Chemoselective reduction of the carbonyl functionality through hydrosilylation: Integrating click catalysis with hydrosilylation in one pot

Article abstract of DOI:10.1021/jo501505j

Herein we report the chemoselective reduction of the carbonyl functionality via hydrosilylation using a copper(I) catalyst bearing the abnormal N-heterocyclic carbene 1 with low (0.25 mol %) catalyst loading at ambient temperature in excellent yield within a very short reaction time. The hydrosilylation reaction of α,β-unsaturated carbonyl compounds takes place selectively toward 1,2-addition (C=O) to yield the corresponding allyl alcohols in good yields. Moreover, when two reducible functional groups such as imine and ketone groups are present in the same molecule, this catalyst selectively reduces the ketone functionality. Further, 1 was used in a consecutive fashion by combining the Huisgen cycloaddition and hydrosilylation reactions in one pot, yielding a range of functionalized triazole substituted alcohols in excellent yields.

Full text of DOI:10.1021/jo501505j

Article
pubs.acs.org/joc
Chemoselective Reduction of the Carbonyl Functionality through
Hydrosilylation: Integrating Click Catalysis with Hydrosilylation in
One Pot
Sudipta Raha Roy, Samaresh Chandra Sau, and Swadhin K. Mandal*
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741252, India
S
* Supporting Information
ABSTRACT: Herein we report the chemoselective reduction of the carbonyl
functionality via hydrosilylation using a copper(I) catalyst bearing the abnormal N-
heterocyclic carbene 1 with low (0.25 mol %) catalyst loading at ambient temperature in
excellent yield within a very short reaction time. The hydrosilylation reaction of α,β-
unsaturated carbonyl compounds takes place selectively toward 1,2-addition (CO) to
yield the corresponding allyl alcohols in good yields. Moreover, when two reducible
functional groups such as imine and ketone groups are present in the same molecule, this
catalyst selectively reduces the ketone functionality. Further, 1 was used in a consecutive
fashion by combining the Huisgen cycloaddition and hydrosilylation reactions in one pot,
yielding a range of functionalized triazole substituted alcohols in excellent yields.
and metal-free catalysis in recent years, poor selectivity, long
reaction times, stringent reaction conditions, and the toxicity of
costly metal catalysts press the need for the development of
more sustainable methods for hydrosilylation reactions.
INTRODUCTION
■
The reduction of the carbonyl moiety to an alcohol via hydride
transfer is a ubiquitous process for the synthesis of fine
chemicals, leading to molecules with hydroxyl functionalities. It
is noteworthy that the abundance of hydroxyl groups in various
drug molecules makes their synthesis an important step during
organic transformations.1 Often, commonly used reducing
agents such as metal hydrides face chemoselectivity issues,
especially when they are aimed at the reduction of carbonyl
groups in the presence of another reducible functional group
such as olefinic double bonds and cyano, nitro, and imine
functionalities.2 Furthermore, generation of metal waste is a
serious environmental concern when these reactions are
performed on larger scales and in a noncatalytic fashion. In
this regard, catalytic hydrosilylation followed by base hydrolysis
has been proved to be an elegant strategy for the reduction of
carbonyl groups.3 In recent years, hydrosilylation of various
organic compounds has made substantial progress and became
a major tool for synthetic organic chemistry to provide an
efficient and versatile access to new compounds.4 In industry,
hydrosilylation has also become an appropriate method to
produce organosilicon compounds, in particular with respect to
the functionalization of polymers.5 Hydrosilanes are normally
inert toward nonactivated carbonyl compounds,6 and con-
sequently several transition-metal complexes have evolved as
catalysts for hydrosilylation reactions.7 Later on, reports on
metal-free hydrosilylation appeared; most of the known metal-
free catalysts operate through either Lewis base or nucleophilic
catalyst activation of the hydrosilane.8 Recently, an organo-
catalytic version of this particular transformation has been
realized.9 Despite the progress made in both transition-metal
In the present study, we use a copper(I) chloro complex (1;
Chart 1)10a as a catalyst supported with an abnormal N-
Chart 1. Copper(I) Chloro Complex 1 with an aNHC
Backbone
heterocyclic carbene for hydrosilylation reactions. N-hetero-
cyclic carbenes (NHCs) have played a major role in the design
of efficient catalysts for a plethora of organic reactions for more
than two decades.11 In 2001, Crabtree, Faller, and co-workers
added a new dimension for designing efficient organometallic
catalysts by introducing the abnormal mode of binding of NHC
to a metal center.12 Later on, several other complexes featuring
the so-called abnormal mode of binding were reported.13 Now
a number of ligand systems have been reported that are
specifically designed to allow the abnormal mode of binding in
a quest for better catalysis.14 It has been observed recently in a
number of reports that abnormal NHC-based catalysts can
Received: July 8, 2014
Published: September 4, 2014
© 2014 American Chemical Society
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outperform their “normal” NHC-based analogues.10d,13a,c,14c
The area of abnormal NHC-based catalyst design was fueled by
the recent isolation of the first aNHC (1,3-bis(2,6-diisopro-
pylphenyl)-2,4-diphenyl-5-ylidene) by Bertrand and co-work-
ers.15 In fact, aNHC was envisaged as the new cornerstone in
the area of organometallic chemistry and catalysis.16 Our group
recently established that the isolated aNHC (1,3-bis(2,6-
diisopropylphenyl)-2,4-diphenyl-5-ylidene) can be used to
design both organometallic and organic catalysts for a number
of important chemical transformations.10 We have reported the
first organocatalytic application of the free aNHC, which
indicated that it can act as a very efficient nucleophile for ring-
opening polymerization of cyclic ester monomers, placing it as
the most efficient organocatalyst among any known NHCs.10d
Also recently we established that the aNHC can be an excellent
building block to design transition-metal-based organometallic
catalysts containing palladium for the Suzuki−Miyaura coupling
of challenging aryl chloride substrates at ambient temperature
under very low catalyst loading conditions.10c More recently,
we have reported the copper−aNHC complex 1 in the Huisgen
cycloaddition reaction of a versatile range of azides and alkyne
substrates at room temperature.10a
temperature. As the use of KOtBu as a source of alkoxide is very
crucial to accelerate the reaction rate (Table 1, entry 1), we
Table 1. Reduction of 2 using 1 as Catalyst with Varying
a
Reaction Conditions
Herein, we describe the chemoselective reduction of
carbonyl moieties in excellent yields at room temperature in
very short periods of time using 1 as the catalyst.
The high longevity of our catalyst with an aNHC ligand,
reported earlier for click catalysis,10a prompted us to integrate
Huisgen cycloaddition reaction (click catalysis) in a consecutive
fashion in the same reaction pot, resulting in a range of triazole-
substituted alcohols in excellent yield.
RESULTS AND DISCUSSION
■
Following the synthetic route previously reported by our
group,10a the aNHC-coordinated copper(I) chloride complex 1
was synthesized in good yield. An initial study was performed
with the model reaction of 4-nitrobenzaldehyde (2) with
phenylsilane (3) in the presence of 1 (5 mol %) at room
temperature in THF (Scheme 1). The progress of the reactions
a
2 (1 mmol) was treated with 3 (1 mmol) in the presence of 1 (1 mol
%) and base (2 mol %) at room temperature in THF (2 mL) unless
b
c
otherwise mentioned. Yield of the corresponding alcohol 4. Reaction
d
was performed in the presence of 2.5 equiv of PMHS. Reaction was
e
f
performed in PhMe. 1.5 mmol of 3 was used. Reaction was
performed on a 2 mmol scale with 1 (0.25 mol %) and KOtBu (0.5
g
mol %). Reaction was performed on a 4 mmol scale with 1 (0.125
Scheme 1. Reduction of 2 using 1 as Catalyst
mol %) and KOtBu (0.25 mol %).
assume aNHC-Cu-OtBu might have been generated in the
reaction mixture, as there is a sharp color change observed
when 2 equiv of KOtBu was added to 1, similar to previously
reported observations.17c,18 Moreover, it may be assumed that
addition of the silane 3 can result in σ-bond metathesis between
aNHC-Cu-OtBu and 3, generating the actual active catalyst
aNHC-Cu-H.7k,18c Despite several stoichiometric attempts, we
have been unable to isolate the copper alkoxide aNHC-Cu-
OtBu or copper hydride species aNHC-Cu-H. The reaction
process was further simplified by adding all of the components
(1 mmol each of 2 and 3, 1 mol % of 1, and 2 mol % of KOtBu)
together in THF. This resulted in a similar conversion to the
desired product 4 after workup in comparison to the stepwise
addition of reagents. Thus, our method utilizes an air-stable
aNHC-copper chloro complex as a precatalyst in the presence
of KOtBu, making the methodology a straightforward one. To
check the effect of the alkoxides, sodium tert-butoxide and
sodium methoxide were used (Table 1, entries 2 and 3)
separately. No significant change in the yield was noticed when
we changed the tert-butoxide countercation from potassium to
sodium. However, altering the alkoxide from tert-butoxide to
was monitored by 1H NMR spectroscopy. After base hydrolysis
and workup, the desired 4-nitrobenzyl alcohol (4) was obtained
in 97% yield within 8 h (Scheme 1).
When the reaction was performed in the absence of catalyst
1, the starting materials remained unchanged even after 12 h.
Earlier Nolan and co-workers had shown that copper NHC
alkoxides are precatalysts for the hydrosilylation reaction of
carbonyl groups with silanes.17 It has been established in the
literature that the most convenient way to prepare a copper
alkoxide is the treatment of a copper halide with a metal
alkoxide in THF/PhMe.18 To accelerate the reaction rate in our
system, 1 (1 mol %) was treated with potassium tert-butoxide
(KOtBu) (2 mol %) in dry THF under an inert atmosphere. To
this solution, when 1 mmol each of 2 and 3 was added, the
hydrosilylation reaction was complete within 10 min at ambient
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methoxide resulted in a detrimental effect on the yield of the
product (72%, Table 1, entry 3). Notably, the hydrosilylation
reaction is not limited to 3 only; no change in reaction time or
yield was observed using diphenylsilane as a source of hydride
(Table 1, entry 4). However, treatment of triphenylsilane with
2 under the optimized conditions requires longer reaction times
to obtain comparable conversions (Table 1, entries 5 and 6).
Importantly, the inexpensive and environmentally benign
silane polymethylhydrosiloxane (PMHS) was also found to
work as an effective reducing reagent under our optimized
conditions (Table 1, entry 7; see below for more details). In
addition to THF, hydrosilylation reactions catalyzed by 1 can
also be performed in PhMe and no change in reactivity was
observed when the reaction was performed in PhMe (Table 1,
entry 8). On the other hand, the reaction failed when it was
performed in protic polar solvents, e.g. EtOH and water, which
may be attributed to the instability of the active metal alkoxide
generated in situ. Increasing the stoichiometry of the silane did
not provide any further beneficial effect in terms of reaction
time or conversion (Table 1, entry 9). It is noteworthy that 2
can undergo reduction to 4 with as little as 0.125 mol % of 1,
although a relatively longer reaction time (25 min) is required
(Table 1, entry 11). However, keeping in view the operational
simplicity for the small-scale reaction, the use of 0.25 mol % of
1 (Table 1, entry 10) was considered as an optimum catalyst
loading.
Table 2. Reduction of Functionalized Aldehydes using
Catalyst 1
a
Next, we investigated the scope of the catalyst 1 (0.25 mol
%) for the reduction of several functionalized aldehydes in the
presence of 3. Under base-free conditions only the activated
aldehyde was reacted after prolonging the reaction time, but on
application of the optimized procedure, several functionalized
aldehydes were reduced in a very short period of time.
Functional groups that are susceptible to reduction, for
example, halide, NO2, and CN, remain unchanged during the
reaction (Table 2, entries 2−7, respectively). It was noticed that
substitution at the ortho or para position of the aryl ring did not
hamper the catalytic activity. Electron-rich as well as electron-
deficient groups on the aryl ring did not show any significant
influence on the performance of the catalyst. Sterically
demanding substrates (Table 2, entry 8) were converted
almost quantitatively to afford the corresponding primary
alcohols in excellent yields. The functional groups susceptible
to base hydrolysis (Table 2, entry 12) survived under our
reaction conditions.
Earlier, it was reported that reductions of the carbonyl
moiety in heterocyclic compounds either inhibit the catalytic
activity or require much larger amounts of catalyst loading and
longer reaction times.7h,k,19 However, no such complications
were observed with this present catalytic system. The reaction
with heterocyclic carbonyl moieties (Table 2, entries 13−15)
proceeded smoothly within very short periods of time in
excellent yield.
a
The aldehyde moiety (2 mmol) was treated with 3 (2 mmol) in the
presence of 1 (0.25 mol %) and KOtBu (0.5 mol %) at room
temperature in THF (2 mL). Yield of the corresponding alcohol
characterized by NMR and MS. Conversion was determined by H
NMR spectroscopy.
b
c
1
challenging substrates such as 2-acetylpyridine, 3-acetylbenzo-
nitrile, and 2-acetylthiophene failed in the presence of a well-
defined normal NHC-copper complex.7k However, the present
catalyst 1 gave excellent yields of reduced products of 2-
acetylpyridine, 3-acetylbenzonitrile, and 2-acetylthiophene (see
entries 6, 8, and 9, Table 3). This result clearly highlights that
our reaction conditions and catalyst outperform catalyst
reported earlier.7k However, a carbonyl moiety with a hydroxyl
functionality (e.g., 4-hydroxyacetophenone, 2-hydroxybenzalde-
hyde) failed to give the corresponding alcohol. A sterically
hindered ketone, e.g. benzophenone (Table 3, entry 11), took a
longer reduction time under the optimized reaction conditions.
Overall, the reduction of ketones took slightly more time in
comparison to that for the corresponding aldehydes.
Encouraged by these results, we explored the scope of
reduction of different aromatic and aliphatic ketones. Several
functionalized ketones were tested to determine the catalyst’s
activity as well as its tolerance to different functional groups
(Table 3). As shown in Table 3, high catalytic efficiency of 1
was observed for a wide substrate scope of aromatic as well as
aliphatic ketones. The functional groups Br (Table 3, entry 2),
NO2 (Table 3, entry 4), and F (Table 3, entry 7) were well
tolerated. Ketones bearing electron-withdrawing groups were
more reactive than ketones containing electron-donating
substituents. It should be noted that the reduction of
Next, we wished to find a cheap, environmentally friendly,
and readily available silane source to establish our methodology
as economical and greener.20 Keeping this perception in mind,
PMHS was used as a reducing agent for the reduction of the
carbonyl functionality (Table 1, entry 7). Very recently,
Nikonov and co-workers reported the reduction of the carbonyl
moiety with PHMS in combination with KOtBu/KOH.8a More
precisely, when 4-nitroacetophenone was treated in the
presence of PMHS (5 equiv) and 5 mol % of KOtBu, almost
quantitative conversion in 45 h was reported. However, when
we treated the same substrate under our optimized conditions
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Table 3. Reduction of Functionalized Ketones using Catalyst
1
Table 4. Reduction of Carbonyl Moiety with PMHS using
Catalyst 1
a
a
a
The ketone moiety (2 mmol) was treated with 3 (2 mmol) in the
presence of 1 (0.25 mol %) and KOtBu (0.5 mol %) at room
temperature in THF (2 mL). Yield of the corresponding alcohol
a
The carbonyl moiety (2 mmol) was treated with PMHS (2.5 equiv, 5
b
mmol) in the presence of 1 (0.25 mol %) and KOtBu (0.5 mol %) at
room temperature in THF (2 mL). Yield of the corresponding
b
characterized by NMR and MS.
alcohol characterized by NMR and MS.
using the present catalyst 1 (Table 4, entry 1), the
corresponding alcohol was obtained in excellent yield within
only 30 min. This observation clearly demonstrates the
superiority of our methodology and highlights the central
role of the catalyst 1 in combination with KOtBu for the
catalytic hydrosilylation using PMHS as a hydride source.
Encouraged by this result, we extended this convenient
method to different functionalized carbonyl moieties. Both
ketones and aldehydes were reduced quantitatively in very short
periods of time. Electron-rich (Table 4, entries 3 and 10) as
well as electron-poor (Table 4, entries 1, 7, and 8) substrates
were reduced with nearly equal efficiency. Heterocyclic
carbonyl compounds were also reduced efficiently (Table 4,
entries 4, 11, and 12) without any complications. As expected,
longer reaction times were required for ketones in comparison
to aldehydes. Nolan and co-workers used Et3SiH as a hydride
source for the hydrosilylation reaction of carbonyl moieties
using NHC-copper complexes as catalysts.7k Later on, the same
group reported cationic copper(I) complexes such as [(IPr)2-
Cu]X (X = BF4, PF6; IPr = N,N′-bis(2,6-diisopropylphenyl)-
imidazol-2-ylidene)17c for the hydrosilylation reaction of the
carbonyl moiety. However, none of these copper catalysts used
the inexpensive and environmentally benign silane PMHS as a
hydride source. However, we found that our present abnormal
NHC-copper complex works efficiently using PMHS as a
reducing agent.
Next, we became interested in the hydrosilylation reaction of
α,β-unsaturated carbonyl compounds, as there is a possibility of
both 1,2-addition (CO) and 1,4-addition (CC). A number
of complexes with different central metals were used as catalysts
for the regioselective hydrosilylation reaction and offered some
interesting unprecedented selectivity.21 Apart from the nature
of the central metal atom of a complex, there are several other
parameters which also affect the selectivity. Apparently, the
copper catalyst prefers 1,4-addition, but by tuning the interplay
between steric and electronic factors of the ligand on copper,
one can change the selectivity.22 Stryker and co-workers
reported that the phosphine ligand has a remarkable effect on
the chemoselectivity of the reduction. They found that, on
addition of dialkylarylphosphines to Stryker’s reagent, 1,4-
reduction is suppressed and an allylic alcohol was the major
product due to preferential 1,2-reduction.23 Chan and co-
workers reported that their catalyst hydridotetrakis-
(triphenylphosphine)rhodium is an efficient catalyst for the
1,4-reduction of α,β-unsaturated carbonyl compounds with
monohydrosilanes.24 Interestingly, when the silane is changed
from monohydrosilanes to di- or trihydrosilanes for the
hydrosilylation reactions, the selectivity changed completely
and the 1,2-reduction predominated.24 When we subjected
trans-cinnamaldehyde (5) to a hydrosilylation reaction in the
presence of 1 under our optimized conditions (Table 5, entry
1), excellent chemoselectivity was obtained toward 1,2-
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observed by 1H NMR spectroscopy (determined by comparing
Table 5. Chemoselective Reduction of α,β-Unsaturated
Carbonyl Compounds
a
the integral value of olefinic protons of the product and starting
1
material in H NMR) even after prolonging the reaction time
and increasing the catalyst loading. Moreover, the attempted
reduction of the conjugated enone 2-cyclohexen-1-one did not
provide any beneficial role in terms of selectivity. While the
reaction of 2-cyclohexen-1-one was complete in 15 min with 3,
we ended up with an equimolar (1:1) mixture of cyclohexenol
and cyclohexanol.
Further, the chemoselective reduction of the carbonyl group
also has been accomplished when the hydrosilylation was
carried out in the presence of both aldehyde and ketone
functionalities.26 When 4-acetylbenzaldehyde (9) was treated
with 3 under the optimized conditions, likewise with a few
other reported catalysts,26a,b the aldehyde group was exclusively
reduced to the corresponding primary alcohol to give 1-(4-
(hydroxymethyl)phenyl)ethanone (10; Scheme 2a). It is worth
mentioning that the compound 10 is a reactive intermediate for
the synthesis of HIV reverse transcriptase and integrase (RT
and RI).27 Though the selectivity of the reaction for the
aldehyde over ketone is reasonably expected and can be
explained in terms of their electrophilicities, it may be noted
that routinely used reagents employed for carbonyl group
reduction, such as sodium borohydride, is too reactive and does
not show any chemoselectivity with 9. The treatment of 9 with
sodium borohydride (1 equiv) in the presence of MeOH at
room temperature shows that both the aldehyde and ketone
functionalities undergo reduction to give 1-(4-(hydroxy-
methyl)phenyl)ethanol (11) in 94% yield.
Interestingly, this catalytic system is tolerant toward imine
functional groups,7j,25a as shown by the complete reduction of
the CO functionality of (E)-1-(4-((4-methoxyphenylimino)-
methyl)phenyl)ethanone (12) in the presence of a CN bond
to give 1-(4-((4-methoxyphenylimino)methyl)phenyl)ethanol
(13; Scheme 2b). In contrast, when 12 was treated with sodium
borohydride (1 equiv) in the presence of MeOH at room
temperature, reduction of both the ketone and imine groups
took place to give 1-(4-((4-methoxyphenylamino)methyl)-
phenyl)ethanol (14) in 94% yield.
a
The α,β-unsaturated carbonyl moiety (2 mmol) was treated with 3 (2
mmol) in the presence of 1 (0.25 mol %) and KOtBu (0.5 mol %) at
room temperature in THF (2 mL). Exclusive selectivity was
determined with H NMR spectroscopy. Yield of the corresponding
alcohol characterized by NMR and MS. Conversion was determined
by comparing the integral values of olefinic protons of the product and
starting material in H NMR.
b
c
1
d
1
addition. It is noteworthy that the α,β-unsaturated carbonyl
compounds upon reduction with silane sometime prefer 1,4-
addition.7j,25 Moreover, treatment of 5 with 2 equiv of silane
(3) under the optimized conditions resulted in exclusively 1,2-
addition reduction, yielding the cinnamyl alcohol exclusively.
However, when we treated 5 in the presence of PMHS, the
selectivity decreased and we got a mixture (68:32) of cinnamyl
alcohol and 3-phenylpropan-1-ol.
Intrigued by these preliminary catalytic results, we examined
several other α,β-unsaturated carbonyl compounds, e.g. 3-
ethoxycyclohex-2-enone (6; Table 5, entry 2), (E)-3-(4-
methoxyphenyl)-1-phenylprop-2-en-1-one (7; Table 5, entry
3), and (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (8; Table 5,
entry 4) separately with 3 under optimized conditions (Table 5,
entries 2−4). Excellent chemoselectivity was obtained to afford
the corresponding allylic alcohol after routine base hydrolysis.
The treatment of 6 with 3 (Table 5, entry 2) gives exclusive
selectivity toward 1,2-addition, but poor conversion was
Finally, some effort was directed to integration of the
Huisgen cycloaddition (click) and hydrosilylation reactions in a
consecutive fashion in one pot. To the best of our knowledge,
no catalyst system has been reported that integrates the
Huisgen cycloaddition and hydrosilylation reactions in one pot
Scheme 2. Selective Reduction of CO Functionality using Catalyst 1
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Scheme 3. Integrating Huisgen Cycloaddition and Hydrosilylation Reactions in One Pot
in a consecutive fashion. The emerging influence of sustainable
chemistry in organic synthesis augmented the need of multiple
catalytic cycles in a single vessel for the synthesis of complex
compounds,28 as it minimizes the time in a cost-effective
manner by eliminating the need for isolation and purification of
intermediates. In biological chemistry, there are several
examples29 in which arrays of catalytic (enzymatic) reactions
are integrated, reminiscent of the concept of multiple
catalysis.30 In these processes, the product of one cycle acts
as the substrate of the next catalytic cycle.31 The synthesis of
aromatic substituted triazole with a hydroxyl functionality
requires a two-step process such as a Huisgen cycloaddition
reaction and catalytic reduction of the carbonyl functionality
followed by hydrolysis. Usually, this can be accomplished in
two different catalytic steps followed by workup using copper
catalyst in a stepwise manner, which is a tedious process. To
integrate these two catalytic steps, however, one needs to use a
robust catalyst which can stay alive during both catalytic
processes, avoiding any workup between these two catalytic
steps. We adopted herein an alternate strategy where we first
synthesized the triazole-containing carbonyl functionality
followed by reduction and hydrolysis to give an aromatic
substituted triazole with a hydroxyl functionality within the
same reaction pot using catalyst 1. We anticipate that this
strategy can be successful because of the stability of the
abnormal NHC-copper complex, which can remain active in a
multistep catalytic process.
with the excellent catalytic activity in hydrosilylation reactions
prompted us to integrate the Huisgen cycloaddition with a
hydrosilylation reaction in the same reaction pot. We
performed all of these multiple catalytic experiments with 1
mol % of catalyst loading. Initially, 4-azidobenzaldehyde (15)
was treated with phenylacetylene in the presence of aNHC
copper(I) complex 1 (1 mol %) at room temperature (Scheme
3). Within 2 h, the reaction mixture solidified, indicating
completion of the Huisgen cycloaddition reaction, and THF
was added in the same pot to make the reaction mixture
homogeneous, followed by addition of phenylsilane (3) and
KOtBu (1 mol %). Immediately after the addition of base, the
color of the solution changed from pale yellow to brown. The
reaction mixture was stirred for 20 min. To our delight, after
the base hydrolysis, we got the desired hydrosilylated product
(4-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyl)methanol (16a) in
excellent yield. To establish the generality of this catalytic
protocol, several other alkyne substrates were treated with 15 in
this consecutive fashion. In all of the reactions, the yields were
observed to be excellent (Scheme 3; 16a−d).
Furthermore, to extrapolate the scope of this multiple
catalysis, 4-azidoacetophenone (17) was treated with different
functionalized alkyne substrates. Without exception, we got the
corresponding 1,2,3-triazole substituted secondary alcohols
(Scheme 3; 18a−d) in excellent yields within very short
periods of time.
CONCLUSION
Earlier we reported the activity of 1 in a number of Huisgen
cycloaddition reactions dealing with a versatile range of
substrates.10a We noticed that the strong binding ability of
the aNHC ligand to the copper center leads to a long-lived
catalyst which stays active for 10 consecutive catalytic cycles
without any reduction in catalytic activity. This result along
■
In conclusion, we have established a copper(I) compound
bearing an abnormal N-heterocyclic carbene as a versatile and
highly efficient catalyst for the chemoselective reduction of the
carbonyl functionality via hydrosilylation, which acts at low
(0.25 mol %) catalyst loading at ambient temperature. Different
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with a screw cap septum. Dry THF (2 mL) was added through the
septum using a syringe, followed by phenylsilane (64 μL, 0.5 mmol, 1
equiv). The final reaction mixture was stirred for 15 min. The reaction
mixture was opened to the air, and MeOH (1 mL) was added followed
by aqueous NaOH (2 M, 2 mL). The resulting mixture was stirred for
1 h and subsequently extracted with DCM (3 × 30 mL). The organic
phase was concentrated in vacuo, and the purity of the residue was
checked by 1H NMR. Flash chromatography (a mixture of EtOAc and
petroleum ether was used as the eluent, and the ratio of EtOAc to
petroleum ether was adjusted accordingly) was then performed unless
the crude product was estimated to be greater than 95% pure.
electron-rich and electron-deficient functionalized aromatic
carbonyls and aliphatic ketones were successfully reduced by
this catalytic protocol, resulting in nearly quantitative yields.
This catalyst is equally effective for heterocyclic carbonyl
compounds and gives the corresponding alcohol after tradi-
tional base workup in good to excellent yields within very short
periods of time. The catalyst can successfully catalyze the
hydrosilylation reaction of α,β-unsaturated carbonyl com-
pounds and prefers selectivity toward 1,2-addition (CO) to
give the corresponding allyl alcohol in good yields. Moreover,
in the same molecule when both imine and ketone groups were
present, this catalyst selectively reduced the ketone function-
ality. All of these results clearly establish the ability of our
catalyst to perform hydrosilylation reactions in a chemo-
selective way. Furthermore, the copper(I) chloro complex 1
was used as a multiple catalyst for combining the Huisgen
cycloaddition and hydrosilylation reactions in one pot. This
unique protocol was generalized with different structural motifs
to synthesize several primary and secondary alcohols with the
triazole scaffold in one pot.
Procedure for the Synthesis of 3-Formylphenyl Acetate
(Substrate Table 2, Entry 12). Acylation was carried out by
modifying the reported procedure.32a 3-Hydroxybenzaldehyde (610
mg, 5 mmol) was dissoved in DCM (10 mL), and the solution was
cooled to 0 °C. Triethylamine (670 mg, 0.92 mL, 6.67 mmol) and a
catalytic amount of dimethylaminopyridine (DMAP) were added to
the stirred solution. Acetyl chloride (431 mg, 0.39 mL, 5.5 mmol) was
added dropwise. The mixture was warmed to room temperature, and
stirred for another 3 h. The solvent was removed in vacuo, and the
reaction mixture was diluted with H2O (5 mL) and extracted with
EtOAc (3 × 5 mL). The combined EtOAc extracts were washed with
saturated brine (15 mL), dried (Na2SO4), and concentrated under
1
reduced pressure to afford the acetylated product (760 mg, 93%). H
EXPERIMENTAL SECTION
■
NMR (CDCl3, 400 MHz) δ (ppm): 2.22 (s, 3H), 7.24−7.26 (m, 1H),
7.44 (t, J = 7.6 Hz, 1H), 7.50−7.51 (m, 1H), 7.62−7.65 (m, 1H), 9.88
(s, 1H).
General Considerations. All manipulations were performed
under a dry and oxygen-free atmosphere (argon) using standard
Schlenk techniques or inside a glovebox maintained at below 0.1 ppm
of O2 and H2O levels, utilizing oven-dried (130 °C) glassware after
evacuation while hot prior to use. All solvents were distilled from Na/
benzophenone prior to use. All chemicals were purchased and used as
Procedure for the Synthesis of (E)-3-(4-Methoxyphenyl)-1-
phenylprop-2-en-1-one (Substrate Table 5, Entry 3). The enone
was synthesized by following the reported procedure.32b Acetophe-
none (600 mg, 5 mmol) in EtOH (2.5 mL) was treated with LiOH·
H2O (20 mg, 0.5 mmol, 10 mol %) with stirring for 10 min at room
temperature (∼25−30 °C) followed by 4-methoxybenzaldehyde (680
mg, 5 mmol, 1 equiv). The mixture was stirred until complete
consumption of the starting materials (45 min, monitored by TLC).
After the completion of the reaction, a yellow precipitate was formed.
EtOH was removed under reduced pressure. The residue was diluted
with water (5 mL), neutralized with 2% aqueous HCl, and extracted
with EtOAc (3 × 5 mL). The combined EtOAc extracts were washed
with brine solution (5 mL), dried (Na2SO4), and concentrated under
reduced pressure to afford the desired product (1.14 g, 96%). 1H
NMR (CDCl3, 500 MHz) δ (ppm): 3.86 (s, 3H), 6.93−6.96 (m, 2H),
7.41 (d, J = 15.5 Hz, 1H), 7.48−7.51 (m, 2H), 7.60−7.61 (m, 3H),
7.78 (d, J = 15.5 Hz, 1H), 8.00−8.02 (m, 2H).
1
received. The H and 13C{1H} NMR spectra were recorded on 400
and 500 MHz spectrometers in CDCl3/DMSO-d6 with residual
undeuterated solvent (CDCl3, 7.26/77.0; DMSO-d6, 2.50/39.5) as an
internal standard. Chemical shifts (δ) are given in ppm, and J values
are given in Hz. The IR spectra were recorded either as KBr pellets
(for solids) or as the neat compound or a CCl4 solution (for liquids)
on the spectrometer. The HR-MS data were obtained using a Q-TOF
instrument. The melting points were measured in a sealed glass tube
on a melting point apparatus and were uncorrected. Open-column
chromatography and thin-layer chromatography (TLC) were
performed on silica gel (CDH silica gel 60−120 mesh). Evaporation
of solvents was performed at reduced pressure using a rotary
evaporator.
General Procedure for the Hydrosilylation of Carbonyl
Compounds. In an oven-dried Schlenk flask fitted with septum,
complex 1 (3 mg, 0.005 mmol, 0.25 mol %) and potassium tert-
butoxide (1.2 mg, 0.01 mmol, 0.5 mol %) were charged inside a
glovebox and stirred in dry THF (2 mL) at room temperature for 5
min before adding phenylsilane (252 μL, 2 mmol, 1 equiv) and the
carbonyl compound (1 mmol) through the septum using a syringe. In
cases where the starting carbonyl substrate is a solid, it was added after
dissolving it in THF. The final reaction mixture was stirred for the
requisite time, and the reaction was monitored by TLC. After
consumption of the starting material, the reaction mixture was opened
to the air and MeOH (1 mL) was added followed by aqueous NaOH
(2 M, 2 mL). The resulting mixture was stirred for 1 h and
subsequently extracted with DCM (3 × 30 mL). The organic phase
was concentrated in vacuo, and the purity of the residue was checked
by 1H NMR spectroscopy. Flash chromatography (a mixture of EtOAc
and petroleum ether was used as the eluent, and the ratio of EtOAc to
petroleum ether was adjusted accordingly) was then performed unless
the crude product was estimated to be greater than 95% pure.
General Procedure for Integration of Huisgen Cycloaddition
and Hydrosilylation Reactions in One Pot. In an oven-dried 25
mL Schlenk flask, alkyne (0.5 mmol), azide (0.5 mmol), and complex
1 (3.2 mg, 1 mol %) were charged inside a glovebox. The reaction
mixture was stirred at room temperature for 2 h. After the
solidification of the reaction mixture, potassium tert-butoxide (1.2
mg, 0.01 mmol, 2 mol %) was added and the Schlenk flask was fitted
Procedure for the Synthesis of (E)-1-(4-((4-
Methoxyphenylimino)methyl)phenyl)ethanone (Scheme 2b,
Substrate 12). A mixture of 3-acetylbenzaldehyde (296 mg, 2
mmol, 1 equiv) and 4-methoxyaniline (246 mg, 2 mmol, 1 equiv) was
stirred at room temperature in EtOH (2 mL). After completion of the
reaction (1 h, monitored by TLC), a yellow precipitate was formed
and the crude mixture was recrystallized from ethanol to afford (E)-1-
(4-((4-methoxyphenylimino)methyl)phenyl)ethanone (409 mg, 82%).
1H NMR (CDCl3, 500 MHz) δ (ppm): 2.66 (s, 3H), 3.84 (s, 3H),
6.94−6.96 (m, 2H), 7.26−7.29 (m, 2H), 7.97−7.99 (m, 2H), 8.03−
8.06 (m, 2H), 8.54 (s, 1H).
Procedure for the Synthesis of 4-Azidobenzaldehyde
(Scheme 3, Substrate 15). Azide formation was carried out by
slightly modifying the reported procedure.32c KF (348 mg, 6 mmol, 1.2
equiv), TMSN3 (690 mg, 6 mmol, 1.2 equiv), and CuCl (50 mg, 0.5
mmol, 10 mol %) were sequentially added to a solution of 4-
formylphenylboronic acid (750 mg, 5 mmol, 1 equiv) in MeOH (4
mL). The resulting solution was then stirred at reflux until the starting
material had disappeared as monitored by TLC. The reaction mixture
was concentrated under reduced pressure, and the crude product was
purified by silica gel chromatography (a mixture of EtOAc and
petroleum ether was used as the eluent, and the ratio of EtOAc to
petroleum ether was adjusted accordingly) to give the desired product,
1
4-azidobenzaldehyde (602 mg, 82%). H NMR (CDCl3, 500 MHz) δ
(ppm): 7.14−7.16 (m, 2H), 7.88−7.89 (m, 2H), 9.94 (s, 1H).
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Article
Following the same procedure, 4-acetylphenylboronic acid was
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 57.3, 107.7, 110.3, 142.5,
153.9. These data are identical with those for Table 4, entry 12.
Thiophen-2-ylmethanol (Table 2, Entry 15).32d Clear liquid, 216
mg, yield 95%. 1H NMR (CDCl3, 500 MHz) δ (ppm): 5.06 (d, J = 1.5
Hz, 2H), 7.26−7.28 (m, 2H), 7.56−7.57 (m, 1H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 59.7, 125.3, 1254, 126.7, 143.9.
1-Phenylethanol (Table 3, Entry 1).32d Clear liquid, 229 mg, yield
94%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.50 (d, J = 6.0 Hz, 3H),
4.90 (q, J = 6.0 Hz, 1H), 7.25−7.30 (m, 1H), 7.35−7.39 (m, 4H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 25.0, 70.2, 125.3, 127.2,
128.3, 145.7. These data are identical with those for Table 4, entry 2.
1-(4-Bromophenyl)ethanol (Table 3, Entry 2).32h White amor-
phous solid, 369 mg, yield 92%. 1H NMR (CDCl3, 400 MHz) δ
(ppm): 1.44 (d, J = 6.8 Hz, 3H), 4.83 (q, J = 6.8 Hz, 1H), 7.23 (d, J =
7.6 Hz, 2H), 7.45 (d, J = 7.6 Hz, 2H). 13C{1H} NMR (CDCl3, 125
MHz) δ (ppm): 25.1, 69.6, 121.0, 127.1, 131.4, 144.7.
converted to the corresponding 4-azidoacetophenone (17; 676 mg,
1
84% yield). H NMR (CDCl3, 500 MHz) δ (ppm): 2.58 (s, 3H),
7.08−7.09 (m, 2H), 7.95−7.97 (m, 2H).
Characterization of the Compounds. Phenylmethanol (Table
2, Entry 1).32d Clear liquid, 207 mg, yield 96%. 1H NMR (CDCl3, 400
MHz) δ (ppm): 4.66 (d, J = 2.5 Hz, 2H), 7.31−7.32 (m, 1H), 7.33−
7.39 (m, 4H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 64.9,
126.9, 127.5, 128.4, 140.7.
(4-Fluorophenyl)methanol (Table 2, Entry 2).32d Clear liquid, 236
1
mg, yield 94%. H NMR (CDCl3, 400 MHz) δ (ppm): 4.65 (s, 2H),
7.00−7.04 (m, 2H), 7.29−7.33 (m, 2H). 13C{1H} NMR (CDCl3, 125
MHz) δ (ppm): 64.4, 115.2 (d, JCF = 21.1 Hz), 128.6 (d, JCF = 8.0
Hz), 136.6, 161.3 (d, JCF = 244.0 Hz).
(4-Chlorophenyl)methanol (Table 2, Entry 3).32d White crystalline
solid, 275 mg, yield 97%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 4.67
(s, 2H), 7.26−7.32 (m, 4H). 13C{1H} NMR (CDCl3, 125 MHz) δ
(ppm): 64.2, 128.2, 128.5, 133.2, 139.1. These data are identical with
those for Table 4, entry 9.
1-(2-Chlorophenyl)ethanol (Table 3, Entry 3).32i Clear liquid, 284
mg, yield 91%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.49 (d, J = 6.1
Hz, 3H), 5.29 (q, J = 6.1 Hz, 1H), 7.19−7.21(m, 1H), 7.26−7.31 (m,
2H), 7.58−7.60 (m, 1H). 13C{1H} NMR (CDCl3, 125 MHz) δ
(ppm): 23.4, 66.9, 126.3, 127.1, 128.3, 129.3, 131.6, 143.0.
(4-Bromophenyl)methanol (Table 2, Entry 4).32d Clear liquid, 340
1
mg, yield 91%. H NMR (CDCl3, 400 MHz) δ (ppm): 4.65 (s, 2H),
7.23 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 64.4, 121.4, 128.5, 131.6, 139.7.
4-(Hydroxymethyl)benzonitrile (Table 2, Entry 5).32e Clear liquid,
1-(4-Nitrophenyl)ethanol (Table 3, Entry 4).32e Yellow amorphous
solid, 317 mg, yield 95%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.51
(d, J = 6.8 Hz, 3H), 5.00 (q, J = 6.8 Hz, 1H), 7.53(d, J = 9.1 Hz, 2H),
8.19 (d, J = 9.1 Hz, 2H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm):
25.3, 69.3, 123.6, 126.1, 146.9, 153.1. These data are identical with
those for Table 4, entry 1.
1
250 mg, yield 94%. H NMR (CDCl3, 400 MHz) δ (ppm): 4.77 (s,
2H), 7.47 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 63.4, 110.2, 118.7, 126.7, 131.9, 146.5.
These data are identical with those for Table 4, entry 8.
1-(4-Methoxyphenyl)ethanol (Table 3, Entry 5).32e Clear liquid,
(4-(Trifluoromethyl)phenyl)methanol (Table 2, Entry 6).32e Clear
liquid, 323 mg, yield 92%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 4.75
(s, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H). 13C{1H}
NMR (CDCl3, 125 MHz) δ (ppm): 64.3, 124.1 (q, JCF = 270.0 Hz,
consist of four peaks 120.9, 123.0, 125.2, 127.4), 125.3 (q, JCF = 3.7
Hz, consists of four peaks 125.3, 125.3, 125.4, 125.4), 126.7, 129.6 (q,
JCF = 32.2 Hz, consist of four peaks 129.3, 129.5, 129.8, 130.1), 144.7.
(4-Nitrophenyl)methanol (Table 2, Entry 7).32d Yellow amorphous
solid, 290 mg, yield 95%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 4.84
(s, 2H), 7.53 (d, J = 8.4 Hz, 2H), 8.22 (d, J = 8.4 Hz, 2H). 13C{1H}
NMR (CDCl3, 125 MHz) δ (ppm): 63.8, 123.6, 126.9, 147.1, 148.3.
These data are identical with those for Table 4, entry 7.
1
282 mg, yield 93%. H NMR (CDCl3, 400 MHz) δ (ppm): 1.48 (d, J
= 6.1 Hz, 3H), 3.80 (s, 3H), 4.86 (q, J = 6.1 Hz, 1H), 6.87(d, J = 8.4
Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H). 13C{1H} NMR (CDCl3, 125 MHz)
δ (ppm): 24.9, 55.2, 69.8, 113.7, 126.6, 137.9, 158.8. These data are
identical with those for Table 4, entry 3.
1-(3-Cyanophenyl)ethanol (Table 3, Entry 6).32j Clear liquid, 258
mg, yield 88%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.48 (d, J = 6.1
Hz, 3H), 4.92 (q, J = 6.1 Hz, 1H), 7.44 (t, J = 8 Hz, 1H), 7.52−7.55
(m, 1H), 7.60 (d, J = 7.6 Hz, 1H), 7.66 (s, 1H). 13C{1H} NMR
(CDCl3, 100 MHz) δ (ppm): 25.1, 68.9, 111.9, 118.8, 128.9, 129.0,
129.9, 130.7, 147.2.
1-(2,6-Difluorophenyl)ethanol (Table 3, Entry 7). Clear liquid, 293
mg, yield 93%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.61 (d, J = 7.0
Hz, 3H), 5.25 (q, J = 7.0 Hz, 1H), 6.83−6.89 (m, 2H), 7.15−7.26 (m,
1H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 23.3, 62.36, 111.6
(dd, JCF = 20.5, 6.0 Hz), 120.5 (t, JCF = 16.5 Hz), 128.9 (t, JCF = 10.7
Hz), 160.7 (dd, JCF = 246.4, 8.9 Hz). HRMS m/z (ESI): calcd for
C8H7F2NaO [M + Na]+ 180.0363, found 180.0368.
(2-Nitrophenyl)methanol (Table 2, Entry 8).32e Clear liquid, 275
1
mg, yield 90%. H NMR (CDCl3, 500 MHz) δ (ppm): 4.97 (s, 2H),
7.47 (dt, J = 9.0, 1.5 Hz, 1H), 7.67 (dt, J = 8.5, 1.5 Hz, 1H), 7.73−7.47
(m, 1H), 8.1 (dd, J = 8.0, 1 Hz, 1H). 13C{1H} NMR (CDCl3, 125
MHz) δ (ppm): 62.5, 124.9, 128.48, 129.9, 134.1, 136.8.
(4-Methylphenyl)methanol (Table 2, Entry 9).32d Clear liquid, 224
1
1-(Pyridin-2-yl)ethanol (Table 3, Entry 8).32i White amorphous
solid, 221 mg, yield 90%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.50
(d, J = 6.1 Hz, 3H), 4.89 (q, J = 6.1 Hz, 1H), 7.21−7.40 (m, 1H),
7.26−7.29 (m, 1H), 7.67−7.70 (m, 1H), 8.53−8.54 (d, J = 4.6 Hz,
1H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 24.2, 66.8, 119.8,
122.2, 136.9, 147.9, 162.9. These data are identical with those for
Table 4, entry 4.
mg, yield 92%. H NMR (CDCl3, 500 MHz) δ (ppm): 2.36 (s, 3H),
4.61 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 7.5 Hz, 2H), 7.25 (d, J = 7.5 Hz,
2H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 65.0, 127.0, 129.1,
137.2, 137.8.
(4-Methoxyphenyl)methanol (Table 2, Entry 10).32d Clear liquid,
1
251 mg, yield 91%. H NMR (CDCl3, 500 MHz) δ (ppm): 3.77 (s,
3H), 4.53 (s, 2H), 6.86 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 55.1, 64.5, 113.7, 128.5,
133.0, 158.9. These data are identical with those for Table 4, entry 10.
(3,5-Dimethoxyphenyl)methanol (Table 2, Entry 11).32f Clear
liquid, 312 mg, yield 93%. 1H NMR (CDCl3, 500 MHz) δ (ppm): 3.77
(s, 6H), 4.59 (d, J = 4 Hz, 2H), 6.36(s, 1H), 6.49 (d, J = 2 Hz, 2H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 55.3, 65.1, 99.5, 104.5,
143.4, 160.9.
1-(Thiophen-2-yl)ethanol (Table 3, Entry 9).32k Clear liquid, 233
mg, yield 91%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.60 (d, J = 6.1
Hz, 3H), 5.12 (q, J = 6.1 Hz, 1H), 6.95−6.98 (m, 2H), 7.24 (d, J = 6.1
Hz, 1H). 13C{1H} NMR (CDCl3, 100 MHz) δ (ppm): 25.1, 66.0,
123.1, 124.3, 126.5, 149.8.
1-Phenylpropan-1-ol (Table 3, Entry 10).32l Clear liquid, 247 mg,
yield 91%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 0.90 (t, J = 7.6 Hz,
3H), 1.75−1.81 (m, 3H, OH merged), 4.58 (t, J = 6.1 Hz, 1H), 7.24−
7.33 (m, 5H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 10.1, 31.8,
76.0, 125.9, 127.5, 128.4, 144.5. These data are identical with those for
Table 4, entry 5.
Pyridin-2-ylmethanol (Table 2, Entry 13).32g Clear liquid, 200 mg,
1
yield 92%. H NMR (CDCl3, 500 MHz) δ (ppm): 4.74 (s, 2H), 7.18
(d, J = 6.0 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.27 (t, J = 5.0 Hz, 1H),
8.50 (s, 1H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 64.2, 120.6,
122.3, 136.8, 148.4, 159.3. These data are identical with those for
Table 4, entry 11.
Diphenylmethanol (Table 3, Entry 11).32m Yellow amorphous
solid, 320 mg, yield 87%. 1H NMR (CDCl3, 400 MHz) δ (ppm): 5.83
(s, 1H), 7.23−7.24 (m, 2H), 7.31−7.38(m, 8H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 76.1, 126.4, 127.4, 128.4, 143.7. These
data are identical with those for Table 4, entry 6.
Furan-2-ylmethanol (Table 2, Entry 14).32h Pale brown liquid, 178
1
mg, yield 91%. H NMR (CDCl3, 400 MHz) δ (ppm): 4.61 (s, 2H),
6.29 (d, J = 3 Hz, 1H), 6.32−6.34 (m, 1H), 7.39 (d, J = 2 Hz, 1H).
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Cyclohexanol (Table 3, Entry 12).32e Clear liquid, 180 mg, yield
90%. H NMR (CDCl3, 400 MHz) δ (ppm): 1.11−1.16 (m, 1H),
(4-(4-(4-Fluorophenyl)-1H-1,2,3-triazol-1-yl)phenyl)methanol
(Scheme 3, 16c). Yellow amorphous solid, 126 mg, yield 94%. Mp:
196−198 °C. IR (νmax): 3436, 2365, 2078, 1637 cm−1. 1H NMR
(DMSO-d6, 500 MHz) δ (ppm): 4.60 (d, J = 5.5 Hz, 2H), 5.37 (d, J =
5.5 Hz, 1H), 7.33−7.37 (m, 2H), 7.57 (d, J = 8.5 Hz, 2H), 7.89 (d, J =
8.5 Hz, 2H), 7.96−7.99 (m, 2H), 9.27 (s, 1H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 62.2, 116.0 (d, JCF = 25.0 Hz), 119.5,
119.7, 127.3 (d, JCF = 12.5 Hz), 127.7, 135.2, 143.3, 146.4, 161.0 (d,
JCF = 237.5 Hz). HRMS m/z (ESI): calcd for C15H13FN3O [M + H]+
270.0964, found 270.0962.
(4-(4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl)phenyl)methanol
(Scheme 3, 16d). Yellow amorphous solid, 130 mg, yield 93%. Mp:
175−177 °C. IR (νmax): 3433, 2365, 2066, 1633, 1522, 1250 cm−1. 1H
NMR (DMSO-d6, 500 MHz) δ (ppm): 3.80 (s, 3H), 4.59 (d, J = 4.5
Hz, 2H), 5.37 (t, J = 4.5 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.55 (d, J =
8.5 Hz, 2H), 7.86−7.90 (m, 4H), 9.16 (s, 1H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 55.2, 62.2, 114.4, 118.5, 119.6, 122.8,
126.7, 127.6, 135.3, 143.2, 147.2, 159.3. HRMS m/z (ESI): calcd for
C16H16N3O2 [M + H]+ 282.1164, found 282.1167.
1-(4-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol (Scheme 3,
18a). Yellow amorphous solid, 124 mg, yield 94%. Mp: 172−174
°C. IR (νmax): 3436, 2356, 2075, 1636 cm−1. 1H NMR (DMSO-d6, 500
MHz) δ (ppm): 1.37 (d, J = 6.5 Hz, 3H), 4.82 (q, J = 6.5 Hz, 1H),
7.38 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.58 (d, J = 8.5 Hz,
2H), 7.89 (d, J = 8.5 Hz, 2H), 7.95 (d, J = 8.5 Hz, 2H), 9.27 (s, 1H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 25.8, 67.5, 119.6, 119.7,
125.3, 126.7, 128.2, 128.9, 130.3, 135.2, 147.2, 148.1. HRMS m/z
(ESI): calcd for C16H16N3O [M + Na]+ 266.1215, found 266.1218.
1-(4-(4-(4-Methylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(Scheme 3, 18b). Yellow amorphous solid, 126 mg, yield 91%. Mp:
168−170 °C. IR (νmax): 3441, 2085, 1635, 1131 cm−1. 1H NMR
(DMSO-d6, 500 MHz) δ (ppm): 1.38 (d, J = 6.5 Hz, 3H), 2.35 (s,
3H), 4.83 (q, J = 6.5 Hz, 1H), 5.34 (d, J = 4 Hz, 1H), 7.31 (d, J = 8.0
Hz, 2H), 7.58 (d, J = 7.5 Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.89 (d, J
= 8.5 Hz, 2H), 9.21 (s, 1H). 13C{1H} NMR (CDCl3, 125 MHz) δ
(ppm): 20.8, 25.8, 67.5, 119.1, 119.7, 125.2, 126.6, 127.5, 127.9, 129.5,
135.2, 137.5, 147.3, 148.0. HRMS m/z (ESI): calcd for C17H17N3O
[M]+ 279.1372, found 279.1375.
1-(4-(4-(4-Fluorophenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(Scheme 3, 18c). Yellow amorphous solid, 131 mg, yield 93%. Mp:
171−173 °C. IR (νmax): 3428, 2314, 1633, 1228 cm−1; 1H NMR
(DMSO-d6, 500 MHz) δ (ppm): 1.37 (d, J = 6.5 Hz, 3H), 4.82 (q, J =
6.5 Hz, 1H), 5.34 (bs, 1H), 7.32−7.36 (m, 2H), 7.58 (d, J = 8.5 Hz,
2H), 7.87 (d, J = 8.5 Hz, 2H), 7.97−7.99 (m, 2H), 9.25 (s, 1H). 13C
NMR (CDCl3, 125 MHz) δ (ppm): 25.8, 67.5, 115.8, (d, JCF = 25.0
Hz), 119.5, 119.7, 126.7, 127.3 (d, JCF = 12.5 Hz), 135.1, 146.3, 148.1,
161.9 (d, JCF = 250.0 Hz). HRMS m/z (ESI): calcd for C16H15FN3O
[M + H]+ 284.1121, found 284.1126.
1-(4-(4-(Pyridin-2-yl)-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(Scheme 3, 18d). Yellow amorphous solid, 119 mg, yield 90%. Mp:
175−177 °C. IR (νmax): 3442, 2310, 1628, 1226 cm−1. 1H NMR
(DMSO-d6, 500 MHz) δ (ppm): 1.37 (d, J = 6.5 Hz, 3H), 4.82 (q, J =
6.5 Hz, 1H), 5.36 (bs, 1H), 7.36−7.38 (m, 1H), 7.57 (t, J = 8.5 Hz,
2H), 7.91 (dt, J = 8.0, 2.0 Hz, 3H), 8.12 (d, J = 8.0 Hz, 1H), 8.64 (d, J
= 4.0 Hz, 1H), 9.28 (s, 1H). 13C{1H} NMR (CDCl3, 125 MHz) δ
(ppm): 25.8, 67.6, 119.8, 119.9, 121.2, 123.3, 126.6, 135.1, 137.3,
148.1, 148.2, 148.6, 149.6. HRMS m/z (ESI): calcd for C15H13N4NaO
[M + Na]+ 288.0987, found 288.0988.
1
1.18−1.28 (m, 4H), 1.50−1.53 (m, 1H), 1.69−1.71(m, 2H), 1.84−
1.86 (m, 2H), 2.20 (s, 1H), 3.54−3.58 (m, 1H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 24.1, 25.4, 35.4, 70.2.
(E)-3-Phenylprop-2-en-1-ol (Table 5, Entry 1).32d Clear liquid, 246
1
mg, yield 92%. H NMR (CDCl3, 500 MHz) δ (ppm): 4.33 (dd, J =
5.5, 1 Hz, 2H), 6.38 (td, J = 16.5, 5 Hz, 1H), 6.63 (d, J = 16 Hz, 1H),
7.25−7.28 (m, 1H), 7.32−7.35 (m, 2H), 7.39−7.41 (m, 2H). 13C{1H}
NMR (CDCl3, 125 MHz) δ (ppm): 63.5, 126.4, 127.6, 128.4, 128.5,
130.9, 136.6.
(E)-3-(4-Methoxyphenyl)-1-phenylprop-2-en-1-ol (Table 5, Entry
3).32n Yellow amorphous solid, 498 mg, yield 89%. 1H NMR (CDCl3,
500 MHz) δ (ppm): 3.81 (s, 3H), 5.36 (d, J = 7 Hz, 1H), 6.25 (dd, J =
15.5, 6.5 Hz, 1H), 6.63 (d, J = 15.5 Hz, 1H), 6.83−6.85 (m, 2H),
7.29−7.33 (m, 3H), 7.36−7.38 (m, 2H), 7.43−7.44 (m, 2H). 13C{1H}
NMR (CDCl3, 125 MHz) δ (ppm): 55.2, 75.2, 113.9, 126.7, 127.7,
127.8, 128.5, 129.2, 129.4, 130.2 142.9, 159.3.
(1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ol (Table 5, Entry 4).32o
1
White amorphous solid, 438 mg, yield 93%. H NMR (CDCl3, 500
MHz) δ (ppm): 5.03 (t, J = 6.5, 1 Hz, 1H), 6.35 (dd, J = 11.5, 16 Hz,
2H), 6.71 (d, J = 16 Hz, 2H), 7.28−7.31 (m, 2H), 7.36−7.38 (m, 4H),
7.44−7.46 (m, 4H). 13C{1H} NMR (CDCl3, 125 MHz) δ (ppm):
73.7, 126.6, 127.8, 128.6, 130.3, 130.9, 136.5.
1-(4-(Hydroxymethyl)phenyl)ethanone (Scheme 2, 10).32e Clear
liquid, 139 mg, yield 93%. 1H NMR (CDCl3, 500 MHz) δ (ppm): 2.6
(s, 3H), 4.77 (s, 2H), 7.45 (d, J = 8 Hz, 2H), 7.94 (d, J = 8 Hz, 2H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 26.6, 64.3, 126.5, 128.5,
136.0, 146.5. 196.2.
1-(4-(Hydroxymethyl)phenyl)ethanol (Scheme 2, Reduction with
NaBH4, 11).32p Clear liquid, 143 mg, yield 94%. 1H NMR (CDCl3, 500
MHz) δ (ppm): 1.49 (d, J = 6.5 Hz, 3H), 4.69 (s, 2H), 4.91 (q, J = 6.5
Hz, 1H), 7.36−7.39 (m, 4H). 13C{1H} NMR (CDCl3, 125 MHz) δ
(ppm): 25.2, 65.1, 70.2, 125.6, 127.2, 140.1, 145.3.
1-(4-((4-Methoxyphenylimino)methyl)phenyl)ethanol (Scheme 2,
13). Pale yellow amorphous solid, 229 mg, yield 90%. Mp: 81−83 °C.
IR (νmax): 3436, 2073, 1625, 1508, 1247 cm−1. 1H NMR (CDCl3, 500
MHz) δ (ppm): 1.52 (d, J = 6.5 Hz, 3H), 3.83 (s, 3H), 4.96 (q, J = 6.5
Hz, 1H), 6.92−6.94 (m, 2H), 7.23−7.25 (m, 2H), 7.47 (d, J = 8 Hz,
2H), 7.87 (d, J = 8 Hz, 2H), 8.47 (s, 1H); 13C{1H} NMR (CDCl3, 125
MHz) δ (ppm): 25.2, 55.4, 69.9, 114.3, 122.1, 125.7, 128.7, 136.5,
144.7, 148.9, 158.1, 158.2. HRMS m/z (ESI): calcd for C16H18NO2
[M + H]+ 256.1259, found 256.1262.
1-(4-((4-Methoxyphenylamino)methyl)phenyl)ethanol (Scheme
2, Reduction with NaBH4, 14). Pale brown amorphous solid, 241
mg, yield 94%. Mp: 82−84 °C. IR (νmax): 3430, 2078, 1637, 1516,
1239, 1118 cm−1. 1H NMR (CDCl3, 500 MHz) δ (ppm): 1.49 (d, J =
6.5 Hz, 3H), 3.74 (s, 3H), 4.27 (s, 2H), 4.89 (q, J = 6.5 Hz, 1H),
6.60−6.62 (m, 2H), 6.76−6.78 (m, 2H), 7.36 (bs, 4H). 13C{1H} NMR
(CDCl3, 125 MHz) δ (ppm): 25.1, 48.9, 55.7, 70.1, 114.1, 114.9,
125.6, 127.6, 138.8, 142.2, 144.7, 152.1. HRMS m/z (ESI): calcd for
C16H20NO2 [M + H]+ 258.1262, found 258.1265.
(4-(4-Phenyl-1H-1,2,3-triazol-1-yl)phenyl)methanol (Scheme 3,
16a).32q Yellow amorphous solid, 119 mg, yield 95%. Mp: 169−171
°C. IR (νmax): 3436, 2339, 1634, 1131 cm−1. 1H NMR (DMSO-d6, 500
MHz) δ (ppm): 4.60 (d, J = 4.5 Hz, 2H), 5.38 (t, J = 4.5 Hz, 1H), 7.38
(t, J = 7.0 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H),
7.91 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 7.5 Hz, 2H), 9.29 (s, 1H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 62.2, 119.5, 119.7, 125.3,
ASSOCIATED CONTENT
* Supporting Information
■
S
127.6, 128.2, 128.9, 130.3, 135.2, 143.3, 147.2.
(4-(4-(4-Methylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)methanol
(Scheme 3, 16b). Yellow amorphous solid, 120 mg, yield 91%. Mp:
176−178 °C. IR (νmax): 3435, 2365, 2078, 1636 cm−1. 1H NMR
(DMSO-d6, 500 MHz) δ (ppm): 2.34 (s, 3H), 4.60 (d, J = 4.0 Hz,
2H), 5.38 (bs, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H),
7.84 (d, J = 7.5 Hz, 2H), 7.89 (d, J = 8.5 Hz, 2H), 9.22 (s, 1H).
13C{1H} NMR (CDCl3, 125 MHz) δ (ppm): 20.8, 62.2, 119.1, 119.7,
Figures giving NMR spectra of a few starting materials, known
compounds, and all of the unknown compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*S.K.M.: tel, 91-9903676563; fax, (+)91-33-48092033; e-mail,
swadhin.mandal@iiserkol.ac.in.
■
125.3, 127.5, 127.6, 129.5, 135.3, 137.6, 143.2, 147.3. HRMS m/z
(ESI): calcd for C16H14N3NaO [M + Na]+ 287.1035, found 287.1039.
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Article
(8) (a) Revunova, K.; Nikonov, G. I. Chem. Eur. J. 2014, 20, 839−
Notes
845. (b) Manas, M. G.; Sharninghausen, L. S.; Balcells, D.; Crabtree, R.
The authors declare no competing financial interest.
́
H. New J. Chem. 2014, 38, 1694−1700. (c) Fernandez-Salas, J. A.;
Manzini, S.; Nolan, S. P. Chem. Commun. 2013, 49, 9758−9760.
(d) Fedorov, A.; Toutov, A. A.; Swisher, N. A.; Grubbs, R. H. Chem.
Sci. 2013, 4, 1640−1645. (e) Buitrago, E.; Zani, L.; Adolfsson, H. Appl.
Organomet. Chem. 2011, 25, 748−752. (f) Addis, D.; Zhou, S.; Das, S.;
Junge, K.; Harloff, J.; Lund, H.; Kosslick, H.; Schulz, A.; Beller, M.
Chem. Asian J. 2010, 5, 2341−2345. (g) Drew, M. D.; Lawrence, N. J.;
Watson, W.; Bowles, S. A. Tetrahedron Lett. 1997, 38, 5857−5860.
(h) Fujita, M.; Hiyama, T. J. Org. Chem. 1988, 53, 5405−5415.
(9) (a) Zhao, Q.; Curran, D. P.; Malacria, M.; Fensterbank, L.;
ACKNOWLEDGMENTS
■
S.R.R. thanks the CSIR for a RA fellowship. S.C.S. thanks the
UGC, New Delhi, India, for a research fellowship. S.K.M.
thanks the SERB (DST), New Delhi, India, for financial
support. The authors also thank the NMR facility of IISER-
Kolkata.
̂
Goddard, J. P.; Lacote, E. Synlett 2012, 23, 433−437. (b) Malkov, A.
REFERENCES
■
V.; Liddon, A. J. P. S.; Ramirez-Lopez, P.; Bendova, L.; Haigh, D.;
Kocovsky, P. Angew. Chem., Int. Ed. 2006, 45, 1432−1435; Angew.
Chem. 2006, 118, 1460−1463. (c) Nishiyama, Y.; Kajimoto, H.;
Kotani, K.; Sonoda, N. Org. Lett. 2001, 3, 3087−3089.
(1) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org.
Biomol. Chem. 2006, 4, 2337−2347.
(2) (a) Jagdale, A. R.; Paraskar, A. S.; Sudalai, A. Synthesis 2009,
660−664. (b) Haddenham, D.; Pasumansky, L.; DeSoto, J.; Eagon, S.;
Singaram, B. J. Org. Chem. 2009, 74, 1964−1970. (c) Baker, B. A.;
(10) (a) Sau, S. C.; Raha Roy, S.; Sen, T. K.; Mullangi, D.; Mandal, S.
K. Adv. Synth. Catal. 2013, 355, 2982−2991. (b) Sen, T. K.; Sau, S. C.;
Mukherjee, A.; Hota, P. K.; Mandal, S. K.; Maity, B.; Koley, D. Dalton
Trans. 2013, 42, 14253−14260. (c) Sau, S. C.; Santra, S.; Sen, T. K.;
Mandal, S. K.; Koley, D. Chem. Commun. 2012, 48, 555−557. (d) Sen,
T. K.; Sau, S. C.; Mukherjee, A.; Modak, A.; Mandal, S. K.; Koley, D.
Chem. Commun. 2011, 47, 11972−11974.
̌
̌ ́
Boskovic, Z. V.; Lipshutz, B. H. Org. Lett. 2008, 10, 289−292.
(d) Meta, C. T.; Koide, K. Org. Lett. 2004, 6, 1785−1787. (e) Khurana,
J. M.; Kukreja, G. Synth. Commun. 2002, 32, 1265−1269. (f) Hays, D.
S.; Scholl, M.; Fu, G. C. J. Org. Chem. 1996, 61, 6751−6752.
(g) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.;
Shah, R. D. J. Org. Chem. 1996, 61, 3849−3862.
(11) (a) N-Heterocyclic Carbenes in Transition Metal Catalysis.
Topics in Organometallic Chemistry; Glorius, F., Ed.; Springer: Berlin,
(3) (a) Smeltz, J. L.; Boyle, P. D.; Ison, E. A. Organometallics 2012,
31, 5994−5997. (b) Park, S.; Brookhart, M. Organometallics 2010, 29,
6057−6064.
́
2007. (b) Dıez-Gonzal
́
ez, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251,
874−883. (c) N-Heterocyclic Carbenes in Synthesis; Nolan, S. P., Ed.;
(4) (a) Peng, D.; Zhang, Y.; Du, X.; Zhang, L.; Leng, X.; Walter, M.
D.; Huang, Z. J. Am. Chem. Soc. 2013, 135, 19154−19166.
(b) Huckaba, A. J.; Hollis, T. K.; Reilly, S. W. Organometallics 2013,
32, 6248−6256. (c) Bornschein, C.; Werkmeister, S.; Junge, K.; Beller,
M. New J. Chem. 2013, 37, 2061−2065. (d) Das, S.; Li, Y.; Junge, K.;
Beller, M. Chem. Commun. 2012, 48, 10742−10744. (e) Enthaler, S.;
́
Wiley-VCH: Weinheim, Germany, 2006. (d) Dıez-Gonzal
Nolan, S. P. Annu. Rep. Prog. Chem. Sect. B 2005, 101, 171−191.
(e) Cesar, V.; Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. Rev.
́
ez, S.;
́
2004, 33, 619−636. (f) Herrmann, W. A. Angew. Chem., Int. Ed. 2002,
41, 1290−1309; Angew. Chem. 2002, 114, 1342−1363.
(12) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J. W.;
̈
Schroder, K.; Inoue, S.; Eckhardt, B.; Junge, K.; Beller, M.; Drieß, M.
̈
Crabtree, R. H. Chem. Commun. 2001, 2274−2275.
Eur. J. Org. Chem. 2010, 25, 4893−4901. (f) Junge, K.; Wendt, B.;
Enthaler, S.; Beller, M. ChemCatChem 2010, 2, 453−460. (g) Shaikh,
N. S.; Junge, K.; Beller, M. Org. Lett. 2007, 9, 5429−5432.
(13) (a) Keitz, B. K.; Bouffard, J.; Bertrand, G.; Grubbs, R. H. J. Am.
Chem. Soc. 2011, 133, 8498−8501. (b) Zeng, X.; Frey, G. D.; Kinjo, R.;
Donnadieu, B.; Bertrand, G. J. Am. Chem. Soc. 2009, 131, 8690−8696.
(c) Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. J. Am. Chem.
Soc. 2004, 126, 5046−5047. (d) Fructos, M. R.; Belderrain, T. R.;
(5) Sprengers, J. W.; de Greef, M.; Duin, M. A.; Elsevier, C. J. Eur. J.
Inorg. Chem. 2003, 3811−3819.
(6) Nishiyama, H.; Furuta, A. Chem. Commun. 2007, 7, 760−762.
(7) Methods using metal hydride-based reagents: (a) Hecker, S. J.;
Heathcock, C. H. J. Am. Chem. Soc. 1986, 108, 4586−4594.
(b) Krishnamurthy, S. J. Org. Chem. 1981, 46, 4628−4629. Methods
using Stryker’s reagent: (c) Lipshutz, B. H.; Chrisman, W.; Noson, K.
J. Organomet. Chem. 2001, 624, 367−371. Methods using NaBH4:
(d) Nutaitis, C. F.; Bernardo, J. E. J. Org. Chem. 1989, 54, 5629−5630.
Recent examples of hydrosilylation using NHC-metal complexes:
(e) Postigoa, L.; Royo, B. Adv. Synth. Catal. 2012, 354, 2613−2618.
(f) Bheeter, L. P.; Henrion, M.; Brelot, L.; Darcel, C.; Chetcuti, M. J.;
Sortais, J. B.; Ritleng, V. Adv. Synth. Catal. 2012, 354, 2619−2624.
́
Nicasio, M. C.; Nolan, S. P.; Kaur, H.; Díaz-Requejo, M. M.; Perez, P.
J. J. Am. Chem. Soc. 2004, 126, 10846−10847. (e) Navarro, O.; Kelly,
R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194−16195.
(f) Viciu, M. S.; Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4,
4053−4056.
(14) (a) Albrecht, M. Chem. Commun. 2008, 3601−3610.
(b) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M.
Chem. Rev. 2009, 109, 3445−3478. (c) Heckenroth, M.; Neels, A.;
Garnier, M. G.; Aebi, P.; Ehlers, A. W.; Albrecht, M. Chem. Eur. J.
2009, 15, 9375−9386. (d) Arnold, P. L.; Pearson, S. Coord. Chem. Rev.
2007, 251, 596−609. (e) Ung, G.; Bertrand, G. Chem. Eur. J. 2011, 17,
8269−8272.
(g) Bez
́
ier, D.; Jiang, F.; Roisnel, T.; Sortais, J. B.; Darcel, C. Eur. J.
ier, D.; Sortais, J. B.;
Inorg. Chem. 2012, 1333−1337. (h) Jiang, F.; Bez
́
(15) Perez, E. A.; Rosenthal, A. J.; Donnadieu, B.; Parameswaran, P.;
Frenking, G.; Bertrand, G. Science 2009, 326, 556−559.
(16) Albrecht, M. Science 2009, 326, 532−533.
Darcel, C. Adv. Synth. Catal. 2011, 353, 239−244. (i) Kandepi, V. V. K.
M.; Cardoso, J. M. S.; Peris, E.; Royo, B. Organometallics 2010, 29,
2777−2782. (j) Tan, M.; Zhang, Y.; Ying, J. Y. Adv. Synth. Catal. 2009,
́
(17) (a) Dıez-Gonzal
L.; Nolan, S. P. Chem. Eur. J. 2008, 14, 158−168. (b) Gonzal
Nolan, S. P. Acc. Chem. Res. 2008, 41, 349−358. (c) Gonzal
́
ez, S.; Stevens, E. D.; Scott, N. M.; Petersen, J.
́
351, 1390−1394. (k) Gonzalez, S. D.; Kaur, H.; Zinn, F. K.; Stevens,
́
ez, S. D.;
ez, S. D.;
E. D.; Nolan, S. P. J. Org. Chem. 2005, 70, 4784−4796. Methods using
silver complexes: (l) Wile, B. M.; Stradiotto, M. Chem. Commun. 2006,
4104−4106. Methods using gold complexes: (m) Lantos, D.; Contel,
M.; Sanz, S.; Bodor, A.; Horvath, I. T. J. Organomet. Chem. 2007, 692,
1799−1805. (n) Ito, H.; Yajima, T.; Tateiwab, J.; Hosomi, A. Chem.
Commun. 2000, 981−982. Methods using ruthenium complexes:
(o) Chatterjee, B.; Gunanathan, C. Chem. Commun. 2014, 50, 888−
890. (p) Do, Y.; Han, J.; Rhee, Y. H.; Park, J. Adv. Synth. Catal. 2011,
353, 3363−3366. Methods using copper complexes: (q) Deschamp,
J.; Chuzel, O.; Hannedouche, J.; Riant, O. Angew. Chem., Int. Ed. 2006,
45, 1292−1297; Angew. Chem. 2006, 118, 1314−1319. (r) Lee, C. T.;
Lipshutz, B. H. Org. Lett. 2008, 10, 4187−4190. (s) Albright, A.;
Gawley, R. E. J. Am. Chem. Soc. 2011, 133, 19680−19683.
́
Scott, N. M.; Nolan, S. P. Organometallics 2006, 25, 2355−2358.
(d) Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics
2004, 23, 1157−1160.
(18) (a) Frey, G. D.; Donnadieu, B.; Soleilhavoup, M.; Bertrand, G.
Chem. Asian J. 2011, 6, 402−405. (b) Deutsch, C.; Krause, N.;
Lipshutz, B. H. Chem. Rev. 2008, 108, 2916−2927. (c) Mankad, N. P.;
Laitar, D. S.; Sadighi, J. P. Organometallics 2004, 23, 3369−3371.
(19) (a) Zheng, J.; Darcel, C.; Sortais, J. B. Catal. Sci. Technol. 2013,
3, 81−84. (b) Dieskau, A. P.; Begouin, J. M.; Plietker, B. Eur. J. Org.
Chem. 2011, 5291−5296. (c) Tran, B. L.; Pink, M.; Mindiola, D. J.
Organometallics 2009, 28, 2234−2243.
9159
dx.doi.org/10.1021/jo501505j | J. Org. Chem. 2014, 79, 9150−9160

The Journal of Organic Chemistry
Article
(20) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin
Trans. 1 1999, 3381−3391.
9, 2965−2968. (m) Bez
́
ier, D.; Jiang, F.; Roisnel, T.; Sortais, J. B.;
Darcel, C. Eur. J. Inorg. Chem. 2012, 1333−1337. (n) Xu, W.; Wang,
R.; Wu, G.; Chen, P. RSC Adv. 2012, 2, 6005−6010. (o) Bayer, A.;
Svendsen, J. S. Eur. J. Org. Chem. 2001, 1769−1780. (p) Dieskau, A.
P.; Begouin, J. M.; Plietker, B. Eur. J. Org. Chem. 2011, 5291−5296.
(q) Michaels, H. A.; Zhu, L. Chem. Asian J. 2011, 2825−2834.
́
(21) (a) Zheng, J.; Elangovan, S.; Valyaev, D. A.; Brousses, R.; Cesar,
V.; Sortais, J.-B.; Darcel, C.; Lugan, N.; Lavigne, G. Adv. Synth. Catal.
2014, 356, 1093−1097. (b) Abbina, S.; Bian, S.; Oian, C.; Du, G. ACS
Catal. 2013, 3, 678−684. (c) Chakraborty, S.; Blacque, O.; Fox, T.;
Berke, H. ACS Catal. 2013, 3, 2208−2217. (d) Chidara, V. K.; Du, G.
Organometallics 2013, 32, 5034−5037. (e) Tondreau, A. M.;
Lobkovsky, E.; Chirik, P. J. Org. Lett. 2008, 10, 2789−2792.
(f) Mori, A.; Fujita, A.; Kajiro, H.; Nishihara, Y.; Hiyama, T.
Tetrahedron 1999, 55, 4573−4582. (g) Keinan, E.; Greenspoon, N. J.
Am. Chem. Soc. 1986, 108, 7314−7325.
̂ ́
(22) Moser, R.; Boskovic, Z. V.; Crowe, C. S.; Lipshutz, B. H. J. Am.
Chem. Soc. 2010, 132, 7852−7853.
(23) (a) Chen, J.-X.; Daeuble, J. F.; Stryker, J. M. Tetrahedron 2000,
56, 2789−2798. (b) Chen, J.-X.; Daeuble, J. F.; Brestensky, D. M.;
Stryker, J. M. Tetrahedron 2000, 56, 2153−2166.
(24) Zheng, G. Z.; Chan, T. H. Organometallics 1996, 14, 70−79.
(25) (a) Castro, L. C. M.; Sortais, J. B.; Darcel, C. Chem. Commun.
2012, 48, 151−153. (b) Jurkauskas, V.; Sadighi, J. P.; Buchwald, S. L.
Org. Lett. 2003, 5, 2417−2420. (c) Ojima, I.; Nihonyanagi, M.;
Kogure, T.; Kumagai, M.; Horiuchi, S.; Nakatsugawa, K.; Nagai, Y. J.
Organomet. Chem. 1975, 94, 449−461. (d) Lipshutz, B. H.; Keith, J.;
Papa, P.; Vivian, R. Tetrahedron Lett. 1998, 39, 4627−4630.
(26) (a) Gopiraman, M.; Babu, S. G.; Khatri, Z.; Wei, K.; Endo, M.;
Karvembu, R.; Kim, I. S. Catal. Sci. Technol. 2013, 3, 1485−1489.
(b) Taniguchi, T.; Curran, D. P. Org. Lett. 2012, 14, 4540−4543.
(c) Xu, W.; Wang, R.; Wu, G.; Chen, P. RSC Adv. 2012, 2, 6005−
6010. (d) He, L.; Ni, J.; Wang, L. C.; Yu, F. J.; Cao, Y.; He, H. Y.; Fan,
K. N. Chem. Eur. J. 2009, 15, 11833−11836. (e) Ward, D.; Rhee, C.
Can. J. Chem. 1989, 67, 1206−1211.
(27) Wang, Z.; Bennett, E. M.; Wilson, D. J.; Salomon, C.; Vince, R.
J. Med. Chem. 2007, 50, 3416−3419.
(28) Tundo, P.; Anastas, P.; Black, D. S.; Breen, J.; Collins, T.;
Memoli, S.; Miyamoto, J.; Polyakoff, M.; Tumas, W. Pure Appl. Chem.
2000, 72, 1207−1228.
(29) (a) Ma, C.; Zhao, C.; Ge, Y.; Shi, C. Clin. Chem. 2012, 58, 384−
390. (b) Ortega, F.; Ehrenberg, M.; Acerenza, L.; Westerhoff, H. V.;
Mas, F.; Cascante, M. Mol. Biol. Rep. 2002, 29, 211−215. (c) Staunton,
J.; Weissman, K. J. Nat. Prod. Rep. 2001, 18, 380−416. (d) Khosla, C.;
Gokhale, R. S.; Jacobsen, J. R.; Cane, D. E. Annu. Rev. Biochem. 1999,
68, 219−253. (e) Katz, L. Chem. Rev. 1997, 97, 2577−2590.
(30) (a) Wasilke, J. C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem.
Rev. 2005, 105, 1001−1020. (b) Tietze, L. F. Chem. Rev. 1996, 96,
115−136.
(31) (a) Chen, H.; Wang, Z.; Zhang, Y.; Huang, Y. J. Org. Chem.
2013, 78, 3503−3509. (b) Candish, L.; Lupton, D. W. Chem. Sci.
2012, 3, 380−383. (c) Wang, J.; Wang, J.; Zhu, Y.; Lu, P.; Wang, Y.
Chem. Commun. 2011, 47, 3275−3277. (d) Yang, T.; Ferrali, A.;
Campbell, L.; Dixon, D. J. Chem. Commun. 2008, 45, 2923−2925.
(e) Enders, D.; Huttl, M. R. M.; Grondal, C.; Raabe, G. Nature 2006,
̈
441, 861−863. (f) Huang, Y.; Walji, A. M.; Larsen, C. H.; MacMillan,
D. W. C. J. Am. Chem. Soc. 2005, 127, 15051−15053. (g) Bruggink, A.;
Schoevaart, R.; Kieboom, T. Org. Process Res. Dev. 2003, 7, 622−640.
(32) (a) Bach, T.; Bergmann, H.; Brummerhop, H.; Lewis, W.;
Harms, K. Chem. Eur. J. 2001, 7, 4512−4521. (b) Bhagat, S.; Sharma,
R.; Sawant, D. M.; Sharma, L.; Chakraborti, A. K. J. Mol. Catal. A:
Chem. 2006, 244, 20−24. (c) Li, Y.; Gao, L. X.; Han, F. S. Chem. Eur. J.
2010, 16, 7969−7972. (d) Shaikh, N. S.; Junge, K.; Beller, M. Org. Lett.
2007, 9, 5429−5432. (e) Fujita, K. I.; Yoshida, T.; Imori, Y.;
Yamaguchi, R. Org. Lett. 2011, 13, 2278−2281. (f) Snyder, S. A.;
Zografos, A. L.; Lin, Y. Angew. Chem., Int. Ed. 2007, 46, 8186−8191.
(g) Chakraborty, S.; Krause, J. A.; Guan, H. Organometallics 2009, 28,
582−586. (h) Castro, L. C. M.; Bzier, D.; Sortais, J. B.; Darcel, C. Adv.
Synth. Catal. 2011, 353, 1279−1284. (i) Azerraf, C.; Gelman, D. Chem.
Eur. J. 2008, 14, 10364−10368. (j) Wu, F.-F.; Zhou, J.-N.; Fang, Q.;
Hu, Y.-H.; Li, S.; Zhang, X.-C.; Chan, A. S. C.; Wu, J. Chem. Asian J.
2012, 7, 2527−2530. (k) Hatano, M.; Suzuki, S.; Ishihara, K. J. Am.
Chem. Soc. 2006, 128, 9998−9999. (l) Liu, S.; Wolf, C. Org. Lett. 2007,
9160
dx.doi.org/10.1021/jo501505j | J. Org. Chem. 2014, 79, 9150−9160