Osmium-Promoted Electrophilic Substitution of Anisoles: A Versatile New Method for the Incorporation of Carbon Substituents

Article abstract of DOI:10.1021/jo961983e

A structurally and electronically diverse set of anisoles are dihapto-coordinated to the π-base pentaammineosmium(II) and treated with a variety of carbon electrophiles (e.g. Michael acceptors, acetals) After deprotonation of a 4H-anisolium intermediate with a tertiary amine base, C(4)-substituted anisole complexes are isolated. The functionalized arenes are removed from the metal center either by mild heating or treatment with an oxidant (e.g. AgOTf, DDQ, CAN). The resulting substituted anisoles are isolated with yields ranging from 55-95%.

Full text of DOI:10.1021/jo961983e

130
J . Org. Chem. 1997, 62, 130-136
Osm iu m -P r om oted Electr op h ilic Su bstitu tion of An isoles: A
Ver sa tile New Meth od for th e In cor p or a tion of Ca r bon
Su bstitu en ts
Stanley P. Kolis, Michael E. Kopach, Ronggang Liu, and W. Dean Harman*
Department of Chemistry, University of Virginia Charlottesville, Virginia 22901
Received October 22, 1996X
A structurally and electronically diverse set of anisoles are dihapto-coordinated to the π-base
pentaammineosmium(II) and treated with a variety of carbon electrophiles (e.g. Michael acceptors,
acetals). After deprotonation of a 4H-anisolium intermediate with a tertiary amine base, C(4)-
substituted anisole complexes are isolated. The functionalized arenes are removed from the metal
center either by mild heating or treatment with an oxidant (e.g. AgOTf, DDQ, CAN). The resulting
substituted anisoles are isolated with yields ranging from 55-95%.
Ta ble 1. Com p lexa tion of Va r iou s An isoles w ith
P en ta a m m in eosm iu m (II)
In tr od u ction
Friedel-Crafts alkylation is considered one of the most
powerful synthetic tools available for attaching carbon
substituents to an arene ring, yet this reaction is not
without its limitations.1 Regioselectivity is typically poor,
and multiple alkylations result in low yields and formi-
dable purification procedures. In addition, isomerization
of primary alkyl groups is commonplace, and the harsh
reaction conditions required are incompatible with many
functional groups.
The π-base pentaammineosmium(II) coordinates arenes
in a dihapto fashion rendering the aromatic π-system
partially localized. In particular, when the arene bears
a single donor group, the metal activates the arene
toward electrophilic addition reactions at C(4).2 In the
case of anisole, phenol, or aniline, a strong π-backbonding
interaction with the metal center stabilizes the resulting
4H-arenium ligand so that this otherwise transient
intermediate is stable toward deprotonation. As a con-
sequence, multiple alkylations of the ring are avoided.
In the following account, we describe a convenient
synthetic procedure for the mild, selective electrophilic
substitution of anisoles with several common carbon
electrophiles in which the individual steps of electrophilic
addition and deprotonation are moderated by the influ-
ence of the osmium(II) metal center.
compd
R2
R3
R4
yield (%)
1
2
3
4
5
6
H
CH3
H
H
H
H
H
H
H
H
CH3
H
96
94
93
96
99
78
CH3
H
OCH3
CF3
H
H
a severely broadened 1H NMR spectrum at 20 °C, but
when the H NMR spectrum of 2 is recorded at -45 °C,
1
the proton signals become well resolved. Cyclic voltam-
metric data for 1-6 indicate a chemically irreversible
oxidation wave ranging from Ep,a ) +0.30 to 0.70 V
(NHE), consistent with data compiled for other η2-arene
complexes.3 As expected, more electron-deficient arenes
form complexes that are more difficult to oxidize, and
their oxidation potentials are observed at the higher end
of this range. Over time, all these η2-arene complexes
undergo substitution for solvent, but the half-life for
solvolysis is sufficiently long (typically, t1/2 > 1 d at 20
°C in CH3CN), so that substitution does not interfere with
the intended alkylation reaction (vide infra). The 2-me-
thylanisole complex 2 is an exception as its substitution
half-life in solution is only 15 min at 20 °C. Extended
exposure of complexes 1-6 to air or harsh oxidants
results in loss of the anisole ligand, so these compounds
are handled and stored under an inert atmosphere.
Electr op h ilic Ad d ition s to An isole Com p lexes. As
described in our preliminary communication,2 the anisole
complex 1 readily undergoes electrophilic substitution at
C(4) with methylacetonitrilium triflate at 20 °C. Other
carbon electrophiles such as Michael acceptors, alkyl
triflates, and acetals fail to react under these conditions.
However, when an acetonitrile solution of 1 is treated
with methyl vinyl ketone in the presence of HOTf at -40
°C, a dark purple color appears due to the formation of
the 4H-anisolium intermediates shown in Figure 1 (vide
Resu lts
Syn t h esis of η2-An isole Com p lexes. The one-
electron reduction of Os(NH3)5(OTf)3 in the presence of
various anisole ligands provides the series of compounds
1-6 often in quantitative yield (Table 1). In all cases
the metal center preferentially binds to the arene across
C(5) and C(6), although a dynamic equilibrium exists
among various linkage isomers. Most compounds show
well resolved 1H NMR resonances for the ring protons
in the range of 4.5-7.0 ppm, where the furthest upfield
peaks correspond to the coordinated methine groups. The
exception is the 2-methylanisole complex (2). It shows
X Abstract published in Advance ACS Abstracts, December 15, 1996.
(1) Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation Chemis-
try: A Century of Discovery; M. Dekker: New York, 1984.
(2) (a) Kopach, M. E.; Gonzalez, J .; Harman, W. D. J . Am. Chem
Soc. 1991, 113, 8972. (b) Kopach, M. E.; Harman, W. D. J . Org. Chem.
1994, 59, 6506.
(3) Harman, W. D.; Sekine, M.; Taube, H. J . Am. Chem. Soc. 1988,
110, 5725.
S0022-3263(96)01983-4 CCC: $14.00 © 1997 American Chemical Society

Osmium-Promoted Electrophilic Substitution of Anisoles
J . Org. Chem., Vol. 62, No. 1, 1997 131
Ta ble 2. Con ju ga te Ad d ition Rea ction s w ith Va r iou s
η2-An isole Com p lexes
F igu r e 1. The reaction of methyl vinyl ketone and the η2-
anisole complex of pentaammineosmium(II).
infra).4 Subsequent treatment of the solution with a
tertiary amine base (-40 °C), deprotonates the arenium
complex at C(4) to yield the C(4)-substituted anisole
complex (7). Addition of this reaction mixture to an
excess of ether/CH2Cl2 induces precipitation of 7 in 95%
yield. Supporting data for the assignment of 7 include
four doublets in the 1H NMR from 4.87 to 6.11 ppm
indicative of a para-substituted η2-arene ligand, and the
appearance of a carbonyl (δ 210.0) and two methylene
resonances (13C and DEPT) confirming the attachment
of the butanone chain. No evidence for other isomers was
detected in the product 1H or 13C NMR spectra. Cyclic
voltammetric data of 7 are also consistent with an η2-
coordinated arene, showing an irreversible anodic peak
at Ep,a ) 0.43 V (NHE).5
In Table 2 the scope of this Michael addition/deproto-
nation sequence is illustrated. Olefins with a single
ketone or aldehyde activating group (7-13) readily react
with the parent anisole complex 1 to give 4-alkylated
anisole derivatives with yields generally >90%. N-
methylmaleimide (14) and 3-butyn-2-one (15) also give
satisfactory results. In cases where a chiral center is
formed adjacent to the ring, a mixture of diastereomers
is often observed for the substituted arene complexes. The
diastereomeric ratio, however, is time dependent as a
result of a 5,6-η2-2,3-η2 linkage isomerization that
effectively epimerizes the asymmetric center formed by
metal coordination (Figure 2). As an example, the
reaction of 1 with 2-cyclohexen-1-one was monitored over
the course of deprotonation and isomerization by 1H
NMR. Initially, the sample of the 4H-anisolium complex
is formed at -40 °C as a 10:1 ratio of diastereomers. After
addition of base (d5-pyridine), the solution of the 4-alky-
lated anisole 12 was allowed to gradually warm to 20
°C. During this period, the diastereomer ratio was
observed to change from 10:1 to its equilibrium ratio of
1:1. In contrast, the closely related 4,4-dimethylcyclo-
hexanone adduct 13 has a significant thermodynamic
preference for one diastereomer (de ) 90%). In general,
if the two substituents on the chiral center differ greatly
in size, a single diastereomer is observed for the 4-sub-
stituted anisole complex (e.g. 8-14; Table 2).
F igu r e 2. The isomerization of an η2-arene complex with a
substituent bearing a stereogenic center.
When the anisole complex is substituted at C(3) by an
electron-donating or electron-withdrawing group, conju-
gate addition still takes place exclusively at C(4) to
generate 3,4-disubstituted anisole complexes (Table 2).
When C(3) is substituted by the electron-withdrawing
substituent CF3 (i.e. 6), the reactivity of the complex is
(4) For an example of a well characterized 4H-anisolium complex
see reference 2b.
(5) Conditions: CH3CN, 100 mV/s, TBAH. See reference 3.

132 J . Org. Chem., Vol. 62, No. 1, 1997
Kolis et al.
Ta ble 3. Con ju ga te Ad d ition Rea ction s w ith th e
1,3-Dim eth oxyben zen e Com p lex 5 via th e 4H-Ar en iu m
In ter m ed ia te 5H
Ta ble 4. Assor ted C(4) Ad d ition Rea ction s w ith Ca r bon
Electr op h iles a n d η2-An isole Com p lexes
decreased substantially and most Michael acceptors fail
to react under the previously demonstrated conditions.
However, when 6 is treated with 3-butyn-2-one and BF3‚
OEt2 at -40 °C, a brilliant purple solution develops that
forms the enone substitution product 18 when treated
with base.
CH2Cl2 (1:1) precipitates compound 23.
A
1H NMR
For the special case of the 1,3-dimethoxybenzene
complex 5, reactions are most conveniently accomplished
by adding the electrophile directly to a sample of the 4H-
anisolium species 5H, the product of a C(4) protonation
of compound 5 (Table 3). Unlike the parent anisolium
species,2b compound 5H is stable indefinitely as a solid
spectrum of 23 indicates the formation of one dominant
diastereomer whose features include four arene reso-
nances in the range of 6.5-5.0 ppm, a single ethoxy group
with diastereotopic methylene protons, and a methyl
signal split into a doublet. Satisfactory results are
obtained even for the hindered acetals formed from
acetone (24) or cyclopentanone (25).
1
at 20 °C. A H NMR spectrum of 5H (20 °C, CD3CN)
shows three olefinic protons, two methoxy groups, and
cis- and trans-ammine signals shifted downfield from its
dimethoxybenzene complex precursor. 13C NMR reso-
nances at 205.7 and 193.5 ppm as well as a methylene
carbon resonance at 35.6 ppm indicate the nonaromatic
nature of the carbocycle.
Acylation or formylation at the 4-position of the anisole
complex 1 is best accomplished either by reaction with
methylacetonitrilium triflate or an ortho ester followed
by hydrolysis. One example of each of these reactions is
provided in Table 4. In the case of nitrilium addition,
the complex is most conveniently isolated as the iminium
salt, whereas the reaction product resulting from triethyl
orthoformate addition is hydrolyzed in situ prior to
isolation. Of note, the iminium-substituted anisole ligand
of complex 28 is unusually resistant to hydrolysis requir-
ing decomplexation before it may be converted into 4′-
methoxyacetophenone (93%). Electrophiles bearing a
labile halide (e.g. acyl and alkyl halides) were avoided
out of concern that precipitation of the osmium complex
as a halide salt would compromise the intended reaction.
In addition, less reactive Michael acceptors (e.g. methyl
acrylate or acrylonitrile) fail to react under the stated
reaction conditions.
When an acetonitrile solution of 5H is treated with a
slight excess of MVK and precipitated from solution, a
new product (19) is isolated whose NMR features are
1
similar to those of 5H, but with additional H and 13C
signals corresponding to an oxobutyl group. Unexpect-
edly, attempts to deprotonate the corresponding aniso-
lium complexes at C(4) by an amine base (e.g. DIEA) fail
to return the 3,4-disubstituted anisole complex. How-
ever, the arene itself (4-(2,4-dimethoxyphenyl)butan-2-
one) may be obtained via exposure of an acetone solution
of 19 to air. The scope of Michael acceptor for 5 is similar
to that for the parent anisole complex 1, and several
examples appear in Table 3.
Several other carbon electrophiles were also screened
for reactivity with the parent anisole complex 1, and
those that give satisfactory results are summarized in
Table 4. The parent anisole complex 1 reacts efficiently
with acetals to form 4-methoxybenzyl ethers. For ex-
ample, when an acetonitrile solution of 1 is cooled to -40
°C and treated with a mixture of HOTf (2-3 equiv) and
acetaldehyde diethyl acetal (1.1 equiv) the solution
becomes deep blue. Upon addition of pyridine, the color
changes back to amber, and subsequent addition to ether/
In the absence of electron-withdrawing groups on the
anisole ring, substituted arenes can be decomplexed by
a simple ligand substitution procedure. Heating a sub-
stituted anisole complex in a coordinating solvent such
as acetonitrile (70 °C, 1 h) results in decomplexation of
the organic ligand and formation of [Os(NH3)5(CH3CN)]3+
.
This inorganic byproduct is easily separable from the
desired organic material by precipitation in ether (see
Experimental Section). In an alternative method, arenes
are readily liberated at lower temperature (20 °C) by use

Osmium-Promoted Electrophilic Substitution of Anisoles
J . Org. Chem., Vol. 62, No. 1, 1997 133
Ta ble 5. Isola ted Yield s for th e Decom p lexa tion of
η2-An isole P r od u cts
F igu r e 3. A formal catalytic cycle for the conversion of anisole
to a C(4)-substituted anisole.
complex 1 in 93% isolated yield, while returning 4-(p-
methoxyphenyl)butan-2-one in 95% yield. While this
cycle is highly efficient for most Michael addition prod-
ucts, yields are somewhat lower for the benzyl ethers
derived from acetals as a result of a more sluggish ligand
substitution rate. Raising the reaction temperature
above 80 °C or changing solvent to methanol results in
significant decomposition of the pentaammineosmium-
(II) system, as well as formation of a new compound that
we believe to be the binuclear species[{Os(NH3)5}2(η2:η2-
anisole)](OTf)4.6
Although 4-substituted anisole complexes can also
undergo electrophilic addition at C(4), the scope of this
reaction appears to be limited to either unhindered (e.g.
MVK or 3-butyn-2-one) or doubly activated (e.g. N-
methylmaleimide) Michael acceptors. For example, when
the 4-methylanisole complex 4 is treated with MVK, the
η2-(R-4-methyl)anisolium species 44 is isolated as the sole
product (97%; Figure 4). In contrast to the 4H-anisolium
complexes bearing a methine proton at C(4), the triflate
salt of 44 is stable indefinitely in the solid state.
Although this material is surprisingly resistant to hy-
drolysis, (e.g. at 25 °C in D2O, t1/2 > 2 h) it may be
converted to the corresponding 4-methyl-η2-cyclohexadi-
enone complex 45 and then oxidized to give 4-methyl-4-
(2-oxobutyl)-2,5-cyclohexadien-1-one in 69% yield. When
the 4-methylansiole complex 4 is combined with N-
methylacetonitrilium triflate, alkylation at C(2) results
in the formation of a 2-methoxy-N-methylacetophenone
imine complex 46. Hydrolysis of 46 followed by oxidation
(AgOTf) gives 5-methyl-2-methoxyacetophenone (47; 55%)
(Figure 4).
of a one-electron oxidant (e.g. AgOTf or CAN). This
approach is particularly useful when the anisole ligand
contains an electron-withdrawing group (e.g. 18, 28), an
alternative coordination site (e.g. 15, 16), or a sensitive
functional group (e.g. 10). Isolated yields of the substi-
tuted anisoles were generally in the range of 80-90% for
either method (Table 5).
In many cases, the pentaammineosmium(II) metal
center may be directly recycled through what formally
is a catalytic cycle (Figure 3). For example, the anisole
complex 1 may be alkylated at C(4) by MVK and
deprotonated to give the 4-alkylated anisole complex 7.
Heating a DMA solution of 7 to 80 °C in the presence of
an excess of anisole regenerates the parent anisole
Discu ssion
The alkylation of anisoles via an electrophilic substitu-
tion mechanism (i.e. Friedel-Crafts methodology) has
several limitations that sometimes compromise its utility
(6) Harman, W. D.; Taube, H. J . Am. Chem. Soc. 1987, 109, 1883.

134 J . Org. Chem., Vol. 62, No. 1, 1997
Kolis et al.
F igu r e 5. Steric interference in addition of a Michael acceptor
to C(2) of an η2-anisole complex.
alkylation of the arene. As mentioned above, the strong
π-basic nature of the osmium(II) group stabilizes the 4H-
arenium fragment through backbonding and deprotona-
tion is not spontaneous in acidic acetonitrile at -40 °C.13
In addition to this thermodynamic feature, deprotonation
is also inhibited as a result of the congested environment
of the acidic sp3 methine proton resulting from the
electrophilic addition (inset A). Given that the carbon
F igu r e 4. A contrast in the reactions of a C(4)-substituted
η2-anisole complex with acetonitrilium ion and methyl vinyl
ketone.
as a tool for organic synthesis. Due to the stability of
the aromatic ring system, reaction conditions required
for alkylation are severe utilizing high temperatures or
harsh Lewis acids to promote the reaction. As a result,
many functional groups are either incompatible (e.g.
aldehydes, ketones, acid-sensitive protecting groups) or
they compromise the effectiveness of the Lewis acid (e.g.
alcohols, amines, amides). Further, primary alkylating
agents often undergo isomerization under the reaction
conditions required for electrophilic substitution.7
By complexing anisole to the pentaammineosmium(II)
system, the arene is rendered more nucleophilic through
the localization of the π-electrons and the donation of
electron-density by metal-to-ligand backbonding. Con-
sider that the pKa for the benzenium cation is estimated
to be -24.0 in acetonitrile,8 whereas that for the pen-
taammineosmium(II) complex is ∼1.9 Thus, coordination
increases the basicity of the arene by approximately 25
orders of magnitude.10 Consequently, a successful elec-
trophilic addition can be carried out under much milder
conditions than for the uncoordinated arene. Michael
additions are accomplished at -40 °C in the presence of
acidic acetonitrile, conditions amenable to sensitive func-
tionalities such as aliphatic aldehydes (e.g. 10). Fur-
thermore, addition of an acetal to anisole is easily
accomplished (Table 4) even though the byproduct is an
alcohol.
electrophile attacks the arene from the exo face,14 the C(4)
proton has an endo orientation and is shielded both by
the electrophile skeleton and the pentaammineosmium
framework. Whereas alcohols readily deprotonate the
exposed exo C(4) proton of the parent 4H-anisolium
complex (even at -40 °C),2b the 4H-anisolium intermedi-
ates for the reactions shown in Table 4 resist rearoma-
tization even though an alcohol is the byproduct of the
acetal addition. As a result, multiple alkylations are
completely avoided.
The high C(4) regioselectivity observed for the electro-
philic addition to the parent anisole complex is also likely
the result of both kinetic and thermodynamic factors. Our
investigation of η2-phenol complexes revealed a thermo-
dynamic preference for the 2,3-η2-2,5-cyclohexadienone
tautomer over its 2,3-η2-2,4-cyclohexadienone isomer,
possibly due to the conjugation in the uncoordinated
portion of the ring π-system. If this relationship holds
for the anisolium systems as well, the addition to C(4)
could be rationalized on thermodynamic grounds. Also
deserving consideration, however, is the steric influence
of the methoxy substituent. Either a 2H- or 4H-aniso-
lium system requires that the methoxy group lie in the
plane of the arene. Molecular models show a steric
interaction of this methyl group and the pentaammine-
osmium framework unless the oxygen substituent adapts
an anti orientation with respect to the metal, and this
arrangement would interfere with the approach of an
electrophile to C(2) (Figure 5). Consider that while both
3-methyl- and 4-methylanisole complexes have substitu-
tion half-lives of several days at 20 °C in CH3CN, the
Previous investigations of phenol11 and aniline12 com-
plexes of pentaammineosmium(II) reveal two important
mechanisms for the stabilization of 4H-arene and are-
nium complexes that prevent the possibility of multiple
(7) For a review of rearrangements of alkylating agents and alkyl
substituents, see reference 1, Chapters 2 and 8 and references therein.
(8) Nagaoka, T.; Berinstain, D; Griller, A. B.; Wayner, D. D. M. J .
Org. Chem. 1990, 55, 3707.
(9) This would correspond to a pKa of about -8 in water for the
osmium(II) complex.
(10) Winemiller, M. D.; Kopach, M. E.; Harman, W. D. Submitted
for publication.
(11) (a) Kopach, M. E.; Hipple, W. G.; Harman, W. D. J . Am. Chem.
Soc. 1992, 114, 1737. (b) Kopach, M. E.; Harman, W. D. J . Am. Chem.
Soc. 1994, 116, 6581.
(12) Kolis, S. P.; Gonzalez, J .; Bright, L. M.; Harman, W. D.
Organometallics 1996, 15, 245.
(13) The pKa for the complex [Os(NH3)5(η2-4H-anisolium)]2+ has been
determined to be -3.6 ( 1 whereas that for acetonitrililium cation is
-10. See reference 10.
(14) We have observed electrophilic addition reactions to aromatic
rings of pentaammineosmium(II) complexes for phenols, anilines,
pyrroles, furans, and napththalenes, and in all cases encountered, the
electrophile adds to the exo face of the ring.

Osmium-Promoted Electrophilic Substitution of Anisoles
J . Org. Chem., Vol. 62, No. 1, 1997 135
F igu r e 7. A comparison of methods for the C(4) alkylation of
a substituted arene (Y ) electron donor group; E ) carbon
electrophile).
F igu r e 6. Reactivity of a C(2)-substituted η2-anisole complex
with methyl vinyl ketone.
The osmium-promoted electrophilic substitution of
arenes (Tables 2-4) is complementary to the chemistry
of aryl cuprates17 or arylboronic acids18 as these strategies
all involve C-C coupling of a nucleophilic arene (Figure
7). Using the described osmium methodology, the active
nucleophile may be directly prepared from the desired
anisole in a single step from Os(NH3)5(OTf)3 under
neutral conditions, without the need of obtaining the
appropriately halogenated arene precursor. Complex-
ation of the arene may be carried out in the presence of
esters, amides, silyl ethers and other common protecting
groups as well as unmasked alcohols or tertiary amines,
and may even be achieved in water or methanol with as
little as 1 equiv of the desired ligand.19 Electrophilic
addition at C(4) is generally accomplished in good yield
even for cases in which a quaternary carbon is formed
(e.g. 9, 24, 25), or when the anisole bears an adjacent
substituent (e.g. CH3, CF3, OCH3 at C(3)). Finally,
substituted anisoles may be recovered and their anisole
precursor regenerated in a single step (Figure 3).
2-methylanisole derivative has a half-life in solution of
∼15 min. Presumably a steric interaction of the methoxy
substituent with the C(2) methyl group forces the meth-
oxy group to adopt a conformation in which it interferes
with the pentaammineosmium(II) framework. The net
result of this is a destabilization of the complex.
Consistent with the observation that the methoxy
group does not prefer being coplanar with a substituent
at C(2), the 2-methylanisole complex does not react in
the same fashion as other 3- or 4-substituted anisole
complexes (Figure 6). Rather, upon subjecting the 2-
methylanisole complex and MVK to the usual electro-
philic addition conditions, a dark green (rather than the
usual dark purple) color is observed. Subsequent de-
complexation and isolation of the organic compound
reveals that the anisole has reacted at the unsubstituted
ortho-position to yield a 1,2,3-trisubstituted arene.15 This
addition is likely accomplished by the metal center
undergoing a rapid linkage isomerization to the C(4)-
C(5) double bond, followed by electrophilic addition to
C(6). This behavior is consistent with behavior of arene
complexes that do not contain an electron-releasing
substituent (e.g. benzene, toluene) and is the focus of
continued studies in these laboratories.
Con clu sion s
Coordination of the pentaammineosmium(II) metal
center to various anisoles dramatically increases the
nucleophilicity of the arene. Reactions occur with a wide
variety of carbon electrophiles in the presence of acidic
acetonitrile at -40 °C to form characterizable 4H-
anisolium intermediates. Upon deprotonation and de-
complexation, the 4-substituted anisole is returned in
overall yields typically greater than 80%.20
The unusually stable nature of the 4H-anisolium
intermediate deserves further comment. As mentioned
above, when C(4) is a quaternary carbon (e.g. 44) or when
C(3) is substituted with a methoxy group (Table 3), the
4H-arenium complex is stable enough to be isolated as
its triflate salt. Remarkably, these 4H-anisolium com-
plexes are moderately stable toward hydrolysis, even in
aqueous solution at 20 °C, and this property is likely a
direct result of the metal π-backbonding. For the C(3)-
substituted 4H-anisolium complex 19, the system is so
stable that neither hydrolysis (80 °C in water!) nor
deprotonation at C(4) (amine bases) has been observed.
For more typical 4H-anisolium complexes, however, the
arene is sufficiently electrophilic that, in addition to
hydrolysis and deprotonation, nucleophilies react at
either C(1) or C(3) thus constituting a general synthetic
approach to nonaromatic ring systems.16
Exp er im en ta l Section 21
Gen er a l P r oced u r e for th e Syn th esis of η2-An isole
Com p lexes. (NH3)5Os(OTf)3 (2.0 g, 2.77 mmol) is slurried in
∼2.0 g of DMA, and ∼10 equiv of the desired anisole ligand
(17) For a good review of ayrlcuprates used in conjugate addition
reactions see Lipshutz, B. H.; Sengupta, S. Organic Reactions; Paquette,
L. A., Ed.; J ohn Wiley and Sons: New York, 1992; Vol. 41.
(18) See for example Cho, C. S.; Motofusa, S.; Ohe, K.; Uemura, S.
J . Org. Chem. 1995, 60, 883.
(19) Call, J . T.; Hughes, K. A.; Harman, W. D.; Finn, M. G. Inorg.
Chem. 1993, 32, 2123.
(20) As
a result of a reviewer’s concern over the cost of the
pentaammineosmium(II) reagent, we wish to disclose that OsO4 may
be purchased at an economical price (Colonial Metals) and may be
converted to Os(NH3)5(OTf)3 in 98% overall yield (see reference 1c).
Using these procedures, the cost of any of the final organic products
presented in Table 5 falls in the range of $30-35/g. This reflects the
cost of osmium over the entire six-step process (taking into account
yields) and assumes no recovery of the metal.
(21) Please see supporting information for full characterization data
for all compounds. For full description of general experimental details,
please see ref 11b.
(15) This compound has been characterized by NMR: 1H NMR
(CDCl3, 300 MHz): δ 6.99 (m, 3H), 3.73 (s, 3H), 2.88 (m, 2H), 2.77 (m,
2H), 2.29 (s, 3H), 2.15 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 208.3 (C),
156.8 (C), 133.9 (C), 131.2 (C), 129.6 (CH), 127.8 (CH), 124.2 (CH),
60.5 (CH3), 44.7 (CH2), 30.2 (CH3), 24.7 (CH2), 16.4 (CH3).
(16) Kopach, M. E.; Kolis, S. P.; Liu, R.; Harman, W. D. Manuscript
in preparation.

136 J . Org. Chem., Vol. 62, No. 1, 1997
Kolis et al.
and activated magnesium (1.0 g) are added. The heteroge-
neous reaction mixture is allowed to stir for ∼1 h, and the
solution is filtered through a fritted glass funnel into ∼400
mL of a 1:1 Et2O/CH2Cl2 solution. The resulting slurry is
filtered through a separate fritted glass funnel, and the
resulting tan or yellow solids are isolated typically in >95%
yield.
(C), 93.1 (CH), 62.0 (CH3), 60.4 (CH3), 53.7 (CH), 44.8 (CH),
44.7 (CH), 38.7 (CH2), 29.8 (CH3), 29.7 (CH2). Cyclic voltam-
metry: Ep,a ) 1.29 V. Anal. Calcd for C15H31N5O12S3F9Os: C,
19.36%; H, 3.36%; N, 7.52%. Found: C, 19.08%; H, 3.24%; N,
7.45%.
[O s (N H 3 )5 (4-(1-E t h o x y e t h a n e )-η2 -5â,6â-a n is o le )]-
(OTf)2 (23): 1.0 equiv of acetaldehyde diethylacetal, 2.5 equiv
of HOTf. Yield: 92%. 1H NMR revealed predominantly one
diastereomer. 1H NMR (d6-acetone): δ 6.53 (dd, J ) 8.4 Hz,
2.1 Hz, 1H), 5.53 (dd, J ) 8.4 Hz, 2.1 Hz, 1H), 5.47 (dd, J )
8.4 Hz, 2.1 Hz, 1H), 5.09 (dd, J ) 8.4 Hz, 2.1 Hz, 1H), 4.71 (br
s, 3H), 4.30 (q, J ) 6.6 Hz, 1H), 3.69 (s, 3H), 3.55 (br s, 12H),
3.40-3.70 (m, 2H), 1.43 (d, J ) 6.6 Hz, 3H), 1.21 (t, J ) 7.2
Hz, 3H). 13C NMR (d6-acetone): δ 170.8 (C), 139.9 (C), 121.0
(CH), 93.2 (CH), 80.5 (CH), 64.3 (CH2), 58.5 (CH), 56.7 (CH),
55.4(CH3), 19.2 (CH3), 15.6 (CH3). Cyclic voltammetry: Ep,a
) 0.40 V.
Gen er a l P r oced u r e for th e Decom p lexa tion of Ar en e
Com p lexes. Meth od A. The desired arene complex (200 mg)
is dissolved in CH3CN (3-5 mL) and is heated in a sealed tube
at 80 °C for ∼1 h. The resulting solution is allowed to cool
and is precipitated in ether. The inorganic salts are filtered
off, and the solvent removed in vacuo to provide the desired
products. The crude products were purified (10:1 hexanes/
ether, SiO2) and subjected to a silica plug before elemental
analysis. Meth od B: The desired anisole complex (200 mg)
is dissolved in acetone or acetonitrile (2-5 g) and treated with
∼1 equiv of an oxidant (DDQ, Ag+, O2) and the inorganic salts
are separated by precipitation in ether and filtration. The
resulting ether solution is concentrated, and the organic
compounds are purified by column chromatography (SiO2)
using 10:1 petroleum ether/ether as the elution solvent or prep
TLC (see supporting information).
[Os(NH3)5(2-Meth yl-η2-5â,6â-a n isole)](OTf)2 (2). Yield:
94%. 1H NMR at 25 °C revealed a fluxional metal complex.
1H NMR (CD3CN/-40 °C): δ 6.85 (t, 1H, J ) 6.3 Hz), 6.13 (d,
1H, J ) 8.3 Hz), 4.92 (t, 1H, J ) 6.0 Hz), 4.72 (d, 1H, J ) 6.0
Hz), 3.97 (br s, 3H), 3.61 (s, 3H), 2.77 (br s, 12 H), 2.02 (s,
3H). 13C NMR (CD3CN/-40 °C): δ 154.4 (C), 135.5 (CH), 125.7
(CH), 103.8 (C), 61.3 (CH), 56.6 (CH), 54.0 (CH3), 16.2 (CH3).
Cyclic voltammetry: Ep,a ) 0.45 V. This compound was
purified as its tetraphenylborate salt via ion-exchange chro-
matography. Anal. Calcd for C56H65ON5B2Os‚H2O: C, 63.82%;
H, 6.41%; N, 6.61%. Found: C, 63.70%; H, 6.42%; N, 6.51%.
[Os(NH3)5(3-Meth yl-η2-5â,6â-a n isole)](OTf)2 (3). Yield:
93%. 1H NMR (CD3CN): δ 6.31 (d, 1H, J ) 8.1 Hz), 5.60 (s,
1H), 5.00 (t, 1H), 4.74 (d, 1H, J ) 8.1 Hz) 4.05 (br s, 3H), 3.65
(s, 3H), 2.90 (br s, 12 H), 2.18 (s, 3H). 13C NMR (CD3CN): δ
168.5 (C), 132.0 (C), 120.2 (CH), 96.4 (CH), 62.0 (CH), 54.8
(CH3), 54.1 (CH), 20.5 (CH3). Cyclic voltammetry: Ep,a ) 0.35
V. Anal Calcd for C10H25N5O7S2F6Os: C, 17.27%; H, 3.62%;
N, 10.00%. Found: C, 17.52%; H, 3.58%; N, 9.64%.
Gen er a l P r oced u r e for Electr op h ilic Su bstitu tion
Rea ction s. The desired anisole complex (1-4; 60-70 mg) is
dissolved in acetonitrile (0.5-1.0 g), the electrophile (1-2
equiv) is added, and the solution is cooled to -40 °C. Cold
triflic acid (2-3 equiv) in acetonitrile (0.5 g) is added, and the
reaction solution immediately turns purple. After 20-30 min,
an excess of a tertiary amine base (pyridine, 2,6-lutidine) is
added, and the solution changes color to amber. The solution
is precipitated into a stirring 1:1 Et2O/CH2Cl2 solution, and
the resulting slurry filtered and the solid dried in vacuo to
yield the substituted anisole complexes. The purity and yields
of the individual reactions are highly dependent upon the
concentration of electrophile and acid used, and the individual
amounts are given before the spectroscopic data for each
compound.
4-(4-Meth oxyp h en yl)p en ta n -2-on e (30). Yield: 93%.
1H-NMR (CDCl3): δ 7.13 (d, J ) 8.4 Hz, 2H), 6.83 (d, J ) 8.4
Hz, 2H), 3.77 (s, 3H), 3.20-3.32 (m, 1H), 2.58-2.76 (m, 2H),
2.05 (s, 3H), 1.23 (d, J ) 6.9 Hz, 3H). 13C NMR (CDCl3): δ
207.9 (C), 157.8 (C), 138.1 (C), 127.5 (CH), 113.7 (CH), 55.1
(CH3), 52.1 (CH2), 34.6 (CH), 30.5 (CH3), 22.1 (CH3).
1-Met h oxy-1-(4-m et h oxyp h en yl)cyclop en t a n e
(42).
Yield: 95%. 1H NMR (CDCl3): δ 7.33 (d, 2 H, J ) 9.0 Hz,
H-C2,6), 6.88 (d, 2 H, J ) 9.0 Hz, H-C3,5), 3.81 (s, 3 H, OCH3),
2.94 (s, 3 H, OCH3), 2.10-2.20 (m, 2 H), 1.75-1.92 (m, 6 H);
13C NMR (CDCl3): δ 158.50 (C), 135.42 (C), 127.86 (CH),
113.31 (CH), 87.91 (C), 55.19 (CH3), 50.37 (CH3), 36.49 (CH2),
23.01 (CH2). Anal. Calcd for C13H18O2: C, 75.69%, H, 8.79%;
Found: C, 75.28%, H, 9.11%. Yield: 95%.
[Os(NH3)5(4-(3-Oxo-bu tyl)-η2-5â,6â-a n isole)](OTf)2 (7):
2.0 equiv of MVK, 1.1 equiv of HOTf. Yield: 96%. 1H NMR
(CD3CN): δ 6.11 (d, 1H, J ) 6.9 Hz), 5.45 (d, 1H, J ) 6.9 Hz),
5.10 (d, 1H, J ) 7.8 Hz), 4.87 (d, 1H, J ) 7.8 Hz), 4.11 (br s,
3H), 3.66 (s, 3H), 3.00 (br s, 12 H), 2.20-3.20 (m, 4H), 2.08 (s,
3H). 13C NMR (CD3CN): δ 210.0 (C), 165.6 (C), 137.8 (C),
113.8 (CH), 91.9 (CH), 61.3 (CH), 54.8 (CH), 54.4 (CH3), 40.2
(CH2), 29.2 (CH3), 28.4 (CH2). Cyclic voltammetry: Ep,a ) 0.43
V. This compound was purified as its tetraphenylborate salt
Ack n ow led gm en t is made to the Camille and Henry
Dreyfus Foundation, the National Science Foundation
(CHE-9212008 and the NYI program), the Alfred P.
Sloan Foundation, and Colonial Metals Inc. (Elkton,
MD; OsO4) for their generous support of this work.
via ion-exchange chromatography. Anal. Calcd for C59H69
-
O2N5B2Os‚2H2O: C, 62.82%; H, 6.52%; N, 6.21%. Found: C,
62.53%; H, 6.42%; N, 6.26%.
[Os(NH 3)5(3-Me t h oxy-4r-(3-oxob u t yl)-4â-H -η2-5â,6â-
a n isoliu m )](OTf)3 (19). η2-3-Methoxy-4H-anisolium (5H, 120
mg, 0.138 mmol) was dissolved in CH3CN (1.4 g), and MVK
(12.5 mg, 0.178 mmol) was added. After 15 min, addition to
ether (40 mL) gave a midnight blue precipitate (122 mg, 94%)
which was collected, washed with ether, and dried in vacuo.
1H NMR (CD3CN): δ 5.98 (s, 1H), 5.08 (d, 1H, J ) 7.5 Hz),
5.01 (d, 1H, J ) 7.5 Hz), 4.81 (br s, 3H), 4.26 (s, 3H), 4.06 (s,
3H), 3.42 (br s, 12 H), 2.40-2.90 (m, 4H), 2.21 (s, 3H). 2.07
(m, 1H). 13C NMR (CD3CN): δ 208.9 (CO), 204.9 (CO), 193.9
Su p p or tin g In for m a tion Ava ila ble: Detailed synthesis
and characterization for all compounds presented herein (10
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O961983E