Biomimetic aerobic C-H olefination of cyclic enaminones at room temperature: Development toward the synthesis of 1,3,5-trisubstituted benzenes

Article abstract of DOI:10.1002/adsc.201300904

A green and mild protocol for the dehydrogenative olefination of cyclic enaminones was devised via palladium catalysis at room temperature using oxygen as the terminal oxidant. The synthetic utility of the olefinated cyclic enaminones afforded a series of

Full text of DOI:10.1002/adsc.201300904

UPDATES
DOI: 10.1002/adsc.201300904
À
Biomimetic Aerobic C H Olefination of Cyclic Enaminones at
Room Temperature: Development toward the Synthesis of 1,3,5-
Trisubstituted Benzenes
Yi-Yun Yua and Gunda I. Georga,*
a
Department of Chemistry, Department of Medicinal Chemistry and the Institute for Therapeutics Discovery and
Development, University of Minnesota, Twin Cities, 717 Delaware St SE, Minneapolis, Minnesota 55414, USA
Fax : (+1)-612-626-6318; e-mail: georg@umn.edu
Received: October 9, 2013; Revised: November 17, 2013; Published online: January 31, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300904.
Abstract: A green and mild protocol for the dehy-
drogenative olefination of cyclic enaminones was
devised via palladium catalysis at room temperature
using oxygen as the terminal oxidant. The synthetic
utility of the olefinated cyclic enaminones afforded
a series of unique 1,3,5-trisubstituted benzenes via
an unanticipated Diels–Alder tandem reaction. The
broad substrate scope and good yields achieved
with this new protocol provide an alternative path-
way for arene functionalization.
common in the current field and is ironically contra-
À
dictory to the goals of C H functionalization (e.g., re-
ducing heavy metal waste).[8] In search for alternative
green oxidants, molecular oxygen is the ideal candi-
À
Keywords: arenes; C H activation; cycloaddition;
olefination; palladium
Introduction
1,3-Dienes and polyenes are important structural
motifs found in many pharmaceutically active com-
pounds and natural products, such as carotenes, vita-
min A, bombykol, etc.[1] Synthesis of these com-
pounds can be categorized into two classes: (i) car-
bonyl olefination reactions,[2] represented by the
Wittig reaction[3] and (ii) cross-olefination coupling,
represented by the Heck reaction.[4] In the interests of
atom economy, new methods that in addition gener-
ate minimal waste are highly desirable.[5]
Dehydrogenative cross-coupling of alkenes, argua-
bly the ideal pathway for diene synthesis, surprisingly
did not attract much attention until very recently. Ex-
amples of this kind are limited.[6] We recently devel-
oped a Pd-catalyzed cross dehydrogenative olefina-
tion of cyclic enaminones (Scheme 1a).[7] Despite the
high yields and broad scope, our protocol requires sto-
ichiometric amounts of a Cu(II) oxidant and an addi-
tive, as well as elevated temperature (808C). This
À
demand for sacrificial heavy metal oxidants is very Scheme 1. C H alkenylation of cyclic enaminones.
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Scheme 2. Biomimetic aerobic Pd catalysis with catechol.
date because of its inexpensive and eco-friendly metry. Herein, we disclose our recent efforts in im-
nature.[5]
proving the C H olefination of cyclic enaminones
À
The obstacle of applying O2 as the sole oxidant is and its unexpected application in the synthesis of
the high activation energy and low concentration of 1,3,5-trisubstituted arenes.
O2 in solutions, which significantly impedes the direct
oxidation of Pd(0). To circumvent the high pressure
of O2 used in early development,[5b,8c] catalytic Results and Discussion
amounts of O2 activators, such as molybdovanado-
phosphoric acid (HPMoV) and benzoquinone, were We started by probing aerobic conditions for the de-
introduced to promote oxidation in a biomimetic ap- hydrogenative olefination of enaminones under at-
proach.[5a,8c,9] Mechanistically, this biomimetic strategy mospheric pressure (Table 1). To better compare the
divides the oxidation process into several intercon- optimization with our first protocol,[7] the same enam-
nected redox cycles and thereby effectively reduces inone 1 and alkene 2 were chosen for the current op-
the initial high energy barrier for electron transfer.[9] timization study. Compared to our reported result
For example, Hosokawa discovered that inexpensive (87%, entry 1),[7] the yield dropped significantly to
catechol and Cu(II) could remarkably enhance Pd(II) 27% under air without a Cu(II) oxidant (entry 2). Ap-
catalysis in the presence of O2 (Scheme 2).[10] Cate- plying pure O2 instead of air increased the yield to
chol is thought to act as ortho-quinone that incorpo- 44% (entry 3). Attempts to use 20 mol% of CuACHTUNGTRENNUNG(OAc)2
rates Cu(II) as a ligand. With regard to dehydrogena- showed no improvement of the yield (entry 4). In
tive cross-couplings of alkenes, the use of O2 as a ter- order to activate O2, catalytic amounts of catechol
minal oxidant is very rare and there has been no were tested (entries 5–7). Initially, the temperature
report of this type of reaction to proceed at room with PdACTHNUGTRNNEUG(OAc)2/CuACHTUTGNREN(NUNG OAc)2/catechol was set at 808C,
temperature.[11] Bꢁckvall reported a versatile biomim- but no beneficial effect was observed (entry 5). After
etic aerobic coupling between two alkenes under low examining various catalyst loadings and temperatures,
catalyst loading.[11e] However, their method, involving we were pleased to see a significant increase of yield
acidic media, failed to deliver a satisfactory outcome to 78% in the presence of Pd
ACHTUNGRTEN(NNUG OAc)2 (10 mol%) with
for cyclic enaminones (Scheme 1b). Cu(OAc)2 and catechol in a 1:1:2 ratio (entry 6). Re-
AHCTUNGTRENNUNG
In our continuing efforts in generating libraries for markably, the coupling proceeded smoothly at room
biological screening, we are particularly interested in temperature. A similar increase on yield was also ob-
functionalizing the non-aromatic cyclic enaminones as served under air, albeit less optimal than that under
unique piperidine surrogates for alkaloid synthesis.[12] O2 (entry 7). A series of common solvents was also as-
Our aforementioned protocol has furnished various sessed in addition to DMF (entries 8–10). Although
alkenylated enaminones, but their synthetic utility no other solvents improved the olefination outcome,
had remained unexplored. In light of the recent ad- the relatively higher yields from polar solvents (e.g.,
À
vances in aerobic C H functionalization, we first de- DMSO, MeCN) indicate that their coordinating abili-
veloped a greener and milder method for dehydro- ty might help to extend the catalyst lifespan, reflect-
genative olefination of cyclic enaminones at room ing on the higher yields. As Hosokawa had reported
temperature (Scheme 1c). Next, we envisioned the re- the importance of interchangeable anionic ligands for
sulting dienes participating in a Diels–Alder reaction the catalyst efficacy,[10a] we next evaluated a few
to gain a quick access to hydroquinolines, a key struc- anions (i.e., TFAÀ, OAcÀ, and ClÀ, entries 11–13).
tural motif in several major classes of alkaloids.[13] The blend of Pd
ACTHNUTRGNEN(GU TFA)2 and CuHCATUNGTREN(NGUN OAc)2 furnished
The serendipitous discovery of a Diels–Alder tandem a higher yield (81%, entry 11) compared to those
reaction, however, led to the formation of a series of from the OAcÀ/ClÀ or TFAÀ/ClÀ systems (entries 12
distinctive 1,3,5-trisubstituted benzenes, which are im- and 13). Presumably, the combination of TFAÀ and
portant structural motifs in material science[14] and OAcÀ may sufficiently increase the electrophilicity of
medicinal chemistry[15] because of their unique sym- the Pd(II) center for palladation, meanwhile balanc-
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Biomimetic Aerobic C H Olefination of Cyclic Enaminones
Table 1. Optimization of aerobic dehydrogenative olefination of enaminones.
Entry[a]
[Pd] (mol%)
[Cu] (mol%)
Atm.
Additive (mol%)
Solvent
Temp. [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
Cu
–
–
(OAc)2 (200)
N2
air
O2
O2
O2
O2
air
O2
O2
O2
O2
O2
O2
O2
KTFA (100)
KTFA (100)
KTFA (100)
KTFA (100)
catechol (10)
catechol (20)
catechol (20)
catechol (20)
catechol (20)
catechol (20)
catechol (20)
catechol (20)
catechol (20)
catechol (20)+4ꢂ MS
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
MeCN
THF
80
80
80
80
87 (81[c])
27
44
41
40
78
66
62
65
39
81
57
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
80
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
9
10
11
12
13
14
DMF
DMF
DMF
DMF
PdCl2 (10)
Pd
Pd
CuCl2 (10)
Cu(OAc)2 (10)
27
91 (89[c])
[a]
Other conditions: 1 (0.10 mmol), 2 (0.40 mmol), balloon (1 atm), solvent (0.5 mL), 24 h (PMP=para-methoxyphenyl).
Yields determined by H NMR with Ph3SiMe (1.0 equiv.) as the internal standard.
Isolated yield. (Detailed optimization is given in the Supporting Information.)
[b]
[c]
1
ing the level of acid by-products (i.e., TFA and speculate that the conformer after migratory insertion
AcOH) not to decompose the acid-sensitive enamin- might favor the b-hydride elimination to furnish a con-
ACHTUNGTRENNUNGones. We also investigated the role of bases and reac- jugated diene, whereas at a higher temperature a sub-
À
tion concentrations (see Table S6 in the Supporting sequent re-insertion of the Pd H species could be
Information). It soon became clear that bases inhibit- promoted to reconstruct the Pd intermediate, which
ed the coupling by reducing the yield to 16% and eventually furnishes an unconjugated diene as a major
more concentrated solutions (0.2–0.4M) were favora- product, presumably due to its thermal stability.
ble in general. Moreover, Stahl reported that molecu- Moreover, the viability of allyl acetate (representing
lar sieves were beneficial for Pd-catalyzed aerobic al- the class of unactivated alkenes) was examined. Un-
cohol oxidation, because they could provide a hetero- fortunately, it failed to afford any desired product.
geneous surface that hindered bulk aggregation of
A collection of enaminones was assessed under the
Pd(0) metal to increase the catalyst stability.[16] optimized conditions as well (Table 2). Bicyclic, elec-
Indeed, the addition of 4ꢂ MS promoted a full con- tron-rich enaminones offered moderate yields (14 and
sumption of enaminone 1 and furnished an optimal 15). Replacing the 2-aryl group (i.e., PMP) with an
isolated yield of 89% (entry 14).
alkyl group (i.e., i-Pr) retained a good yield (83%,
Next, we embarked on examining the scope of the 16). However, removing the 2-PMP group caused
reaction (Table 2). Acrylates were excellent alkene a significant yield decline (to 57%, 17). The reason
sources providing yields of up to 89% (3–6). The behind this observation is yet to be elucidated. As we
vinyl phosphonate, vinyl ketone, acrylamide, and sty- reported before,[7,18] N-phenylenaminone is a less ef-
rene were all well tolerated (7–10). In contrast, disub- fective substrate, possibly due to its attenuated nucle-
stituted alkenes gave significantly lower yields (11– ophilicity. Indeed, it afforded a lower yield (32%, 18)
13), possibly due to steric hindrance from the sub- compared to the N-benzyl analogue (57%, 17). It is
stituents that might hinder the migratory insertion. In- worth mentioning that the N-H enaminone, N-Cbz
terestingly, double bond isomerization, common in enaminone, and E-enaminone were again all incom-
prior reports,[17] was not observed when more than patible under the current aerobic conditions (19–21),
one b-hydrogen was present in the alkenes. Only con- albeit consistent with our previous studies.[18,19] Our
jugated (to enaminone) dienes (12 and 13) were iso- attempts on the uracil scaffold (22) were unfortunate-
lated. This is contrary to our earlier olefination proto- ly not successful either. Nonetheless, we have devised
col,[7] where unconjugated (to enaminone) dienes a greener and milder method to alkenylate cyclic en-
were favored at an elevated temperature (808C). We aminones with comparable yields to our first protocol.
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Table 2. Scope of aerobic dehydrogenative olefination of enaminones.[a]
[a]
Conditions: enaminone (0.10 mmol), alkene (0.40 mmol), PdACTHNUGTRNNEUG(TFA)2 (10 mol%), CuACHUTNGTERN(NUGN OAc)2 (10 mol%), catechol
(20 mol%) and 4ꢂ molecular sieves (ca. 30 mg) under O2 (balloon) in DMF (0.5 mL) at room temperature for 24 h. Iso-
lated yields.
This is also the first example of cross dehydrogenative O2 present in the reaction.[20a,c,21] Afterwards a retro-
couplings of alkenes taking place at room tempera- Michael fragmentation released methylamine[22] to
ture.
To explore the synthetic utility of our new protocol,
afford 1,3,5-trisubstituted benzene 27.
Available methods to synthesize 1,3,5-trisubstituted
we proposed a Diels–Alder reaction to transform the benzenes mostly depend on commercially available
alkenylated enaminones to hydroquinoline analogues, 1,3,5-trihalobenzenes (or the like) as precursors with
a common structural feature in many alkaloids.[13] In an established substitution pattern.[14,23] There is
fact, similar amino-substituted dienes have been em- a lack of general, regioselective methods to generate
ployed to regio- and stereoselectively construct the unsymmetrical 1,3,5-trisubstituted benzenes, which are
octahydroquinoline scaffold in the Comins group.[20] more valuable in medicinal chemistry than the sym-
Surprisingly, our attempts on the Diels–Alder reac- metrical ones.[15] Encouraged by our results, we con-
tion between diene 23 and dienophile 24 resulted in sidered the potential of the Diels–Alder tandem reac-
the formation of compound 27 instead of the antici- tion to devise an alternative useful method to synthe-
pated 25 (Scheme 3). Presumably, the multiple elec- size 1,3,5-trisubstituted benzenes. We hence tested
tron-withdrawing substituents and the amino leaving a series of conditions for the Diels–Alder tandem re-
group in cycloadduct 25 promoted aromatization with action (Tables S7–S9 in the Supporting Information).
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Biomimetic Aerobic C H Olefination of Cyclic Enaminones
Table 3. Synthesis of 1,3,5-trisubstituted benzenes via the
Diels–Alder tandem reaction.[a]
Scheme 3. Formation of 1,3,5-trisubstituted benzenes.
After screening solvents, microwave techniques, tem-
peratures, reaction time, and stoichiometry, we found
that 8.0 equiv. of dienophiles in toluene at 1608C for
24 h delivered the optimal outcome.
The scope of this tandem reaction was then investi-
gated (Table 3). A wide range of electron-deficient di-
enophiles (e.g., vinyl sulfone, vinyl ketone, acrylates,
acrylonitrile, vinyl phosphonate) was viable under the
conditions with yields up to 86% (27–33). However,
the maleimide-generating arene 34 was only obtained
in a low yield (16%). Although styrene was not reac-
tive as a dienophile, the flexibility of our protocol al-
lowed us to install styrene beforehand (as R3 in diene
10) via the dehydrogenative olefination, and the
tandem reaction thereafter could furnish biphenyls 35
and 36. When acrylic acid was used, the expected
compound 40 was not detected (Scheme 4a). Instead,
a decarboxylation occurred to form 37. Enaminone
diene 14 was also subjected to the tandem reaction.
Surprisingly, compound 38 was obtained as the final
product (Scheme 4b). Due to the unique structural
feature in adduct 42, we postulate that a retro-Man-
nich reaction took place instead of a retro-Michael
fragmentation. It is worth noting that the Diels–Alder
reaction exhibited excellent regioselectivity, furnish-
ing a distinctive 1,3,5-trisubstitution pattern. In addi-
tion, no octahydroquinoline products (such as 25)
were left after any of these transformations.
[a]
Conditions: 23 (0.07 mmol, R1 =Me, R2 =PMP, R3 =
CO2Me), dienophile (0.56 mmol) in toluene (1 mL) at
1608C, 24 h. Isolated yields.
[b]
[c]
[d]
[e]
Based on recovered 23.
10 was used as the diene (R1 =Bn, R2 =PMP, R3 =Ph).
Acrylic acid was used as the dienophile.
14 was used as the diene.
The advantages of the new tandem reaction in re-
gioselectively functionalizing arenes are three-fold. (i)
A series of electron-withdrawing groups (EWGs) are
compatible. Due to the nature of the dehydrogenative
alkenylation and the normal electron demand Diels–
Alder reaction, electron-deficient alkenes are pre- ring from commercially available vinyl reagents in
ferred in both reactions (Table 2 and Table 3). In par- one step, which eliminates the prefunctionalization
ticular, functionalities such as sulfone (27) and phos- needed in other methods.[24] (ii) The new protocol
phonate (33) can now be installed onto the phenyl provides a direct pathway to synthesize unsymmetrical
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It is worth noting that most of the products (27–37)
are also chalcones, a major class of flavonoids that ex-
hibit a broad spectrum of pharmacological activities
(e.g., anti-inflammatory, antiproliferative, antioxidant,
and anticancer effects).[26] Previous chalcone synthe-
ses, such as the Claisen–Schmidt condensation[27] or
Pd-catalyzed cross-coupling methods,[28] paid most at-
tention to constructing the vinyl ketone linkage of
chalcones. Their utilization has been mostly limited
by the availability of aryl coupling precursors. In con-
trast, our approach focuses on the regioselective di-
versification of arenes, and therefore does not depend
as much on the availability of aryl precursors. We
expect that the capability to synthesize unique 1,3,5-
trisubstituted benzenes shall facilitate the generation
of distinctive chalcone libraries for medicinal study.
Scheme 4. Tandem reactions featuring (a) decarboxylation
and (b) retro-Mannich fragmentation.
1,3,5-EWG-benzenes. The synthesis of this class of
arenes is not easy via conventional approaches. For Conclusions
instance, the classical electrophilic substitution would
suffer severe deactivation by additional EWGs. We have improved the dehydrogenative olefination
Metal-catalyzed/mediated cross-couplings would re- method for cyclic enaminones via a biomimetic ap-
quire meticulously 1,3,5-prefunctionalized benzenes proach. The new protocol uses O2 as the terminal oxi-
with different (pseudo)halogens.[15] As to C H func- dant and significantly reduces the heavy metal oxi-
À
À
tionalization, meta-selectivity has just started to gain dant Cu
N
more attention with limited conditions and substrate olefination reaction shows comparable scope and pro-
scope.[25] (iii) The distribution of functional groups can ceeds smoothly at room temperature, which is report-
also be easily controlled (e.g., symmetrical 28 vs. un- ed for the first time for the dehydrogenative cross-
symmetrical 32). Remarkably, several products, such couplings of alkenes.
as 38, have three orthogonal functionalities that might
Our synthetic development of olefinated cyclic en-
be modified in a chemoselective manner. In addition, aminones unveiled a Diels–Alder tandem reaction,
compounds 35 and 36 have also demonstrated the which led to a series of distinctive 1,3,5-trisubstituted
flexibility of changing the sequence of alkenes used in benzenes, including chalcones, with good yields. This
each step to afford satisfactory yields.
unexpected transformation shall offer an alternative
Lastly, we also probed the feasibility of a “one-pot, approach to synthesize both symmetrical and unsym-
two-step” synthesis of 1,3,5-trisubstituted benzene 43 metrical 1,3,5-trisubstituted benzenes and chalcones
directly from enaminone
1
(Scheme 5). Cyclic for material science and medicinal study, respectively.
enaminone 1 was sequentially subjected to the aero-
ACHTUNGTRENNUNG
bic olefination conditions, followed by the Diels–
Alder conditions with no purification in between,
which eventually furnished 51% of the desired prod-
uct 43. Albeit unoptimized, our preliminary results
indeed reveal the potential of simply changing al-
kenes and raising temperatures to generate diverse
trisubstituted benzenes in a very convenient manner.
Experimental Section
General Information
All reactions were carried out in clear 2-dram vials used
without drying. All reagents and anhydrous solvents were
purchased and directly used without further purification or
drying. Flash column chromatography was carried out on
silica gel (230–400 mesh). TLC was conducted on 250
1
micron, F254 silica gel plates. H NMR spectra were recorded
at 400 MHz and 13C NMR spectra at 100 MHz with com-
plete proton decoupling. Chemical shifts are reported as
ppm relative to chloroform (CHCl3: 7.26 ppm for 1H,
77.16 ppm for 13C). Data are reported as follows: chemical
shift, multiplicity (s=singlet, d=doublet, t=triplet, q=
quartet, br=broad, m=multiplet), coupling constants (Hz)
and integration. IR spectra of solids were obtained by dis-
solving the sample in CH2Cl2 on an NaCl plate. High-resolu-
Scheme 5. One-pot synthesis of trisubstituted benzene 43.
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Biomimetic Aerobic C H Olefination of Cyclic Enaminones
tion mass spectrometry was performed on an ESI-TOF in-
strument. Melting points were uncorrected.
3.81 (s, 3H), 3.72 (d, J=3.3 Hz, 3H), 3.69 (d, J=3.2 Hz,
3H), 2.92 (dd, J=16.4, 7.3 Hz, 1H), 2.70 (dd, J=16.3,
6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=188.2, 160.0,
157.3, 145.4 (d, J=8.0 Hz), 134.7, 129.6, 129.4, 128.9, 128.3,
128.0, 114.8, 106.7 (d, J=22.0 Hz), 104.5 (d, J=189.5 Hz),
60.1, 58.2, 55.5, 52.3 (d, J=5.3 Hz), 52.3 (d, J=5.3 Hz), 44.3;
FT-IR (NaCl): n=3156, 2953, 2930, 2851, 1654, 1600, 1513,
1457, 1442, 1392, 1358, 1298, 1194, 1179, 1059, 1035, 991,
868, 832 cmÀ1; HR-MS (ESI+) m/e=450.1447, calculated
for [M+Na]+ C23H26NO5PNa: 450.1441.
Preparation of Starting Materials
For details on the synthesis of starting materials, see the
Supporting Information.
General Procedures for the Dehydrogenative Aerobic
Olefination of Cyclic Enaminones
(E)-1-Benzyl-2-(4-methoxyphenyl)-5-styryl-2,3-dihydro-
pyridin-4(1H)-one (10): Prepared by the general procedure
described above and isolated as a yellow solid; yield:
17.0 mg (46%); mp 54–568C. Analytical data are consistent
with those from our previous report.[7]
(E)-1-Benzyl-5-[2-(methoxycarbonyl)-1-methylvinyl]-2-(4-
methoxyphenyl)-2,3-dihydropyridin-4(1H)-one (11): Pre-
pared by the general procedure described above and isolat-
ed as a waxy solid; yield: 7.0 mg (19%). Analytical data are
consistent with those from our previous report.[7]
In a 2-dram vial, cyclic enaminone (0.10 mmol) was mixed
with PdACHTUNGTRENNUNG(TFA)2 (3.3 mg, 0.01 mmol), CuACHTUTGNREN(NNGU OAc)2 (1.8 mg,
0.01 mmol), catechol (2.2 mg, 0.02 mmol) and 4ꢂ molecular
sieves (ca. 30 mg). To the mixture was added alkene
(0.40 mmol), followed by DMF (0.5 mL). The vial was
purged with O2 and then sealed with an O2 balloon attached.
After being stirred at room temperature for 24 h, the reac-
tion was diluted with acetone (2 mL). The mixture was fil-
tered through Celite, and the filter cake was washed with
acetone (20 mL). The filtrate was then concentrated under
reduced pressure and purified by flash column chromatogra-
phy on silica gel.
(E)-1-Benzyl-5-[2-(tert-butoxycarbonyl)vinyl]-2-(4-meth-
oxyphenyl)-2,3-dihydropyridin-4(1H)-one (3): Prepared by
the general procedure described above and isolated as
a light yellow solid; yield: 35.1 mg (89%); mp 64–688C. An-
alytical data are consistent with those from our previous
report.[7]
(E)-1-Benzyl-5-[2-(methoxycarbonyl)vinyl]-2-(4-methoxy-
phenyl)-2,3-dihydropyridin-4(1H)-one (4): Prepared by the
general procedure described above and isolated as a yellow-
ish solid; yield: 28.0 mg (78%); mp 52–558C. Analytical
data are consistent with those from our previous report.[7]
(E)-1-Benzyl-5-[2-(n-butoxycarbonyl)vinyl]-2-(4-methoxy-
phenyl)-2,3-dihydropyridin-4(1H)-one (5): Prepared by the
general procedure described above and isolated as a yellow-
ish solid; yield: 34.2 mg (85%); mp 102–1048C. Analytical
data are consistent with those from our previous report.[7]
(E)-5-[2-(Benzoxycarbonyl)vinyl]-1-benzyl-2-(4-methoxy-
phenyl)-2,3-dihydropyridin-4(1H)-one (6): Prepared by the
general procedure described above and isolated as a yellow-
ish solid; yield: 37.4 mg (87%); mp 49–528C. Analytical
data are consistent with those from our previous report.[7]
(E)-1-Benzyl-2-(4-methoxyphenyl)-5-(3-oxobut-1-enyl)-
2,3-dihydropyridin-4(1H)-one (7): Prepared by the general
procedure described above and isolated as a yellowish solid;
yield: 23.7 mg (69%); mp 49–528C. Analytical data are con-
sistent with those from our previous report.[7]
(E)-1-Benzyl-5-[2-(tert-butoxycarbonyl)propenyl]-2-(4-
methoxyphenyl)-2,3-dihydropyridin-4(1H)-one (12): Pre-
pared by the general procedure described above and isolat-
ed as
a
waxy solid; yied: 12.2 mg (37%). 1H NMR
(400 MHz, CDCl3): d=7.58 (s, 1H), 7.50 (d, J=0.9 Hz, 1H),
7.39–7.33 (m, 3H), 7.22–7.12 (m, 4H), 6.88 (d, J=8.6 Hz,
2H), 4.54 (t, J=7.0 Hz, 1H), 4.41 (d, J=14.9 Hz, 1H), 4.26
(d, J=14.9 Hz, 1H), 3.81 (s, 3H), 2.92 (dd, J=16.4, 7.1 Hz,
1H), 2.73 (dd, J=16.5, 6.9 Hz, 1H), 1.90 (d, J=1.2 Hz, 3H),
1.50 (s, 9H); 13C NMR (100 MHz, CDCl3) d=188.5, 168.4,
159.9, 154.5, 135.4, 131.9, 130.0, 129.3, 128.7, 128.4, 128.0,
123.0, 114.7, 107.3, 80.0, 60.1, 58.1, 55.5, 43.5, 28.4, 15.2; FT-
IR (NaCl): n=3035, 2981, 1640, 1594, 1513, 1466, 1442,
1391, 1368, 1299, 1176, 1121, 1035, 833 cmÀ1; HR-MS
(ESI+):
m/e=456.2144,
calculated
for
[M+Na]+
C27H31NO4Na: 456.2145.
(E)-1-Benzyl-2-(4-methoxyphenyl)-5-[(2-oxodihydrofuran-
3(2H)-ylidene)methyl]-2,3-dihydropyridin-4(1H)-one (13):
Prepared by the general procedure described above and iso-
lated as a yellowish solid; yield: 21.2 mg (57%); mp 59–
628C. Analytical data are consistent with those from our
previous report.[7]
(E)-3-[2-(tert-Butoxycarbonyl)vinyl]-7,8,9,9a-tetrahydro-
1H-quinolizin-2(6H)-one (14): Prepared by the general pro-
cedure described above and isolated as a yellowish solid;
yield: 15.5 mg (59%); mp 122–1248C. Analytical data are
consistent with those from our previous report.[7]
(E)-(trans)-3-[2-(tert-Butoxycarbonyl)vinyl]-1-methyl-
4a,5,6,7,8,8a-hexahydroquinolin-4(1H)-one (15): Prepared
by the general procedure described above and isolated as
a yellowish solid; yield: 16.4 mg (59%); mp 146–1488C. An-
alytical data are consistent with those from our previous
report.[7]
(E)-1-Benzyl-5-[2-(dimethylcarbamoyl)vinyl]-2-(4-meth-
oxyphenyl)-2,3-dihydropyridin-4(1H)-one (8): Prepared by
the general procedure described above and isolated as
a yellow solid; yield: 29.4 mg (80%); mp 51–538C. Analyti-
cal data are consistent with those from our previous
report.[7]
(E)-1-Benzyl-5-[2-(diethoxyphosphinyl)vinyl]-2-(4-meth-
oxyphenyl)-2,3-dihydropyridin-4(1H)-one (9): Prepared by
the general procedure described above and isolated as
a yellow wax; yield: 27.4 mg (68%). 1H NMR (400 MHz,
CDCl3): d=7.50 (s, 1H), 7.42–7.34 (m, 3H), 7.18–7.07 (m,
4H), 6.95 (dd, J=24.7, 17.1 Hz, 1H), 6.87 (d, J=8.5 Hz,
2H), 6.52 (dd, J=22.2, 17.0 Hz, 1H), 4.51 (t, J=6.8 Hz,
1H), 4.42 (d, J=14.9 Hz, 1H), 4.25 (d, J=14.9 Hz, 1H),
(E)-1-Benzyl-5-[2-(tert-butoxycarbonyl)vinyl]-2-isopropyl-
2,3-dihydropyridin-4(1H)-one (16): Prepared by the general
procedure described above and isolated as a yellow wax;
1
yield: 27.0 mg (83%). H NMR (400 MHz, CDCl3): d=7.43–
7.35 (m, 4H), 7.25 (d, J=7.0 Hz, 2H), 7.08 (d, J=15.6 Hz,
1H), 6.50 (d, J=15.6 Hz, 1H), 4.58 (d, J=15.0 Hz, 1H),
4.48 (d, J=15.1 Hz, 1H), 3.32–3.22 (m, 1H), 2.63 (dd, J=
16.6, 7.6 Hz, 1H), 2.47 (dd, J=16.6, 2.3 Hz, 1H), 2.22 (dq,
J=13.4, 6.7 Hz, 1H), 1.46 (s, 9H), 0.98 (d, J=6.8 Hz, 3H),
Adv. Synth. Catal. 2014, 356, 1359 – 1369
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Yi-Yun Yu and Gunda I. Georg
0.92 (d, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
188.7, 168.6, 155.9, 138.9, 135.6, 129.4, 128.9, 127.6, 113.1,
105.9, 79.2, 61.8, 59.8, 37.5, 29.7, 28.4, 19.8, 18.1; FT-IR
(NaCl): n=3052, 2975, 2932, 1685, 1654, 1594, 1496, 1455,
n=3055, 2987, 2956, 1730, 1664, 1601, 1572, 1513, 1422,
1208, 1173, 1032, 1002, 896, 830 cmÀ1; HR-MS (ESI+): m/e=
377.1005, calculated for [M+Na]+ C20H18O6Na: 377.0996.
(E)-1-Butyl 3-methyl-5-[3-(4-methoxyphenyl)acryloyl] iso-
phthalate (30): Prepared by the general procedure described
above and isolated as a yellow wax; yield: 23.2 mg (75%).
1H NMR (400 MHz, CDCl3): d=8.85 (s, 1H), 8.82 (s, 2H),
7.86 (d, J=15.3 Hz, 1H), 7.64 (d, J=8.1 Hz, 2H), 7.45 (d,
J=15.3 Hz, 1H), 6.96 (d, J=8.2 Hz, 2H), 4.40 (t, J=7.2 Hz,
2H), 4.00 (s, 3H), 3.87 (s, 3H), 1.81 (m, 2H), 1.50 (h, J=7.4,
6.9 Hz, 2H), 1.00 (t, J=8.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=188.7, 165.8, 165.4, 162.2, 146.3, 139.3, 134.1,
133.4, 133.3, 131.8, 131.3, 130.7, 127.4, 118.8, 114.7, 65.8,
55.6, 52.8, 30.9, 19.4, 13.9; FT-IR (NaCl): n=3053, 2962,
2936, 1725, 1664, 1601, 1572, 1513, 1464, 1443, 1424, 1386,
1288, 1204, 1173, 1109, 1065, 1032, 986, 828 cmÀ1; HR-MS
1439, 1391, 1367, 1319, 1271, 1241, 1151, 1093, 990, 859 cmÀ1
;
HR-MS (ESI+): m/e=378.2038, calculated for [M+Na]+
C22H29NO3Na: 378.2040.
(E)-1-Benzyl-5-[2-(tert-butoxycarbonyl)vinyl]-2,3-dihydro-
pyridin-4(1H)-one (17): Prepared by the general procedure
described above and isolated as a yellowish oil; yield:
17.7 mg (59%). Analytical data are consistent with those
from our previous report.[7]
(E)-5-[2-(tert-Butoxycarbonyl)vinyl]-1-phenyl-2,3-dihy-
dropyridin-4(1H)-one (18): Prepared by the general proce-
dure described above and isolated as a yellowish solid;
yield: 9.0 mg (32%); mp 150–1528C. Analytical data are
consistent with those from our previous report.[7]
(ESI+):
C46H48O12Na: 815.3038.
(E)-1-Benzyl 3-methyl-5-[3-(4-methoxyphenyl)acryloyl]
m/e=815.3044,
calculated
for
[2M+Na]+
General Procedures for the Synthesis of 1,3,5-
Trisubstituted Benzenes via the Tandem Reaction
isophthalate (31): Prepared by the general procedure de-
scribed above and isolated as a yellow wax; yield: 24.0 mg
1
(86%). H NMR (400 MHz, CDCl3): d=8.88 (s, 1H), 8.85 (s,
In a 2-dram vial, alkenylated cyclic enaminone (0.07 mmol)
was mixed with alkene (0.56 mmol) and toluene (1 mL). The
vial was then sealed and stirred at 1608C. After 24 h, the re-
action mixture was cooled, concentrated under reduced
pressure, and then purified by flash chromatography on
silica gel.
1H), 8.82 (s, 1H), 7.85 (d, J=15.5 Hz, 1H), 7.64 (d, J=
7.8 Hz, 2H), 7.50–7.37 (m, 6H), 6.96 (d, J=7.8 Hz, 2H),
5.44 (s, 2H), 3.99 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=188.6, 165.8, 165.2, 162.2, 146.3, 139.4, 135.7,
134.2, 133.6, 133.5, 131.5, 131.4, 130.8, 128.8, 128.7, 128.6,
127.4, 118.8, 114.7, 67.6, 55.6, 52.8; FT-IR (NaCl): n=3055,
2987, 1728, 1664, 1601, 1588, 1572, 1513, 1422, 1201, 1173,
1030, 986, 896, 829 cmÀ1; HR-MS (ESI+): m/e=453.1314,
calculated for [M+Na]+ C26H22O6Na: 453.1309.
(E)-Methyl 3-cyano-5-[3-(4-methoxyphenyl)acryloyl]ben-
zoate (32): Prepared by the general procedure described
above and isolated as a light yellow solid; yield: 16.6 mg
(80%); mp 257–2598C. 1H NMR (400 MHz, CDCl3): d=
8.82 (s, 1H), 8.49 (s, 1H), 8.45 (s, 1H), 7.87 (d, J=15.4 Hz,
1H), 7.65 (d, J=7.2 Hz, 2H), 7.38 (d, J=15.4 Hz, 1H), 6.97
(d, J=6.8 Hz, 2H), 4.01 (s, 3H), 3.88 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=187.3, 164.7, 162.5, 147.3, 140.0,
136.3, 135.8, 133.0, 132.1, 130.9, 127.1, 117.9, 117.4, 114.8,
113.8, 55.6, 53.2; FT-IR (NaCl): n=3156, 2957, 2932, 2254,
1794, 1731, 1662, 1600, 1571, 1513, 1465, 1444, 1382, 1307,
1287, 1225, 1173, 1096, 1034, 987, 827 cmÀ1; HR-MS (ESI+):
m/e=344.0891, calculated for [M+Na]+ C19H15NO4Na:
344.0893.
(E)-Methyl 3-[3-(4-methoxyphenyl)acryloyl]-5-(methylsul-
fonyl)benzoate (27): Prepared by the general procedure de-
scribed above and isolated as a yellow solid; yield: 15.0 mg
(82%); mp 185–1878C. 1H NMR (400 MHz, CDCl3): d=
8.89 (s, 1H), 8.77 (s, 1H), 8.72 (s, 1H), 7.89 (d, J=15.4 Hz,
1H), 7.65 (d, J=7.8 Hz, 2H), 7.42 (d, J=15.5 Hz, 1H), 6.96
(d, J=7.8 Hz, 2H), 4.02 (s, 3H), 3.88 (s, 3H), 3.15 (s, 3H);
13C NMR (100 MHz, CDCl3): d=187.6, 164.9, 162.5, 147.3,
142.2, 140.4, 134.0, 132.5, 131.8, 131.1, 131.0, 127.1, 118.1,
114.7, 55.6, 53.1, 44.5; FT-IR (NaCl): n=3055, 2987, 1732,
1665, 1592, 1571, 1513, 1422, 1325, 1308, 1212, 1174, 1149,
1060, 1030, 984, 961, 896, 828 cmÀ1; HR-MS (ESI+): m/e=
397.0716, calculated for [M+Na]+ C19H18O6SNa: 397.0716.
(E)-Methyl 3-acetyl-5-[3-(4-methoxyphenyl)acryloyl]ben-
zoate (28): Prepared by the general procedure described
above and isolated as a yellow solid; yield: 17.5 mg (66%);
1
mp 72–748C. H NMR (400 MHz, CDCl3): d=8.83 (s, 1H),
8.78 (s, 1H), 8.75 (s, 1H), 7.86 (d, J=15.5 Hz, 1H), 7.65 (d,
J=7.7 Hz, 2H), 7.46 (d, J=15.4 Hz, 1H), 6.96 (d, J=7.8 Hz,
2H), 4.00 (s, 3H), 3.87 (s, 3H), 2.72 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=196.8, 188.7, 165.9, 162.3, 146.4,
139.5, 137.9, 133.4, 132.9, 132.0, 131.5, 130.8, 127.3, 118.7,
114.7, 55.6, 52.8, 27.1; FT-IR (NaCl); n=3055, 2987, 1728,
1693, 1664, 1599, 1572, 1513, 1422, 1361, 1195, 1173, 1031,
985, 829 cmÀ1; HR-MS (ESI+): m/e=361.1044, calculated for
[M+Na]+ C20H18O5Na: 361.1046.
(E)-Dimethyl 5-[3-(4-methoxyphenyl)acryloyl] isophtha-
late (29): Prepared by the general procedure described
above and isolated as a yellow solid; yield: 20.3 mg (73%);
mp 111–1138C. 1H NMR (400 MHz, CDCl3); d=8.88 (s,
1H), 8.84 (s, 2H), 7.88 (d, J=15.4 Hz, 1H), 7.66 (d, J=
7.6 Hz, 2H), 7.46 (d, J=15.3 Hz, 1H), 6.97 (d, J=8.7 Hz,
2H), 4.01 (s, 6H), 3.89 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=188.6, 165.8, 162.3, 146.3, 139.4, 134.2, 133.4,
131.4, 130.8, 127.4, 118.8, 114.7, 55.6, 52.8; FT-IR (NaCl):
(E)-Methyl
3-(dimethoxyphosphoryl)-5-[3-(4-methoxy-
phenyl)acryloyl]benzoate (33): Prepared by the general pro-
cedure described above and isolated as a yellow wax; yield:
1
6.0 mg (23%). H NMR (400 MHz, CDCl3): d=8.83 (s, 1H),
8.64 (d, J=12.1 Hz, 1H), 8.60 (d, J=12.1 Hz, 1H), 7.87 (d,
J=15.6 Hz, 1H), 7.65 (d, J=8.6 Hz, 2H), 7.44 (d, J=
15.5 Hz, 1H), 6.96 (d, J=8.6 Hz, 2H), 3.99 (s, 3H), 3.88 (s,
3H), 3.83 (d, J=11.1 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=188.5, 165.7, 162.3, 146.6, 139.4 (d, J=13.9 Hz), 136.4 (d,
J=10.9 Hz), 135.7 (d, J=11.0 Hz), 133.2 (d, J=3.0 Hz),
131.4 (d, J=15.2 Hz), 130.9, 129.1 (d, J=191.5 Hz), 127.3,
118.6, 114.7, 55.6, 53.2 (d, J=5.8 Hz), 52.9; FT-IR (NaCl):
n=3055, 2987, 1738, 1638, 1512, 1422, 1174, 1033, 896 cmÀ1
;
HR-MS (ESI+): m/e=427.0929, calculated for [M+Na]+
C20H21O7PNa: 427.0917.
(E)-4-Methoxycarbonyl-6-[3-(4-methoxyphenyl)acryloyl]-
isoindoline-1,3-dione (34): Prepared by the general proce-
1366
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1359 – 1369

À
UPDATES
Biomimetic Aerobic C H Olefination of Cyclic Enaminones
dure described above and isolated as a bright yellow solid;
yield: 4.4 mg (16%); mp 165–1678C. 1H NMR (400 MHz,
CDCl3): d=8.61 (s, 1H), 8.56 (s, 1H), 7.89 (d, J=15.5 Hz,
2H), 7.65 (d, J=8.7 Hz, 2H), 7.40 (d, J=15.5 Hz, 1H), 6.97
(d, J=8.7 Hz, 2H), 4.05 (s, 3H), 3.88 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=187.5, 165.9, 165.0, 164.5, 162.7,
147.7, 144.0, 134.7, 134.4, 132.7, 131.0, 130.8, 127.0, 125.4,
118.1, 114.8, 55.7, 53.4; FT-IR (NaCl): n=3413, 3055, 2987,
1783, 1744, 1638, 1513, 1421, 1173, 896 cmÀ1; HR-MS
“One-Pot, Two-Step” Procedure for the Synthesis of
Benzene 43
In a 2-dram vial, cyclic enaminone 1 (0.10 mmol) was mixed
with PdACHTNURGTENN(UG TFA)2 (3.3 mg, 0.01 mmol), CuACHTUNTGERN(NUGN OAc)2 (1.8 mg,
0.01 mmol), catechol (2.2 mg, 0.02 mmol) and 4ꢂ molecular
sieves (ca. 30 mg). To the mixture was added tert-butyl acry-
late (0.40 mmol), followed by DMF (0.5 mL). The vial was
purged with O2 and then sealed with an O2 balloon attached.
After being stirred at room temperature for 24 h, the reac-
tion mixture was filtered through Celite, and the filter cake
was washed with acetone (20 mL). The filtrate was then con-
centrated and mixed with methyl acrylate (0.80 mmol) and
toluene (1 mL). The vial was then sealed and stirred at
1608C. After 24 h, the reaction mixture was cooled, concen-
trated, and then purified by flash chromatography on silica
gel to afford product 43 as a yellow wax; yield: 20.1 mg
(ESI+):
C20H15NO6Na: 388.0792.
m/e=388.0791,
calculated
for
[M+Na]+
(E)-3-Cyano-5-[3-(4-methoxyphenyl)acryloyl]-1,1’-biphen-
yl (35): Prepared by the general procedure described above
and isolated as a yellow solid; yield: 10.5 mg (46%); mp 61–
1
638C. H NMR (400 MHz, CDCl3): d=8.42 (s, 1H), 8.24 (s,
1H), 8.06 (s, 1H), 7.88 (d, J=15.5 Hz, 1H), 7.70–7.62 (m,
4H), 7.51 (m, 3H), 7.40 (d, J=15.7 Hz, 1H), 6.98 (d, J=
7.8 Hz, 2H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
188.4, 162.4, 146.7, 143.3, 140.1, 138.3, 134.0, 131.2, 130.8,
130.5, 129.4, 129.0, 127.3, 127.2, 118.6, 118.3, 114.7, 113.6,
55.6; FT-IR (NaCl): n=3155, 2929, 2254, 1794, 1710, 1663,
1597, 1571, 1513, 1465, 1382, 1342, 1308, 1288, 1206, 1173,
1095, 1049, 1032, 985, 827 cmÀ1; HR-MS (ESI+): m/e=
362.1153, calculated for [M+Na]+ C23H17NO2Na: 362.1151.
(E)-3-Methoxycarbonyl-5-[3-(4-methoxyphenyl)acryloyl]-
1,1’-biphenyl (36): Prepared by the general procedure de-
scribed above and isolated as a yellow solid; yield: 13.0 mg
(52%); mp 124–1268C. 1H NMR (400 MHz, CDCl3): d=
8.61 (s, 1H), 8.48 (s, 1H), 8.42 (s, 1H), 7.86 (d, J=15.5 Hz,
1H), 7.73–7.62 (m, 4H), 7.52–7.40 (m, 4H), 6.96 (d, J=
8.0 Hz, 2H), 4.00 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=189.7, 166.6, 162.1, 145.8, 142.3, 139.5, 139.4,
132.1, 131.3, 131.3, 130.6, 129.2, 128.4, 128.2, 127.6, 127.4,
119.4, 114.6, 55.6, 52.6; FT-IR (NaCl): n=3055, 2987, 1723,
1662, 1599, 1572, 1513, 1438, 1422, 1349, 1197, 1173, 1048,
1031, 983, 896, 828 cmÀ1; HR-MS (ESI+): m/e=395.1254,
calculated for [M+Na]+ C24H20O4Na: 395.1254.
1
(51%). H NMR (400 MHz, CDCl3): d=8.81–8.76 (m, 3H),
7.85 (d, J=15.6 Hz, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.45 (d,
J=15.5 Hz, 1H), 6.96 (d, J=8.7 Hz, 2H), 3.99 (s, 3H), 3.87
(s, 3H), 1.64 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
188.9, 166.0, 164.5, 162.2, 146.2, 139.2, 134.0, 133.4, 133.3,
133.0, 131.2, 130.7, 127.4, 118.9, 114.7, 82.5, 55.6, 52.8, 28.3;
HR-MS (ESI+): m/e=397.1650, calculated for [M+H]+
C23H25O6: 397.1646.
Acknowledgements
We greatly appreciate the financial support from the National
Institutes of Health (GM081267) and the University of Min-
nesota through the Vince and McKnight Endowed Chairs (to
G.I.G.). We also thank Prof. Jin-Quan Yu and Prof. Dale L.
Boger for kindly providing equipment for GC-MS and LC-
MS analyses respectively.
(E)-Methyl
3-[3-(4-methoxyphenyl)acryloyl]benzoate
References
(37): Prepared by the general procedure described above
and isolated as an off-white solid; yield: 7.6 mg (33%); mp
93–958C. 1H NMR (400 MHz, CDCl3): d=8.65 (s, 1H),
8.29–8.14 (m, 2H), 7.83 (d, J=15.5 Hz, 1H), 7.61 (dd, J=
20.1, 8.0 Hz, 3H), 7.44 (d, J=15.5 Hz, 1H), 6.95 (d, J=
8.0 Hz, 2H), 3.97 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=189.5, 166.4, 161.9, 145.5, 138.8, 133.4, 132.7,
130.6, 130.4, 129.4, 128.9, 127.4, 119.2, 114.5, 55.4, 52.4; FT-
IR (NaCl); n=3155, 2984, 2955, 2929, 1793, 1722, 1660,
1595, 1572, 1512, 1466, 1382, 1305, 1291, 1208, 1173, 1096,
1034, 830 cmÀ1; HR-MS (ESI+): m/e=319.0946, calculated
for [M+Na]+ C18H16O4Na: 319.0941.
[1] G. Wang, S. Mohan, E.-i. Negishi, Proc. Natl. Acad. Sci.
USA 2011, 108, 11344–11349.
[2] M. Majewski, D. M. Gleave, Tetrahedron Lett. 1989, 30,
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[3] B. E. Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863–
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[4] W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2–7.
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[6] X. Shang, Z.-Q. Liu, Chem. Soc. Rev. 2013, 42, 3253–
3260.
tert-Butyl 3-acetyl-5-cyanobenzoate (38): Prepared by the
general procedure described above and isolated as a color-
less oil; yield: 8.1 mg (48%). H NMR (400 MHz, CDCl3):
[7] Y.-Y. Yu, M. J. Niphakis, G. I. Georg, Org. Lett. 2011,
13, 5932–5935.
1
d=8.71 (s, 1H), 8.42 (s, 1H), 8.37 (s, 1H), 2.67 (s, 3H), 1.63
(s, 9H); 13C NMR (100 MHz, CDCl3): d=195.3, 163.0, 138.2,
136.8, 135.1, 134.1, 133.0, 117.4, 113.7, 83.4, 28.2, 26.8; FT-IR
(NaCl): n=3055, 2986, 2931, 2238, 1721, 1698, 1639, 1552,
1422, 1371, 1330, 1158, 1129, 978, 896, 844 cmÀ1; HR-MS
[8] a) C. Yeung, V. Dong, Chem. Rev. 2011, 111, 1215–
1292; b) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev.
2011, 111, 1780–1824; c) J. Le Bras, J. Muzart, Chem.
Rev. 2011, 111, 1170–1214; d) S. H. Cho, J. Y. Kim, J.
Kwak, S. Chang, Chem. Soc. Rev. 2011, 40, 5068–5083.
[9] J. Piera, J.-E. Bꢁckvall, Angew. Chem. 2008, 120, 3558–
3576; Angew. Chem. Int. Ed. 2008, 47, 3506–3523.
(ESI+):
C14H15NO3Na: 268.0944.
m/e=268.0943,
calculated
for
[M+Na]+
Adv. Synth. Catal. 2014, 356, 1359 – 1369
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1367

UPDATES
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1359 – 1369

À
UPDATES
Biomimetic Aerobic C H Olefination of Cyclic Enaminones
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