mþ], 269
1
single dimer. The FT-IR and H NMR spectra showed
no olefinic signals, thus it is proposed that elimination of
water and in situ dimerization of the resulting alkene
leads to indane derivative 8.
S
S
CHO
NCS (4 eq.), AgNO3 (5 eq.)
CH3CN / H2O (4:1), rt
+ AgCl
(86%)
(96%)
6a α - substituted
6b β - substituted
5a
5b
Scheme 2.

A. Moshtaghi Zenouz / Tetrahedron Letters 45 (2004) 2967–2971
2969
CHO
CH(CH3)OH
CH3Li / Et2O
-17 0C
81%
7
6a
p-toluenesulfonic acid
monohydrate/benzene
Reflux, 4 h
CH3
CH2=CH
57%
8
Scheme 3.
(100) [Mþ)3CO], 208 (18) [Mþ)Cr (CO)3], 52 (81) [Crþ];
Anal. Calcd for C19H16CrO3: C, 66.28; H, 4.83. Found:
C, 66.47; H, 4.53.
126.19 (CH), 126.44 (CH), 129.64 (CH), 129.79 (CH),
130.23 (CH), 139.14 (C), 140.35(C), 140.41 (C), 140.46
(C), 141.44 (C); MS (70 eV): m=z ð%Þ ¼ 275 (100) [Mþ],
260 (45), 248 (25), 235 (9), 207 (86), 192 (50), 179 (14),
156 (13), 130 (17), 115 (23), 104 (37), 91 (13), 78 (11);
Anal. Calcd for C20H21N: C, 87.22; H, 7.68; N, 5.08.
Found: C, 87.17; H, 7.91; N, 4.68.
1.2. General procedure for the nucleophilic additions to
complex 2
The [Cr(arene)(CO)3] complex (1.0 mmol) in THF
(10 ml) at )78 ꢁC was added in one portion to a solution
of the nucleophile (1–1.1 mmol in THF, 10 ml, )78 ꢁC).
HMPA (2 ml) was added dropwise at this stage. The
mixture was then stirred for the time and at the tem-
perature indicated in the Table 1. After recooling to
)78 ꢁC, a cold ()78 ꢁC) solution of I2 (5–6 mmol in THF
(10 ml)) was added rapidly via cannula. After a few
minutes the cooling bath was removed, and the tem-
perature slowly (1 h) raised to 20 ꢁC and stirred at this
temperature for 4 h. The mixture was diluted with Et2O
(40 ml) and washed with aq NaHSO3 (10%, 3 · 30 ml),
aq HCl (1 N, 3 · 30 ml), satd NaHCO3 (20 ml), H2O
(2 · 30 ml), and brine (30 ml). The organic layer was
dried (MgSO4) and the solvent removed on a rotavapor
to give the crude product.
1.5. 5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-1-yl-ace-
tonitrile 4a
Mp 104 ꢁC; IR (KBr): m ¼ 3061 (w), 3015 (m), 2930 (s),
2893 (m), 2235 (m), 1491 (s), 1457 (s),760 (s), 737
1
(m) cmꢁ1; H NMR (400 MHz, CDCl3): d 3.1 (m, 8H),
3.65 (s, 2H, CH2CN), 6.9–7.1 (m, 7H, ArH); 13C NMR
(100 MHz, CDCl3): d 22.02 (CH2), 29.2 (CH2), 33.82
(CH2), 34.14 (CH2), 35.51 (CH2), 118.07 (CN), 126.24
(CH), 126.45 (CH), 126.59 (CH), 127.22 (CH), 127.66
(C), 129.45 (CH), 129.57 (CH), 130.48 (CH), 138.51 (C),
139.52 (C), 139.83 (C), 141.9 (C); MS (70 eV):
m=z ð%Þ ¼ 247 (100) [Mþ], 232 (48), 220 (15), 207 (46),
192 (30), 178 (8), 155 (8), 128 (12), 115 (28), 104 (54), 91
(18), 91 (18), 78 (21); Anal. Calcd for C18H17N: C, 87.41;
H, 6.93; N, 5.66. Found: C, 87.07; H, 6.92; N, 5.85.
1.3. 2-(5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-1-yl)-
2-methylpropionitrile 3a
1.6. 5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-2-yl-ace-
tonitrile 4b
1H NMR (400 MHz, CDCl3):
C(CH3)2CN), 3.08 (m, 8H), 6.95–7.12 (m, 7H, ArH).
d
1.53 (s, 6H,
1H NMR (400 MHz, CDCl3): d 3.1 (m, 8H), 3.55 (s, 2H,
CH2CN), 6.9–7.1 (m, 7H, ArH).
1.4. 2-(5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-2-yl)-
2-methylpropionitrile 3b
1.7. 2-(5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-1-yl)-
1,3-dithiane 5a
Mp 57.5–58.5 ꢁC; IR (KBr): m ¼ 3066 (w), 3015 (m),
Mp 138 ꢁC; IR (KBr): m 3050 (w), 3018 (w), 2978 (w),
2930 (m), 2903 (m), 858 (w), 1489 (w), 1465 (m), 1448
2975 (m), 2931 (w), 2235 (m), 1500 (m), 1489 (m), 1462
1
(m), 1450 (m), 893 (m), 829 (s), 735 (s) cmꢁ1; H NMR
1
(m), 1275 (m), 772 (m), 761 (s), 750 (s) cmꢁ1; H NMR
(400 MHz, CDCl3): d 1.62 (s, 6H, C(CH3)2CN), 3.08 (m,
8H), 6.95–7.12 (m, 7H, ArH); 13C NMR (100 MHz,
CDCl3): d 26.16 (CH3), 34.85 (CH2), 34.96 (CH2), 35.14
(CH2), 35.34 (CH2), 36.7 (C), 122.50 (CH), 124.72 (CN),
(400 MHz, CDCl3): d 1.8–2.0 (m, 1H –C(5)), 2.1–2.3 (m,
1H–C(5)), 2.85 (dt, J1 ¼ 13:9 Hz, J2 ¼ 3:5 Hz, 2H–
C(4,6)), 3.05 (m, 8H), 3.17 (t, J ¼ 6:8 Hz, 2H), 5.45 (s,

2970
A. Moshtaghi Zenouz / Tetrahedron Letters 45 (2004) 2967–2971
1H–C(2)), 6.78 (d, J ¼ 7:3 Hz, 1H, ArH), 6.9 (m, 5H,
ArH), 7.3 (d, J ¼ 7:3 Hz, 1H, ArH); 13C NMR
(100 MHz, CDCl3): d ¼ 25:3 (CH2), 28.8 (CH2), 32.6
(CH2), 34.1 (CH2), 35.4 (CH2), 36.1 (CH2), 48.7 (CH),
126.0 (CH), 126.2 (CH), 126.4 (CH), 126.5 (CH), 129.3
(CH), 130.24 (CH), 130.27 (CH), 136.5 (C), 137.7 (C),
139.8 (C), 140.1 (C), 141.2 (C); MS (70 eV):
m=z ð%Þ ¼ 326 (32) [Mþ], 251 (100), 219 (15), 205 (7),
147 (42), 91 (7); Anal. Calcd for C20H22S2: C, 73.57; H,
6.79. Found: C, 73.75; H, 6.81.
147.96 (C), 191.98 (CHO); MS (70 eV): m=z ð%Þ ¼ 236
(100) [Mþ], 221 (29), 207 (29), 193 (25), 178 (17), 131 (6),
115 (14), 104 (42), 91 (15).
1.11. 1-(5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-1-
yl)ethanol 7a
Mp 65 ꢁC; IR (KBr): m ¼ 3258 (s, br), 3060 (w), 3015 (w),
2971 (m), 2925 (w), 2891 (w), 2837 (w), 1491 (s), 1452 (s),
1369 (m), 1304 (m), 1112 (s), 1087 (s), 1067 (s), 1015 (m),
;
999 (m), 760 (s), 735 (m) cmꢁ1 1H NMR (400 MHz,
CDCl3): d 1.48 (d, 3H, J ¼ 6:5 Hz), 1.6 (br d, 1H,
J ¼ 3 Hz), 3.0–3.2 (m, 8H), 5.1–5.3 (m, 1H), 6.8–7.1 (m,
6H, ArH), 7.25 (d, 1H, J ¼ 7 Hz, ArH); 13C NMR
(50 MHz, CDCl3): d ¼ 24:55 (CH3), 28.23 (CH2), 34.43
(CH2), 35.11 (CH2), 35.67 (CH2), 66.91 (CH), 122.92
(CH), 126.08 (CH), 126.25 (CH), 126.29 (CH), 129.3
(CH), 129.43 (CH), 129.58 (CH), 137.21 (C), 140.28 (C),
140.34 (C), 141.25 (C), 143.02 (C); MS (70 eV):
m=z ð%Þ ¼ 252 (14) [Mþ], 234 (100), 219 (40), 205 (28),
193 (16), 178 (8), 129 (20), 105 (28), 91 (19); Anal. Calcd
for C18H20O: C, 85.67; H, 7.99. Found: C, 85.40; H, 7.92.
1.8. 2-(5,6,11,12-Tetrahydrodibenzo[a,e]cycloocten-2-yl)-
1,3-dithiane 5b
Mp 132.5–133.5 ꢁC; IR (KBr): m ¼ 3018 (w), 2948 (m),
2928 (m), 2855 (w), 1494 (m), 1458 (m), 1436 (m), 1411
(m), 1281 (s), 1171 (m), 779 (m), 759 (s) cmꢁ1; 1H NMR
(400 MHz, CDCl3): d 1.8–2.0 (m, 1H), 2.05–2.25 (m,
1H), 2.86 (dt, J1 ¼ 13:8 Hz, J2 ¼ 3:4 Hz, 2H–C(4, 6)),
3.03 (m, 10H), 5.05 (s, 1H–C(2)), 6.8–7.2 (m, 7H, ArH);
13C NMR (50 MHz, CDCl3): d 25.3 (CH2), 32.1 (CH2),
35.09 (CH2), 35.11 (CH2), 35.2 (CH2), 35.26 (CH2), 51.3
(CH), 125.4 (CH), 126.2 (CH), 128.98 (CH), 129.6 (CH),
129.76 (CH), 130.1 (CH), 136.8 (C), 140.6 (C), 141.17
(C), 141.3 (C); MS (70 eV): m=z ð%Þ ¼ 326 (100) [Mþ],
252 (69), 237 (18), 219 (14), 207 (8), 205 (8), 192 (7), 147
(14), 115 (12), 104 (23), 91 (16).
1.12. Dimer 8
Mp 65 ꢁC; IR (KBr): m ¼ 3061 (w), 3015 (m), 2950 (s),
1
2890 (m), 1490 (s), 1453 (s), 756 (s), 736 (m) cmꢁ1; H
NMR (400 MHz, CDCl3): d 1.2 (d, J ¼ 7:2 Hz), 3H, 1.3
(m, 2H), 2.9–3.2 (m, 18H), 6.8–7.0 (m, 13H, ArH); 13C
NMR (100 MHz, CDCl3): d 23.12 (CH3), 28.87 (CH2),
30.33 (CH2), 34.47 (CH2), 34.91 (CH2), 35.09 (CH2),
35.32 (CH2), 35.59 (CH2), 37.34 (CH), 38.41 (CH2),
43.51 (CH2), 46.22 (CH), 123.14 (CH), 125.65 (CH),
125.91 (CH), 125.94 (CH), 126.09 (CH), 126.17 (CH),
127.83 (CH), 128.76 (CH), 129.51 (CH), 129.54 (CH),
129.65 (CH), 129.68 (CH), 136.90 (C), 138.28 (C),
140.17 (C), 140.45 (C), 141.15 (C), 144.08 (C), 144.94
(C), 147.39 (C); MS (70 eV): m=z ð%Þ ¼ 469 (39)
[Mþ+1], 468 (100) [Mþ, dimer], 453 (3.5), 349 (13.6), 261
(5.3), 245 (5.4), 234 (6.2), 219 (4.7) 205 (3.3), 193 (3.3),
105 (7.7), 91 (5.7).
1.9.
carboxaldehyde 6a
5,6,11,12-Tetrahydrodibenzo[a,e]cyclooctene-1-
Mp 94–95 ꢁC; IR (KBr): m ¼ 3080 (w), 3015 (w), 2978
(w), 2937 (w), 2891 (w), 2842 (w), 2718 (m), 1691 (s), 1583
(m), 1474 (m), 1448 (m), 762 (s) cmꢁ1
;
1H NMR
(400 MHz, CDCl3): d 3.10–3.23 (m, 6H), 3.56 (t,
J ¼ 7 Hz, 2H), 6.80–7.15 (m, 6H, ArH), 7.47–7.53 (dd,
J1 ¼ 7 Hz, J2 ¼ 2 Hz, 1H, ArH), 10.2 (s, 1H, CHO); 13C
NMR (50 MHz, CDCl3): d 27.8 (CH2), 33.6 (CH2), 34.8
(CH2), 35.4 (CH2), 126.14 (CH), 126.22 (CH), 126.34
(CH), 129.36 (CH), 129.92 (CH), 130.97 (CH), 134.0 (C),
135.59 (CH), 139.41(C), 139.69 (C), 142.3 (C), 142.76
(C), 192.96 (CHO); MS (70 eV): m=z ð%Þ ¼ 236 (100)
[Mþ], 221 (34), 207 (9), 203 (12), 193 (15), 178 (16), 131
(32), 115 (15), 104 (32), 104 (32), 91 (16); Anal. Calcd for
C17H16O: C, 86.40; H, 6.82. Found: C, 86.17; H, 6.84.
Acknowledgements
The author sincerely acknowledges all the members of
the Organic Chemistry Department of Justus Liebig
University of Giessen, especially Prof. J. Ipaktschi, for
their kind and valuable cooperation.
1.10. 5,6,11,12-Tetrahydrodibenzo[a,e]cyclooctene-2-
carboxaldehyde 6b
Mp 89–91 ꢁC; IR (KBr): m ¼ 3080 (w), 3040 (w), 2954
(m), 2853 (m), 2830 (w), 2784 (w), 2739 (w), 1684 (s),
1604 (m), 1446 (m), 1249 (s), 1172 (s), 835 (s), 767
References and notes
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Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
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1
(s) cmꢁ1; H NMR (400 MHz, CDCl3): d 3.08–3.25 (m,
8H), 6.95 (m, 4H, ArH), 7.12 (d, J ¼ 7:4 Hz, 1H, ArH),
7.45 (m, 2H, ArH), 9.85 (s, 1H, CHO); 13C NMR
(50 MHz, CDCl3): d 34.56 (CH2), 34.64 (CH2), 34.82
(CH2), 35.26 (CH2), 126.38 (CH), 126.47 (CH), 128.15
(CH), 129.68 (CH), 129.85 (CH), 130.43 (CH), 130.73
(CH), 134.91 (C), 139.57 (C), 139.70 (C), 141.36 (C),
€
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