Reactions of zirconacyclopentadienes with nitrosobenzene. Characterization of zirconacycle intermediates and formation of N-phenylpyrroles

Article abstract of DOI:10.1021/om010873h

Nitrosobenzene inserts into the Zr-C bond of zirconacyclopentadienes to give seven-membered zirconacyclic rings. The resulting insertion products are readily converted to N-phenylpyrroles and (in one case) a 3,3-spiroindole derivative.

Full text of DOI:10.1021/om010873h

Organometallics 2001, 20, 5515-5517
5515
Rea ction s of Zir con a cyclop en ta d ien es w ith
Nitr osoben zen e. Ch a r a cter iza tion of Zir con a cycle
In ter m ed ia tes a n d F or m a tion of N-P h en ylp yr r oles
Masaaki Nakamoto and T. Don Tilley*
Center for New Directions in Organic Synthesis, Department of Chemistry,
University of California at Berkeley, Berkeley, California 94720-1460
Received October 4, 2001
Sch em e 1
Summary: Nitrosobenzene inserts into the Zr-C bond
of zirconacyclopentadienes to give seven-membered zir-
conacyclic rings. The resulting insertion products are
readily converted to N-phenylpyrroles and (in one case)
a 3,3-spiroindole derivative.
Zirconocene-coupling methods are now well-estab-
lished as important synthetic routes to a variety of
heterocyclic compounds and functionalized molecules.1
In one manifestation of this chemistry, a zirconocene
reagent couples with two alkynes to produce a zircona-
cyclopentadiene in high yield and high regioselectivity.
These zirconacyclopentadienes are useful synthons for
heterocycles, which are obtained by reactions with main-
group-element dihalides in procedures originally devel-
oped by Nugent and Fagan.2 However, for the synthesis
of heterocycles by this method, product yields can
depend strongly on reaction conditions and the nature
of substituents on the halide derivative and the zir-
conacycle. For this reason, a number of modifications
to the original synthetic method have been explored.3
Previously, we found that zirconocene coupling reactions
involving SO2 may be used to produce thiophene-1-
oxides in high yield in reactions that feature “oxo
transfer” (oxygen transfer to zirconium; eq 1, E ) SO).
(eq 1, E ) RCH).5 In further investigations of such oxo-
transfer reactions, we have found that nitrosobenzene
reacts with zirconacyclopentadienes via insertion into
a Zr-C bond, and this insertion chemistry has been
used to produce pyrroles (eq 1, E ) RN)6 and an
unexpected indole derivative.
Tetramethylzirconacyclopentadiene2c,7 (1a ) reacted
with nitrosobenzene in toluene at -78 °C to form an
insertion product (2a ) in 75% yield (Scheme 1). The
zirconacycle 2a was isolated as light yellow, air-stable
crystals by flash column chromatography (Al2O3, hex-
ane/ether) followed by recrystallization from acetonitrile
at -30 °C. The molecular structure of 2a (Figure 1)
consists of a seven-membered ring resulting from inser-
tion of the NdO double bond into the zirconacycle of 1a
and a strong Zr‚‚‚N interaction. At room temperature
this reaction also produced 2a (60%), as well as tetra-
methylfuran (30%), azoxybenzene (15%), and azoben-
1
zene (10%) (by H NMR spectroscopy and GC-MS). In
the presence of AlCl3 (1 equiv), the selectivity of this
process toward production of 2a is dramatically im-
proved (to >90%).
The slow thermolysis of 2a in benzene-d6 at 80 °C
occurred over ca. 2 weeks and produced tetramethyl-
N-phenylpyrrole8 (3a ) in 90% yield. This reaction is
dramatically accelerated by the addition of a Lewis acid
such as AlCl3, trimethylsilyl triflate, or B(C6F5)3. For
example, when 1 equiv of AlCl3 was added to a benzene-
d6 solution of 2a at room temperature, the conversion
to 3a and Cp2ZrCl2 occurred within 10 min and was
essentially quantitative. With 1 equiv of B(C6F5)3 as the
added Lewis acid, the reaction was somewhat slower,
Thus, SO2 reacts cleanly with a range of zirconacyclo-
pentadienes to afford thiophene 1-oxides and zir-
conocene oxide, [Cp2ZrO]n,4 and this method results in
significantly higher yields than can be obtained with
thionyl chloride as the sulfoxide-transfer reagent.2c This
strategy has recently been employed by Xi in the
synthesis of cyclopentadienes, via reactions of zircona-
cyclopentadienes with aldehydes in the presence of AlCl3
(1) Reviews: (a) Negishi, E. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 5,
pp 1163-1184. (b) Broene, R. D.; Buchwald, S. L. Science 1993, 261,
1696-1701. (c) Takahashi, T.; Kotora, M.; Hara, R.; Xi, Z. Bull. Chem.
Soc. J pn. 1999, 72, 2591-2602.
(2) (a) Fagan, P. J .; Nugent, W. A. J . Am. Chem. Soc. 1988, 110,
2310-2312. (b) RajanBabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan,
P. J . J . Am. Chem. Soc. 1988, 110, 7128-7135. (c) Fagan, P. J .; Nugent,
W. A.; Calabrese, J . C. J . Am. Chem. Soc. 1994, 116, 1880-1889.
(3) See for example: Ura, Y.; Li, Y.; Tsai, F.-Y.; Nakajima, K.;
Kotora, M.; Takahashi, T. Heterocycles 2000, 52, 1171-1189.
(4) (a) J iang, B.; Tilley, T. D. J . Am. Chem. Soc. 1999, 121, 9744-
9745. (b) Suh, M.; J iang, B.; Tilley, T. D. Angew. Chem., Int. Ed. 2000,
39, 2870-2873.
(5) Xi, Z.; Li, P. Angew. Chem., Int. Ed. 2000, 39, 2950-2952.
(6) Pyrroles from zirconocene imine complexes: (a) Buchwald, S. L.;
Wannamaker, M. W.; Watson, B. T. J . Am. Chem. Soc. 1989, 111, 776-
777. From cobaltacyclopentadienes: (b) Wakatsuki, Y.; Kuramitsu, T.;
Yamazaki, H. Tetrahedron Lett. 1976, 4549-4552. For recent work
on pyrrole syntheses: (c) Kelin, A. V.; Sromek, A. W.; Gevorgyan, V. J .
Am. Chem. Soc. 2001, 123, 2074-2075. (d) Dieter, R. K.; Yu, H. Org.
Lett. 2000, 2, 2283-2286 and references therein.
(7) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron Lett.
1986, 27, 2829-2832.
(8) Hogeveen, H.; Kingma, R. F.; Kok, D. M. J . Org. Chem. 1982,
47, 1909-1915.
10.1021/om010873h CCC: $20.00 © 2001 American Chemical Society
Publication on Web 11/15/2001

5516 Organometallics, Vol. 20, No. 26, 2001
Communications
F igu r e 2. ORTEP diagram of 4.
F igu r e 1. ORTEP diagram of 2a .
of PhNO or lead to other products. For example, the
reaction of tetraethylzirconacyclopentadiene7 with PhNO
(with or without AlCl3 present) in toluene produced a
complex reaction mixture. Heating PhNO with Cp2Zr-
[1,4-(Me3Si)2-2,3-Ph2C4]10 did not give an insertion
product, but eventually the free alkyne Me3SiCtCPh
was observed. For tetraphenylzirconacyclopentadiene,7
the major product from the reaction with PhNO was
tetraphenylfuran (mp 184-186 °C, lit.11 mp 185-186
°C; 40-50% yield).
Sch em e 2
Bicyclic zirconacyclopentadienes 1b12 and 1c13 were
found to readily undergo insertions with nitrosobenzene
(Scheme 2). In the case of the six-membered ring (n )
2, 1b), the insertion to give 2b proceeded in moderate
yield (40%), and its thermolysis gave the tetrahy-
droisoindole derivative 3b in 92% yield (from 2b). The
AlCl3-promoted formation of 3b led to an isolated yield
of 59% (from 1b). In contrast, the reaction of 1c (n ) 1)
with nitrosobenzene took a different course, to afford
the zirconacycle 4 in 64% yield after recrystallization
from ether. The structure of 4 was confirmed by an
X-ray crystallographic analysis (Figure 2). Zirconacycle
4 was efficiently converted to the indole derivative 5
such that only a 55% yield of 3a (as the only product)
was observed after heating at 60 °C in benzene-d6 for
24 h.
The most convenient synthetic route to the pyrrole
involves adding both PhNO and AlCl3 (1 equiv) to the
zirconacyclopentadiene 1a . When this reaction was
carried out at 0 °C in toluene, the pyrrole 3a was
produced in an isolated yield of 85%.
1
(95%, by H NMR, benzene-d6 solution) by heating at
It is interesting to compare our results involving
nitrosobenzene to those of Xi and Li, who reported
similar chemistry for isoelectronic benzaldehyde. In the
latter case, zirconacyclopentadienes were found to be
unreactive toward benzaldehyde at room temperature.5
This appears to reflect a higher reactivity for ni-
trosobenzene toward insertion.9 Note, however, that Xi
proposed a different mechanism for the reaction with
benzaldehyde, involving transmetalation to form an
aluminacyclopentadiene, which then reacts with the
aldehyde. In the reactions with nitrosobenzene, trans-
metalation is probably not involved, since Lewis acids
which cannot undergo this process also accelerate the
conversion to products. We propose that the role of the
Lewis acid in both reactions (involving nitrosobenzene
and benzaldehyde) is to facilitate insertion of the EdO
functionality into the Zr-C bond (with E-C bond
formation). In addition, the Lewis acid clearly plays a
role in promoting the elimination of [Cp2ZrO]n from the
initial insertion product.
80 °C for 12 h or by the reaction with AlCl3 at room
temperature for 1 h. It is also possible to obtain 5
directly from the reaction of zirconacyclopentadiene 1c
with nitrosobenzene in the presence of AlCl3 without
isolation of 4, in good yield (70%). Compound 5 was fully
characterized by various means, including mass spec-
1
trometry and NMR spectroscopy. In particular, the H
and 13C NMR spectra are consistent with the 3,3-
spiroindole structure shown in Scheme 2. The 13C NMR
shift of 68.6 ppm (C6D6) for the spiro carbon atom and
other spectroscopic features agree with the correspond-
ing values reported for a closely related spiroindole
derivative.14 A tentative assignment of the product as
the E isomer is based on a relatively upfield shift for
(9) Doxsee, K. G.; J uliette, J . J . J .; Weakly, T. J . R.; Zientara, K.
Inorg. Chim. Acta 1994, 222, 305-325.
(10) Erker, G.; Zwettler, R. J . Organomet. Chem. 1991, 409, 179-
188.
(11) Eisch, J . J .; Galle, J . E.; Kozima, S. J . Am. Chem. Soc. 1986,
108, 379-385.
The synthesis of pyrroles from zirconacyclopenta-
dienes appears to be quite sensitive to steric factors,
such that bulkier groups in the R-position of the met-
allacycle (e.g., Et, SiMe3, and Ph) prevent the insertion
(12) Negishi, E.; Holmes, S. J .; Tour, J . M.; Miller, J . A.; Cederbaum,
F. E.; Swanson, D. R.; Takahashi, T. J . Am. Chem. Soc. 1989, 111,
3336-3346.
(13) Nugent, W. A.; Thorn, D. L.; Harlow, R. L. J . Am. Chem. Soc.
1987, 109, 2788-2796.

Communications
Organometallics, Vol. 20, No. 26, 2001 5517
Sch em e 3
5. Attempts to observe an intermediate in this trans-
formation (by H NMR spectroscopy) were not success-
1
ful. Some support for the proton-transfer step of this
mechanism was observed by monitoring the thermolysis
of 4. In rigorously dry chloroform-d, pure 4 remained
unchanged for several days at elevated temperature (80
°C). However, in wet chloroform-d, the transformation
to product is complete within 12 h at 40 °C.
In summary, we report the synthesis of two pyrroles
from simple zirconacyclopentadiene starting materials,
using an oxo-transfer reaction. This chemistry has also
produced an unexpected indole derivative. Future efforts
will address the further development of this synthetic
method.
the vinyl proton (4.67 ppm), which may be due to its
proximity to the aromatic ring system of 5.
A possible mechanism to account for the formation
of zirconacycle 4 and the following transformation to
indole 5 is given in Scheme 3. Insertion of nitrosoben-
zene into the Zr-C bond occurs as it does for 1a and
1b, to generate intermediate A. Due to strain in the five-
membered ring, intermediate A could undergo N-O
bond scission and electrophilic substitution on the
benzene ring. Subsequent recyclization and proton
transfer in B would then give zirconacycle 4. Finally,
elimination of [Cp2ZrO]n and proton transfer could give
Ack n ow led gm en t is made to the National Science
Foundation, for their generous support of this work. The
Center for New Directions in Organic Synthesis is
supported by Bristol-Myers Squibb as Sponsoring Mem-
ber. M.N. thanks the J apan Society for the Promotion
of Science for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: Text and tables
giving synthesis, characterization, and crystallographic details
for 2-5. This material is available free of charge via the
Internet at http://pubs.acs.org.
(14) Shiraishi, H.; Nishitani, T.; Sakaguchi, S.; Ishii, Y. J . Org.
Chem. 1998, 63, 6234-6238.
OM010873H