Mechanistic Insights into Rhenium-Catalyzed Regioselective C-Alkenylation of Phenols with Internal Alkynes

Article abstract of DOI:10.1002/chem.201903910

A (μ-aryloxo)rhenium complex was isolated and confirmed as a key precatalyst for rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes. The reaction exclusively provided ortho-alkenylphenols; the formation of para or multiply alkenylated phenols and hydrophenoxylation (O-alkenylation) products was not observed. Several mechanistic experiments excluded a classical Friedel–Crafts-type mechanism, leading to the proposed phenolic hydroxyl group assisted electrophilic alkenylation as the most plausible reaction mechanism. For this purpose, the use of rhenium, a metal between the early and late transition metals in the periodic table, was key for the activation of both the soft carbon–carbon triple bond of the alkyne and the hard oxygen atom of the phenol, at the same time. ortho-Selective alkenylation with allenes also provided the corresponding adducts with a substitution pattern different from that obtained by the addition reaction with alkynes.

Full text of DOI:10.1002/chem.201903910

A Journal of
Accepted Article
Title: Mechanistic Insights into Rhenium-Catalyzed Regioselective C-
Alkenylation of Phenols with Internal Alkynes
Authors: Masahito Murai, Masaki Yamamoto, and Kazuhiko Takai
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201903910
Link to VoR: http://dx.doi.org/10.1002/chem.201903910
Supported by

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
Mechanistic Insights into Rhenium-Catalyzed Regioselective C-
Alkenylation of Phenols with Internal Alkynes
Masahito Murai,*[a,b] Masaki Yamamoto,[a] and Kazuhiko Takai*[a]
Abstract: A (-aryloxo)rhenium complex was isolated and
confirmed as a key precatalyst for rhenium-catalyzed ortho-
alkenylation (C-alkenylation) of unprotected phenols with
alkynes. The reaction exclusively provided ortho-alkenylphenols,
and formation of para- or multiply alkenylated phenols and
further study could provide valuable new insights into the design
of more efficient rhenium-catalyzed transformations.[6]
Phenol units are important and fundamental structural motifs
found in many natural products, biologically active compounds,
and pharmaceuticals.[7] Thus, regioselective functionalization of
hydrophenoxylation (O-alkenylation) products were not observed. unprotected phenol derivatives is
a fundamental, but still
Several mechanistic experiments excluded a classical Friedel-
Crafts type mechanism, leading to the proposed phenolic
hydroxyl group-assisted electrophilic alkenylation as the most
plausible reaction mechanism. For this purpose, the use of
rhenium, a metal between the early and late transition metals in
the periodic table, was key for the activation of both the soft
carboncarbon triple bond of the alkyne and the hard oxygen
atom of the phenol at the same time. ortho-Selective
alkenylation with allenes also provided the corresponding
adducts with a substitution pattern different from that obtained
by the addition reaction with alkynes.
nontrivial research subject due to the ready availability and
synthetic versatility of phenol derivatives. Chelation-assisted
functionalization by heteroatom-containing directing groups
introduced on the phenolic hydroxy group is one promising
strategy.[8] However, this approach requires preactivation of
starting molecules and additives (bases, ligands). Thus,
development of an operationally simple and direct regioselective
C-alkenylation method for unprotected phenols remains
challenging. Unfortunately, sporadic studies on the direct C-
alkenylation of unprotected phenol derivatives (CC bond
forming alkenylation) via addition to alkynes have been
reported.[9] However, three main obstacles exist for alkenylation
of unprotected phenols. First, an unprotected phenolic hydroxy
group has an acidic proton, and usually acts as an oxygen-
based nucleophile to provide O-alkenylated adducts via
hydrophenoxylation (CO bond formation).[10] Although the
reaction course could be changed by interaction of phenol and
alkyne in the transition state, the directing ability of the phenolic
hydroxy group in well-established late transition metal-catalyzed
CH bond functionalization appears to be relatively weak.[11]
Second, controlling the regiochemistry of the addition reaction is
difficult as indicated by the inherent strong ortho/para-orientation
of a phenolic hydroxy group. This lack of selectivity has been
suppressed by the introduction of substituents on the phenol
rings. Third, some phenol derivatives are sensitive toward
oxidants and acids, and require mild conditions for their
transformations. Since the pioneering work by Yamaguchi and
coworkers on ortho-selective alkenylation with terminal alkynes
using a stoichiometric amount of SnCl4 or GaCl3,[12] several
regioselective C-alkenylation have been reported. However,
existing intermolecular catalytic addition protocols are suitable
only for electronically activated alkynoates and terminal
acetylenes.[13]
Introduction
Catalytic functionalization of unactivated CH bonds is
a
straightforward and atom-economical approach to target
molecules without requiring tedious prefunctionalization of the
starting materials.[1] While late transition metal complexes
containing elements such as ruthenium, rhodium, and palladium
etc, are frequently used as catalysts, what we focused on as an
attractive new candidate was a rhenium, a group 7 metal located
in the middle of early and late transition metals in the periodic
table.[2] In particular, rhenium carbonyl complexes turned out to
be very reactive, and many catalytic transformations based on
the cleavage of not only CH bonds but also CC and BH
bonds have been achieved.[2,3] Despite their unique catalytic
performance, understanding the origin of unique reactivity based
on the isolation of catalytically active rhenium carbonyl species
has remained elusive, which is surprising because many reports
on the photophysical properties and wire-performance of
structurally
well-characterized
rhenium-based
functional
molecules having bipyridyl or cyclopentadienyl ligands have
been published.[4] Although Wang and coworkers recently
reported the isolation and characterization of a catalytically
active five-membered ring rhenacycle intermediate for
[4+1]annulation reaction of azobenzenes and aldehydes,[5]
Very recently, we found that the dirhenium decacarbonyl,
Re2(CO)10, could serve as an efficient catalyst for intermolecular
ortho-selective C-alkenylation of phenols with internal alkynes
(eq 1).[14] The reaction did not require external ligands or
additives to provide functionalized alkenylphenols with high
atom-efficiency. Elucidation of the reaction mechanism is crucial
for expanding the synthetic diversification of phenol chemistry.
In an effort to clarify the origin of this unique catalytic
performance of transition metal complexes,[15] the present study
[a]
[b]
Prof. Dr. M. Murai, M. Yamamoto, Prof. Dr. K. Takai
Division of Applied Chemistry, Graduate School of Natural Science
and Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku,
Okayama 700-8530, Japan
Prof. Dr. M. Murai
describes results from
a mechanistic investigation of the
Department of Chemistry, Graduate School of Science, Nagoya
University, Furo, Chikusa, Nagoya 464-8602, Japan
E-mail: masahito.murai@chem.nagoya-u.ac.jp
ktakai@cc.okayama-u.ac.jp
regioselective alkenylation of phenols based on the isolation of a
reactive rhenium precatalyst.[16]
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
Alkenylation was also applied to biologically active estron. The
reaction proceeded selectively at the least sterically hindered
position to afford 1c in 50% yield without affecting the
stereogenic center or carbonyl group. This result demonstrates
the potential of the current alkenylation for late-stage
modification of biologically active molecules.[19] Thiophenol was
also applicable as a substrate, and alkenylation proceeded even
with electronically unactivated 6-dodecyne to give the expected
alkenylation product 1d in 60% yield.
Results and Discussion
Regioselective Catalytic Alkenylation of Phenols with
Internal Alkynes: Our recent work revealed that Re2(CO)10 and
[HRe(CO)4]n effectively promoted ortho-alkenylation leading to
1a, whereas [ReBr(CO)3(thf)]2 and ReBr(CO)5 did not possess
any catalytic activity with the recovery of phenol intact (Table
1).[14] The major stereoisomer had the Z configuration, and
formation of regioisomers was not observed. As expected from
the previous work,[10] several catalysts, including Ru3(CO)12,
promoted hydrophenoxylation leading to 2 and 2ꞌ selectively
without formation of 1a (eq 2). Neither 2 nor 2ꞌ was converted to
1a upon treatment with Re2(CO)10, indicating that the current
ortho-alkenylation leading to 1a did not proceed via typical
hydrophenoxylation. Other metal complexes, such as Cr(CO)6,
Mo(CO)6, W(CO)6, Mn2(CO)10, ReCl5, Fe2(CO)9, Ir4(CO)12,
AgOTf, AuCl3, and GaCl3 did not show any catalytic activity and
the phenol was recovered intact. Chlorobenzene gave the best
result among the solvents tested, and alkenylation did not occur
in polar solvents (DMF, THF, and MeCN).[17]
Table 2. Rhenium-catalyzed ortho-selective alkenylation of phenols
and thiophenol (see ref. 14 for the other scope)
Combination of this regioselective C-alkenylation with DDQ-
promoted dehydrogenative cyclization[20] allowed rapid
construction of a benzofuran skeleton (eq 3). Note that synthesis
of 3-alkyl-2-arylbenzofurans was reported by Sahoo et al. via
[3+2]cycloaddition reaction of phenol with alkylarylacetylenes,
Table 1. Effects of catalyst
[10b]
and their isomers, 2-alkyl-3-arylbenzofurans, could be
obtained selectively in the current protocol. Overall, addition of
phenols to alkynes can provide
a divergent approach to
variously functionalized heterocycles, with the potential to be
useful in the pharmaceutical industry.
Isolation, Structural Characterization, and Reactivity of (-
Aryloxo)rhenium Intermediates:
A
mechanistic study
commenced with obtaining insights into the unique reactivity of
Re2(CO)10. Treatment of 2-naphthol with Re2(CO)10 in
chlorobenzene at 160 °C for 16 h followed by the addition of
THF produced the (-naphthoxo)rhenium complex, [Re2(-
ONaph)3(CO)6][Re(CO)3(thf)3] (4), as a colorless powder (eq
3).[21] The structure of 4 was unambiguously determined by
single crystal X-ray diffraction (Figure 1). The ORTEP drawing
confirmed a dinuclear rhenium structure bridged by three aryloxo
ligands. Elemental analysis also supported this proposed
structural formula.
In addition to the scope demonstrated in the recent our
report,[14] alkenylation with 1-aryl-1-propyne containing
a
cyclopropyl group on the benzene ring also provided the
corresponding adduct 1b in 83% yield, without the detection of
any cyclopropane ring-opening adducts (Table 2).[18]
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
The reactivity of 4 was confirmed through the following control
experiments. First, stoichiometric reaction of the isolated 4 with
1-phenyl-1-propyne did not provide 1-alkenyl-2-naphthol 1e,
suggesting that the naphthoxo ligand on a rhenium center of 4
was not reactive toward alkenylation (eq 4). In contrast, 4
showed the excellent catalytic performance in alkenylation with
2-naphthol (eq 5). These results indicate that alkenylation
occurred on a rhenium center of a (-naphthoxo)rhenium
species with a bridged naphthoxo ligand intact. The catalytic
performance of 4 was high enough to promote alkenylation even
at 120 °C, while formation of alkenylated product 1e was not
observed when Re2(CO)10 was employed as a catalyst at this
temperature (eq 6). The reaction profile for the alkenylation of 2-
1
naphthol was monitored at 160 °C by H NMR, which revealed
that the induction period and sigmoidal reaction profile observed
with Re2(CO)10, were not present with 4 (Figure S1 in SI). This
appears to be consistent with the in situ formation of 4 from
Re2(CO)10 and 2-naphthol in THF.
Figure 1. X-ray crystal structure of [Re2(-ONaph)3
(CO)6][Re(CO)3(thf)3] 4. Hydrogen atoms are omitted for clarity,
and thermal ellipsoids are drawn at the 50% probability level.
Blue: Re, red: O, black: C. See Table S1 in SI for details.
Re2(CO)10 was reported to convert into tetrameric [Re(-
OH)(CO)3]4 by reaction with H2O under photoirradiation via the
formation
of
trimeric
[HRe(CO)4]3.[22]
Thus,
[Re2(-
ONaph)3(CO)6][Re(CO)3(thf)3] (4) is thought to form via
a
mechanism similar to that as shown in Scheme 1. Monitoring the
reaction mixture by 1H NMR spectra confirmed that the
appearance of the characteristic signal corresponded to a
bridging hydride ligand of [HRe(CO)4]3 at -17.3 ppm in toluene-
d8.[23] This peak gradually disappeared, and the isolable complex
4 was finally formed upon treatment of THF.
Scheme 1. Proposed mechanism for the formation of (-
naphthoxo)rhenium complex 4 (R = 2-Naph)
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
Second, crossover reaction of phenol with 1-phenyl-1-propyne
in the presence of 20 mol%-Re of 4 provided 1e in 89% yield
(based on the number of rhenium units of 4) along with 1a in
80% yield (eq 7). Although the original naphthoxo ligand on a
regioselective C-alkenylation are illustrated in Scheme 2, which
shows the reaction of phenol with 1-phenyl-1-propyne.
Considering the results obtained from eqs 4 and 5, “Re” in
Scheme 2 represents “Re(OPh)(CO)3”. In Path A, nucleophilic
attack of the phenol to alkyne occurs regioselectively at the
ortho-position of the phenolic hydroxy group, which is assisted
by coordination of both phenol and alkyne to a rhenium center in
intermediate A. Because rhenium is located in the middle of
early and late transition metals in the periodic table, we believe
that they can possess both soft and hard Lewis acidity. Thus,
low-valent rhenium carbonyl complexes could interact with both
the soft carboncarbon triple bonds of alkynes and the hard
oxygen atom of phenols at the same time, promoting the
addition reaction. Another possible mechanism involves
carborhenation or hydrorhenation of arylrhenium species C
followed by reductive elimination to regenerate the rhenium
active species (Path B). Finally, Path C involves hydrogen atom
transfer from the arylrhenium species C to the alkyne followed
by radical recombination and reductive elimination. Path C was
proposed based on a recent mechanistic study on rhenium-
catalyzed alkylation of phenols with alkenes.[16c]
rhenium center of
4 was unreactive, it could be easily
interchanged with free phenol. This interchange released free 2-
naphthol, which then was converted to 1e by alkenylation
promoted by the corresponding (phenoxo)rhenium species.
Third, the phenolic hydroxyl group was key to control the
reactivity and selectivity of the addition reaction. The use of
anisole, acetanilide, and ethyl benzoate, which are common
substrates for regioselective functionalization based on CH
bond activation,[24] in place of phenol did not afford any
alkenylated products with recovery of these aromatic
compounds (eq 8). Fourth, the current alkenylation occurred by
direct addition to the triple bond of alkynes, because reaction
with phenylallene, which could be potentially generated by
isomerization of 1-phenyl-1-propyne, did not produce any 1e (eq
9).
A roughly linear relation between the yield of 1e and time was
observed during the initial stage of the reaction at 160 °C (Figure
2(a)), and the initial rate of alkenylation was one third-order-
dependent on catalyst loading (Figure 2(b)). This order
dependency indicates that alkenylation was promoted by the
mononuclear rhenium species, such as [ReI(OPh)(CO)3(thf)],
generated prior to the turnover limiting transition state.
Scheme 2. Possible reaction mechanism for C-alkenylation of
phenol (Re = Re(OPh)(CO)3)
Reversible H/D exchange observed upon treatment of phenol-
d5 with Re2(CO)10 under standard conditions suggested the
formation of arylrhenium species C (eq 10 and Figure S2 in SI).
Considering the number of potentially cleavable CH bonds (2
for ortho positions and 1 for the para position), the exchange
rate of deuterium atoms at the para position was greater than
that at the ortho position after 30 min. However, alkenylation
products at the para position were not observed with most of
alkynes in the current alkenylation (see eq 15 for an exception
using sterically hindered (phenylethynyl)silane). These
experimental results can be rationalized by the following three
explanations. (1) Reductive elimination to yield para-alkenylated
products did not occur after the reversible insertion of
Figure 2. (a) Reaction profile for alkenylation of 2-naphthol in PhCl
at 160 °C with 1 mol% (〇), 2 mol% (●), 6 mol% (●), 10 mol% (●),
and 20 mol% (●) of 4. (b) Plot of initial rate for the formation of 1e
vs concentration of 4.
Reaction Mechanism and Reactivity of (-Aryloxo)rhenium
Intermediates: Three possible mechanisms for the current
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
arylrhenium species into the triple bond of the alkyne. (2)
Arylrhenium species C did not participate in a catalytic cycle of
the ortho-alkenylation reaction. (3) The aforementioned H/D
exchange occurred not via formation of C, but through
nucleophilic attack of the phenol to the phenoxy proton of other
phenol activated by Re2(CO)10 through coordination to the
phenoxy oxygen atom. Either way, Path B can be ruled out as
the reaction mechanism, because the CC bond was reportedly
formed preferentially on the methyl group-substituted alkynyl
carbon by insertion of the ArRe(CO)n bond into the triple bond
of 1-phenyl-1-propyne, resulting in production of the regioisomer
opposite of 1a.[25]
Figure 3. Reaction profile for alkenylation of para-substituted
phenol (X = OMe ●, Me ●, H ●, Cl 〇) with 1-phenyl-1-
propyne at 160 °C with 2.5 mol% of Re2(CO)10.
It is difficult to rule out completely the possibility of a radical
pathway (Path C). The common radical inhibitors, such as
TEMPO and Galvinoxyl free radical, shut down the current
alkenylation, not due to trapping of reactive radical species but
because due to deactivation of reactive phenoxyrhenium
species.[26] This is further supported by results of addition of a
radical scavenger, 9,10-dihydroanthracene, that did not contain
any heteroatoms, and did not result in the inhibition or
disturbance of the alkenylation (eq 11). In addition to these
results, electronic effects of substituents (see Figure 3) and the
stereochemistry of the initial adducts (see Figure 4) indicate that
Path A is more plausible than the radical pathway (Path C) for
the current alkenylation reaction.
This was confirmed by the stereoselectivity profile observed for
alkenylation with 4-chlorophenol depicted in Figure 4. Although
E-1h was obtained selectively at the early stage of the reaction,
the ratio of Z-1h increased with time. The E-1h was thought to
be produced directly by quenching of alkenylrhenium
intermediate B in Scheme 2, while Z-1h was derived from the
rapid and competitive isomerization of E-1h. The rapid
isomerization occurred by heating a pure E-1h (E / Z = >98 / 2)
with Re2(CO)10 to produce a mixture of stereoisomers of 1h (E /
Z = 18 / 82) (eq 12). Note that this isomerization occurred even
without Re2(CO)10. Although rhenium-assisted interconversion
between E- and Z-1h cannot be ruled out, isomerization
proceeded mainly via rapid 1,5-H shift. Thus, these results
support the participation of intermediate B in Path A in the
current regioselective alkenylation. (3) Partial deuterium
incorporation on the alkenyl carbon was observed in alkenylation
with phenol-d5, which can be rationalized by considering the
derhenation process of intermediate B in Scheme 2 by proton on
the oxygen atom or the deuterium on the phenol ring (eq 13). (4)
A value of 1.16 for the parallel kinetic isotope value (kH / kD) was
obtained from two side-by-side reactions of phenol vs phenol-d5
We believe that the chelation-assisted electrophilic
alkenylation mechanism (Path A in Scheme 2), in which the
phenolic hydroxyl group controlled regioselectivity of the addition
reaction as a coordinating directing group,[27] is the most
plausible based on the following four observations. (1) The time-
dependent reaction profile for 4-methoxyphenol, p-cresol, phenol,
and 4-chlorophenol, monitored by 1H NMR, revealed that
alkenylation proceeded most rapidly with electron-rich 4-
methoxyphenol (Figure 3). This reactivity trend is consistent with
an electrophilic aromatic substitution mechanism. The induction
period observed in Figure 3 is consistent with in-situ dissociation
of (-aryloxo)rhenium species, [Re2(-OAr)3(CO)6][Re(CO)3(thf)3],
to the monomeric rhenium carbonyl species, Re(OAr)(CO)3. (2)
Stereoselectivity of the alkenylation changed during the reaction,
and the stereochemistry of the initial alkenylation product was E.
Figure 4. Ratio of E-1h ● and Z-1h ● for alkenylation of 4-
cholorophenol with 1-phenyl-1-propyne at 160 °C with 2.5 mol%
of Re2(CO)10.
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
with 1-phenyl-1-propyne indicating that CH bond cleavage was
not involved in the rate-determining step (eq 14). This is
consistent with Path A, where CH bond cleavage should occur
relatively fast because it regenerates the aromaticity of the
phenol ring.
Regioselective Alkenylation of Phenols with Allenes: As
shown in eq 9, the use of arylallene in place of 1-aryl-1-propyne
did not provide the alkenylated product. However, further study
revealed that 2-naphthol added to the less sterically hindered
double bond of cyclohexylallene to produce 5a (eq 16). Both
isolated 4 and Re2(CO)10 catalyzed this addition reaction. The
central carbon atom of the accumulated double bond of the
allene was selectively attacked by the aromatic ring, which
accompanied by addition of a hydrogen atom to the terminal
carbon atom.[29] Thus, the substitution pattern of the resultant
alkenylated products 5 was opposite to that of 1 obtained from
the addition reaction with alkynes (Figure 4).
As demonstrated in eq 8, the phenolic hydroxyl group plays a
key role in controlling reactivity as well as selectivity for the
current alkenylation of phenols. Different regioselectivity was
observed in the alkenylation with trimethyl(phenylethynyl)silane
(eq 15, Si = SiMe3). In this case, alkenylation occurred mainly at
the para position of the phenolic hydroxyl group to produce 1i’,
probably due to prevention of ortho-alkenylation through steric
repulsion between the bulky silyl groups and the rhenium center.
Figure 4. Comparison of regioselectivity
Alkenylation with cyclooctylallene provided the corresponding
adduct 5b in moderate yield (Table 3). Neither multiply
alkenylated products nor alkenylation at the para position was
Table 3. Rhenium-catalyzed regioselective alkenylation of
(thio)phenols with allenesa
Therefore,
intermolecular
nucleophilic
attack
of
the
phenoxyrhenium species to -alkyne rhenium species might
occur predominantly in this case. Because this intermolecular
attack occurred preferentially at para position of the phenolic
hydroxyl group to minimize the steric repulsion, the para-
alkenylation product 1i’ was obtained as a major compound.
Note that rapid migration of the silyl group from the alkenyl
terminal carbon of the initial adduct to its phenolic hydroxyl
group was observed to yield the overall adduct as a silylether in
this reaction. As expected, para-alkenylated adduct 1j’ was
obtained as the sole product by using (phenylethynyl)silane
containing a bulkier triisopropylsilyl group. This result supports
the participation of intermediate A (see Path A of Scheme 2) in
ortho-selective alkenylation, which was assisted by coordination
of both the phenol and alkyne to a rhenium center.[28]
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
observed. A similar outcome was obtained for the reaction of
benzylallenes, silylallenes, and 1,2-tridecadiene, did not provide
any adducts in reaction with phenol due to their competitive
oligomerization. Thiophenol was also applicable as a substrate,
and the expected 2-alkenylthiophenol 5f was obtained in 74%
yield without hydrothiophenoxylation products. In reaction with
phenol.
4-Methoxyphenol
reacted
smoothly
with
cyclohexylallene to provide 5d, and a potentially coordinating
methoxy group did not disturb the site-selectivity.[24]
Regioselective alkenylation occurred for 5-indanol at the less
sterically hindered ortho position of the phenol ring to provide 5e. thiophenols, even 1,2-tridecadiene gave the corresponding
However, reactivity of allenes was significantly affected by the
substitution pattern, and di- and monosubstituted allenes having
less sterically demanding acyclic alkyl chains, including
adduct 5g in high yield.
ppm, acetone-d6 at 2.05 ppm) as the internal standard. 13C NMR was
recorded with complete proton decoupling and the chemical shifts are
reported relative to CDCl3 at 77.00 ppm or acetone-d6 at 29.84 ppm. The
following abbreviations are used; brs: broad singlet, s: singlet, d: doublet,
t: triplet, q: quartet, m: multiplet. IR spectra were recorded on a
SHIMADZU IRAFFINITY-1 100V J. High-resolution mass spectra
(HRMS) was measured with JEOL JMS-700 MStation FAB-MS. Melting
points were measured on a Yanaco micromelting point apparatus and
are uncorrected.
Conclusions
A mechanistic study of a recently reported rhenium-catalyzed
ortho-selective monoalkenylation of phenols[14] was conducted.
The use of a rhenium carbonyl complex as a catalyst was
essential, and X-ray single crystallographic analysis revealed
that formation of a (-aryloxo)rhenium complex was key for
these unique transformations. This is a rare example of isolation
of reactive rhenium carbonyl precatalysts.[5,6] Several control
experiments revealed that phenolic hydroxyl group-assisted
electrophilic alkenylation is the most plausible as a reaction
mechanism, instead of classic Friedel-Crafts type electrophilic
functionalization (proceeds with ortho- and para-orientation to
yield a mixture of mono- and multiple adducts). Because
rhenium, a group 7 metal located in the middle of early and late
transition metals in the periodic table, low-valent rhenium
carbonyl complexes could activate both soft carboncarbon
triple bonds of an alkyne and hard oxygen atoms of phenol at
the same time, and might promote the current rare class of
addition reactions.
General Procedure for Rhenium-Catalyzed ortho-Selective
Alkenylation of Phenol Derivatives with Alkynes. A flame-dried test
tube was charged with Re2(CO)10 (3.3 mg, 5.0 mol), phenol derivatives
(0.20 mmol), alkynes (0.30 mmol), and chlorobenzene (0.10 mL), and
o
then the resulting mixture was stirred at 160 C for 4 h. The residue was
directly subjected to flash column chromatography on silica gel to afford
the corresponding alkenylated phenols 1.
One-Pot Synthesis of 2-Methyl-3-phenylbenzofuran (3): A flame dried
test tube was charged with Re2(CO)10 (3.3 mg, 5.0 mol), phenol (18.8
mg, 0.20 mmol), 1-phenyl-1-propyne (34.8 mg, 0.30 mmol), and
chlorobenzene (0.10 mL), and then the resulting mixture was stirred at
o
160 oC for 4 h. The reaction mixture was cooled down to 25 C, and 2,3-
Based on successful addition reactions with internal alkynes,
alkenylation with allenes was also demonstrated. Thiophenols
as well as phenols can be used as substrates, and formation of
classic hydrophenoxylation (O-alkenylation) products were never
observed in these reactions. Although high temperatures were
required, these reactions proceeded with readily available
starting materials under neutral conditions without additional
ligands. The synthetic potential of the current alkenylation was
also demonstrated by the concise synthesis of a benzofuran
derivative, which is a basic core of many biologically active
compounds and medicines. These results offer new insights into
the reactivity of phenols, and open up their new potential as a
readily available and inexpensive chemical feedstock.
dichloro-5,6-dicyano-1,4-benzoquinone (24.9 mg, 0.50 mmol) and
chlorobenzene (2.0 mL) were added. After stirring at 120 oC for additional
24 h, the reaction mixture was cooled down to 25 oC, and 2,3-dichloro-
5,6-dicyano-1,4-benzo- quinone (24.9 mg, 0.50 mmol) was added again.
After stirring at 120 oC for additional 24 h, the residue was directly
subjected to flash column chromatography on silica gel with hexane /
EtOAc = 5 / 1 as the eluent to afford 26.2 mg (0.13 mmol, 63% yield) of 3
1
as a colorless oil. H NMR (400 MHz, CDCl3):  2.55 (s, 3H), 7.20-7.29
(m, 2H), 7.35-7.39 (m, 1H), 7.45-7.53 (m, 5H), 7.57-7.59 (m, 1H). The
analytical data match those reported in the literature.[30]
Synthesis of [Re2(ONaph)3(CO)6][Re(CO)3(thf)3] Complex 4.
A
flame-dried Schlenk flask was charged with Re2(CO)10 (326 mg, 0.50
mmol), 2-naphthol (721 mg, 5.0 mmol), and chlorobenzene (1.0 mL), and
then the resulting mixture was stirred at 160 oC for 16 h. The solvent was
removed under reduced pressure, and the residue was dissolved in THF
(3.0 mL) at 25 oC. Precipitation of solid was observed soon, which was
collected, dried under reduced pressure, and recrystallized from THF /
Experimental Section
General Methods. All reactions were carried out in dry solvent under an
argon atmosphere. Chlorobenzene was purchased from Tokyo Chemical
Industry, and was dried by the usual methods, distilled, and degassed
with an argon gas for 20 min before use. Phenol-d5 and Re2(CO)10 were
purchased from Sigma-Aldrich. Unless otherwise noted, other chemicals
obtained from commercial suppliers were used without further purification.
Column chromatography was performed with silica gel 60N (neutral, 40-
50 m) purchased from Kanto Chemical. 1H (400 or 300 MHz) and 13C
o
hexane at -20 C twice to afford 240.0 mg (0.16 mmol, 22% yield) of (-
naphthoxo)rhenium complex 4 as a colorless powder. Although the yield
of 4 was determined to be 66% by 1H NMR analysis of the crude product,
the amount isolated after purification by recrystallization was low due to
1
the difficulty of removing unreacted 2-naphthol completely. H NMR (400
MHz, acetone-d6): 1.77-1.80 (m, 12H), 3.61-3.64 (m, 12H), 7.25 (t, J =
8.4 Hz, 1H), 7.39 (t, J = 6.8 Hz, 1H), 7.62 (dd, J = 2.0 Hz, 9.2 Hz, 1H),
7.69 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H),
7.83 (d, J = 9.2 Hz, 1H). 13C NMR (100 MHz, acetone-d6): 26.2, 68.1,
109.7, 109.8, 119.1, 119.2, 123.7, 127.0, 128.5, 129.4, 130.3, 136.0,
197.1, 197.2. IR (KBr / cm-1): 2960, 2021, 1915, 1888, 1593, 1460, 1246,
(100 MHz) NMR spectra were recorded on
a JEOL JNN-LA400
spectrometer. Proton chemical shifts are reported in ppm based on the
solvent resonance resulting from incomplete deuteration (CDCl3 at 7.26
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
877. Anal. Calcd for (C17H15O5Re)3: C, 42.06; H, 3.11. Found: C, 42.45;
H, 3.15.
Patra, R. Watile, S. Agasti, T. Naveen, D. Maiti, Chem. Commun. 2016,
52, 2027. j) R.-J. Mi, J. Sun, F. E. Kühn, M.-D. Zhou, Z. A. Xu, Chem.
Commun. 2017, 53, 13209.
[9]
For reviews on hydroarylation of arenes with unactivated alkynes, see:
a) R. Manikandan, M. Jeganmohan, Org. Biomol. Chem. 2015, 13,
10420. b) V. P. Boyarskiy, D. S. Ryabukhin, N. A. Bokach, A. V.
Vasilyev, Chem. Rev. 2016, 116, 5894. c) M. Petrini, Chem. Eur. J.
2017, 23, 16115.
Acknowledgements
This work was financially supported by a Grant-in-Aid for
Scientific Research (A) (No. 18H03911 to K.T.) and Scientific
Research (B) (No. 18H03911 to M.M.) from MEXT, Japan.
[10] For intermolecular hydrophenoxylation (CO bond formation) of
unactivated alkynes, see: a) D. H. Camacho, S. Saito, Y. Yamamoto,
Tetrahedron Lett. 2002, 43, 1085. b) M. R. Kuram, M. Bhanuchandra, A.
K. Sahoo, J. Org. Chem. 2010, 75, 2247. c) S. Gaillard, J. Bosson, R. S.
Ramón, P. Nun, A. M. Z. Slawin, S. P. Nolan, Chem. Eur. J. 2010, 16,
13729. d) M. E. Richard, D. V. Fraccica, K. J. Garcia, E. J. Miller, R. M.
Ciccarelli, E. C. Holahan, V. L. Resh, A. Shah, P. M. Findeis, R. A.
Stockland Jr. Beilstein J. Org. Chem. 2013, 9, 2002. e) Y. Oonishi, A.
Gómez-Suárez, A. R. Martin, S. P. Nolan, Angew. Chem. Int. Ed. 2013,
52, 9767. f) M. J. Moure, R. SanMartin, E. Domίnguez, Adv. Synth.
Catal. 2014, 356, 2070. g) A. Gómez-Suárez, Y. Oonishi, A. R. Martin,
S. V. C. Vummaleti, D. J. Nelson, D. B. Cordes, A. M. Z. Slawin, L.
Cavallo, S. P. Nolan, A. Poater, Chem. Eur. J. 2016, 22, 1125. h) F.
Lazreg, S. Guidone, A Gómez-Herrera, F. Nahra, C. S. J. Cazin, Dalton
Trans. 2017, 46, 2439.
Keywords: Phenol • Rhenium • Alkenylation • Regioselective
[1]
a) E. W. Colvin, Silicon Reagents in Organic Synthesis, Academic
Press, London, 1988. b) Z. Rappoport and Y. Apeloig, Chemistry of
Organosilicon Compounds, Wiley-VCH, New York, 2001. c) E. G.
Rochow, Silicon and Silicones, Springer-Verlag, New York, 1987. For
recent reviews, see: a) C.-S. Wang, P. H. Dixneuf, J.-F. Soulꢀ, Chem.
Rev. 2018, 118, 7532. b) P. Gandeepan, L. Ackermann, Chem 2018, 4,
199. c) C. Sambiagio, D. Schönbauer, R. Blieck, T. Dao-Huy, G.
Pototschnig, P. Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-Delord, T.
Besset, B. U. W. Maes, M. Schnürch, Chem. Soc. Rev. 2018, 47, 6603.
d) M. Murai, K. Takai, Synthesis 2019, 51, 40, and references cited
therein.
[11] The variety of catalytic CH bond functionalizations of unprotected
phenol derivatives is limited. 2-Arylphenols were used as substrates in
most of the reactions. See: a) M. Miura, T. Tsuda, T. Satoh, M. Nomura,
Chem. Lett. 1997, 1103. b) Y. Kawamura, T. Satoh, M. Miura, M.
Nomura, Chem. Lett. 1999, 961. c) R. Dorta, A. Togni, Chem. Commun.
2003, 760. d) B. Xiao, T.-J. Gong, Z.-J. Liu, J.-H. Liu, D.-F. Luo, J. Xu, L.
Liu, J. Am. Chem. Soc. 2011, 133, 9250. e) J. Zhao, Y. Wang, Y. He, L.
Liu, Q. Zhu, Org. Lett. 2012, 14, 1078. f) K. Inamoto, J. Kadokawa, Y.
Kondo, Org. Lett. 2013, 15, 3962. g) J. Nan, Z. Zuo, L. Luo, L. Bai, H.
Zheng, Y. Yuan, J. Liu, X. Luan, Y. Wang, J. Am. Chem. Soc. 2013,
135, 17306. h) A. Seoane, N. Casanova, N. Quiñones, J. L.
Mascareñas, M. Gulías, J. Am. Chem. Soc. 2014, 136, 7607. i) Z. Yu, B.
Ma, M. Chen, H.-H. Wu, L. Liu, J. Zhang, J. Am. Chem. Soc. 2014, 136,
6904. j) S. Kujawa, D. Best, D. J. Burns, H. W. Lam, Chem. Eur. J.
2014, 20, 8599. k) C. Zhang, J. Ji, P. Sun, J. Org. Chem. 2014, 79,
3200. l) K. V. N. Esguerra, Y. Fall, L. Petitjean, J.-P. Lumb, J. Am.
Chem. Soc. 2014, 136, 7662. m) A. Seoane, N. Casanova, N.
Quiñones, J. L. Mascareñas, M. Gulías, J. Am. Chem. Soc. 2014, 136,
834. n) A. Libman, H. Shalit, Y. Vainer, S. Narute, S. Kozuch, D. Pappo,
J. Am. Chem. Soc. 2015, 137, 11453. o) M. Salman, Z.-Q. Zhu, Z.-Z.
Huang, Org. Lett. 2016, 18, 1526. p) J.-L. Dai, N.-Q. Shao, J. Zhang,
R.-P. Jia, D.-H. Wang, J. Am. Chem. Soc. 2017, 139, 12390.
[2]
[3]
For reviews, see: a) Y. Kuninobu, K. Takai, K. Chem. Rev. 2011, 111,
1938. b) G. Mao, Q. Huang, C. Wang, Eur. J. Org. Chem. 2017, 3549.
For recent examples, see: a) M. Murai, M. Nakamura, K. Takai, Org.
Lett. 2014, 16, 5784. b) S. Hori, M. Murai, K. J. Am. Chem. Soc.
2015, 137, 1452. c) M. Murai, T. Omura, Y. Kuninobu, K. Takai,
Chem. Commun. 2015, 51, 4583. d) T. Nakagiri, M. Murai, K. Takai,
Org. Lett. 2015, 17, 3346. e) M. Murai, E. Uemura, S. Hori, K. Takai,
Angew. Chem. Int. Ed. 2017, 56, 5862. f) M. Murai, E. Uemura, K.
Takai, ACS Catal. 2018, 8, 5454. g) M. Murai, T. Ogita, K. Takai,
Chem. Commun. 2019, 55, 2332.
[4]
a) V. W. W. Yam, C. H. Tao, Carbon-Rich Compounds: From Molecules
to Materials; M. M. Haley, R. R. Tykwinski, Eds. Wiley-VCH, Weinheim,
2006, pp 421-475. b) H. Takeda, K. Koike, T. Morimoto, H. Inumaru, O.
Ishitani, Advances in Inorganic Chemistry 2011; 63, pp 137-186. c) K. A.
Grice, C. P. Kubiak, Advances in Inorganic Chemistry 2014, 66, 163-
188. (d) Y. Kuramochi, O. Ishitani, H. Ishida, Coord. Chem. Rev. 2018,
373, 333.
[5]
[6]
X. Geng, C. Wang, Org. Lett. 2015, 17, 2434.
For representative examples of organic reaction promoted by
stoichiometric amount of structurally characterized rhenium carbonyl
complexes, see: a) L. Carlucci, D. M. Proserpio, G. D’Alfonso,
Organometallics 1999, 18, 2091. b) M. A. Reynolds, I. A. Guzei, R. J.
Angelici, Organometallics 2001, 20, 1071. c) R. D. Adams, V. Rassolov,
Y. O. Wong, Angew. Chem. Int. Ed. 2014, 53, 11006. d) R. D. Adams,
V. Rassolov, Y. O. Wong, Angew. Chem. Int. Ed. 2016, 55, 1324. e) R.
D. Adams, P. Dhull, J. D. Tedder, Inorg. Chem. 2018, 57, 7957. f) R. D.
Adams, P. Dhull, J. D. Tedder, Chem. Commun. 2018, 54, 3255.
a) J. H. P. Tyman, Synthetic and Natural Phenols; Elsevier: 1996. b) M.
Yamaguchi, The Chemistry of Phenols; Z. Rappoport, Ed. John Wiley &
Sons, Ltd, Chichester, 2003, pp 661-712. c) D.-G. Yu, F. de Azambuja,
F. Glorius, Angew. Chem. Int. Ed. 2014, 53, 7710.
[12] a) M. Yamaguchi, A. Hayashi, M. Hirama, J. Am. Chem. Soc. 1995, 117,
1151. b) M. Yamaguchi, M. Arisawa, Y. Kido, M. Hirama, Chem.
Commun. 1997, 1663. c) M. Yamaguchi, Pure Appl. Chem. 1998, 70,
1091.
[13] For catalytic C-alkenylation of unprotected phenol derivatives, see: a) K.
Kobayashi, M. Yamaguchi, Org. Lett. 2001, 3, 241. b) B. M. Trost, F. D.
Toste, K. Greenman, J. Am. Chem. Soc. 2003, 125, 4518. c) C.
Nevado, A. M. Echavarren, Chem. Eur. J. 2005, 11, 3155. d) J. S.
Yadav, B. V. Subba Reddy, M. K. Gupta, U. Dash, S. K. Pandey,
Synlett 2007, 809. e) J. S. Yadav, B. V. Subba Reddy, S. Sengupta, S.
K. Biswas, Synthesis 2009, 1301. f) A. Arcadi, F. Blesi, S. Cacchi, G.
Fabrizi, A. Goggiamani, F. Marinelli, Org. Biomol. Chem. 2012, 10,
9700. g) V. K. Tao, G. M. Shelke, R. Tiwari, K. Parang, A. Kumar, Org.
Lett. 2013, 15, 2190. h) T. Nemoto, N. Matsuo, Y. Hamada, Adv. Synth.
Catal. 2014, 356, 2417. For ortho-alkenylation of 1-naphthols, see: i) T.
Satoh, Y. Nishinaka, M. Miura, M. Nomura, Chem. Lett. 1999, 615.
[14] M. Murai, M. Yamamoto, K. Takai, Org. Lett. 2019, 21, 3441.
[15] a) Y. Nishida, N. Hosokawa, M. Murai, K. Takai, J. Am. Chem. Soc.
2015, 137, 114. b) M. Murai, Y. Takeuchi, K. Yamauchi, Y. Kuninobu, K.
Takai, Chem. Eur. J. 2016, 22, 6048. c) M. Murai, R. Taniguchi, N.
[7]
[8]
a) C. Huang, B. Chattopadhyay, V. Gevorgyan, J. Am. Chem. Soc.
2011, 133, 12406. b) T.-J. Gong, B. Xiao, Z.-J. Liu, J. Wan, J. Xu, D.-F.
Luo, Y. Fu, L. Liu, Org. Lett. 2011, 13, 3235. c) M. C. Reddy, M.
Jeganmohan, Eur. J. Org. Chem. 2013, 1150. d) B. Li, J. Ma, Y. Liang,
N. Wang, S. Xu, H. Song, B. Wang, Eur. J. Org. Chem. 2013, 1950. e)
H.-X. Dai, G. Li, X.-G. Zhang, A. F. Stepan, J.-Q. Yu, J. Am. Chem. Soc.
2013, 135, 7567. f) Y. Shen, G. Liu, Z. Zhou, X. Lu, Org. Lett. 2013, 15,
3366. g) X. Cong, J. You, G. Gao, J. Lan, Chem. Commun. 2013, 49,
662. h) B. Liu, H.-Z. Jiang, B.-F. Shi, J. Org. Chem. 2014, 79, 1521. i) T.
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
Hosokawa, Y. Nishida, H. Mimachi, T. Oshiki, K. Takai, J. Am. Chem.
Soc. 2017, 139, 13184. d) M. Murai, R. Okada, S. Asako, K. Takai,
Chem. Eur. J. 2017, 23, 10861.
[22] a) M. Herberhold, G. Sꢁss, G. Angew. Chem. Int. Ed. Engl. 1975, 14,
700. (b) D. R. Gard, T. L.; Brown, J. Am. Chem. Soc. 1982, 104, 6340.
[23] For X-ray study of [HRe(CO)4]3, see: a) N. Masciocchi, A. Sironi, G.
D’Alfonso, J. Am. Chem. Soc. 1990, 112, 9395. For structural data of
related rhenium hydride complexes, see: b) A. Davison, J. A.
McCleverty, G. Wilkinson, J. Chem. Soc. 1963, 1133. c) R. D. Wilson, R.
Bau, J. Am. Chem. Soc. 1976, 98, 4687. d) N. Masciocchi, G. D’Alfonso,
W. Kockelmann, W. Schäferc, A. Sironi, Chem. Commun. 1997, 1903.
e) M. Bergamo, T. Beringhelli, G. D’Alfonso, J. Am. Chem. Soc. 1998,
120, 2971. See also ref. 6.
[16] For rhenium-catalyzed ortho-selective alkylation of phenols, see: (a) Y.
Kuninobu, T. Matsuki, K. Takai, J. Am. Chem. Soc. 2009, 131, 9914. b)
Y. Kuninobu, M. Yamamoto, M. Nishi, T. Yamamoto, T. Matsuki, M.
Murai, K. Takai, Org. Synth. 2017, 94, 280. Mechanistic study for this
alkylation of phenols, see: c) D. Lehnherr, X. Wang, F. Peng, M.
Reibarkh, M. Weisel, K. M. Maloney. Organometallics 2019, 38, 103.
[17] Investigation of solvents with 2.5 mol% of Re2(CO)10 at 160 °C for 4 h:
Yield of 1a was 80% (E / Z = 17 / 83) in toluene, 75% (18 / 82) in n-
octane, 65% (17 / 83) in CH2ClCH2Cl, 30% (17 / 83) in 1,4-dioxane, 5%
(16 / 84) in THF, 0% in MeCN, 0% in DMF, and 57% (16 / 84) without
solvents. Effect of temperature with 2.5 mol% of Re2(CO)10 in
chlorobenzene for 4 h: Yield of 1a was 89% (16 / 84) at 160 °C, 60%
(17 / 83) at 140 °C, and 0% at 120 °C.
[24] For methoxy group-directed CH bond functionalization, see: a) J.
Oyamada, M. Nishiura, Z. Hou, Angew. Chem. Int. Ed. 2011, 50, 10720.
b) J. Oyamada, Z. Hou, Angew. Chem. Int. Ed. 2012, 51, 12828. c) X.
Shi, M. Nishiura, Z. Hou, J. Am. Chem. Soc. 2016, 138, 6147. d) X. Shi,
M. Nishiura, Z. Hou, Angew. Chem. Int. Ed. 2016, 55, 14812. e) C. Xue,
Y. Luo, H. Teng, Y. Ma, M. Nishiura, Z. Hou, ACS Catal. 2018, 8, 5017.
f) F. Romanov-Michailidis, B. D. P. Ravetz, D. W. Paley, T. Rovis, J.
Am. Chem. Soc. 2018, 140, 5370.
[18] For alkenylation under the conditions shown below, 74% yield of
[Re(OPh)(CO)3(thf)]2 4’ was obtained based on the Re2(CO)10
employed. This result suggested that two equivalents of phenol
derivatives relative to the amount of Re2(CO)10 were consumed in the
formation of the (-aryloxo)rhenium complex, and did not participate in
catalytic alkenylation. Thus, the maximum yield listed in Table 2 was
95%.
[25] a) Y. Kuninobu, Y. Nishina, A. Kawata, M. Shouho, K. Takai, Pure Appl.
Chem. 2008, 80, 1149. b) Y. Kuninobu, K. Takai, Bull. Chem. Soc. Jpn.
2012, 85, 656.
[26] Attempted rhenium-catalyzed alkenylation of phenol with 1-phenyl-1-
propyne did not provide 1a in the presence of 2,2,6,6-
tetramethylpiperidine and anthraquinone, which implies that the common
radical trapping experiments using TEMPO and Galvinoxyl free radical
were not able to rule out the possibility of Path A.
[27] Because formation of para-alkenylated phenols was not observed in the
current alkenylation unless a sterically hindered silylacetylene was used
(see eq 15), intermolecular nucleophilic attack of phenols to alkynes
without proceeding through intermediate A in Scheme 2 can be ruled out.
[28] The use of (3,3-dimethyl-1-butyn-1-yl)benzene as an alkyne gave the
corresponding ortho-alkenylated product in less than 20% yield without
[19] T. Cernak, K. D. Dykstra, S. Tyagarajan, P. Vachal, S. W. Krska, Chem.
Soc. Rev. 2016, 45, 546.
[20] G. Cardillo, R. Cricchio, L. Merlini, Tetrahedron 1971, 27, 1875.
[21] Isolation and structural characterization of the dinuclear complex,
[Re(-OAr)(CO)3]2, was reported in the previous our report (see ref 14),
while trinuclear complex, [Re2(-OAr’)3(CO)6][Re(CO)3(thf)3] was
isolated in the current work. The difference should be derived from
ligand (Ar = 2-iminophenoxy and Ar’ = 2-naphthoxy), and coordination
by imino group of 2-iminophenoxy ligand blocked the formation of a
trinuclear complex in the previous study. Additionally, the structure of
phenoxorhenium complex was deduced to be “[Re(-OPh)(CO)3]2”
based on the result of elemental analysis in the previous study. The
reason is commented in footnote 16 of the previous study as follows:
“Since all attempts to obtain the exact molecular weight of
[Re(OPh)(CO)3(thf)]n by mass spectrometry failed, the number of
rhenium nuclei was unclear. A tentative structure for the dimer is shown
in Scheme 2. Catalyst loading in this study was calculated based on the
number of rhenium units.”. Although the structure of naphthoxorhenium
complex was found to be trinuclear in the current study, the exact
structure of phenoxorhenium complex is still unclear.
forming other regioisomers. Thus,
a silyl group at the -position
enhanced the electronically deficient character at the benzyl position of
(phenylethynyl)silane, which accelerated alkenylation at this position.
The more sterically bulky tri(isopropyl)silyl group might prevent the
oligomerization of the alkyne, which increased the overall yield of the
alkenylated product. In contrast, alkenylation did not occur even with
(phenylethynyl)silanes, when anisole, acetanilide, or ethyl benzoate was
used in place of phenol. Thus, a phenolic hydroxyl group is crucial to
produce
a catalytically active phenoxyrhenim species, even for
alkenylation at the para position.
[29] Similar regioselectivity was reported in the hydroarylation of pyridine
derivatives to allenes. See: G. Song, B. Wang, M. Nishiura, Z. Hou,
Chem. Eur. J. 2015, 21, 8394.
[30] M. P. Kumar, R.-S. Liu, J. Org. Chem. 2006, 71, 4951-4955.
This article is protected by copyright. All rights reserved.

10.1002/chem.201903910
Chemistry - A European Journal
FULL PAPER
Table of Contents
FULL PAPER
Masahito Murai,* Masaki Yamamoto,
Kazuhiko Takai*
Page No. – Page No.
Mechanistic Insights into Rhenium-
Catalyzed Regioselective C-Alkenylation
of Phenols with Internal Alkynes
A (-aryloxo)rhenium complex was isolated and confirmed as a key precatalyst for
rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected (thio)phenols
with internal alkynes. Several control experiments revealed that phenolic hydroxyl
group-assisted electrophilic alkenylation is the most plausible as a reaction
mechanism, instead of classic Friedel-Crafts type electrophilic functionalization.
ortho-Selective alkenylation of phenols with allenes was also demonstrated.
This article is protected by copyright. All rights reserved.