Stereoselective tandem 1,4-addition reactions for benzenes: A comparison of Os(II)5 Re(I), and W(0) systems

Article abstract of DOI:10.1021/ja047108p

The arene ligand in the complex TpRe(CO)(Melm)(η²-benzene) (Tp = hydridotris(pyrazolyl)-borate; Melm = N-methylimidazole) undergoes tandem electrophile/nucleophile 1,4-addition reactions. Subsequent oxidative demetalation affords cis-3,6-disubstituted 1,4-cyclohexadienes (46-84%). Common organic electrophiles such as acetals and Michael acceptors were successfully added to the bound benzene to generate η³-benzenium complexes, which then were treated with a silyl ketene acetal, silyl vinyl ether, phenyllithium, or malonate ester to afford 1,4-dialkylated dihydrobenzene complexes. The d⁶ transition metal analogues TpW(NO)(PMe ₃)(η²-benzene) and [Os(NH₃) ₅(η²-benzene)]²⁺ also undergo 1,4-dialkylation reactions, and the relative ability of all three metals to activate arenes is compared.

Full text of DOI:10.1021/ja047108p

Published on Web 10/05/2004
Stereoselective Tandem 1,4-Addition Reactions for Benzenes:
A Comparison of Os(II), Re(I), and W(0) Systems
Fei Ding and W. Dean Harman*
Contribution from the Department of Chemistry, UniVersity of Virginia, P.O. Box 400319,
CharlottesVille, Virginia 22904-4319
Received May 17, 2004; E-mail: wdh5z@virginia.edu
Abstract: The arene ligand in the complex TpRe(CO)(MeIm)(η2-benzene) (Tp ) hydridotris(pyrazolyl)-
borate; MeIm ) N-methylimidazole) undergoes tandem electrophile/nucleophile 1,4-addition reactions.
Subsequent oxidative demetalation affords cis-3,6-disubstituted 1,4-cyclohexadienes (46-84%). Common
organic electrophiles such as acetals and Michael acceptors were successfully added to the bound benzene
to generate η3-benzenium complexes, which then were treated with a silyl ketene acetal, silyl vinyl ether,
phenyllithium, or malonate ester to afford 1,4-dialkylated dihydrobenzene complexes. The d6 transition
metal analogues TpW(NO)(PMe3)(η2-benzene) and [Os(NH3)5(η2-benzene)]2+ also undergo 1,4-dialkylation
reactions, and the relative ability of all three metals to activate arenes is compared.
Introduction
Transition metals have been used widely to promote the
dearomatization of benzenes.1 Electron-deficient metal frag-
ments such as {Cr(CO)3},{Mn(CO)3}+,1,2 and more recently
{Mo(CO)3}3 activate η6-coordinated arenes toward a nucleo-
philic addition. In some cases, this action can be followed by
an electrophilic addition to the cyclohexadienyl ligand, some-
times concomitant with CO insertion, giving rise to trans-5,6-
disubstitued 1,3-cyclohexadienes. As a complementary meth-
odology, we have explored the chemistry of the pentaammine-
osmium(II) fragment, which, through back-bonding, functions
as an electron donor when dihapto-coordinated to an arene.
These complexes readily undergo reactions with electrophilic
reagents.4 The resultant η3-arenium complexes can react with
various nucleophiles to provide cis-3,6-disubstituted 1,4-cyclo-
hexadienes, which in turn can be liberated from the metal by
oxidation (Figure 1).5 Due to the high Brønsted acidity of
osmium(II)-arenium complexes (pKa ranges from -8 to -10),6
the yield of this tandem addition sequence is generally low,
especially for more basic nucleophiles,5 where deprotonation
often preempts the intended nucleophilic addition reaction
(Figure 1).
Figure 1. Tandem addition sequence for an osmium(II)-η2-benzene
complex.
particular, the {TpRe(CO)(MeIm)} and {TpW(NO)(PMe3)}
fragments are capable of forming complexes with benzene that
rival the thermal stability of [Os(NH3)5(η2-benzene)]2+ 10
We
.
anticipated that the rhenium and tungsten benzene complexes
would be more reactive toward electrophiles than their osmium
counterpart due to their greater ability to back-bond.9 In addition,
the resulting arenium complex would be less susceptible to
deprotonation by an intended nucleophile.11-13 We herein report
that tandem 1,4-additions to benzene can be realized with these
new Re(I) and W(0) reagents, with improved yields and a wider
scope of nucleophile than is possible with the analogous
osmium(II)-mediated reactions.
Recently, we have developed a series of second generation
π-bases using rhenium,7 molybdenum,8 and tungsten.9 In
(1) Pape, A. R.; Kaliappan, K. P.; Ku¨ndig, E. P. Chem. ReV. 2000, 100, 2917-
2940.
(2) Semmelhack, M. F. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
U.K., 1995; Vol. 12, pp 979-1015.
(8) Meiere, S. H.; Keane, J. M.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. J.
Am. Chem. Soc. 2003, 125, 2024-2025.
(9) Graham, P. M.; Meiere, S. H.; Sabat, M.; Harman, W. D. Organometallics
2003, 22, 4364-4366.
(3) Ku¨ndig, E. P.; Fabritius, C.-H.; Grossheimann, G.; Robvieux, F.; Romanens,
P.; Bernardinelli, G. Angew. Chem., Int. Ed. Engl. 2002, 41, 4577-4579.
(4) Harman, W. D. Chem. ReV. 1997, 97, 1953-1978.
(5) Ding, F.; Kopach, M. E.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc.
2002, 124, 13080-13087.
(10) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Sabat, M.; Harman, W. D.
Organometallics 2001, 20, 1038-1040.
(11) Valahovic, M. T.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. J. Am. Chem.
Soc. 2002, 124, 3309-3315.
(6) Winemiller, W. D.; Kopach, M. E.; Harman, W. D. J. Am. Chem. Soc.
1997, 119, 2096-2102.
(7) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Carrig, E. H.; Sabat, M.;
Harman, W. D. Organometallics 2001, 20, 3661-3671.
(12) Friedman, L. A.; Harman, W. D. J. Am. Chem. Soc. 2001, 123, 8967-
8973.
(13) Friedman, L. A.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2002, 124,
7395-7404.
9
13752
J. AM. CHEM. SOC. 2004, 126, 13752-13756
10.1021/ja047108p CCC: $27.50 © 2004 American Chemical Society

Tandem 1,4-Addition Reactions for Benzene
A R T I C L E S
Table 1. Products and Yields of Tandem Addition Reactions to
Benzenea
Figure 2. Tandem addition reaction sequence for the rhenium(I)-benzene
complex 1.
a [Re] ) TpRe(CO)(MeIm); [Os] ) [Os(NH3)5]2+
.
(MeIm)(olefin) complex.14 Unlike TpRe(CO)(MeIm)(η2-ethyl-
ene), which has a reversible redox couple at -0.03 V,14
complexes 3A and 3B exhibit chemically irreversible anodic
peaks (each at 0.21 V). This difference is likely to be due to
the presence of bulky substituents on the ligand, which facilitate
the ligand substitution process. Upon oxidative demetalation
with silver triflate (AgOTf) at 75 °C, cyclohexadiene 4 was
isolated in 84% overall yield from the benzene complex 1 (see
Figure 2).
Figure 3. NOE interactions confirming the stereochemical assignment of
diastereomers 3A and 3B.
Results and Discussion
Methyl vinyl ketone (MVK) failed to add to the pentaam-
mineosmium(II)-benzene complex,5 most likely because this
reaction was preempted by polymerization of MVK under the
acidic conditions required. However, when complex 1 was
treated with MVK in the presence of TBSOTf followed by
MMTP, 5 was isolated in 76% yield upon its decomplexation
(Table 1). Similar to other cis-3,6-disubstituted 1,4-cyclohexa-
dienes, 1H NMR data for 5 reveals symmetric splitting of
olefinic protons around 5.63 ppm and strong homoallylic
coupling between the H1 and H4 protons (3.13 and 2.77 ppm).
Alternatively, phenyllithium (in the presence of copper cyanide)
was found to react with the benzenium intermediate 2, giving
the 1-aryl-4-alkyl addition product 6 in 71% yield.
When TpRe(CO)(MeIm)(η2-benzene) (1) was treated with
dimethoxymethane (DMM) in the presence of triflic acid
(HOTf), under optimal reaction conditions found for the
[Os(NH3)5(η2-benzene)]2+, decomposition of the complex was
accompanied by the appearance of benzene. The use of other
reaction promoters such as trifluoroacetic acid or lithium triflate
along with DMM resulted in either recovery or decomposition
of the starting complex, depending on the reaction temperature.
However, when a mixture of 1 and DMM in acetonitrile was
treated with TBSOTf at -20 °C, a benzenium species 2 was
1
observed by H NMR with a 1:1 diastereomeric ratio (2A:2B;
Compared with the pentaammineosmium(II), the strongly
electron-donating fragment TpRe(CO)(MeIm), stabilizes the
benzenium complexes that result from electrophilic addition. In
addition, the bulky ligand set of this fragment hinders the
nucleophile from deprotonating the sp3 carbon (C1). This
notion is clearly demonstrated in the nucleophilic addition of
trimethylsiloxypropene or dimethyl malonate to the benzenium
Figure 2). A COSY spectrum of this mixture reveals two isolated
spin systems for the allyl protons at 5.04, 4.72, 4.55 ppm and
5.09, 4.80, 4.49 ppm. Due to extensive overlap of signals, the
Tp region (6-8 ppm) of the spectrum could not be assigned,
and NOE data failed to reveal the orientation of the arenium
ligands. However, when a solution of the benzenium complex
2 was treated with 1-methoxy-2-methyl-1-(trimethylsiloxy)-
propene (MMTP) at -20 °C, complex 3 was isolated as a
mixture of two coordination diastereomers (Figure 2), which
were separated through preparatory TLC on silica. 1D NOE
experiments allowed the assignment of 3A and 3B, as shown
in Figure 3.
ligand of {TpRe(CO)(MeIm)} compared to {Os(NH3)5}2+
.
The vinyl ether 2-trimethylsiloxypropene readily adds as a
nucleophile to the osmium(II)-benzenium complex at
-40 °C,5 but it showed no reaction with the rhenium analogue
(2). However, in the presence of sodium iodide, the desired
reaction between 2 and this vinyl ether proceeded to form 7 in
46% yield. When the pentaammineosmium(II) complex was
treated with DMM followed by dimethyl malonate and DBU,
benzyl methyl ether was observed with no detectable amount
of the tandem addition product. In contrast, in the presence of
Apparently, the regio- and diastereoselectivity of the tandem
addition reaction follows the same pattern as observed for the
pentaammineosmium(II) benzene complex, where a cis-3,6-
dialkylated-1,4-cyclohexadiene complex is formed. IR spectra
of complexes 3A and 3B show CtO stretching frequencies at
1788 and 1786 cm-1, respectively, consistent with a TpRe(CO)-
(14) Friedman, L. A.; Meiere, S. H.; Brooks, B. C.; Harman, W. D. Organo-
metallics 2001, 20, 1699-1702.
9
J. AM. CHEM. SOC. VOL. 126, NO. 42, 2004 13753

A R T I C L E S
Ding and Harman
Figure 4. Tandem addition reaction sequence with an η2-toluene complex.
Figure 5. 1,4-Dialkylation addition with a tungsten(0)-η2-benzene com-
plex.
DBU, dimethyl malonate reacted smoothly with the benzenium
complex 2 (prepared in situ), affording 8 in an overall 56%
yield. As seen in Table 1, the yields for the rhenium(I)-promoted
reactions are generally superior to those realized with osmium,
largely due to the increased stability of the arenium intermediates
for the group VII metal. When the benzene complex 1 was
treated with the weaker electrophiles acrylonitrile or methyl
acrylate and TBSOTf followed by MMTP, an intractable
mixture resulted. For the latter case, proton data for the complex
mixture suggested that 2 equiv of methyl acrylate added in a
Michael-Michael ring closure sequence, similar to that observed
earlier in our laboratories for an osmium(II)-η2-aniline com-
plex,15 but the mixture of purported isomers could not be
separated.
When complex 11 was combined with MVK under these
conditions, the subsequent treatment of this reaction mixture
with pyridine followed by AgOTf afforded 4-phenylbutan-2-
one18 in 90% yield. Following the addition of MVK, a variety
of nucleophiles were tested, including those reported in Table
1 and vinylmagnesium bromide. Subsequent demetalation with
AgOTf at room temperature followed by heating yielded only
the monosubstituted benzene. Apparently, the benzenium result-
ing from Michael addition was stabilized by the tungsten
fragment to a greater extent relative to the osmium and rhenium
analogues, resulting in a diminished electrophilicity of the
benzenium complex. We reasoned that the reactivity of the
benzenium ligand for this tungsten system could be increased
by the one-electron oxidation of the metal. Indeed, when a cold
solution of the purported benzenium intermediate prepared from
11 and MVK was treated with the oxidant Cu(OTf)2 at -78 °C
immediately after the addition of dimethyl malonate and DBU,
cyclohexadiene 12 was isolated in 25% yield (Figure 5).
Interestingly, even slightly milder oxidants such as AgOTf did
not promote the nucleophilic addition of malonate. Finally, we
note that while no η2-benzene complexes of a second-row
transition metal have been shown to undergo tandem addition
reactions, the complex TpMo(NO)(MeIm)(η2-naphthalene) un-
dergoes protonation followed by MMTP addition to afford a
1,2-dihydronaphthalene in 80% yield.8
The coordination of the {TpRe(CO)(MeIm)} fragment to
toluene results in multiple new species (four major) in equilib-
rium, as both regio- and stereoisomers are now possible.
Whereas the benzene complex 1 decomposed in the presence
of HOTf, when the toluene complex (9) was treated with HOTf
followed by MMTP, the 1,4-cyclohexadiene 10 was formed in
62% yield, after its oxidative decomplexation with AgOTf
(Figure 4). Despite a mixture of both linkage and stereoisomers
for 9, a single organic product was isolated (Figure 4). As was
observed for the osmium analogue, protonation occurs at the
ortho carbon and addition to the 1H-arenium intermediate occurs
at C4. Unfortunately, we have not been successful in adding
acetals or Michael acceptors to the toluene or xylene complexes,
most likely as a result of the very short substitution half-life
for these more sterically hindered arene complexes. Anisole,
on the other hand, forms a complex with TpRe(CO)(MeIm) that
is more substitution inert than 1, and the π-donating methoxy
group greatly facilitates the addition of carbon electrophiles at
C4. A full investigation into rhenium and tungsten anisole and
4H-anisolium chemistry is forthcoming.16
Previously, we have reported that η2-naphthalene complexes
of rhenium17 and molybdenum8 undergo 1,2- or 1,4-tandem
addition reactions similar to those reported herein. The more
delocalized nature of the C-C bonds in benzene, relative to
PAHs, make dearomatization of the former a particularly
difficult challenge. However, the complex TpW(NO)(PMe3)-
(η2-benzene) (11) was recently reported as being synthesized
from W(CO)6.9 The fragment {TpW(NO)(PMe3)} is thought
to be an even stronger π-base than its rhenium analogue.
Consistent with this notion, complex 11 readily decomposes,
even at -40 °C, in the presence of various acids including
HOTf, BF3‚Et2O, TBSOTf, MSA, and TFA. Nevertheless, the
mild Brønsted acid Ph2NH2OTf can be used at -40 °C (or
TBSOTf at -78 °C) as a promoter for electrophilic addition.
Experimental Section
General Procedure. All the reactions were performed under nitrogen
1
in a Vacuum Atmospheres Co. glovebox. H and 13C NMR spectra
were collected on a 300 or 500 MHz Varian INOVA spectrometer.
Chemical shifts are reported in parts per million relative to tetrameth-
ylsilane (TMS) using the deuterated solvents as the internal reference,
and coupling constants are reported in Hertz. COSY and HETCOR
experiments were carried out by using the standard parameters. The
following abbreviations will be used to discriminate among the
pyrazolyl rings: COTp ) pyrazolyl ring trans to CO, OTp ) pyrazolyl
ring trans to the olefin, ImTp ) pyrazolyl ring trans to MeIm. Infrared
spectra (IR) were recorded on a MIDAC Prospect Series (Model PRS)
spectrometer as a glaze (evaporated diethyl ether) on a Horizontal
Attenuated Total Reflectance (HATR) accessory (Pike Industries).
Electrochemical experiments were performed under a dinitrogen
atmosphere using a PAR Model 362 potentiostat driven by a PAR
Model 175 universal programmer. Cyclic voltammograms (CV) were
recorded (Kipp and Zonen BD90 XY recorder) at 100 mV/s (25 °C) in
a standard three-electrode cell from +1.7 to -1.7 V with a glassy carbon
working electrode, dimethylacetamide (DMA) solvent, and tetrabutyl-
ammonium hexafluorophosphate (TBAH) electrolyte. All potentials are
reported versus NHE (normal hydrogen electrode) using cobaltocene
(E1/2 ) -780 mV) as an internal standard. HRMS determination was
performed in the laboratory of mass spectrometry at the University of
Illinois, Urbana-Champaign.
(15) Gonzalez, J.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 1993, 115,
8857-8858.
(16) Manuscript submitted for publication.
(17) Ding, F.; Valahovic, M. T.; Keane, J. M.; Anstey, M. R.; Sabat, M.; Trindle,
C. O.; Harman, W. D. J. Org. Chem. 2004, 69, 2257-2267.
(18) Oi, S.; Moro, M.; Ito, H.; Honma, Y.; Miyano, S.; Inoue, Y. Tetrahedron
2002, 58, 91-97.
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13754 J. AM. CHEM. SOC. VOL. 126, NO. 42, 2004

Tandem 1,4-Addition Reactions for Benzene
A R T I C L E S
Reagents. All the solvents and electrophiles were purified via
distillation under nitrogen or passage through an activated alumina
column under nitrogen. The syntheses of TpRe(CO)(MeIm)(η2-benzene)
and TpW(NO)(PMe3)(η2-benzene) were previously reported,4,9 as were
compounds 4, 6, 7, and 10.3
Diastereomer 3B (Rf ) 0.24, 34 mg, 27%) CV Ep.a ) 211 mV (NHE).
1
IR (HATR, glaze): νBH ) 2476 cm-1, νCO ) 1786, 1723 cm-1. H
NMR (500 MHz) (acetonitrile-d3): δ 7.92 (1H, d, J ) 2.2, OTp-H5),
7.83 (1H, d, J ) 1.9, COTp-H5), 7.76 (1H, d, J ) 2.2, OTp-H3), 7.73
(1H, d, J ) 1.2, COTp-H3), 7.67 (1H, d, J ) 1.9, ImTp-H5), 7.63 (1H,
m, Im), 7.41 (1H, d, J ) 1.6, ImTp-H3), 6.85 (1H, dd, J ) 1.6, 1.6,
Im), 6.80 (1H, dd, J ) 1.6, 1.6, Im), 6.37 (1H, dd, J ) 2.2, 2.2, COTp-
H4), 6.21 (1H, dd, J ) 2.2, 2.2, OTp-H4), 6.05 (1H, dd, J ) 1.9, 1.9,
ImTp-H4), 5.71 (1H, m, H2), 5.53 (1H, m, H3), 3.64 (3H, s, COOCH3),
3.49 (1H, m, H4), 3.29 (1H, dd, J ) 9.3, 7.0, CH2OCH3), 3.17 (3H, s,
MeIm), 3.13 (1H, dd, J ) 9.3, 2.6, CH2OCH3), 3.08 (3H, s, CH2OCH3),
2.89 (1H, m, H1), 2.42 (1H, d, J ) 9.9, H6), 1.73 (1H, dd, J ) 9.9,
1.6, H5). 1.10 (3H, s, gem Me), 0.91 (3H, s, gem Me). 13C NMR (125
MHz): δ 199.2 (CtO), 179.0 (CdO), 145.6 (OTp-C5), 142.9 (ImTp-
C3), 141.8 (COTp-C3), 139.3 (ImTp-C5), 137.0 (OTp-C5), 136.5 (COTp-
C5), 135.3 (Im), 132.0 (Im), 129.8 (C2), 126.1 (C3), 122.4 (Im), 106.9
Compound 4 (Example of One-Pot Procedure). To the rhe-
nium(I)-benzene complex (50 mg, 0.085 mmol), CH3CN (10 mg, 0.128
mmol) and 0.5 g of DMM were added and the solution was cooled to
-20 °C before TBSOTf (34 mg, 0.13 mmol) was added and allowed
to sit for 12 min. A chilled acetonitrile (0.3 g) solution (-20 °C) of
MMTP (84 mg, 0.48 mmol) was added and allowed to sit for 0.5 h
and then 0.5 h at 25 °C. AgOTf (22 mg, 0.086 mmol) was added and
the reaction mixture was transferred to a 75 °C oil bath for 1.0 h. After
cooling to 25 °C the solvents were evaporated, and 1 mL of water was
added to dissolve the oil-like residue. Then 40 mL of ether was added.
The ether layer was then evaporated, and the residue was dissolved in
chloroform and subjected to chromatography. The elution of 10% ethyl
acetate in hexanes on silica gel yielded the product (16 mg, 84%, Rf )
0.30) visualized by the stain of iodine. In the case of methyl vinyl
ketone as the electrophile, tetrahydrofuran (THF) was used as the
reaction solvent.
(
COTp-C4), 106.7 (OTp-C4), 106.4 (ImTp-C4), 56.6 (CH2OCH3), 56.5
(COOCH3), 52.1 (CH2OCH3), 49.5 (CH2OCH3), 47.3 (C6), 47.2 (C5),
41.1 (C4), 41.3 (MeIm), 34.6 (C1), 23.0 (gem Me), 22.9 (gem Me).
2-Methyl-2-[4-(3-oxobutyl)cyclohexa-2,5-dienyl]propionic Acid
Methyl Acid (5). Rf ) 0.42. Yield: 76%. 1H NMR (300 MHz,
CDCl3): δ 5.63 (4H, m, H2,3,5,6), 3.70 (3H, s, OMe), 3.13 (1H, m,
H4), 2.77 (1H, m, H1), 2.44 (2H, m, CHCH2CH2), 2.13 (3H, s, COMe),
1.71 (2H, m, CH2CH2CO), 1.14 (6H, s, gem Me). 13C NMR (75 MHz,
CDCl3): δ 178.1 (CO), 130.8,125.7 (CH), 52.0 (CH3), 45.8 (quaternary),
43.0 (CH), 40.7 (CH2), 30.1 (CH3), 29.6 (CH2), 22.5 (2×CH3). Carbonyl
resonance for the ketone was not observed. HRMS. Calcd. for
C15H23O3+: 251.1647. Found: 251.1647. Purity (1H NMR): >90%.
2-(4-(Methoxymethyl)cyclohexa-2,5-dienyl)malonic Acid Dimeth-
yl Ester (8). Rf ) 0.25. For further purification, 20% EtOAc in hexanes
was used. Rf ) 0.42. yield 56%. 1H NMR (300 MHz, CDCl3): δ 5.77
(4H, m, H2, 3, 5, 6), 3.73 (6H, s, COOCH3), 3.54 (1H, m, H4), 3.36
(1H, d, J ) 8.8, COCHCO), 3.34 (3H, s, CH2OCH3), 3.29 (2H, d, J )
6.6, CHCH2OCH3), 2.97 (1H, m, H1). 13C NMR (75 MHz, CDCl3): δ
168.5 (CO), 128.7 (CH), 126.4 (CH), 77.1 (CH2), 59.2 (CH), 57.8
(CH3), 52.6 (2 × CH3), 37.1 (CH), 36.2 (CH). HRMS. Calcd for
C13H19O5+: 255.1233. Found: 255.1233. Purity (1H NMR): >95%.
[TpRe(CO)(MeIm)(2,3,4-η3-(1-Methoxymethyl-1H-benzenium]-
(OTf) (2). To the benzene complex 1 (50 mg, 0.085 mmol), 0.5 g of
CD3CN and DMM (7 mg, 0.09 mmol) were added and then cooled to
-20 °C before TBSOTf (22 mg, 0.083 mmol) was added. Two
diastereomers were observed (1H NMR) with a 1:1 ratio. Due to
1
overlapping, resonances for the Tp ligand could not be assigned. H
NMR (500 MHz, -20 °C): δ 6.43 (2 × 1H, m, H3), 5.33 (2 × 1H, m,
H2), 5.09, 5.04 (each 1H, d, J ) 2.0, H6), 4.80, 4.72 (each 1H, dd, J
) 2.0, 2.0, H5), 4.55, 4.49 (each 1H, d, J ) 2.0, H4), 3.83, 3.77 (each
1H, m, H1), 3.67, 3.63 (each 2 × 1H, m, CH2OCH3), 3.32, 3.32 (each
3H, s, CH2OCH3). 13C NMR (125 MHz, -20 °C): δ 131.8, 130.4 (C3),
126.2, 125.8 (C2), 97.4, 92.9 (C6), 97.3 (2 × C4), 78.6, 74.3 (C5),
74.2 (2 × CH2OCH3), 54.7 (2 × CH2OCH3).
TpRe(CO)(MeIm)(5,6-η2-(Methyl 2-[4-(methoxymethyl)cyclohexa-
2,5-dien-1-yl]-2-methylpropanoate)) (3). An acetonitrile solution (1.0
g) of TpRe(CO)(MeIm)(η2-benzene) (100 mg, 0.170 mmol) and DMM
(20 mg, 0.26 mmol) was cooled to -20 °C and treated with a chilled
(-20 °C) acetonitrile solution (0.3 g) of TBSOTf (68 mg, 0.26 mmol).
After 12 min the reaction was treated with a chilled (-20 °C)
acetonitrile solution (0.5 g) of MMTP (168 mg, 0.966 mmol). After
an hour, 2,6-lutidene (30 mg, 0.28 mmol) was added and then the
reaction mixture was added dropwise into 30 mL of stirring hexanes.
The oily precipitate was loaded onto a 500 µm TLC silica plate and
eluted with 1:1 hexanes:ethyl acetate. The desired bands were cut off
and washed with acetonitrile (1.0 g). The solvents were removed under
reduced pressure to yield the product as a yellow solid. Diastereomer
3A (Rf ) 0.36, 32 mg, 26%) CV Ep.a ) 214 mV (NHE). IR (HATR,
2-[4-(3-Oxybutyl)cyclohexa-2,5-dienyl]malonic Acid Dimethyl
Ester (12). To a solution of 11 (50 mg, 0.086 mmol) in THF (0.5 g),
MVK (9 mg, 0.13 mmol) was added and cooled to -78 °C. A solution
of TBSOTf (34 mg, 0.13 mmol) in THF (0.3 g) was also chilled and
added to the above solution to react for 10 min, during which time, a
solution of DBU (66 mg, 0.43 mmol) and dimethyl malonate (57 mg,
0.43 mmol) in THF (0.3 g) and a separate solution of Cu(OTf)2 (31
mg, 0.085 mmol) in THF (1.0 g) were also cooled to -78 °C. The
mixture of DBU and dimethyl malonate was then added to the reaction
mixture immediately before the copper(II) solution was added. The
reaction mixture was allowed to stand for 30 min at -78 °C and then
at 20 °C for 15 min. Water (1.0 g) was added, and the reaction solution
was transferred to a 75 °C oil bath and allowed to sit for 1 h. The
elution of 10% ethyl acetate in hexanes yielded the product as clear
1
glaze): νBH ) 2476 cm-1, νCO ) 1788, 1720 cm-1. H NMR (500
MHz) (acetonitrile-d3): δ 7.91 (1H, d, J ) 1.9, OTp-H5), 7.86 (1H, d,
J ) 2.6, COTp-H5), 7.76 (1H, d, J ) 2.6, COTp-H3), 7.71 (1H, m, Im),
7.65 (1H, d, J ) 1.9, OTp-H3), 7.59 (1H, d, J ) 1.9, ImTp-H5), 7.32
(1H, d, J ) 1.9, ImTp-H3), 6.84 (1H, dd, J ) 1.6, 1.6, Im), 6.54 (1H,
m, MeIm), 6.38 (1H, dd, J ) 2.6, 2.6, COTp-H4), 6.19 (1H, dd, J )
1.9, 1.9, OTp-H4), 6.05 (1H, dd, J ) 1.9, 1.9, ImTp-H4), 5.76 (1H, m,
H3), 5.46 (1H, m, H2), 3.67 (3H, s, COOCH3), 3.49 (3H, s, MeIm),
3.42 (1H, dd, J ) 6.1, 2.6, CH2OCH3), 3.31 (1H, m, H4), 3.16 (1H, d,
J ) 8.3, CH2OCH3), 3.13 (3H, s, CH2OCH3), 3.07 (1H, m, H1), 2.28
(1H, dd, J ) 9.9, 1.3, H5), 1.98 (1H, dd, J ) 9.9, 1.3, H6). 1.09 (3H,
s, gem Me), 0.89 (3H, s, gem Me). 13C NMR (125 MHz): δ 199.0
(CtO), 179.2 (CdO), 143.3 (OTp-C5), 143.0 (ImTp-C3), 139.7 (Im),
139.5 (ImTp-C5), 137.1 (COTp-C5), 136.7 (COTp-C3), 135.2 (OTp-C3),
129.6 (C3), 129.4 (Im), 126.7 (C2), 122.6 (Im), 107.0 (COTp-C4), 106.8
(OTp-C4), 106.5 (ImTp-C4), 82.5 (quaternary), 58.6 (CH2OCH3), 58.4
(CH2OCH3), 53.1 (COOCH3), 52.1 (CH2OCH3), 49.0 (C5), 48.9 (C6),
48.7 (MeIm), 40.8 (C1), 34.6 (C4), 23.1 (gem Me), 22.2 (gem Me).
1
oil (6 mg, 25%, Rf ) 0.46) after solvent evaporation. H NMR (300
MHz, CDCl3): δ 5.68 (m, 4H), 3.75 (s, 6H), 3.52 (dd, J ) 8.1, 8.1,
1H), 3.33 (d, J ) 7.9, 1H), 2.81 (m, 1H), 2.40 (t, J ) 8.1, 8.1, 2H),
2.14 (s, 3H), 1.71 (m, 2H).
Conclusion
In all, four different d6 transition metals (Os(II), Re(I), W(0),
and Mo(0)) have been shown to promote tandem addition
reactions with arenes. Of the heavy metals, the tungsten system
{TpW(NO)(PMe3)} appears to be the most electron-rich,
reacting with electrophiles under the mildest conditions (lower
acidity, weaker electrophiles). Somewhat less nucleophilic is
the system {TpRe(CO)(MeIm)}, and the least activating of the
9
J. AM. CHEM. SOC. VOL. 126, NO. 42, 2004 13755

A R T I C L E S
Ding and Harman
three heavy metal systems is {Os(NH3)5}2+. In contrast, the
osmium(II) system provides a benzenium complex that is most
readily attacked by mild nucleophiles. The rhenium system is
somewhat less electrophilic, and the tungsten system is seem-
ingly inert to arenium addition unless addition of the nucleophile
is accompanied by an increase in the metal oxidation state. These
osmium(II)-benzenium complexes are also the most acidic,
however, making their deprotonation at C4 a serious side
reaction.5 The molybdenum system, while showing a capacity
for arene activation with naphthalene, does not form a complex
that with benzene sufficiently inert to allow its isolation. Taking
these observations into account, the rhenium system {TpRe-
(CO)(MeIm)} appears to be the best suited to promoting the
target reaction of 1,4-dialkylation of benzene.
Acknowledgment is made to the donors of the Petroleum
Research Fund, administered by the ACS, for partial support
of this research (ACS-PRF No. 36638-AC1). This work was
also supported by the NSF (Grants CHE0111558 and 9974875)
and the NIH (Grant NIGMS: R01-GM49236).
Supporting Information Available: Proton and carbon NMR
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
JA047108P
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13756 J. AM. CHEM. SOC. VOL. 126, NO. 42, 2004