Novel Cp2LnX-mediated coupling-cyclization of propargyl bromide: A new construction of the benzene ring skeleton

Article abstract of DOI:10.1039/b200107a

In the presence of Cp₂LnX-HgCl₂, the treatment of RC≡CCH₂Br with Mg leads to the formation of benzene derivatives C₆H₄R₂-1,2 (R = H, Ph) in moderate yield, which provides a new method for the construction of the benzene ring skeleton.

Full text of DOI:10.1039/b200107a

Novel Cp2LnX-mediated coupling–cyclization of propargyl bromide: a
new construction of the benzene ring skeleton
Ruyi Ruan,a Jie Zhang,a Xigeng Zhou*ab and Ruifang Cai*a
a Laboratory of Molecular Catalysis and Innovative Material, Department of Chemistry, Fudan University,
Shanghai 200433, People’s Republic of China. E-mail: xgzhou@fudan.edu.cn
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, People’s Republic of China
Received (in Cambridge, UK) 4th January 2002, Accepted 30th January 2002
First published as an Advance Article on the web 13th February 2002
In the presence of Cp2LnX–HgCl2, the treatment of
RC·CCH2Br with Mg leads to the formation of benzene
derivatives C6H4R2-1,2 (R = H, Ph) in moderate yield,
which provides a new method for the construction of the
benzene ring skeleton.
catalyst Cp2ErCl (A) may be isolated in an adduct form of
Cp2Er(m-Cl)(m-Br)MgBr(THF)3 (B)‡ by directly concentrating
and cooling the reaction mixture of entry 1.
To expand the scope of this remarkable coupling–cyclization
and reveal the effect of the substituents, we investigated the
reaction of substituted propargyl bromide. In the presence of
Cp2ErCl, the reaction of PhC·CCH2Br with Mg proceeded
smoothly to give the corresponding coupling–cyclization prod-
uct o-terphenyl (1b) in 15 ~ 40% isolated yield (entries 3–5).§
However, in contrast to the case of unsubstituted propargyl
bromide, the generation of 1b was always accompanied by the
formation of a small amount of the coupling product
PhC·CCH2CH2C·CPh (2) under identical conditions. This may
be attributed to the increasing steric repulsive interactions
between the substrate phenyl substituent and the catalyst
ancillary ligand, which is unfavorable to the occurrence of the
cyclization reaction. Notably, if excess Mg is used (entry 5), the
yield of 1b decreases drastically from 30 to 15%. In addition,
the yield of 1b increases with increasing amounts of the catalyst
(entries 3 and 5). All these results imply that the reaction of
propargyl bromide with Mg is in competition with the
coupling–cyclization reaction. Thus, for the organolanthanide-
catalyzed coupling–cyclization of propargyl bromide, use of
Mg with smaller surface area and more catalyst results in
increased cyclization yields. These observations indicate that
the coupling–cyclization is sensitive to the nature of the
substrates and the stoichiometric ratio.
During the past 20 years, tremendous progress has been made in
the area of organolanthanide catalysis. It has been found that
lanthanocene complexes are highly active and selective cata-
lysts for many unsaturated C–C and C–N bond transformations
such as isomerization, hydrogenation, hydroboration, hydro-
silylation, hydroamination, hydrophosphination, oligomeriza-
tion/polymerization and so on.1–5 However, it is noteworthy
that lanthanocene halides are much less used as catalysts than
the corresponding alkyls, hydrides and aminates in these
transformation reactions, despite being quite easy to prepare
and store.1–6 On the other hand, although the chemistry of
propargyl/allenyl complexes has been extensively studied and
proven to contribute immensely to organic synthesis, no
example of selective synthesis of benzene derivatives by the
metal-mediated intermolecular coupling–cyclization of propa-
rgyl halides has been reported up to now.7–10 Additionally,
relatively little is also known about organolanthanide propargyl
complexes.11–13 We report herein an unprecedented Cp2LnCl-
mediated coupling–cyclization of propargyl bromide, which
provides a convenient way to construct the benzene ring
skeleton.
Initially, the synthesis of lanthanide propargyl complexes
was attempted by the treatment of Cp2LnCl with the Grignard
reagent HC·CCH2MgBr. Interestingly, when propargyl bro-
mide was present in excess, the GC-MS data for hydrolyzed
products of the reaction mixture indicated the formation of
benzene (1a). Apparently, the reaction was promoted by
Cp2ErCl, since no benzene was obtained without Cp2ErCl under
otherwise identical reaction conditions.
The
diamagnetic
Cp2YCl-catalyzed
reaction
of
1
PhC·CCH2Br with Mg was closely monitored by H NMR
spectroscopy at room temperature and at constant catalyst
concentration (Fig. 1).¶ The kinetic data clearly show that some
new aryl resonances appear between d 7.2 and 7.5 ppm and their
strength increases with the time, while the resonance at d 4.32
ppm that is assigned to the CH2 protons of PhC·CCH2Br
fragment weaken gradually.
This unprecedented bis(cyclopentadienyl)lanthanide chlo-
ride-mediated intermolecular coupling–cyclization of unsat-
urated halides provides a new method for the one-pot formation
of benzene derivatives and prompted us to explore other
protocols suitable for the catalytic formation of benzene.† The
results are summarized in Table 1. As expected, the addition of
a small amount of Cp2LnCl to a mixture of HC·CCH2Br and
Mg (entry 2) resulted in the catalytic formation of benzene in
30% GC yield. Furthermore, after stopping the reaction, the
A plausible reaction pathway for the formation of 1 is given
in Scheme 1. In the first step of the catalytic cycle, bis(cyclo-
Table 1 Cp2ErCl-catalyzed coupling–cyclization of propargyl bromide
C6H4R2-1,2
Entry
R
Cp2ErCl/Mg/RC·CCH2Br
(Yield, %)
1
2
3
4
5
H
H
Ph
Ph
Ph
1+1+2
60a
30a
40
23
15
1+20+20
1+1+2
1+10+20
1+20+20
Fig. 1 1H NMR chemical shifts of aromatic protons for the progress of the
coupling–cyclization using Cp2YCl as catalyst in THF-d8 at room
temperature.
a GC yields.
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CHEM. COMMUN., 2002, 538–539
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NMR (500 MHz, DCCl3): d 7.25 ~ 7.46 (m). 13C NMR (500 MHz, DCCl3):
d 132.75, 130.68, 129.20, 128.37, 127.74, 127.46, 127.28. MS (relative
abundance): M+ (100), 215(58). 202 (20), 115 (23), 77 (3). IR (KBr): 3054,
1597, 1571, 1488, 1442, 1274, 1071, 1028, 918, 755, 692, 530, 510, 453.
¶ A magnesium strip (10 mg, 412 mmol) was weighed into an NMR tube. On
the high-vacuum line, THF-d8 (1.0 ml) was vacuum transferred into the
tube. Then, Cp2YCl (8 mg, 31 mmol) was added. PhCCCH2Br (120 ml, 830
mmol) was syringed in when the catalyst solution had frozen. The tube was
sealed and the frozen reaction mixture was warmed to rt. After the mixture
was shaken, the progress of the reaction was monitored by 1H NMR
spectroscopy from intensity changes in the substrate and product reso-
nances. The relative concentration of either functional group was measured
from the corresponding peak area, standardized to the area of Cp2YCl.
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Scheme 1
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pentadienyl)lanthanide chloride reacts with the Grignard rea-
3
gent RC·CCH2MgBr to produce the active h -propargyl
1
lanthanide intermediate, which can transform into the h -
proparyglic isomer, and then couples with the remaining
propargyl bromide to form the p-1,5-dihexyne lanthanide
complex. The subsequent cyclization leads to the formation of
1 via [2+2] cycloaddition, followed by rearrangement.14,15 In
accord with this hypothesis, in the case of substituted propargyl
bromide, when PhC·CCH2Br is combined with Mg in the
presence of Cp2LnCl, the only observable product was 1b.
Surprisingly, reaction of Cp2ErCl and 2 gave 1b in rather low
yield. Further investigations into the mechanism of the
formation of benzene derivatives and its scope and generality
are currently in progress.
In conclusion, the benzene ring is an important building block
for many organic compounds and of abundant occurrence in
natural products. However, the methods for highly selective
one-pot synthesis of the benzene ring skeleton are limited.15
The Cp2LnX-catalyzed reaction of propargyl bromide and Mg
provides a new method for the construction of the benzene ring
skeleton due to the ready availability of starting materials with
different substitution patterns.
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This research was supported by NNSF of China, the Research
Fund for the Doctoral Program of Higher Education, and the
Shuguang Foundation of the Shanghai Education Commis-
sion.
Notes and references
† All manipulations of air- and moisture-sensitive compounds were
performed under purified argon or nitrogen using Schlenk techniques. 60
mg (0.18 mmol) of Cp2ErCl, 0.22 ml (2.0 mmol) of HC·CCH2Br, 25 ml of
THF and a minimal amount of HgCl2 (2 mg, 7.4 mmol) were loaded into a
reaction vessel equipped with a magnetic stirbar. Next, Mg strip (24.3 mg,
1.0 mmol) was added to the stirring solution. After the Mg strip had
disappeared, the reaction was stirred at rt for a further 2 days. The yield of
1a (30%) was estimated by 1H NMR and GC-MS after the product was
isolated from the catalyst by vacuum transfer. 1H NMR (500 MHz, DCCl3):
d 7.36 (s). MS (relative abundance): M+ (100), 51(21).
‡ Although the rough structure of Cp2Er(m-Cl)(m-Br)MgBr(THF)3 was
confirmed by elemental analysis and X-ray crystallographic data, the
refinement of accurate metric parameters was not possible due to severe
disorder of chloride and bromide atoms.
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§ A procedure analogous to that for 1a was used in the synthesis of 1b. After
the reaction had completed, saturated aqueous NaHCO3 was added to the
reaction mixture. The organic layer was separated and the aqueous layer was
extracted with ether. The extraction was concentrated at reduced pressure
and then chromatographed on silica gel using n-hexane, then a mixture of n-
hexane and ethyl acetate in the ratio of 20+1 as the eluent. The eluate was
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1
concentrated by rotary evaporation to yield 1b as a light yellow solid. H
CHEM. COMMUN., 2002, 538–539
539