Hydroarylation of arynes catalyzed by silver for biaryl synthesis

Article abstract of DOI:10.1021/ja500292x

A new biaryl synthesis via silver-catalyzed hydroarylation of arynes from acyclic building blocks with unactivated arenes in intra- and intermolecular manners has been developed. The previously observed Diels-Alder reactions of arynes with arene were not observed under the current silver-catalyzed conditions. Deuterium scrambling and DFT calculations suggest a stepwise electrophilic aromatic substitution mechanism through the formation of a Wheland-type intermediate followed by a water-catalyzed proton transfer in the final step of the hydroarylation.

Full text of DOI:10.1021/ja500292x

Article
pubs.acs.org/JACS
Hydroarylation of Arynes Catalyzed by Silver for Biaryl Synthesis
Nam-Kyu Lee,† Sang Young Yun,† Phani Mamidipalli,† Ryan M. Salzman,† Daesung Lee,*,† Tao Zhou,‡
and Yuanzhi Xia*,‡
†Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, United States
‡College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang Province 325035, P.R. China
S
* Supporting Information
ABSTRACT: A new biaryl synthesis via silver-catalyzed
hydroarylation of arynes from acyclic building blocks with
unactivated arenes in intra- and intermolecular manners has
been developed. The previously observed Diels−Alder
reactions of arynes with arene were not observed under the
current silver-catalyzed conditions. Deuterium scrambling and
DFT calculations suggest a stepwise electrophilic aromatic
substitution mechanism through the formation of a Wheland-type intermediate followed by a water-catalyzed proton transfer in
the final step of the hydroarylation.
The biaryl motif is an important structural feature in many
natural products, pharmaceuticals, and functional materials.
Therefore, a variety of synthetic methods to form aryl−aryl
bonds have been developed.1 One common approach is the
transition-metal-catalyzed cross-coupling (Negishi, Stille, Ku-
mada, and Suzuki) (a, Scheme 1),1c,d which, despite its high
electron-rich arenes by arynes.4 On the other hand, Ueda5a and
Hoye5b reported that the hexadehydro-Diels−Alder reaction of
acyclic precursors 1 generate aryne intermediates 2,6 which
undergo [4 + 2] cycloaddition rather than hydroarylation with
arenes such as benzene to form product 3 (Scheme 2).7 At this
Scheme 2. Distinctive Reactivity of Arynes toward Arenes
with and without Silver Catalyst
a
Scheme 1. Catalytic Biaryl Formation
a
TM = transition-metal complex, X = halides, pseudohalides,
sulfonates, M = organometallic group.
efficiency and regiochemical control, requires preactivated aryl
precursors such as aryl halide and aryl metal species. Recently,
more atom-economical and greener alternatives such as direct
C−H arylation (b, Scheme 1)1e−h and oxidative coupling of
arenes (c, Scheme 1)1h have emerged. In the direct arylations,
the Ar−Ar bond is formed through the activation of an aryl C−
H bond by aryl-metal species (Ar−Pd, Ar−Rh, and Ar−Ru)
generated from aryl halides. On the other hand, in the oxidative
couplings, the aryl-metal species are generated via C−H bond
activation by a catalyst in the presence of oxidants.
Different from the transition-metal-based catalytic processes,
aryne2-based biaryl synthesis was first reported by Huisgen3a in
1958 and has continued to evolve through the research of
several groups.3 However, all of these reported methods require
strongly activated aryl nucleophiles such as Grignard, lithium,
and cuprate reagents. Recently, Daugulis and co-workers
reported intra- and intermolecular arylation of C−H bonds in
juncture, we hypothesized that if the [4 + 2] cycloaddition with
benzene is suppressed, the electrophilic aryne species would
participate in a Friedel−Crafts8-type electrophilic aromatic
substitution reaction, which would then lead to an effective
hydroarylation9 to form various biaryls. Since the reactive aryne
intermediate is generated via cycloaddition and the silver-
activated arynes10−12 would have high enough reactivity toward
arenes, neither the prefunctionalization of reacting arenes nor
the use of an oxidant is necessary for this hydroarylation
process.
Received: January 10, 2014
Published: March 2, 2014
© 2014 American Chemical Society
4363
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368

Journal of the American Chemical Society
Article
The feasibility of this aryne-based hydroarylation was
demonstrated by our recent observation where the in situ
generated arynes from multiynes, in the presence of silver salt,
resulted in an effective alkane C−H functionalization.10a This
novel C−H bond activation by arynes is considered to be the
consequence of the involvement of carbene-like species 4.1a,13
We surmise that the unusual reactivity of silver-complexed
arynes can provide a powerful tool for hydroarylation via either
direct activation of C(sp2)−H bonds or an electrophilic
aromatic substitution in both intra- and intermolecular manners
to deliver the final products 5 and 6.
Table 1. Intermolecular Hydroarylation of Silver Complexed
Arynes
To exploit this catalyst-modulated aryne reactivity, we
planned to test the feasibility of an intramolecular C(sp2)−H
bond insertion. First, symmetrical substrate 1a that contains
potentially competing C(sp3)−H and C(sp2)−H bonds on the
tert-butyldiphenylsilyl group was subjected to typical reaction
conditions (Scheme 3). Indeed, with 10 mol % silver
Scheme 3. Competition between C(sp2)−H and C(sp3)−H
Bonds
hexafluoroantimonate (AgSbF6) as the catalyst, the insertion
reactions on both the C(sp2)−H and C(sp3)−H bonds
occurred, affording products 5a and 5a′ in a 1:3.5 ratio. On
the other hand, with silver triflate (AgOTf) a similar efficiency
was observed but with a reversed 1.5:1 selectivity. Other silver
salts containing different counterions or different transition-
metal complexes also effected the insertion but in relatively low
yields.14
Once the feasibility of C(sp2)−H insertion was demon-
strated, we examined its generality with various substrates
(Table 1). For C(sp2)−H insertion, AgOTf consistently
showed superior performance compared to AgSbF6. This is
the opposite in C(sp3)−H insertion where AgOTf tended to
generate a triflate adduct. Similar to the beneficial effects of the
gem-dialkyl groups on ring closure reactions,15 the two alkyl or
aryl groups on the silyl groups of the silyl-tethered substrate 1
confer the expected gem-dialkyl effect. Therefore, the efficiency
of C(sp2)−H insertion with substrates 1b−1g is generally
higher than that with substrates 1h and 1i that contain a
nitrogen or an oxygen tether.
Under optimized conditions with AgOTf (10 mol %) in
toluene at 90 °C, substrates 1b and 1c afforded five-membered
silacyclic products 5b and 5c in 87 and 67% yields, respectively
(entries 1 and 2). It is worthwhile to note that the reaction of
substrate 1c afforded an insertion product of only a C(sp2)−H
bond even though the n-pentyl group can still undergo
insertion with its C(sp3)−H bonds. The different insertion
behavior of 1c compared to that of 1a seems to be caused by
the lack of gem-dimethyl effect when the n-pentyl moiety of 1c
is engaged in the insertion as opposed to the gem-dimethyl
effect the tert-butyl group in 1a would have. The substrates 1d−
g, which contain a dimethylsilylmethylene tether, provided six-
a
b
Isolated yield. Si−C(sp2) bond was hydrolyzed during silica gel
column chromatography.
membered ring silacyclic products 5d−g in 92−96% yields
(entries 3−6). The bromide-containing aryl isoindoline
derivative 5f was also generated in excellent yield (96%).
However, nitrogen- and oxygen-tethered substrates 1h and 1i
afforded six-membered fused cycles 5h and 5i in only 49 and
50% yield, respectively (entries 7 and 8). Desilylation of the
resulting silacyclic compounds 5d−5f with TBAF (entry 9)
efficiently afforded isoindoline derivatives containing biaryl
moiety with toluene (6d), p-xylene (6e), and 2-bromotoluene
(6f).
Although effective, the intramolecular C(sp2)−H insertion is
limited to form only five- and six-membered rings. As shown in
Scheme 4, longer tether-containing systems 1j and 1k
4364
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368

Journal of the American Chemical Society
Article
Scheme 4. Diels−Alder Reaction Rather Than C(sp2)−H
Insertion
Table 2. Optimization of the Reaction Conditions
b
entry catalyst (10 mol %)
solvent
temperature (°C) yield (%)
1
2
AgSbF6
AgOTf
benzene
benzene90
benzene
benzene
benzene
benzene
CH3CN
c-hexane
CH2Cl2
PhCl
90
90
90
90
50
25
90
90
40
90
72
63
10
10
5
3
Cu(OTf)2
In(OTf)3
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
participated in only an intramolecular Diels−Alder reaction5b to
generate 3j and 3k rather than undergoing C(sp2)−H insertion
to produce seven-membered ring-containing hydroarylation
products 5j and 5k.
4
5
6
0
7
0
8
0
To overcome this ring-size dependency in intramolecular
hydroarylation, we turned our attention to intermolecular
counterparts. Because we noticed that the C(sp3)−H insertion
was relatively ineffective without the gem-dialkyl substituent at
the propargylic site of the substrates,12 we have chosen
ynamide16 derived unsymmetrical bis-1,3-diyne 1l as a testing
substrate for intermolecular hydroarylation (Scheme 5).
9
trace
70
10
a
b
3 Equivalent was used when the solvent is not benzene. Isolated
yield.
bis-1,3-diynes and triynes (Table 3). The formation of single
isomeric products 6na−6nd as well as 6o was observed by
reacting nonsymmetrical bis-1,5-diynes 1n and 1o containing a
terminal alkynyl moiety with benzene, p-xylene, mesitylene,
iodobenzene, and 2-bromo-1,3-dimethylbenzene. The high
regioselectivity of these reactions can be rationalized by the
selectivity trend that Garg18a and Houk18b identified for
indolynes. It is worth noting that the known ene reaction of
xylene and mesitylene with aryne7d was not observed in the
current system. Among the halobenzenes (chorobenzene,
bromobenzene and iodobenzene) examined in the reaction
with 1o, only iodobenzene showed marginal reactivity and
afforded 6o as a single isomer (entry 5). The reaction of 1n
with 2-bromo-1,3-dimethylbenzene, however, afforded 6nd
efficiently (61%), which indicates that the electronic factor in
the arene is crucial for successful hydroarylation. A butyl group-
containing bis-1,3-diynes 1p also afforded single isomer ortho-
6p (entry 6). Triynes containing an amide or ester tether (1q−
1s) also afforded single isomeric biaryl products (6q−6s) after
a longer reaction time of 8 h rather than the typical 5 h for
other substrates (entries 7−10). Substrate 1s, containing a
conjugated triyne moiety, showed similar reactivity and
regioselectivity and afforded 6s in 63% yield (entry 10). A set
of arenes (entry 11) that is seemingly reactive enough in
hydroarylation either afforded low yield or showed no reactivity
in the reaction with substrate 1n.
For the reaction of symmetrical bis-1,3-diynes 1m, 1t, and
1u, the regioselectivity depends on the nature of the substituent
on the 1,3-diyne moiety (Table 4). Ethyl-containing substrate
1t afforded 6t with slight preference of the phenyl
incorporation at the ortho-position relative to the ethyl group
(m:o = 2:1) (entry 1). By increasing the steric bulkiness to
secondary alkyl such as the cyclopropyl group in 1m and to
SiMe3 in 1u, the ratio of isomers of 6m and 6u progressively
changed and ultimately favored the phenyl incorporation at the
meta-position with slight preference in 6u (entries 2 and 3).
To gain insight into the mechanism of this hydroarylation,
we carried out a competition experiment with benzene and
Scheme 5. Initial Attempt for Intermolecular C(sp2)−H
Bond Insertion
Gratifyingly, when 1l was treated with AgOTf in benzene at
95 °C, biaryl compound 6p was obtained predominantly along
with only a trace amount of C−H insertion product 6l′ and
trifluoromethanesulfonate adduct 7l. As expected, Diels−Alder
reaction product 3l was not observed indicating the reactivity
difference of aryne with and without a silver catalyst.
With these encouraging preliminary results in hand, we
further examined an intermolecular hydroarylation employing
cyclopropyl-substituted bis-1,3-diyne 1m and benzene as the
trapping agent (Table 2). When AgSbF6 (10 mol %, 90 °C) was
employed, complete conversion was observed within 5 h, and
the isolated product was identified as the expected biaryl
product 6m (72%) with a 1:1 ratio of isomers (entry 1).
AgOTf, which tends to give a triflate adduct, exhibited a similar
reaction profile, but the yield was slightly lower (63%). Other
metal triflates such as Cu(OTf)2 and In(OTf)3 were found to
be inefficient (entries 3 and 4). A reaction temperature as high
as 90 °C seems to be necessary because at lower temperatures
either low conversion or no reaction was observed (entries 5
and 6).
When nonaromatic solvents were used together with 300
mol % benzene, no desired product was formed (entries 7−9),
but in chlorobenzene, benzene adduct 6m was obtained in 70%
yield without contamination by a chlorobenzene adduct (entry
10).17
Next, we explored the prowess of the intermolecular
hydroarylation employing both symmetrical and unsymmetrical
1
benzene-d6, the product of which was analyzed by H NMR
and high-resolution mass spectrometry. This proved the
existence of isotopormers I−IV in a 1:0.3:0.5:0.8 ratio (Scheme
6). The observed 1:1 ratio of products derived from benzene (I
4365
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368

Journal of the American Chemical Society
Article
Table 3. Intermolecular Hydroarylation of Silver Complexed
Arynes
Scheme 6. Competition with Benzene and Deuterated
Benzene
+ II) and benzene-d6 (III + IV) indicates that there is no
deuterium kinetic isotope effect. Furthermore, the formation of
a significant amount of crossover products II (12%) and III
(21%) implies that the reaction proceeded through a stepwise
mechanism rather than a concerted C−H insertion process.
To further clarify this suggestive mechanistic data, we carried
out DFT calculations19 for the reaction of a simplified model
substrate with benzene (Scheme 7).
Scheme 7. Energy Profiles for the Hydroarylation Calculated
at the PCM-M06/6-31G*/LanL2DZ Level19
a
b
c
Isolated yield. Plus 20% regioisomer (para to bromide). Plus 12%
d
regioisomer (para to iodine). 5 h of reaction time instead of 5 h.
In the calculation, Ag-complexed aryne IN120 interacted
strongly with benzene to form Wheland-type intermediate IN2.
Starting from this intermediate, three different reaction
pathways were calculated including 1,2- (Path A) and 1,3-
proton shift (Path B), and water-catalyzed proton transfer
(Path C).19 In path A, 1,2-proton shift through TS1 led to
carbenoid intermediate IN3, which ultimately provided silver-
coordinated hydroarylation product IN4 through TS2. The 1,3-
proton transfer in Path B has a significantly lower activation
barrier (5.9 kcal/mol) to reach transition state TS3, which
collapses to the same product IN4. Considering the formation
of crossover product II and III in Scheme 5, we surmise that
the proton transfer is either mediated by an adventitious water
molecule or by a bimolecular process. When a water molecule
was placed around the H to be removed (O−H = 3.2 Å), no H-
Table 4. Regioselectivity in Symmetrical bis-1,3-Diynes
a
entry
substrate
R
product
ratio (o:m)
yield (%)
1
2
3
1t
1m
1u
Et
6t
6m
6u
2:1
1:1
2:3
76%
72%
cyclopropyl
SiMe3
b
53%
a
b
Isolated yield as an inseparable mixture of isomers. Plus 10%
flourinated product.
4366
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368

Journal of the American Chemical Society
Article
Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem., Int.
Ed. 2012, 51, 10236. (h) Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39,
540.
bonded complex was located, and the simultaneous formation
of intermediate IN5 occurred. In the following step, however,
no transition state for protodemetalation involving proton
donation from the hydronium ion was found. Instead, a slight
displacement of the hydronium ion toward the Ag−C bond
rendered the direct formation of product complex IN6. Similar
reaction profiles were found when calculated with a cationic
silver species without the ligand (SbF6), although the water-
catalyzed path had a sizable activation barrier (10.6 kcal/mol)
for the proton transfer.19 Based on these calculated energy
profiles and the observed deuterium scrambling results, the
most probable mechanism for the current hydroarylation
involves the conversion of aryne-silver complex IN1 to
Wheland-type intermediate IN2 followed by a water-catalyzed
proton transfer.21,22
In summary, we have explored silver-catalyzed intra- and
intermolecular hydroarylations of arynes that render an
effective new biaryl synthesis from acyclic building blocks.
Under the current silver-catalyzed conditions, the previously
observed intermolecular Diels−Alder reaction of arynes with
arene was not observed. The regioselectivity of C−H insertion
in intermolecular reactions depends on both steric and
electronic factors in the aryne intermediates. For the
corresponding intramolecular insertion reactions, however,
due to geometrical constraint of the short tether between the
aryne and arene moieties, uniform regioselectivity was
observed. Through this hydroarylation of arynes, various
indoline, isoindoline, isoindolinone, and dihydroisobenzofuran
derivatives containing a biaryl moiety were synthesized. The
deuterium scrambling experiments and DFT calculations
suggest that the hydroarylation occurs via a stepwise electro-
philic aromatic substitution mechanism involving the formation
of a Wheland-type intermediate followed by a water-catalyzed
proton transfer in the final step instead of the direct insertion
into the C(sp2)−H bond of arenes by silver-activated arynes.
(2) Reviews on arynes: (a) Kessar, S. V. in Comprehensive Organic
Synthesis, Trost, B. M.; Fleming, I., Eds:, Pergamon Press: New York,
1991; Vol. 4, pp 483−515. (b) Pellissier, H.; Santelli, M. Tetrahedron
2003, 59, 701. (c) Wenk, H. H.; Winkler, M.; Sander, W. Angew.
Chem., Int. Ed. 2003, 42, 502. (d) Sanz, R. Org. Prep. Proc. Int. 2008,
40, 215−291. (e) Chen, Y.; Larock, R. C. In Modern Arylation Methods;
Ackermann, L., Eds.; Wiley-VCH: Weinheim, Germany, 2009.
(f) Kitamura, T. Aust. J. Chem. 2010, 63, 987. (g) Tadross, P. M.;
Stoltz, B. M. Chem. Rev. 2012, 112, 3550. (h) Wu, C.; Shi, F. Asian J.
Org. Chem. 2013, 2, 116.
(3) (a) Huisgen, R.; Sauer, J.; Hauser, A. Chem. Ber. 1958, 91, 2366.
(b) Meyers, A. I.; Pansegrau, P. D. J. Chem. Soc., Chem. Commun.
1985, 690. (c) Hart, H.; Harada, K.; Du, C.-J. F. J. Org. Chem. 1985,
50, 3104. (d) Leroux, F.; Schlosser, M. Angew. Chem., Int. Ed. 2002, 41,
4272. (e) Henderson, J. L.; Edwards, A. S.; Greaney, M. F. Org. Lett.
2007, 9, 5589. (f) Liu, Z.; Larock, R. C. Angew. Chem., Int. Ed. 2007,
46, 2535. (g) Becht, J.-M.; Gissot, A.; Wagner, A.; Mioskowski, C.
Chem.Eur. J. 2003, 9, 3209. (h) Abboud, M.; Mamane, V.; Aubert,
E.; Lecomte, C.; Fort, Y. J. Org. Chem. 2010, 75, 3224.
(4) (a) Bajracharya, G. B.; Daugulis, O. Org. Lett. 2008, 10, 4625.
(b) Truong, T.; Daugulis, O. J. Am. Chem. Soc. 2011, 133, 4243.
(c) Truong, T.; Daugulis, O. Org. Lett. 2012, 14, 5964.
(5) (a) Miyawaki, K.; Suzuki, R.; Kawano, T.; Ueda, I. Tetrahedron
Lett. 1997, 38, 3943. (b) Hoye, T. R.; Baire, B.; Niu, D.; Willoughby,
P. H.; Woods, B. P. Nature 2012, 490, 208.
(6) (a) Meyerson, S.; Fields, E. K. Tetrahedron Lett. 1967, 571.
(b) Bradley, A. Z.; Johnson, R. P. J. Am. Chem. Soc. 1997, 119, 9917.
(c) Kociolek, M. G.; Johnson, R. P. Tetrahedron Lett. 1999, 40, 4141.
(d) Kimura, H.; Torikai, K.; Miyawaki, K.; Ueda, I. Chem. Lett. 2008,
37, 662. (e) Tsui, J. A.; Sterenberg, B. T. Organometallics 2009, 28,
4906. (f) Ajaz, A.; Bradley, A. Z.; Burrell, R. C.; Li, W. H. H.; Daoust,
K. J.; Bovee, L. B.; DiRico, K. J.; Johnson, R. P. J. Org. Chem. 2011, 76,
9320. (g) Karmakar, R.; Mamidipalli, P.; Yun, S. Y.; Lee, D. Org. Lett.
2013, 15, 1938. (h) Niu, D.; Willoughby, P. H.; Baire, B.; Woods, B.
P.; Hoye, T. R. Nature 2013, 501, 531. (i) Karmakar, R.; Yun, S. Y.;
Wang, K.-P.; Lee, D. Org. Lett. 2014, 16, 6. (j) Niu, D.; Hoye, T. R.
Nat. Chem. 2014, 6, 34.
(7) Reaction of beznyne with arenes: (a) Miller, R. G.; Stiles, M. J.
Am. Chem. Soc. 1963, 85, 1798. (b) Stiles, M.; Burckhardt, U.; Freund,
G. J. Org. Chem. 1967, 32, 3718. (c) Friedman, L.; Lindow, D. F. J. Am.
Chem. Soc. 1968, 90, 2329. (d) Brinkley, J. M.; Friedman, L.
Tetrahedron Lett. 1972, 40, 4141. (e) Tabushi, I.; Yamda, H.; Yoshida,
Z.; Oda, R. Bull. Chem. Soc. Jpn. 1977, 50, 285.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details, characterization data, NMR spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
dsunglee@uic.edu
xyz@wzu.edu.cn
Notes
(8) (a) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew. Chem., Int.
Ed. 2004, 43, 550. (b) Olah, G. A. Friedel Crafts Chemistry; Wiley-
Interscience: New York, 1973.
(9) Reviews on hydroarylation: (a) Jia, C.; Kitamura, T.; Fujiwara, Y.
Acc. Chem. Res. 2001, 34, 633. (b) Foley, N. A.; Lee, J. P.; Ke, Z.;
Gunnoe, T. B.; Cundari, T. R. Acc. Chem. Res. 2009, 42, 585.
(c) Bandini, M. Chem. Soc. Rev. 2011, 40, 1358. (d) Nakao, Y. Chem.
Rec. 2011, 11, 242. (e) Andreatta, J. R.; McKeown, B. A.; Gunnoe, T.
B. J. Organomet. Chem. 2011, 696, 305.
(10) (a) Yun, S. Y.; Wang, K. P.; Lee, N.-K.; Mamidipalli, P.; Lee, D.
J. Am. Chem. Soc. 2013, 135, 4668. (b) Wang, K.-P.; Yun, S. Y.;
Mamidipalli, P.; Lee, D. Chem. Sci. 2013, 4, 3205.
(11) Silver additive effects on benzyne reactivity with arenes:
(a) Friedman, L. J. Am. Chem. Soc. 1967, 89, 3071. (b) Crews, P.;
Beard, J. J. Org. Chem. 1973, 38, 529. (c) Vedejs, E.; Shepherd, R. A.
Tetrahedron Lett. 1970, 11, 1863. (d) Tabushi, I.; Yamda, H.; Yoshida,
Z.; Oda, R. Bull. Chem. Soc. Jpn. 1977, 50, 291.
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the University of Illinois at Chicago for
financial support (LAS AFS). Y.X. acknowledges support from
the NSFC (21002073 and 21372178).
REFERENCES
■
(1) For reviews, see: (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
Chem. Rev. 2003, 103, 893. (b) Bringmann, G.; Gulder, T.; Gulder, T.
A. M.; Breuning, M. Chem. Rev. 2011, 111, 563. (c) Seechurn, C. C. C.
J.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem., Int. Ed.
(12) For review of metal-aryne complexes, see: (a) Bennett, M. A.;
Wenger, E. Chem. Ber. 1997, 130, 1029. For seminal reports:
́
(b) Boulho, C.; Oulie, P.; Vendier, L.; Etienne, M.; Pimienta, V.;
́
2012, 51, 5062. (d) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.;
Locati, A.; Bessac, F.; Maseras, F.; Pantazis, D. A.; McGrady, J. E. J.
Am. Chem. Soc. 2010, 132, 14239. (c) Hassan, M. R.; Kabir, S. E.;
Nicholson, B. K.; Nordlander, E.; Uddin, Md. N. Organometallics 2007,
Lemaire, M. Chem. Rev. 2002, 102, 1359. (e) Alberico, D.; Scott, M. E.;
Lautens, M. Chem. Rev. 2007, 107, 174. (f) McGlacken, G. P.;
Bateman, L. M. Chem. Soc. Rev. 2009, 38, 2447. (g) Kuhl, N.;
4367
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368

Journal of the American Chemical Society
Article
26, 4627. (d) Deaton, K. R.; Gin, M. S. Org. Lett. 2003, 5, 2477.
(e) Wada, K.; Pamplin, C. B.; Legzdins, P.; Patrick, B. O.; Tsyba, I.;
Bau, R. J. Am. Chem. Soc. 2003, 125, 7035. (f) Hughes, R. P.; Laritchev,
R. B.; Williamson, A.; Incarvito, C. D.; Zakharov, L. N.; Rheingold, A.
L. Organometallics 2003, 22, 2134. (g) Retbøll, M.; Edwards, A. J.; Rae,
A. D.; Willis, A. C.; Bennett, M. A.; Wenger, E. J. Am. Chem. Soc. 2002,
124, 8348. (h) Frid, M.; Per
Chem. Soc. 1999, 121, 9469.
́
ez, D.; Peat, A. J.; Buchwald, S. L. J. Am.
(13) Hansmann, M. H.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K.
Angew. Chem., Int. Ed. 2013, 52, 2593.
(14) 5a and 5a′ could be separated and fully characterized; see
Supporting Information for details.
(15) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735.
(16) Recent reviews on ynimides: (a) Wang, X.-N.; Yeom, H.-S.;
Fang, L.-C.; He, S.; Ma, Z.-X.; Kedrowski, B. L.; Hsung, R. P. Acc.
Chem. Res. 2013, 47, 560. (b) DeKorver, K. A.; Li, H.; Lohse, A. G.;
Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev. 2010, 110,
5064. (c) Evano, G.; Coste, A.; Jouvin, K. Angew. Chem., Int. Ed. 49,
2840.
(17) The chlorobenzene-incorporated product was not detected. For
the reactions of benzyne with chlorobenzene, see refs 6e and 8d.
(18) Recent theoretical studies on arynes, see: (a) Goetx, A. E.;
Bronner, S. M.; Cisneros, J. D.; Melamed, J. M.; Paton, R. S.; Houk, N.
K.; Garg, N. K. Angew. Chem., Int. Ed. 2012, 51, 2758. (b) Bronner, S.
M.; Mackey, J. L.; Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2012,
134, 13966. (c) Cheong, P. H.-Y.; Paton, R. S.; Bronner, S. M.; Im, G.-
Y. J.; Garg, N. K.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 1267.
(19) All calculations were carried out with the Gaussian 09 suite of
computational programs. The energies given in Scheme 7 are relative
solvation free energies (ΔGsol) and gas-phase relative free energies
(ΔG298). Computational details and citation of the software are given
in the Supporting Information.
(20) Carbene-type structure 4 is one of many possible heuristic
representations of Ag-aryne complex. The structure used in the DFT
calculation starts with another representation IN1. The relationship
between these structures can be shown as follows.
(21) For examples of water-catalyzed H-migrations in other systems:
(a) Xia, Y.; Liang, Y.; Chen, Y.; Wang, M.; Jiao, L.; Huang, F.; Liu, S.;
Li, Y.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 3470. (b) Shi, F.-Q.; Li,
X.; Xia, Y.; Zhang, L.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 15503.
(22) Calculation results indicate that in the absence of water benzene
solvent can also catalyse the proton transfer from IN2. See Supporting
Information for details.
4368
dx.doi.org/10.1021/ja500292x | J. Am. Chem. Soc. 2014, 136, 4363−4368