Coupling reaction of zirconacyclopentadienes with dihalonaphthalenes and dihalopyridines: A new procedure for the preparation of substituted anthracenes, quinolines, and isoquinolines

Article abstract of DOI:10.1021/ja016848k

Reactions of tetraiodobenzene with zirconacyclopentadienes, which were conveniently prepared from two alkynes (or diynes) and zirconocene complexes, afforded 1,2,3,4-tetrasubstituted diiodonaphthalene derivatives in good isolated yields. These 1,2,3,4-tetrasubstituted diiodonaphthalene derivatives could be converted to 1,2,3,4,5,6,7,8-octasubstituted anthracene derivatives by reaction with a second zirconacyclopentadiene. When the two zirconacyclopentadienes were different, unsymmetrical anthracenes such as 1,2,3,4-tetraethyl-5,6,7,8-tetraphenylanthracene (68% isolated yield) were obtained. On the other hand, treatment of a 2,3-dihalopyridine such as 2-bromo-3-iodopyridine with zirconacyclopentadienes gave 5,6,7,8-tetrasubstituted quinoline derivatives in good to high yields. 3,4-Dihalopyridines such as 4-chloro-3-iodopyridine reacted with zirconacyclopentadienes to afford 5,6,7,8-tetrasubstituted isoquinoline derivatives in good to high yields.

Full text of DOI:10.1021/ja016848k

Published on Web 01/05/2002
Coupling Reaction of Zirconacyclopentadienes with
Dihalonaphthalenes and Dihalopyridines: A New Procedure
for the Preparation of Substituted Anthracenes, Quinolines,
and Isoquinolines
Tamotsu Takahashi,*,† Yanzhong Li,† Petr Stepnicka,† Masanori Kitamura,†
Yanjun Liu,† Kiyohiko Nakajima,‡ and Martin Kotora†
Contribution from the Catalysis Research Center and Graduate School of Pharmaceutical
Sciences, Hokkaido UniVersity, Japan, CREST, Japan Science and Technology Corporation,
Sapporo 060-0811, Japan, and Department of Chemistry, Aichi UniVersity of Education, Igaya,
Kariya, Aichi 448-8542, Japan
Received August 14, 2001. Revised Manuscript Received October 30, 2001
Abstract: Reactions of tetraiodobenzene with zirconacyclopentadienes, which were conveniently prepared
from two alkynes (or diynes) and zirconocene complexes, afforded 1,2,3,4-tetrasubstituted diiodonaphthalene
derivatives in good isolated yields. These 1,2,3,4-tetrasubstituted diiodonaphthalene derivatives could be
converted to 1,2,3,4,5,6,7,8-octasubstituted anthracene derivatives by reaction with a second zirconacy-
clopentadiene. When the two zirconacyclopentadienes were different, unsymmetrical anthracenes such
as 1,2,3,4-tetraethyl-5,6,7,8-tetraphenylanthracene (68% isolated yield) were obtained. On the other hand,
treatment of a 2,3-dihalopyridine such as 2-bromo-3-iodopyridine with zirconacyclopentadienes gave 5,6,7,8-
tetrasubstituted quinoline derivatives in good to high yields. 3,4-Dihalopyridines such as 4-chloro-3-
iodopyridine reacted with zirconacyclopentadienes to afford 5,6,7,8-tetrasubstituted isoquinoline derivatives
in good to high yields.
Introduction
In this paper, we report the details of our method for the
coupling of dihaloarenes with zirconacyclopentadienes5 and its
application to the synthesis of substituted anthracenes,6 substi-
tuted quinolines,7 and isoquinolines.8
Fused aromatic ring extension is an attractive and useful
method for the construction of new polycyclic aromatic
compounds in organic synthesis.1,2 The most direct and simplest
ideal method is the intermolecular cycloaddition of two alkynes
to an arene as shown in eq 1.
To perform this type of direct aromatic ring extension, we
have investigated the coupling reaction of dihaloarenes and
metalacyclopentadienes, which can be conveniently prepared
from two alkynes and transition metals as shown in eq 2.3,4
By this method, the substituents can be conveniently intro-
duced into extended aromatic rings. For example, the benzo
rings of quinolines and isoquinolines were highly substituted.
(2) Fused aromatic ring extension, see (a) Takahashi, T.; Kitamura, M.; Shen,
B.; Nakajima, K. J. Am. Chem. Soc. 2000, 122, 12876. (b) Bowles, D. M.;
Anthony, J. E. Org. Lett. 2000, 2, 85. (c) Ihmels, H. Eur. J. Org. Chem.
1999, 1595. (d) Hennings, D. D.; Iwama, T.; Rawal, V. H. Org. Lett. 1999,
1, 1205. (e) Yamato, T.; Sakaue, N.; Shinoda, N.; Matsuo, K. J. Chem.
Soc., Perkin Trans. 1 1997, 1193. (f) Netka, J.; Crump, S. L.; Richborn,
B. J. Org. Chem. 1986, 51, 1189.
(3) Preliminary result was reported: see Takahashi, T.; Hara, R.; Nishihara,
Y.; Kotora, M. J. Am. Chem. Soc. 1996, 118, 5154-5155.
(4) Naphthalene formation from aryl halide or arylmetal compounds and two
alkynes by use of transition metals, see (a) Wu, G.; Rheingold, A. L.; Feib,
S. J.; Heck, R. F. Organometallics 1987, 6, 1941. (b) Wu, G.; Rheingold,
A. L.; Heck, R. F. Organometallics 1986, 5, 1922. (c) Sakakibara, T.;
Tanaka, Y.; Yamasaki, T.-I. Chem. Lett. 1986, 797. (d) Whitesides, G.
M.; Ehmann, W. J. J. Am. Chem. Soc. 1979, 92, 5625. (e) Herwig, W.;
Metlesics, W.; Zeiss, H. J. Am. Chem. Soc. 1959, 81, 6203.
† Hokkaido University and Japan Science and Technology Corporation.
‡ Aichi University of Education.
(1) For a review on aromatic ring formation, see (a) Watson, M. D.;
Fethtenko¨tter, A.; Mu¨llen, K. Chem. ReV. 2001, 101, 1267. (b) Fu, P. P.;
Harvey, R. G. Chem. ReV. 1978, 78, 317.
9
576 VOL. 124, NO. 4, 2002 J. AM. CHEM. SOC.
10.1021/ja016848k CCC: $22.00 © 2002 American Chemical Society

Coupling Reactions of Zirconacyclopentadienes
A R T I C L E S
Scheme 1
step proceeds, the second coupling of the intermediate 4 is, in
turn, an intramolecular coupling and is fast. Therefore, we did
not observe the formation of o-dienylhalobenzene derivatives.
Furthermore, at least one halogen should be iodine for the
intermolecular coupling. Dibromobenzene did not react at all.
The second halogen can be bromine because of the intramo-
lecular coupling.3
When the reaction was carried out without DMPU, naphtha-
lenes were formed only in low yields (up to 20%), and
moreover, they were accompanied by a number of other
unidentified products. Our study showed that a gradual pre-
cipitation of a yellow powder from the reaction mixture was
observed on addition of 2 equiv of CuCl to zirconacyclopen-
tadienes without DMPU. Although the yellow powder could
not be characterized because of its unstability, an organocopper
intermediate such as 5 or its polymer was assumed to be formed
since quantitative formation of zirconocene dichloride was
observed by the 1H NMR study. Addition of 3 equiv of DMPU
dissolved the yellow powder to give a dark-brown solution that
readily reacted with 1,2-diiodobenzene 2 to give naphthalenes
3. It is reasonable to assume that DMPU breaks up the polymeric
structure of the organocopper compound by coordinating the
copper atoms and also increases the solubility in THF. Both
CuCl and DMPU were added to the reaction mixture in all
reactions described below.
Results and Discussion
Reaction of Dihalobenzene with Zirconacyclopentadienes
(Scheme 1). When diiodobenzene (2) was treated with zircona-
cyclopentadienes (1)5 in the presence of CuCl9 together with 3
equiv of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(DMPU), the coupling reaction proceeded to give 1,2,3,4-tetra-
substituted naphthalene derivatives (3) as we preliminarily
reported.3 The rate-determining step of the coupling reaction is
the first intermolecular coupling step. Once the first coupling
Preparation of Dihalonaphthalene Derivatives. When tetra-
iodobenzene 610 was used, the ring extension occurred on both
sides of the tetraiodobenzene to give octahomosubstituted
anthracenes 7, as shown in eq 3.3 Extension of two aromatic
(5) For symmetrical zirconacyclopentadienes, see (a) Negishi, E.; Holmes, S.
J.; Tour, J.; Miller, J. A.; Cederbaum, F. E.; Swanson, D. R.; Takahashi,
T. J. Am. Chem. Soc. 1989, 111, 3336-3346. (b) Buchwald, S. L.; Nielsen,
R. B. J. Am. Chem. Soc. 1989, 111, 2870-2874. (c) Negishi, E.;
Cederbaum, F. E.; Takahashi, T. Tetrahedron Lett. 1986, 27, 2829-2832.
For unsymmetrical zirconacyclopentadienes, see (d) Xi, Z.; Hara, R.;
Takahashi, T. J. Org. Chem. 1995, 60, 4444-4448. (e) Takahashi, T.; Xi,
Z.; Rousset, C. J.; Suzuki, N. Chem. Lett. 1993, 1001-1004. (f) Takahashi,
T.; Kageyama, M.; Denisov, V.; Hara, R.; Negishi, E. Tetrahedron Lett.
1993, 34, 687-690. (g) Takahashi, T.; Swanson, D. R.; Negishi, E. Chem.
Lett. 1987, 623-626. (h) Van Wagenen, B. C.; Livinghouse, T. Tetrahedron
Lett. 1989, 30, 3495-3498. (i) See ref 5b.
(6) For substituted anthracenes or fused aromatic compounds, see (a) Qiao,
X.; Ho, D. M.; Pascal, R. A., Jr. Angew. Chem., Int. Ed. Engl. 1997, 36,
1531. (b) Benkhoff, J.; Boese, R.; Kla¨rner, F. G. Liebigs Ann. Recl. 1997,
501-516. (c) Pascal, R. A., Jr.; McMillan, W. D.; Van Engen, D.; Eason,
R. G. J. Am. Chem. Soc. 1987, 109, 4660-4665. (d) Matsuura, A.;
Nishinaga, T.; Komatsu, K. Tetrahedron Lett. 1997, 38, 3427.
(7) For substituted quinolines, see (a) Suginome, M.; Fukuda, T.; Ito, Y. Org.
Lett. 1999, 1, 1977. (b) Beller, M.; Thiel, O. R.; Trauthwein, H.; Hartung,
C. G. Chem. Eur. J. 2000, 6, 2513. (c) Ubeda, J. I.; Villacampa, M.;
Avendano, C. Synlett 1997, 285. (d) Larock, R. C.; Kuo, M.-Y. Tetrahedron
Lett. 1991, 32, 569-572.
(8) For substituted isoquinolines, see (a) Roesch, K. R.; Larock, R. C. Org.
Lett. 1999, 1, 553. (b) Lorsbach, B. A.; Bagdanoff, J. T.; Miller, R. B.;
Kurth, M. J. J. Org. Chem. 1998, 63, 2244. (c) Roesch, K. R.; Larock, R.
C. J. Org. Chem. 1998, 63, 5306-5307. (d) Beugelmans, R.; Chastanet,
J.; Roussi, G. Tetrahedron 1984, 40, 311-314. (e) Tokunaga, M.; Eckert,
M.; Wakatsuki, Y. Angew. Chem., Int. Ed. Engl. 1999, 38, 3221-3223.
(9) For the first transmetalation of zirconacyclopentadienes to CuCl for further
reactions, see (a) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N.
Organometallics 1994, 13, 4183-4185. See also (b) Takahashi, T.; Kotora,
M.; Xi, Z. J. Chem. Soc., Chem. Commun. 1995, 361-362. (c) Takahashi,
T.; Hara, R.; Nishihara, Y.; Kotora, M. J. Am. Chem. Soc. 1996, 118, 5154-
5155. (d) Xi, C.; Huo, S.; Mahmaoud, A.; Hara, R.; Takahashi, T.
Tetrahedron Lett. 1997, 38, 4099-4102. (e) Kotora, M.; Umeda, C.; Ishida,
T.; Takahashi, T. Tetrahedron Lett. 1997, 38, 8355-8358. (f) Ura, Y.; Li,
Y.; Xi, Z.; Takahashi, T. Tetrahedron Lett. 1998, 39, 2787-2790. (g)
Kotora, M.; Xi, C.; Takahashi, T. Tetrahedron Lett. 1998, 39, 4321-4324.
(h) Takahashi, T.; Sun, W.-H.; Liu, Y.; Nakajima, K.; Kotora, M.
Organometallics 1998, 17, 3841-3843. (i) Takahashi, T.; Xi, Z.; Yamazami,
A.; Liu, Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1998, 120, 1672-
1680. (j) Kotora, M.; Noguchi, Y.; Takahashi, T. Collect. Czech. Chem.
Commun. 1999, 64, 1119-1124. (k) Yamamoto, Y.; Ohno, T.; Itoh, K.
Chem. Commun. 1999, 1543-1544. (l) Takahashi, T.; Sun, W.-H.;
Nakajima, K. Chem. Commun. 1999, 1595-1596. (m) Xi, C.; Kotora, M.;
Nakajima, K.; Takahashi, T. J. Org. Chem. 2000, 65, 945-950. (n)
Takahashi, T.; Sun, W.-H.; Duan, Z.; Shen, B. Org. Lett. 2000, 2, 1197-
1199. (o) Duan, Z.; Sun, W.-H.; Liu, Y.; Takahashi, T. Tetrahedron Lett.
2000, 41, 7471-7474. (p) Li, Y.; Ura, Y.; Tsai, F.-Y.; Xu, F.; Takahashi,
T. Heterocycles 2001, 54, 943-955. (q) Doherty, S.; Knight, J. G.; Robins,
E. G.; Scanlan, T. H.; Champkin, P. A.; Clegg, W. J. Am. Chem. Soc.
2001, 123, 5110-5111. See also (r) Lipshutz, B. H.; Segi, M. Tetrahedron
1995, 51, 4407.
rings occurs stepwise and the coupling of the tetraiodobenzene
with the first zirconacyclopentadiene is faster than that of the
second zirconacyclopentadiene. The reaction of the second
zirconacyclopentadiene is relatively slow. Therefore, the diiodo-
naphthalene 8 could be selectively prepared. As shown in eq 4,
reaction of zirconacyclopentadiene 1b with 1,2,4,5-tetraiodo-
benzene 6 gave diiodonaphthalene derivative 8b. The structure
of 8b was confirmed by X-ray analysis.
Results are shown in Table 1. The optimal yields were
obtained in the reaction of 1 equiv of zirconacyclopentadienes
(10) Mattern, D. L. J. Org. Chem. 1984, 49, 3051.
(11) Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais, F.; Queguiner,
G. Tetrahedron 2000, 56, 1349.
9
J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002 577

A R T I C L E S
Takahashi et al.
Table 1. Formation of Linear Diiodonaphthalene Derivatives by
Reaction of Zirconacyclopentadienes with
1,2,4,5-Tetraiodobenzene 6
Table 2. Formation of Substituted Anthracenes 9 by the Reaction
of Zirconacyclopentadienes with Diiodoarenes 8
a At 50 °C.
with 2 equiv of 6. Thus, the reaction of both of alkyl and aryl
homosubstituted zirconacyclopentadienes gave good yields of
diiodonaphthalenes 8a-c. Unsymmetrically alkyl-aryl substi-
tuted zirconacyclopentadiene 1f afforded the corresponding di-
iodonaphthalene 8f in good yield as well. The use of bicyclic
zirconacyclopentadienes allowed the introduction of two rings
in one step and furnished diiodotetrahydroanthracenes 8d and
8e.
Formation of Substituted Anthracenes. The diiodonaph-
thalene derivatives 8 were used for further coupling reactions
with zirconacyclopentadienes 1 to give unsymmetrically sub-
stituted anthracene derivatives 9, as shown in eq 5.
a Reaction temperature, 50 °C; reaction time, 12 h.
reaction with diiodonaphthalene required a longer reaction time,
compared with the reaction with diiodobenzene or tetraiodo-
benzene. The structure of 9a was confirmed by X-ray analysis.
The use of 8e in the reactions with tetraethyl- (1a), tetrapropyl-
(1b), and tetrabutylzirconacyclopentadiene (1g) gave the cor-
responding alkyl/phenyl-substituted anthracenes 9d-f. This
methodology was also suitable for the preparation of unsym-
metrically substituted anthracenes such as 9g and 9h.
Formation of Substituted Quinoline Derivatives. 2,3-
Dibromopyridine did not react with zirconacyclopentadienes as
observed in the case of dibromobenzene even in the presence
of CuCl and DMPU. 2-Bromo-3-iodopyridine 10 could be selec-
tively prepared as a crystalline compound by the reaction of
2,3-dibromopyridine with n-BuLi followed by iodination. The
thus-prepared 2-bromo-3-iodopyridine 10 reacted with 1a in the
presence of 2 equiv of CuCl and 3 equiv of DMPU at 50 °C to
give the corresponding quinoline 11a in 85% yield as shown
in eq 6. The results are shown in Table 3. Tetrapropyl-substituted
zirconacyclopentadiene 1b afforded the corresponding quinoline
11b in 63% yield in 3 h. On the other hand, the reaction of
tetraphenylzirconacyclopentadiene with 10 required prolonged
Some results are shown in Table 2. The reaction of tetraeth-
ylzirconacyclopentadiene 1a and tetrapropylzirconacyclopen-
tadiene 1b with 8b and 8c in the presence of 2 equiv of CuCl
and 3 equiv of DMPU gave unsymmetrically substituted
anthracenes 9a, 9b, and 9c, respectively, at 50 °C for 12 h. The
9
578 J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002

Coupling Reactions of Zirconacyclopentadienes
A R T I C L E S
Table 3. Quinoline-Forming Reaction of Zirconacyclopentadienes
with 2-Bromo-3-iodopyridine 10
It is interesting to note that when 1a was treated with
2-chloro-3-iodopyridine (12) instead of 10, chlorodienylpyridine
(14) was obtained in 10% yield along with the formation of the
desired product 11a (78%). This result clearly indicates that
the first carbon-carbon bond formation proceeded at the iodo-
pyridine moiety and the second carbon-carbon bond formation
occurred on the chloropyridine moiety as shown in Scheme 2.
Scheme 2
Formation of Substituted Isoquinolines. The above-
mentioned strategy was also conveniently applied to the
synthesis of isoquinolines. In this case, 1 reacted with 4-chloro-
3-iodopyridine 15 under the above-mentioned conditions to yield
substituted isoquinolines in good yields, as shown in eq 8. The
a At 50 °C. b GC yields. Isolated yields are given in parentheses.
reaction time (18 h) to obtain only a rather modest yield (35%)
of 5,6,7,8-tetraphenylquinoline (11c). Similarly, tricyclic quino-
line derivatives 11d and 11e were obtained from reaction of
bicyclic zirconacyclopentadienes 1h and 1i with 10 after 18 h,
respectively.
results are shown in Table 4. The reactions of tetraalkyl-
substituted zirconacyclopentadienes with 15 furnished the
corresponding isoquinolines 16a-c in good to high yields in 1
h at 50 °C. However, the reaction of phenyl-substituted bicyclic
zirconacyclopentadiene 1e gave rise to isoquinoline 16d with a
side ring in only moderate yield. Reactions of 15 with
unsymmetrically substituted zirconacyclopentadienes, such as
2,3-dibutyl-4,5-diethylzirconacyclopentadiene 1k, gave a 1:1
mixture of regioisomers of 16e and 16f (eq 9).
The reaction of 10 with unsymmetrically substituted zircona-
cyclopentadiene provided a mixture of 11f and 11g in a 2.7:1
ratio, as shown in eq 7. Fortunately, both isomers were readily
separated by column chromatography and the structure of 11f
was determined by X-ray structural analysis.
Experimental Section
General Information. All reactions involving air- or moisture-
sensitive organometallic reagents were carried out under dry nitrogen.
THF was distilled over sodium and benzophenone. 1,3-Dimethyl-
3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU; Aldrich, 98%) was
9
J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002 579

A R T I C L E S
Takahashi et al.
Table 4. Isoquinoline-Forming Reaction of 1 with 15b
548.0438, found 548.0449. Anal. Calcd for C22H30I2: C, 48.19; H, 5.52;
I, 46.29. Found: C, 48.02; H, 5.52; I, 46.42.
6,7-Diiodo-1,2,3,4-tetraphenylnaphthalene (8c). A light yellow
solid (77%): 1H NMR (CDCl3, Me4Si) δ 6.77-6.82 (m, 10H), 7.13-
7.24 (m, 10H), 8.14 (s, 2H); 13C NMR (CDCl3, Me4Si) δ 104.87,
125.59, 126.65, 126.90, 127.77, 130.98, 131.08, 132.72, 137.44, 137.65,
138.19, 139.87, 140.36; IR (KBr) 3056, 1599, 1547, 1493, 1438, 1441,
1074, 1026, 1001, 924, 897, 747, 698 cm-1; HRMS calcd for C34H22I2
683.9811, found 683.9837.
1,2,3,4-Tetrahydro-6,7-diiodo-9,10-dipropylanthracene (8d). A
colorless solid (57%): 1H NMR (CDCl3, Me4Si) δ 1.07 (t, J ) 7.4 Hz,
6H), 1.51-1.63 (m, 4H), 1.79-1.83 (m, 4H), 2.83-2.89 (m, 8H), 8.47
(s, 2H); 13C NMR (CDCl3, Me4Si) δ 14.68, 22.80, 23.36, 27.81, 29.86,
102.38, 131.58, 132.88, 135.16, 135.29; IR (KBr) 2951, 2867, 2930,
2916, 1553, 1476, 1451, 1111, 926, 893, 870, 820 cm-1; HRMS calcd
for C20H24I2 517.9968, found 517.9963.
1,2,3,4-Tetrahydro-6,7-diiodo-9,10-diphenylanthracene (8e). A
colorless solid (75%): 1H NMR (CDCl3, Me4Si) δ 1.56-1.61 (m, 4H),
2.44-2.49 (m, 4H), 7.13-7.17 (m, 4H), 7.33-7.46 (m, 6H) 7.75 (s,
2H); 13C NMR (CDCl3, Me4Si) δ 21.67, 28.40, 102.26, 126.39, 127.73,
128.95, 130.86, 134.48, 135.62, 135.72, 137.67; IR (KBr) 2940, 2934,
2924, 2859, 1601, 1493, 1441, 1073, 924, 911, 885, 750, 700 cm-1
HRMS calcd for C26H20I2 585.9655, found 585.9668.
;
6,7-Diiodo-1,2-dimethyl-3,4-diphenylnaphthalene (8f). A colorless
solid (54%): 1H NMR (CDCl3, Me4Si) δ 2.17 (s, 3H), 2.64 (s, 3H),
a GC yields. Isolated yields are given in parentheses. b Reaction tem-
perature, 50 °C; reaction time, 1 h.
6.94-7.01 (m, 5H), 7.10-7.25 (m, 5H) 7.96 (s, 1H), 8.65 (s, 1H); 13
C
NMR (CDCl3, Me4Si) δ 15.27, 19.02, 103.13, 104.45, 126.24, 126.62,
127.53, 127.59, 129.93, 130.21, 130.98, 131.98, 132.76, 133.97, 134.90,
135.81, 138.04, 138.44, 140.91, 141.50; IR (KBr) 3056, 3021, 1601,
1493, 1451, 1030, 785, 758, 698 cm-1; HRMS calcd for C24H18I2
559.9498, found 559.9520.
Reaction of Zirconacyclopentadienes with Diiodoarenes 8. The
reactions were conducted under the same conditions as for the
preparation of 8. Column chromatography on silica gel (99/1 hexane/
AcOEt) afforded the corresponding products 9.
dried over calcium hydride and distilled under reduced pressure.
Zirconocene dichloride (Nichia Chemical Industries, Ltd.), ethylmag-
nesium chloride (solution in THF, Kanto), and copper chloride (Wako
Pure Chemical Industries, Ltd., 99.9%) were used as received. All other
materials were of reagent-grade quality and were used as obtained from
Tokyo Kasei Kogyo Co., Ltd., Aldrich Chemical Co., Inc., and Kanto
Chemical Co., Inc.
1H and 13C NMR spectra were recorded for CDCl3 or C6D6 (con-
taining 1% TMS) solutions on a Bruker-400 or Jeol JNM-AL300 NMR
spectrometer. GC analysis was performed on a Shimadzu GC-14A
instrument equipped with a fused silica capillary column (Shimadzu
CBP1-M25-O25) and a Shimadzu C-R6A-Chromatopac integrator.
1,2,3,4-Tetraethyl-5,6,7,8-tetrapropylanthracene (9a). A light
green solid (57%): 1H NMR (CDCl3, Me4Si) δ 1.12 (t, J ) 7.2 Hz,
6H), 1.19 (t, J ) 7.4 Hz, 6H), 1.28 (t, J ) 7.5 Hz, 6H), 1.42 (t, J )
7.4 Hz, 6H), 1.57-1.68 (m, 4H), 1.74-1.84 (m, 4H), 2.78 (t, J ) 8.3
Hz, 4H), 2.87 (q, J ) 7.5 Hz, 4H), 3.18 (t, J ) 8.3 Hz, 4H), 3.25 (q,
J ) 7.5 Hz, 4H), 8.70 (s, 2H); 13C NMR (CDCl3, Me4Si) δ 15.02,
15.09, 15.38, 15.92, 22.06, 22.98, 24.56, 25.02, 31.65, 32.84, 119.37,
128.73, 129.04, 133.51, 134.68, 135.81, 136.62; IR (KBr) 2960, 2928,
2868, 1478, 1468, 1453, 1090, 1061, 887, 879, 868, 735 cm-1; Anal.
Calcd for C34H50: C, 89.01; H, 10.99. Found: C, 88.69; H, 11.15.
1,2,3,4-Tetraethyl-5,6,7,8-tetraphenylanthracene (9b). A colorless
solid (68%): 1H NMR (CDCl3, Me4Si) δ 1.12 (t, J ) 7.3 Hz, 6H),
1.21 (t, J ) 7.4 Hz, 6H), 2.77-2.93 (m, 8H), 6.81-6.92 (m, 10H),
7.21-7.29 (m, 10H), 8.32 (s, 2H); 13C NMR (CDCl3, Me4Si) δ 15.06,
15.81, 21.87, 22.94, 122.69, 125.22, 126.36, 126.53, 127.44, 129.61,
129.86, 131.45, 135.01, 137.49, 137.64, 138.10, 139.95, 140.85; IR
(KBr) 3054, 3025, 2971, 2961, 2870, 1601, 1493, 1443, 1071, 1061,
1028, 885, 754, 698 cm-1; HRMS calcd for C46H42 594.3287, found
594.3259.
1,2,3,4-Tetraphenyl-5,6,7,8-tetrapropylanthracene (9c). A color-
less solid (58%): 1H NMR (CDCl3, Me4Si) δ 0.82 (t, J ) 7.3 Hz, 6H),
1.06 (t, J ) 7.3 Hz, 6H), 1.47-1.59 (m, 8H), 2.66-2.71 (m, 4H), 2.74-
2.80 (m, 4H), 6.83-6.93 (m, 10H), 7.20-7.29 (m, 10H), 8.24 (s, 2H);
13C NMR (CDCl3, Me4Si) δ 14.55, 14.99, 24.22, 24.91, 31.60, 32.71,
122.73, 125.22, 126.30, 126.54, 127.53, 129.81, 129.83, 131.36, 131.44,
133.77, 136.59, 137.52, 138.11, 139.99, 140.83; IR (KBr) 3058, 3023,
2957, 2930, 2870, 1603, 1491, 1368, 1090, 1073, 1028, 891, 806, 747,
698 cm-1; HRMS calcd for C50H50 650.3913, found 650.3924.
7,8,9,10-Tetraethyl-1,2,3,4-tetrahydro-5,12-diphenylnaph-
thacene (9d). A colorless solid (53%): 1H NMR (CDCl3, Me4Si) δ
1.07 (t, J ) 7.4 Hz, 6H), 1.18 (t, J ) 7.4 Hz, 6H), 1.72-1.77 (m, 4H),
Formation of Diiodonaphthalenes 8 by the Reaction of Zircona-
cyclopentadienes with 1,2,4,5-Tetraiodobenzene 6: Typical Experi-
mental Procedure. To a solution of a corresponding zirconacyclopen-
tadiene 1, prepared in situ from Cp2ZrCl2 (292 mg, 1 mmol), n-BuLi
(2 mmol), and an alkyne (2 mmol) in THF (10 mL), were added DMPU
(0.36 mL, 3.0 mmol), CuCl (200 mg, 2.0 mmol), and tetraiodobenzene
6 (1.16 g, 2.0 mmol), and the mixture was heated to 50 °C. The reaction
mixture was quenched by addition of 3 N HCl and extracted with Et2O
(3 × 30 mL). The organic layer was separated, dried with magnesium
sulfate, and concentrated in vacuo, leaving a dark oily residue. Column
chromatography on silica gel (hexane) afforded the corresponding
product 8.
1,2,3,4-Tetraethyl-6,7-diiodonaphthalene (8a). A colorless solid
(54%): 1H NMR (CDCl3, Me4Si) δ 1.22 (t, J ) 7.4 Hz, 6H), 1.27 (t,
J ) 7.5 Hz, 6H), 2.80 (q, J ) 7.5 Hz, 4H), 2.99 (q, J ) 7.5 Hz, 4H),
8.52 (s, 2H); 13C NMR (CDCl3, Me4Si) δ 15.57, 15.64, 21.44, 22.85,
102.64, 131.95, 134.45, 135.46, 139.59; IR (KBr) 2967, 2928, 2901,
2868, 1555, 1443, 1057, 911, 876 cm-1; HRMS calcd for C18H22I2
491.9811, found 491.9819.
6,7-Diiodo-1,2,3,4-tetrapropylnaphthalene (8b). A pale yellow
solid (61%): 1H NMR (CDCl3, Me4Si) δ 1.09 (t, J ) 7.3 Hz, 6H),
1.09 (t, J ) 7.3 Hz, 6H), 1.51-1.65 (m, 8H), 2.68 (t, J ) 8.4 Hz, 4H),
2.88 (t, J ) 8.3 Hz, 4H), 8.47 (s, 2H); 13C NMR (CDCl3, Me4Si) δ
14.80, 15.02, 24.53, 24.72, 30.78, 32.57, 102.56, 132.10, 133.16, 135.51,
138.60; IR (KBr) 2957, 2926, 2870, 1555, 1464, 1455, 1377, 1115,
1086, 990, 966, 882, 875, 818 cm-1; HRMS calcd for C22H30I2
9
580 J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002

Coupling Reactions of Zirconacyclopentadienes
A R T I C L E S
2.70-2.87 (m, 12H), 7.37-7.58 (m, 10H), 8.00 (s, 2H); 13C NMR
(CDCl3, Me4Si) δ 14.93, 15.82, 21.83, 22.86, 23.09, 29.36, 121.38,
126.86, 128.37, 128.82, 129.61, 130.41, 132.59, 134.81, 136.77, 136.97,
140.52; IR (KBr) 3054, 3027, 2973, 2963, 2932, 2872, 1591, 1493,
123.40, 148.11, 148.39, 148.77; IR (KBr) 1551, 1381, 1125, 1005, 795,
716 cm-1; EI-MS m/z (relative abundance, %) 285 (82), 283 (84) (M+ •),
204 (100, [M - Br]+); HRMS calcd for C5H3BrNI 282.8493, found
282.8500. Anal. Calcd for C5H3BrNI: C, 21.15; H, 1.07; N, 4.93.
Found: C, 21.29; H, 1.08; N, 4.87.
1462, 1451, 1441, 1262, 1071, 1057, 1030, 878, 802, 745, 702 cm-1
HRMS calcd for C38H40 496.3130, found 496.3143.
;
General Procedure for Preparation of Quinolines (11). To a
solution of the corresponding zirconacyclopentadiene 1, prepared in
situ from Cp2ZrCl2 (292 mg, 1 mmol), n-BuLi (2 mmol), and an alkyne
(2 mmol) in THF (10 mL) were added DMPU (0.36 mL, 3.0 mmol),
CuCl (200 mg, 2.0 mmol), and 2-bromo-3-iodopyridine 10 (284 mg,
1.0 mmol), and the mixture was heated to 50 °C. The reaction mixture
was quenched by addition of saturated aqueous sodium hydrogen
carbonate solution. The organic layer was separated, dried with
magnesium sulfate, and evaporated in vacuo, leaving a dark oily residue.
Column chromatography on silica gel (4/1 hexane/Et2O) afforded the
corresponding products 11. For 11c, 3/1 hexane/Et2O was used.
5,6,7,8-Tetraethylquinoline (11a). A yellowish waxy solid (81%,
GC yield 85%): 1H NMR (CDCl3, Me4Si) δ 1.21-1.30 (m, 9H), 1.32
(t, J ) 7.4 Hz, 3H), 2.86 (q, J ) 7.5 Hz, 2H), 2.90 (q, J ) 7.6 Hz,
2H), 3.06 (q, J ) 7.6 Hz, 2H), 3.35 (q, J ) 7.4 Hz, 2H), 7.29 (dd, J
) 8.4 and 4.1 Hz, 1H), 8.03 (dd, J ) 8.4 and 1.5 Hz, 1H), 8.85 (dd,
J ) 4.1 and 1.5 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 15.74, 15.76,
15.81, 15.84, 20.93, 21.24, 22.66, 22.96, 119.71, 125.53, 132.15, 135.02,
138.32, 138.51, 141.53, 146.22, 147.86; IR (KBr) 2971, 2932, 2870,
1595, 1584, 1566, 1491, 1478, 1462, 1453, 1061, 789 cm-1; HRMS
calcd for C17H23N 241.1830, found 241.1828.
5,6,7,8-Tetrapropylquinoline (11b). A colorless viscous oil (63%,
GC yield 67%): 1H NMR (CDCl3, Me4Si) δ 1.05-1.12 (m, 12H),
1.51-1.73 (m, 8H), 2.71-2.81 (m, 4H), 2.93-2.99 (m, 2H), 3.22-
3.29 (m, 2H), 7.27 (dd, J ) 4.0 and 8.6 Hz, 1H), 8.24 (dd, J ) 8.6 and
1.7 Hz, 1H), 8.82 (dd, J ) 4.0 and 1.7 Hz, 1H); 13C NMR (CDCl3,
Me4Si) δ 14.76, 14.94, 15.01, 15.05, 24.67, 24.83, 24.92, 24.98, 30.09,
30.70, 32.43, 32.73, 119.59, 125.69, 132.18, 133.71, 137.16, 137.63,
140.62, 146.34, 147.76; IR (neat) 3069, 2959, 2932, 2870, 1595, 1584,
1564, 1489, 1466, 1377, 1360, 1086, 909, 884, 783, 735 cm-1; HRMS
calcd for C21H30N ([M - H]+) 296.2378, found 296.2383.
1,2,3,4-Tetrahydro-5,12-diphenyl-7,8,9,10-tetrapropylnaph-
thacene (9e). A colorless solid (50%): 1H NMR (CDCl3, Me4Si) δ
0.80 (t, J ) 7.3 Hz, 6H), 1.04 (t, J ) 7.3 Hz, 6H), 1.39-1.55 (m, 8H),
1.72-1.77 (m, 4H), 2.62-2.75 (m, 12H), 7.35-7.57 (m, 10H), 7.93
(s, 2H); 13C NMR (CDCl3, Me4Si) δ 14.54, 14.98, 23.10, 24.08, 24.91,
29.36, 31.57, 32.65, 121.42, 126.79, 128.45, 129.04, 129.56, 130.34,
132.46, 133.56, 135.86, 136.97, 140.55; IR (KBr) 2955, 2930, 2868,
1591, 1468, 1455, 1441, 1090, 1071, 1028, 889, 750, 702 cm-1; HRMS
calcd for C42H48 552.3756, found 552.3766.
7,8,9,10-Tetrabutyl-1,2,3,4-tetrahydro-5,12-diphenylnaph-
thacene (9f). A colorless solid (46%): 1H NMR (CDCl3, Me4Si) δ
0.81 (t, J ) 7.3 Hz, 6H), 0.96 (t, J ) 7.4 Hz, 6H), 1.14-1.26 (m, 4H),
1.36-1.50 (m, 12H), 1.70-1.77 (m, 4H), 2.64-2.78 (m, 12H), 7.36-
7.57 (m, 10H), 7.94 (s, 2H), 13C NMR (CDCl3, Me4Si) δ 13.90, 13.95,
23.10, 23.33, 23.50, 29.08, 29.36, 29.98, 33.07, 33.73, 121.38, 126.81,
128.43, 129.07, 129.53, 130.30, 132.48, 133.59, 135.86, 136.98, 140.63;
IR (KBr) 3058, 3025, 2957, 2932, 2859, 1591, 1493, 1462, 1441, 1103,
1071, 1030, 884, 750, 702 cm-1; HRMS calcd for C46H56 608.4382,
found 608.4401.
1,2,3,4-Tetraethyl-5,6-dimethyl-7,8-diphenylanthracene (9g). A
colorless solid (54%): 1H NMR (CDCl3, Me4Si) δ 1.06 (t, J ) 7.5 Hz,
3H), 1.22 (t, J ) 7.4 Hz, 3H), 1.28 (t, J ) 7.5 Hz, 3H), 1.45 (t, J )
7.4 Hz, 3H), 2.26 (s, 3H), 2.77-2.92 (m, 9H), 3.27-3.35 (m, 2H),
7.07-7.25 (m, 10H), 8.16 (s, 1H), 8.81 (s, 1H); 13C NMR (CDCl3,
Me4Si) δ 14.98, 15.40, 15.53, 15.84, 18.99, 21.82, 22.05, 22.90, 23.01,
118.37, 123.35, 125.89, 126.10, 127.27, 127.40, 128.96, 129.29, 129.50,
129.86, 130.23, 130.41, 130.84, 131.31, 134.79, 135.05, 136.66, 136.85,
137.38, 138.92, 140.22, 141.89; IR (KBr) 3056, 2968, 2928, 2872, 1601,
1595, 1491, 1485, 1443, 1090, 1061, 1028, 874, 802, 748, 700 cm-1
HRMS calcd for C36H38 470.2973, found 470.2973.
;
5,6-Dimethyl-7,8-diphenyl-1,2,3,4-tetrapropylanthracene (9h). A
colorless solid (56%): 1H NMR (CDCl3, Me4Si) δ 0.79 (t, J ) 7.2 Hz,
3H), 1.06-1.15 (m, 6H), 1.23 (t, J ) 7.2 Hz, 3H), 1.43-1.67 (m, 6H),
1.81-1.89 (m, 2H), 2.27 (s, 3H), 2.68-2.80 (m, 6H), 2.86 (s, 3H),
3.20-3.25 (m, 2H), 7.09-7.26 (m, 10H), 8.10 (s, 1H), 8.77 (s, 1H);
13C NMR (CDCl3, Me4Si) δ 14.50, 15.00, 15.07, 15.10, 15.42, 18.98,
24.16, 24.39, 24.94, 31.57, 32.70, 32.84, 118.38, 123.44, 125.90, 126.05,
127.37, 127.41, 129.19, 129.25, 129.77, 130.15, 130.41, 130.80, 131.24,
133.58, 133.81, 135.96, 136.57, 136.67, 138.84, 140.27, 141.88; IR
(KBr) 2957, 2951, 2926, 2868, 1595, 1482, 1468, 1453, 1441, 1414,
1377, 1084, 1071, 1032, 1007, 889, 860, 768, 752, 698 cm-1; HRMS
calcd for C40H46 526.3600, found 526.3584.
5,6,7,8-Tetraphenylquinoline (11c). An off-white solid (35%): mp
225-7 °C; H NMR (CDCl3, Me4Si) δ 6.78-6.90 (m, 10H), 7.11-
1
7.28 (m, 11H), 7.95 (dd, J ) 8.5 and 1.8 Hz, 1H), 8.89 (dd, J ) 4.2
and 1.8 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 120.79, 125.54, 125.58,
126.30, 126.66, 126.69, 126.77, 127.10, 127.14, 127.67, 131.20, 131.57,
134.90, 138.44, 138.85, 139.47, 139.69, 139.95, 140.10, 142.43, 146.28,
150.16; IR (KBr) 3029, 1601, 1495, 1472, 1441, 1074, 1024, 1001,
802, 741, 696 cm-1; HRMS calcd for C33H22N ([M - H]+) 432.1752,
found 432.1772.
5,10-Diethyl-6,7,8,9-tetrahydrobenzo[g]quinoline (11d). A color-
less waxy solid (65%, GC yield 71%): 1H NMR (CDCl3, Me4Si) δ
1.18 (t, J ) 7.5 Hz, 3H), 1.25 (t, J ) 7.4 Hz, 3H), 1.84 (q, J ) 3.3 Hz,
4H), 2.88-2.94 (m, 2H), 2.95-3.04 (m, 4H), 3.32 (q, J ) 7.5 Hz,
2H), 7.27 (dd, J ) 8.6 and 4.0 Hz, 1H), 8.26 (dd, J ) 8.6 and 1.4 Hz,
1H), 8.85 (dd, J ) 1.4 and 4.0 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ
14.35, 14.45, 20.10, 20.52, 22.96, 23.06, 27.44, 27.67, 119.62, 124.87,
131.81, 133.64, 134.65, 136.75, 137.84, 145.39, 147.94; IR (KBr) 2961,
2896, 2865, 1593, 1582, 1563, 1489, 1453, 1427, 1063, 1040, 781,
752 cm-1; HRMS calcd for C17H21N 239.1674, found 239.1674.
5,9-Dibutyl-6,7-dihydro-1H-cyclopenta[g]quinoline (11e). A color-
less wax (31%, GC yield 58%): 1H NMR (CDCl3, Me4Si) δ 0.96 (q,
J ) 7.6 Hz, 6H), 1.42-1.52 (m, 4H), 1.54-1.69 (m, 4H), 2.16 (q, J )
7.5 Hz, 2H), 2.92-2.99 (m, 2H), 3.06 (t, J ) 7.5 Hz, 2H), 3.10 (t, J
) 7.5 Hz, 2H), 3.17-3.23 (m, 2H), 7.31 (dd, J ) 8.5 and 4.1 Hz, 1H),
8.28 (dd, J ) 8.5 and 1.6 Hz, 1H), 8.85 (dd, J ) 4.1 and 1.6 Hz, 1H);
13C NMR (CDCl3, Me4Si) δ 14.05, 14.21, 23.13, 23.24, 25.02, 28.59,
29.10, 31.79, 32.09, 32.57, 32.76, 119.22, 126.06, 130.68, 131.88,
133.85, 141.22, 144.34, 146.89, 147.55; IR (KBr) 2951, 2934, 2867,
1,2,3,4,5,6,7,8-Octaphenylanthracene (9i). A pale yellow powder
1
(59%); the solubility of this compound is very low. H NMR (C6D6,
Me4Si, 70 °C) δ 6.79-7.26 (m, 40H), 8.34 (s, 2H); IR (KBr) 3081,
3025, 1601, 1493, 1443, 1073, 1030, 764, 752, 698 cm-1; HRMS calcd
for C62H42 786.3287, found 786.3293.
2-Bromo-3-iodopyridine (10). 2,3-Dibromopyridine (2.36 g, 10
mmol) was dissolved in diethyl ether (50 mL); the solution was cooled
to -78 °C, and n-BuLi (6.7 mL 1.57 M, 10.5 mmol) was slowly added.
After the mixture was stirred for 15 min at -78 °C, a solution of iodine
(2.67 g, 10.5 mmol) in diethyl ether (50 mL) was added; the mixture
was stirred for a further 5 min at -78 °C and then allowed to warm to
room temperature within 30 min. After quenching by addition of
saturated aqueous sodium hydrogen carbonate solution, usual workup
afforded a crude product, which was crystallized from hot methanol to
give 2-bromo-3-iodopyridine as an off-white crystalline solid: Yield
1
1.66 g (59%); mp 101-101.5 °C; H NMR (CDCl3, Me4Si) δ 7.00
(dd, J ) 4.6 and 7.9 Hz, 1H), 8.11 (dd, J ) 1.7 and 7.9 Hz, 1H), 8.35
2855, 1615, 1595, 1578, 1495, 1464, 1451, 1103, 1088, 783 cm-1
HRMS calcd for C20H27N 281.2143, found 281.2147.
;
(dd, J ) 1.6 and 4.6 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 99.45,
9
J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002 581

A R T I C L E S
Takahashi et al.
5-Phenyl-10-propyl-6,7,8,9-tetrahydrobenzo[g]quinoline (11f) and
10-phenyl-5-propyl-6,7,8,9-tetrahydrobenzo[g]quinoline (11g). For
11f, a white solid (23%, GC yield 49%): 1H NMR (CDCl3, Me4Si) δ
1.13 (t, J ) 7.3 Hz, 3H), 1.65-1.77 (m, 4H), 1.81-1.90 (m, 2H), 2.58
(t, J ) 6.5 Hz, 2H), 3.05 (t, J ) 6.5 Hz, 2H), 3.30-3.38 (m, 2H), 7.12
(dd, J ) 8.6 and 4.1 Hz, 1H), 7.18-7.23 (m, 2H), 7.37-7.50 (m, 3H),
7.60 (dd, J ) 8.6 and 1.7 Hz, 1H), 8.82 (dd, J ) 4.1 and 1.7 Hz, 1H);
13C NMR (CDCl3, Me4Si) δ 14.89, 22.78, 23.00, 23.42, 27.60, 29.18,
29.42, 119.70, 126.08, 127.09, 128.49, 130.29, 134.20, 134.45, 135.77,
136.94, 138.04, 139.25, 145.14, 148.19; IR (neat) 3058, 3025, 2955,.
2934, 2870, 1595, 1574, 1563, 1499, 1487, 1474, 1453, 1443, 1117,
1073, 785, 756, 700 cm-1; HRMS calcd for C22H23N 301.1830, found
301.1841. For 11g, a white wax (14%, GC yield 18%): 1H NMR
(CDCl3, Me4Si) δ 1.13 (t, J ) 7.3 Hz, 3H), 1.61-1.75 (m, 4H), 1.81-
1.90 (m, 2H), 2.62 (t, J ) 6.5 Hz, 2H), 3.00 (t, J ) 6.5 Hz, 2H), 3.02-
3.09 (m, 2H), 7.23-7.51 (m, 6H), 8.33 (dd, J ) 8.6 and 1.6 Hz, 1H),
8.75 (dd, J ) 4.1 and 1.6 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 14.73,
22.70, 23.02, 23.67, 27.43, 29.86, 29.93, 119.62, 125.22, 126.66, 128.13,
130.28, 131.72, 134.04, 135.39, 137.83, 138.05, 140.02, 145.91, 148.87;
IR (KBr) 3056, 2957, 2940, 2867, 1597, 1578, 1572, 1563, 1497, 1482,
1460, 1449, 1429, 1381, 1354, 1325, 1107, 1071, 926, 916, 791, 764,
708 cm-1; HRMS calcd for C22H22N ([M - H]+) 300.1742, found
300.1752.
nate solution and extracted with Et2O (3 × 30 mL). The organic layer
was separated, dried with magnesium sulfate, and concentrated in vacuo,
leaving a dark oily residue. Column chromatography on silica gel (hex-
ane/EtOAc) afforded the corresponding product 16. For 16a (9/1), 16b
(13/1), 16c (25/1), and 16d (5/1) the indicated mixtures were used.
5,6,7,8-Tetraethylisoquinoline (16a). A yellow solid (65%): 1H
NMR (CDCl3, Me4Si) δ 1.1-1.25 (m, 9H), 1.31 (t, J ) 7.5 Hz, 3H),
2.7-2.9 (m, 4H), 2.96 (q, J ) 7.2 Hz, 2H), 3.13 (t, J ) 7.5 Hz, 2H),
7.73 (d, J ) 6.0 Hz, 1H), 8.74 (d, J ) 6.0 Hz, 1H), 9.83 (s, 1H); 13C
NMR (CDCl3, Me4Si) δ 15.34, 15.53, 15.70, 16.37, 21.10, 21.25, 22.44,
23.03, 117.87, 126.20, 133.96, 134.39, 137.35, 139.69, 142.28, 143.77,
151.57; IR (KBr) 2969, 2932, 2872, 1611, 1489, 1464, 1383, 1055,
828, 756 cm-1; HRMS calcd for C17H23N 241.1831, found 241.1850.
5,6,7,8-Tetrapropylisoquinoline (16b). A yellow solid (70%, GC
83%): 1H NMR (CDCl3, Me4Si) δ 1.06-1.16 (m, 12H), 1.5-1.8 (m,
8H), 2.7-2.8 (m, 4H), 2.96 (t, J ) 8.0 Hz, 2H), 3.11(t, J ) 8.3 Hz,
2H), 7.77 (d, J ) 5.1 Hz, 1H), 8.80 (br s, 1H), 9.90 (br s, 1H); 13C
NMR (CDCl3, Me4Si) δ 14.78, 15.01 (2C), 15.05, 24.48, 24.75, 24.92,
25.47, 30.54, 30.69, 32.22, 32.80, 117.92, 126.42, 133.22, 134.12,
136.24, 138.80, 142.32, 142.73, 151.65; IR (KBr) 2957, 2930, 2872,
1611, 1485, 1466, 1455, 1377, 1265, 1240, 1213, 1086, 1059, 822,
734 cm-1; HRMS calcd for C21H31N 297.2457, found 297.2449.
5,6,7,8-Tetrabutylisoquinoline (16c). A yellow liquid (74%): 1H
NMR (CDCl3, Me4Si) δ 0.95 (t, J ) 7.2 Hz, 3H), 0.96-1.1 (m, 9H),
1.45-1.8 (m, 16H), 2.7-2.9 (m, 4H), 2.98 (t, J ) 6.4 Hz, 2H), 3.13
(t, J ) 6.4 Hz, 2H), 7.80 (br s, 1H), 8.82 (br s, 1H), 9.89 (br s, 1H);
13C NMR (CDCl3, Me4Si) δ 13.85, 13.93, 14.03, 23.36, 23.48, 23.53,
23.56, 28.07, 28.17, 29.54, 30.14, 33.29, 33.43, 33.63, 34.22, 117.79,
126.53, 133.19, 134.01, 136.25, 138.71, 142.21, 142.63, 151.50; IR
(CHCl3 solution) 2959, 2930, 2872, 2861, 1613, 1462, 1379, 1105,
1061, 727, 666 cm-1 HRMS calcd for C25H39N 353.3083, found
353.3089.
The identification of 11f was done by single-crystal X-ray structural
analysis.
2-Chloro-3-iodopyridine (12). 3-Amino-2-chloropyridine (10 mmol)
and 5 mL of concentrated HCl were put in a 200-mL flask with 3 g of
ice. An aqueous solution of NaNO2 (11 mmol of NaNO2 dissolved in
20 mL of H2O) was added dropwise to the flask, and the solution was
kept at 0 °C for 15 min. Then 34 mmol of KI aqueous solution was
slowly added and kept standing for 12 h at room temperature. Usual
workup gave the desired product as a slightly yellow solid: Yield 90%;
1H NMR (CDCl3, Me4Si) δ 6.90-6.99 (m, 1H), 8.10-8.20 (m, 1H),
8.30-8.40 (m, 1H); 13C NMR (CDCl3, Me4Si) δ 94.91, 123.16, 148.67,
5,10-Diphenyl-6,7,8,9-tetrahydrobenzo[g]isoquinoline (16d). A
yellow solid (42%): 1H NMR (CDCl3, Me4Si) δ 1.6-1.9 (m, 4H),
2.5-2.8 (m, 4H), 7.2-7.8 (m, 11H), 8.28 (br s, 1H), 8.75 (br s, 1H);
13C NMR (CDCl3, Me4Si) δ 22.61, 22.66, 28.98, 29.55, 118.25, 126.39,
127.41, 127.51, 128.60, 128.69, 130.00, 130.05, 133.47, 135.35, 136.56,
137.99, 138.18, 138.50, 138.70, 141.83, 150.99; IR (KBr) 3058, 2940,
1599, 1495, 1441, 1379, 1030, 750, 704 cm-1; HRMS calcd for C25H21N
335.1674, found 335.1671.
148.77, 154.29; IR (KBr) 1557, 1389, 1136, 1059, 1015, 797, 721 cm-1
HRMS calcd for C5H3ClNI 238.8999, found 238.8991.
;
2-Chloro-3-{3-(4,5-diethyl-3Z,5E-octa-3,5-dienyl)}pyridine (14).
Yellow liquid: 1H NMR (CDCl3, Me4Si) δ 0.55 (t, J ) 7.6 Hz, 3H),
0.89 (t, J ) 7.5 Hz, 3H), 0.90 (t, J ) 7.6 Hz, 3H), 1.02 (t, J ) 7.5 Hz,
3H), 1.76 (dq, J ) 7.5 and 7.4 Hz, 2H), 1.80-1.90 (m, 1H), 1.91-
2.09 (m, 1H), 2.11-2.40 (m, 3H), 2.50-2.65 (m, 1H), 5.02 (t, J ) 7.4
Hz, 1H), 7.09 (dd, J ) 7.5 and 4.7 Hz, 1H), 7.30 (dd, J ) 7.2 and 2.0
Hz, 1H), 8.20 (dd, J ) 4.6 and 1.9 Hz, 1H); 13C NMR (CDCl3, Me4Si)
δ 12.86, 12.91, 13.36, 13.84, 20.79, 22.44, 23.36, 24.98, 121.36, 131.66,
131.70, 133.27, 138.93, 140.35, 144.56, 146.79, 150.95; IR (neat) 2967,
2932, 2872, 1574, 1557, 1454, 1389, 1198, 1123, 1115, 1065, 866,
800, 754 cm-1; HRMS calcd for C17H24ClN 277.1597, found 277.1595.
4-Chloro-3-iodopyridine (15). 4-Chloropyridine (10 mmol) was
dissolved in THF (50 mL), the solution was cooled to -78 °C, and
LDA (10 mmol) was slowly added. After the mixture was stirred for
1 h at -78 °C, iodine (10 mmol) was added. The mixture was warmed
to room temperature and stirred for 3 h. Then it was quenched by water.
Usual workup and column chromatography on silica gel (5/1 hexane/
Et2O) afford 15 as a slightly yellow solid: Yield 56%; 1H NMR (CDCl3,
Me4Si) δ 7.37 (d, J ) 5.1 Hz, 1H), 8.38 (d, J ) 5.1 Hz, 1H), 8.89 (s,
1H); 13C NMR (CDCl3, Me4Si) δ 97.88, 124.78, 147.80, 149.46, 158.24;
IR (KBr) 1549, 1455, 1387, 1264, 1115, 1071, 1009, 820, 731, 677
cm-1; HRMS calcd for C5H3ClNI 238.8999, found 238.8980.
5,6-Dibutyl-7,8-diethylisoquinoline (16e) and 7,8-Dibutyl-5,6-
diethylisoquinoline (16f). Column chromatography on silica gel (15/1
hexane/EtOAc) afforded an inseparable mixture of 16e and 16f (68%)
as a yellow solid. Major to minor isomer ratio was 2:1. Major isomer:
1H NMR (CDCl3, Me4Si) δ 1.01 (t, J ) 6.4 Hz, 6H), 1.24 (t, J ) 7.5
Hz, 3H), 1.27 (t, J ) 7.4 Hz, 3H), 1.44-1.65 (m, 8H), 2.7-2.9 (m,
4H), 2.95-3.3 (m, 4H), 7.8 (br s, 1H), 8.83 (br s, 1H), 9.92 (br s, 1H);
13C NMR (CDCl3, Me4Si) δ 13.84, 14.02, 15.34, 15.51, 21.26, 23.13,
23.45, 23.57, 28.06, 29.43, 33.66, 34.19, 117.69, 126.41, 133.83, 134.21,
136.35, 138.55, 142.24, 143.67, 151.65; HRMS calcd for C21H31N
297.2456, found 297.2450. Minor isomer: 1H NMR (CDCl3, Me4Si)
δ 0.94 (t, J ) 7.2 Hz, 6H), 1.24 (t, J ) 7.5 Hz, 3H), 1.27 (t, J ) 7.4
Hz, 3H), 1.35-1.8 (m, 8H), 2.9-3.3 (m, 8H), 7.81 (br s, 1H), 8.83 (br
s, 1H), 9.92 (br s, 1H); 13C NMR (CDCl3, Me4Si) δ 13.84, 13.91, 15.68,
16.34, 21.11, 22.55, 23.34, 23.50, 28.14, 30.03, 33.24, 33.48, 118.00,
126.51, 133.31, 134.12, 137.23, 139.71, 142.29, 142.61, 151.43; HRMS
calcd for C21H31N 297.2456, found 297.2450.
General Procedure for Preparation of Isoquinolines (16). To a
solution of the corresponding zirconacyclopentadiene 1, prepared in
situ from Cp2ZrCl2 (292 mg, 1 mmol), n-BuLi (2 mmol), and an alkyne
(2 mmol) in THF (10 mL), were added DMPU (0.36 mL, 3.0 mmol),
CuCl (200 mg, 2.0 mmol), and 3-iodo-4-chloropyridine 15 (239 mg,
1.0 mmol), and the mixture was heated to 50 °C. The reaction mixture
was quenched by addition of saturated aqueous sodium hydrogen carbo-
Supporting Information Available: Crystallographic data,
positional and thermal parameters, and lists of bond lengths and
angles for 8b, 9a, and 11f (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA016848K
9
582 J. AM. CHEM. SOC. VOL. 124, NO. 4, 2002