Tempering the reactivities of postulated α-oxo gold carbenes using bidentate ligands: Implication of tricoordinated gold intermediates and the development of an expedient bimolecular assembly of 2,4-disubstituted oxazoles

Article abstract of DOI:10.1021/ja307948m

2,4-Oxazole is an important structural motif in various natural products. An efficient modular synthesis of this structure has been achieved via a [3 + 2] annulation between a terminal alkyne and a carboxamide using a gold-catalyzed oxidation strategy. The postulated reactive intermediate, a terminal α-oxo gold carbene, previously known to be highly electrophilic and hence unlikely to be trapped by stoichiometric external nucleophiles, is coerced to react smoothly with the carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate ligand such as Mor-DalPhos; in stark contrast, often-used ligands such as monodentate phosphines and N-heterocyclic carbenes are totally ineffective. The role of these bidentate phosphines in this reaction is attributed to the formation of a tricoordinated gold carbene intermediate, which is less electrophilic and hence more chemoselective when reacting with nucleophiles. The success in using bidentate phosphine ligands to temper the reactivities of in situ-generated gold carbenes is likely to open many new opportunities to apply oxidative gold catalysis to the development of novel methods, and the implication of tricoordinated gold intermediates in homogeneous gold catalysis should stimulate further advances in gold catalysis.

Full text of DOI:10.1021/ja307948m

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Communication
Tempering the Reactivities of Postulated #-Oxo Gold
Carbenes by Bidentate Ligands: Implication of Tricoordinated
Gold Intermediates and the Development of an Expedient
Bimolecular Assembly of 2,4-Disubstituted Oxazoles
Yingdong Luo, Kegong Ji, Yu-Xue Li, and Liming Zhang
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 05 Oct 2012
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Tempering the Reactivities of Postulated αꢀOxo Gold Carbenes by Bidentate
Ligands: Implication of Tricoordinated Gold Intermediates and the Development of
an Expedient Bimolecular Assembly of 2,4ꢀDisubstituted Oxazoles
Yingdong Luo, † Kegong Ji,† Yuxue Li‡ and Liming Zhang†*
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Ling Ling Road 345,
Shanghai 200032, China‡
RECEIVED DATE (automatically inserted by publisher); zhang@chem.ucsb.edu
Abstract: 2,4ꢀOxazole is an important structural motif in various
natural products. An efficient modular synthesis of this structure
is achieved via a [3+2] annulation between a terminal alkyne and
a carboxamide by using a goldꢀcatalyzed oxidation strategy. The
postulated reactive intermediate, a terminal αꢀoxo gold carbene,
previously known to be highly electrophilic and hence impropable
to be trapped by stoichiometric external nucleophiles, is coerced
to react smoothly with a carboxamide en route to the oxazole ring
by a P,Nꢀ or P,Sꢀbidentate ligand such as MorꢀDalPhos; in stark
contrast, often used ligands including monodentate phosphines
and NHCs are totally ineffective. The role of these bidentate
phosphines in this reaction is attributed to the formation of a
tricoordinated gold carbene intermediate, which is less
electrophilic and hence more chemoselective when reacting with
nucleophiles. The success in using bidentate phosphine ligands to
temper the reactivities of inꢀsitu generated gold carbenes would
likely open many new opportunities to apply the oxidative gold
catalysis to the development of novel methods, and the
implication of tricoordinated gold intermediates in homogeneous
gold catalysis should stimulate further advance in gold catalysis.
Figure 1. Selected natural products containing 2,4ꢀdisubstituted oxazole
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moieties.
Scheme 1. A) alkynes as surrogates of hazardous αꢀdiazo
ketones in the generation of αꢀoxo gold carbene intermediates; B)
its application for the synthesis of 2,4ꢀdisubstituted oxazoles in a
[3+2] annulation
2,4ꢀDisubstituted oxazole is a structural motif found in many
bioactive natural products including (ꢀ)ꢀhennoxazole A1 and
phorboxazoles2 (Figure 1). Biosynthetically it is formed via postꢀ
translational modifications of serineꢀcontaining peptides via
sequential cyclization, dehydration and oxidative aromatization.
Chemical syntheses3 of this functionality can often be achieved
via sequential dehydrative cyclization4 and dehydrogenation5 of
substituted N-(2ꢀhydroxyethyl)amides. Though this multiꢀstep
linear approach proves to be reliable, the construction of this
important motif through a oneꢀstep bimolecular annulation6
would offer excellent step economy and desirable synthetic
convergence. Several elegant protocols of this nature,7 however,
have their own limitations. Herein we disclose a new development
featuring goldꢀcatalyzed oxidative [3+2] annulations between
readily available terminal alkynes and carboxamides under mild
reaction conditions. A key intermediate implicated in the catalytic
cycle is a gold(I) complex of triꢀcoordination, which is rare in
gold catalysis.8
typically be generated via metalꢀcatalyzed dediazotization of αꢀ
diazo ketones,12,13 this strategy provides a safe, stepꢀeconomic and
scalable alternative in the case of metal gold by using readily
available alkynes as substrates. Unfortunately, all the reactions
developed so far have relied on rapid trapping of the gold
carbenes via either facile intramolecular processes or by the
reaction solvent.6b In the latter case, we developed a rapid
synthesis of 2,5ꢀdisubstituted oxazoles in a [2+2+1] manner using
nitrile as both the solvent and the trapping reagent.6b Otherwise,
the reaction tends to be messy, which could be attributed to a lack
of chemoselectivity by the αꢀoxo gold carbene intermediate due to
its high electrophilicity. This rationale is further corroborated by
the observation that it can abstract chloride from the reaction
solvent dichloroethane.9d The highly electrophilic nature of the αꢀ
oxo gold carbene moiety, especially for those without additional
substitutions at the carbene center, can be understood by invoking
the relatively weak back donation by the electronegative gold.14
As a result, it is highly challenging to trapping these highly
electrophilic gold carbenes with stoichiometric external
nucleophiles.
We have recently developed a strategy of goldꢀcatalyzed
intermolecular alkyne oxidations (Scheme 1A),6b,9,10 where αꢀoxo
gold carbenes are postulated as key reactive intermediates. A
range of versatile synthetic methods have been developed based
on this design by us6b,9 and others,11 offering strong support for
the intermediacy of these gold carbenes and revealing their potent
electrophilicities. While αꢀoxo metal carbenes/carbenoids can
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Not deterred, we set out to discover catalysts and conditions
different from MorꢀDalPhos by having smaller cyclohexyl groups
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that would overcome this daunting challenge. The targeted
reaction was a [3+2] annulation between a terminal alkyne and a
carboxamides for the formation of 2,4ꢀdisubstituted oxazoles. The
design is rationalized in Figure 2B: the αꢀoxo gold carbene
intermediate A could be attacked by an amide by its carbonyl
oxygen, yielding the imidate B upon protodeauration; cyclization
of B would generate the oxazolinol C, the in situ dehydration of
which would afford the desired product.
on the phosphorus atom, led to a lower yet acceptable yield (entry
11); however, DavePhos was completely ineffective (entry 12).
These data suggested that the position of the amino group is
critical for the desired chemistry, the steric congestion is
beneficial and the morpholine oxygen is inconsequential. A much
higher yield (87%) was achieved when the carboxamide was the
limiting reagent and 1.5 equiv of the alkyne was used (entry 13).
Other more conventional solvents such as DCE (entry 14) and
toluene (entry 15) were less conducive to this reaction presumably
due to side reactions involving the solvents. It remains to be
pointed out that in order to avoid further oxidation of the gold
carbene intermediate by the remaining 8ꢀmethylquinoline Nꢀoxide
to form αꢀketoaldehyde, the oxidant had to be introduced to the
reaction flask slowly by a syringe pump so that its concentration
remained low during the reaction.
Table 1. Optimization of reaction conditions.a
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Table 2 . Reaction Scopea,b
entry 1a/2a
catalyst
Ph3PAuNTf2 (5 mol %)
CyꢀJohnPhosAuNTf2 (5 mol %)
IPrAuNTf2 (5 mol %)
(4ꢀCF3Ph)3PAuNTf2 (5 mol %)
BrettPhosAuNTf2 (5 mol %)
yieldb
0c
3c
1
2
3
4
5
6
7
8
9
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1
2
5
0c
0c
0c
4%c
58%
37%
30%
3b, 79%
3e, 73%
3c, 72%
3f, 60%
3d, 79%c
3g, 73%
MorꢀDalPhosAuNTf2 (5 mol %)
MorꢀDalPhosAuCl (5 mol %)/AgSbF6 (5 mol %)
MorꢀDalPhosAuCl (5 mol %)/AgOTf (5 mol %)
4c
6
1:1.2 MorꢀDalPhosAuCl (5 mol %)/NaBArF4 (10 mol %) 64%
10 1:1.2 MeꢀDalPhosAuCl (5 mol %)/NaBArF4 (10 mol %) 64%
11 1:1.2
12 1:1.2
L1AuCl (5 mol %)/NaBArF4 (10 mol %)
52%
0c
DavePhosAuCl (5 mol %)/NaBArF4 (10 mol %)
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9
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13 1.5:1 MorꢀDalPhosAuCl (5 mol %)/NaBArF4 (10 mol %) 87%d
14 1.5:1 MorꢀDalPhosAuCl (5 mol %)/NaBArF4 (10 mol %) 59%e
15 1.5:1 MorꢀDalPhosAuCl (5 mol %)/NaBArF4 (10 mol %) 78%f
The reaction was run with everything except the oxidant in a vial
a
capped with a septum, and the oxidant was introduced into the reaction
3h, 73%
3k, 95%
3i, 79%
3l, 83%
3j, 55%
b
10
11
12d
mixture slowly using a syringe pump. The initial [1a] = 0.1 M.
Measured by H NMR using diethyl phthalate as the internal standard.
1
c
<20% of 1ꢀdodecyne left, and the crude 1H NMR mostly messy. d 81%
Isolated yield. e DCE as solvent. f Toluene as solvent.
3m, 63%
Table 1 shows the reaction discovery and subsequent condition
optimization. We chose chlorobenzene as the reaction solvent in
order to avoid solvent participation.6b,9d Initially, no desired
reaction was detected with various typical gold catalysts of
ranging electronic and steric characteristics (entries 1ꢀ4). The only
exception was BrettPhosAuNTf2,9c,15 but the expected oxazole 3a
was formed in a pitiful 4% yield (entry 5). These results
highlighted the low selectivities associated with the highly
reactive αꢀoxo gold carbenes. By expanding the types of ligands
examined, we fortuitously came upon MorꢀDalPhos, a P,Nꢀ
bidentate ligand developed by Stradiotto.16 With Morꢀ
DalPhosAuNTf2 as the catalyst, the reaction yield, to our
amazement, jumped to 58% (entry 6). The effect of the counter
13d
14d
15d
3n, 82%
3q, 73%
3o, 71%
3r, 67%
3p, 71%
3s, 70%
16d,e
17
18
19
20d
ꢀ
anion was examined. While SbF6 (entry 7) and OTfꢀ (entry 8)
fared worse, [BArF ]ꢀ, a nonꢀcoordinating and lipophilic anion
3t, 63%
3u, 53%
4
a
developed by Kobayashi,17 improved the reaction yield by a
significant 6% (entry 9). The reactive catalyst in this case can be
readily generated in situ, driven by the precipitate of insoluble
NaCl in PhCl. Other ligands with substituted amino groups were
also tested. MeꢀDalPhos,16 a ligand in the same series as Morꢀ
DalPhos, led to an identical result (entry 10), and L1,16a a ligand
1/2 = 1.5/1; initially [2] = 0.1 M; the oxidant was introduced to the
reaction vial by a syringe pump. Isolated yield. 2 equiv. of the alkyne
b
c
d
and 3 equiv. of the oxides used. The alkyne was added along with the
oxide by a syringe pump. e Reaction temperature: 100 ˚C.
With the optimized reaction conditions in hand, the reaction
scope was then examined. First, a range of carboxamides were
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tested using 1ꢀdodecyne as the alkyne component (entries 1ꢀ10).
congested to be a Hꢀbond acceptor (Scheme 2). The
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Benzamides with electronꢀdonating (i.e., in the cases of 3a and
entry 1) and weakly electronꢀwithdrawing (entries 3ꢀ5) paraꢀ
substituents and without any substitution (entry 2) all underwent
the reaction smoothly, affording 2,4ꢀdisubstituted oxazoles in
accetable to good yields. With furanꢀ2ꢀcarboxamide or thiopheneꢀ
2ꢀcarboxamide, the biheteroaryl 3g or 3h were obtained without
any event in accidently the same 73% yield (entries 6 and 7). The
reaction also worked with α,βꢀunsaturated carboxamides. While
3j was isolated in only 55% yield by using crotonamide (entry 9),
the reaction proceeded efficiently with cinnamamide (entry 8) and
especially well with 3,3ꢀdimethylacrylamide (entry 10, 95% yield).
The reaction, however, did not work with aliphatic
carboxamides,18 and poor yields (<30%) were observed with
benzamides with strongly electronꢀwithdrawing para substituents
such as acetyl and nitro groups and with ortho substitutions such
as Me and F due to their decreased nucleophilicities and/or
increased steric hindrance.
ineffectiveness of DavePhos provides some circumvential
evidence for this conclusion. In addition, we prepared the related
P,Sꢀbidentate ligands, L2 and L3 (see SI for their preparation). To
our delight, their corresponding gold complexes promoted the
oxazole formation with efficiencies close to that by MorꢀDalPhos
(Figure 2). The structure of L3AuCl was secured via Xꢀray
diffraction studies and is shown in the Figure as well. As sulfides
are not considered as Hꢀbond acceptors, these reaction outcomes
effectively ruled out the participation of the orthoꢀheteroatoms via
Hꢀbonding. The dramatic impact by these hetereoatoms (N or S)
suggests that they might alternatively be involved in
coordination20 to the formally cationic gold center in the
postulated metal carbene moiety. As shown in Scheme 2, such a
tricoordinated gold center in E/E’ should be less electronꢀ
deficient than the dicoordinated one in D, therefore rendering it
more capable of backꢀdonating electrons to the carbene center.
Consequently, the carbene center would be less cationic due to
decreased contribution by the mesomeric cationic form E’. The
thusꢀtempered electrophilicity of the gold carbene is likely the key
to achieving its chemoselective trapping by carboxamides for the
formation of 2,4ꢀdisubstituted oxazoles. The slightly higher yields
in the cases of L3 vs. L2 (Figure 2) and MorꢀDalPhos vs. L1 are
consistent with tricoordinated gold carbene intermediates as the
bigger substituents on the heteroatoms of L3 and MorꢀDalPhos
would better facilitate their formation via steric coercion.9e
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Scheme 2. Rationale for the role of MorꢀDalPhos in the gold
catalysis
Figure 2. New efficacious sulfideꢀfunctionalized phosphines as ligand for
the gold catalysis and the Ortep drawing of of L3AuCl (with 50%
ellipsoid probability).
DꢀMe (0.0 kcal/mol)
EꢀMe (ꢀ5.4 kcal/mol)
Figure 3. The partially optimized structure D with fixed AuꢀN distance of
2.930 Å and the fully optimized structure E. The selected bond lengths
are in angstroms, bond angles are in degrees. The relative energies ∆E are
in kcal/mol. Calculated at PBE1PBE/6ꢀ311+G** level
With respect to the alkyne, both cyclohexylacetylene (entry 11)
and cyclopropylacetylene (entry 12) were suitable substrates. In
the former case, the oxazole 3l was isolated in a good 85% yield.
In contrast, its analog with the anisyl group replaced with a
phenyl group was obtained in only 18% yield7h using the
BlümleinꢀLewy method.19 Linear aliphatic terminal alkynes with
remote functional groups such as NPhth (entry 13), TIPSꢀ
protected HO group (entry 14), chloro (entry 15) and acetoxy
(entry 16) were also allowed. When these groups were placed at
propargyl or homopropargyl positions, the reaction became much
less efficient, due to their interferences with the gold carbene
moiety. Not withstanding, when a weakly nucleophilic phenyl
group was present (entry 17), the reaction could still afford an
acceptable yield. Phenylacetylene (entry 18) and those containing
electronꢀdonating pꢀsubstituents (entries 19 and 20) were suitable
alkynes as well, and the triaryl products were formed in
serviceable yields. On the other hand, pꢀnitrophenylacetylene led
to a mere ~30% yield of the expected oxazole product (R’ =
anisyl, data not shown).
To provide further support for the involvement of the
tricoordinated gold carbene E, we resorted to DFT calculations.
As shown in Figure 3, the dicoordinated gold carbene DꢀMe (R in
D is Me) was partially optimized by fixing the distance between
Au and N at 2.930 Å, the same as that found in the Xꢀray
structure of MorꢀDalPhosAuCl,16b and the tricoordinated species
E-Me (R in E is Me) was fully optimized. The latter was 5.4
kcal/mol more stable than the former, therefore strongly
supporting the role of E in the catalysis. Moreover, the summed
NBO charge for all the atoms in the indicated box decreases from
+0.346 to +0.246 upon nitrogen coordination, which supports our
reasoning that the electrophilicity of the carbene center might be
attenuated in the process. An additional notable change upon the
formatin of E-Me is that the AuꢀC bond was shortened by 0.034
Å, suggesting an increased back donation by the gold center.
Tricoordinated gold complexes, such as (Ph3P)2AuCl21 and
XantPhosAuCl,22 though amply documented in literature, have
surprisingly had little relevance in homogeneous gold(I) catalysis.
The only exception we are aware of is a dehydrogenative
silylation reaction between alcohols and R3SiH involving
XantPhosAuCl.22ꢀ23 Considering the vast majority of gold
To explain why MorꢀDalPhos and the related MeꢀDalPhos
were so effective and the role of the neighbouring amino group,
we first thought that Hꢀbonding might be at play.16b However, by
inspecting the Xꢀray structure of MorꢀDalPhosAuCl16b it is
apparent that the nitrogen atom, with its lone electron pair
pointing to and thereby shielded by the gold center, is too
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He, W.; Xie, L.; Xu, Y.; Xiang, J.; Zhang, L. Org. Biomol. Chem. 2012, 10,
3168ꢀ3171; (e) Wang, Y.; Ji, K.; Lan, S.; Zhang, L. Angew. Chem., Int. Ed.
2012, 51, 1915ꢀ1918.
catalysis involving π systems, this revelation that tricoordinated
gold(I) species can attenuate the electrophilicity of carbene
centers and hence enable new reactions will likely spur further
development in homogeneous gold(I) catalysis via the use of
designed effacacious bidentate ligands.
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(10) For selected exampels of goldꢀcatalyzed intramolecular alkyne oxidation, see: (a)
Shapiro, N. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 4160ꢀ4161; (b) Li,
G.; Zhang, L. Angew. Chem., Int. Ed. 2007, 46, 5156ꢀ5159; (c) Yeom, H. S.;
Lee, J. E.; Shin, S. Angew. Chem., Int. Ed. 2008, 47, 7040ꢀ7043; (d) Hashmi, A.
S.; Bührle, M.; Salathé, R.; Bats, J. Adv. Synth. Catal. 2008, 350, 2059ꢀ2064;
(e) Davies, P. W.; Albrecht, S. J. C. Angew. Chem., Int. Ed. 2009, 48, 8372ꢀ
8375; (f) Li, C.ꢀW.; Lin, G.ꢀY.; Liu, R.ꢀS. Chem. Eur. J. 2010, 16, 5803ꢀ5811.
(11) (a) Davies, P. W.; Cremonesi, A.; Martin, N. Chem. Commun. 2011, 47, 379ꢀ
381; (b) Qian, D.; Zhang, J. Chem. Commun. 2011, 47, 11152ꢀ11154; (c) Vasu,
D.; Hung, H.ꢀH.; Bhunia, S.; Gawade, S. A.; Das, A.; Liu, R.ꢀS. Angew. Chem.,
Int. Ed. 2011, 50, 6911ꢀ6914; (d) Liu, R.ꢀS.; Dateer, R. B.; Pati, K. K. Chem.
Commun. 2012, 48, 7200ꢀ7202; (e) Bhunia, S.; Ghorpade, S.; Huple, D. B.; Liu,
R.ꢀS. Angew. Chem., Int. Ed. 2012, 51, 2939ꢀ2942; (f) Qian, D.; Zhang, J.
Chem. Commun. 2012, 48, 7082ꢀ7084.
In summary, we have developed a gold(I)ꢀcatalzyed modular
synthesis of 2,4ꢀdisubstituted oxazoles via [3+2] annulations
between readily available terminal alkynes and aromatic/alkenic
carboxamides under mild reaction conditions. The key reaction
intermediate is an αꢀoxo gold carbene, generated via goldꢀ
promoted oxidation of a terminal alkyne. Contrary to our previous
observations that this type of intermediates with various
monodentate phosphines or NHC as the ligand to the metal center
is highly electrophilic and challenging to be efficiently trapped by
stoichiometric external nucleophiles, we discovered for the first
time that the use of a P,Nꢀ or P,Sꢀbidentate ligand especially Morꢀ
DalPhos significantly tempered its reactivities, thereby permitting
efficient attack by a carboxamide en route to the formation of the
oxazole ring. The nature of this reactivity modulation is attributed
to the formation of a tricoordinated gold carbene spieces by
engaging the nonꢀphosphorus heteroatom, which is strongly
supported by DFT calculations. The rare involvment of
tricoordinated gold complexes in homogeneous gold catalysis and
their role in modulating reactivities of cationic gold intermediates
makes this discovery important and should stimulate new advance
in this intensely researched field.
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(12) (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides;
Wiley: New York, 1998; (b) Taber, D. F. In Carbon-Carbon
Σ -Bond
Formation; Pattenden, G., Ed.; Pergamon Press: Oxford, England ; New York,
1991; Vol. 3, p 1045ꢀ1062; (c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev.
2003, 103, 2861ꢀ2903.
(13) For earlier reportes with αꢀdiazoester substrates, see: (a) Fructos, M. R.;
Belderrain, T. R.; de Fremont, P.; Scott, N. M.; Nolan, S. P.; DiazꢀRequejo, M.
M.; Perez, P. J. Angew. Chem. Int. Ed. 2005, 44, 5284ꢀ5288; (b) Fructos, M. R.;
de Frémont, P.; Nolan, S. P.; DíazꢀRequejo, M. M.; Pérez, P. J. Organometallics
2006, 25, 2237ꢀ2241; (c) Prieto, A.; Fructos, M. R.; Mar DíazꢀRequejo, M.;
Pérez, P. J.; PérezꢀGalán, P.; Delpont, N.; Echavarren, A. M. Tetrahedron 2009,
65, 1790ꢀ1793; (d) Noey, E. L.; Luo, Y.; Zhang, L.; Houk, K. N. J. Am. Chem.
Soc. 2012, 134, 1078–1084; (e) Pagar, V. V.; Jadhav, A. M.; Liu, R.ꢀS. J. Am.
Chem. Soc. 2011, 133, 20728ꢀ20731.
(14) Seidel, G.; Mynott, R.; Fürstner, A. Angew. Chem., Int. Ed. 2009, 48, 2510ꢀ
2513.
(15) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc.
2008, 130, 13552ꢀ13554.
(16) (a) Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem.,
Int. Ed. 2010, 49, 4071ꢀ4074; (b) Hesp, K. D.; Stradiotto, M. J. Am. Chem. Soc.
2010, 132, 18026ꢀ18029.
(17) Nishida, H.; Takada, N.; Yoshimura, M.; Sonoda, T.; Kobayashi, H. Bull. Chem.
Soc. Jpn. 1984, 57, 2600ꢀ2604.
(18) Instead observed were the related carboxymethyl ketones, formed due to
hydrolysis of the imidate intermediates of type B (R = alkyl).
(19) (a) Blümlein, F. O. Ber. 1884, 17, 2578ꢀ2581; (b) Lewy, M. Ber. 1887, 20,
2576ꢀ2580.
(20) For a case where a pendant aryl group can interact with cationic gold center, see:
PérezꢀGalán, P.; Delpont, N.; HerreroꢀGómez, E.; Maseras, F.; Echavarren, A.
M. Chem. Eur. J. 2010, 16, 5324ꢀ5332.
(21) Bowmaker, G. A.; Dyason, J. C.; Healy, P. C.; Engelhardt, L. M.; Pakawatchai,
C.; White, A. H. J. Chem. Soc., Dalton Trans. 1987, 1089ꢀ1097.
(22) Ito, H.; Takagi, K.; Miyahara, T.; Sawamura, M. Org. Lett. 2005, 7, 3001ꢀ3004.
(23) Ito, H.; Saito, T.; Miyahara, T.; Zhong, C.; Sawamura, M. organometallics
2009, 28, 4829ꢀ4840.
Acknowledgment We are grateful for the generous financial
support by NIH (R01 GM084254) and NSF (CAREER CHEꢀ
0969157). LZ dedicates this work to Professor Masato Koreeda
on the occasion of his 70th birthday.
Supporting Information Available: Experimental procedures,
compound characterization data and computational details are
available free of charge via the Internet at http://pubs.acs.org.
REFERENCES:
(1) Ichiba, T.; Yoshida, W. Y.; Scheuer, P. J.; Higa, T.; Gravalos, D. G. J. Am.
Chem. Soc. 1991, 113, 3173ꢀ3174.
(2) Searle, P. A.; Molinski, T. F. J. Am. Chem. Soc. 1995, 117, 8126ꢀ8131.
(3) For selected reviews, see: (a) Boyd, G. V. Sci. Synth. 2001, 11, 383ꢀ480; (b)
Yeh, V. S. C. Tetrahedron 2004, 60, 11995ꢀ12042.
(4) (a) Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 907ꢀ910; (b) Phillips, A.
J.; Uto, Y.; Wipf, P.; Reno, M. J.; Williams, D. R. Org. Lett. 2000, 2, 1165ꢀ
1168; (c) Crosignani, S.; Young, A. C.; Linclau, B. Tetrahedron Lett. 2004, 45,
9611ꢀ9615.
(5) (a) Williams, D. R.; Lowder, P. D.; Gu, Y.ꢀG.; Brooks, D. A. Tetrahedron Lett.
1997, 38, 331ꢀ334; (b) Barrish, J. C.; Singh, J.; Spergel, S. H.; Han, W. C.;
Kissick, T. P.; Kronenthal, D. R.; Mueller, R. H. J. Org. Chem. 1993, 58, 4494ꢀ
4496; (c) Meyers, A. I.; Tavares, F. Tetrahedron Lett. 1994, 35, 2481ꢀ2484.
(6) For oneꢀstep modular synthesis of 2,5ꢀdisubstituted oxazoles, see: (a) Jiang, H.ꢀ
F.; Huang, H.ꢀW.; Cao, H.; Qi, C.ꢀR. Org. Lett. 2010, 12, 5561ꢀ5563; (b) He,
W.; Li, C.; Zhang, L. J. Am. Chem. Soc. 2011, 8482ꢀ8485.
(7) For examples of oneꢀstep bimolecular annulations of oxazoles, see: (a) Theilig,
G. Chem. Ber. 1953, 86, 96ꢀ109; (b) Huisgen, R.; Blaschke, H. Tetrahedron
Lett. 1964, 5, 1409ꢀ1413; (c) Hammar, W. J.; Rustad, M. A. J. Heterocycl.
Chem. 1981, 18, 885ꢀ8; (d) Schuh, K.; Glorius, F. Synthesis 2007, 2007, 2297ꢀ
2306; (e) Shi, B.; Blake, A. J.; Lewis, W.; Campbell, I. B.; Judkins, B. D.;
Moody, C. J. J. Org. Chem. 2009, 75, 152ꢀ161; (f) Zhang, X.; Teo, W. T.; Chan,
P. W. H. J. Organomet. Chem. 2011, 696, 331ꢀ337; (g) Ritson, D. J.; Spiteri, C.;
Moses, J. E. J. Org. Chem. 2011, 76, 3519ꢀ3522; (h) Kuwano, R.; Kameyama,
N.; Ikeda, R. J. Am. Chem. Soc. 2011, 133, 7312ꢀ7315.
(8) For selected reviews, see: (a) Fürstner, A.; Davies, P. W. Angew. Chem., Int. Ed.
2007, 46, 3410ꢀ3449; (b) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180ꢀ3211;
(c) Arcadi, A. Chem. Rev. 2008, 108, 3266ꢀ3325; (d) JiménezꢀNúñez, E. s.;
Echavarren, A. M. Chem. Rev. 2008, 108, 3326ꢀ3350; (e) Li, Z.; Brouwer, C.;
He, C. Chem. Rev. 2008, 108, 3239ꢀ3265; (f) Abu Sohel, S. M.; Liu, R.ꢀS.
Chem. Soc. Rev. 2009, 38, 2269ꢀ2281; (g) Wang, S.; Zhang, G.; Zhang, L.
Synlett 2010, 692ꢀ706; (h) Xiao, J.; Li, X. Angew. Chem., Int. Ed. 2011, 50,
7226ꢀ7236.
(9) (a) Ye, L.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258ꢀ
3259; (b) Ye, L.; He, W.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 8550ꢀ8551;
(c) Ye, L.; He, W.; Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 3236ꢀ3239; (d)
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