Metal-free oxidative ipso-carboacylation of alkynes: Synthesis of 3-acylspiro[4,5]trienones from N-arylpropiolamides and aldehydes

Article abstract of DOI:10.1021/jo5005982

A general and metal-free radical route to synthesis of 3-acylspiro[4,5] trienones is established that utilizes TBHP (tert-butyl hydrogenperoxide) as an oxidation and a reaction partner to trigger the oxidative ipso-carboacylation of N-arylpropiolamides with aldehydes. This method offers a new difunctionalization of alkynes through oxidative cross coupling of the aldehyde C(sp²)-H bond with an ipso-aromatic carbon.

Full text of DOI:10.1021/jo5005982

Article
pubs.acs.org/joc
Metal-Free Oxidative Ipso-Carboacylation of Alkynes: Synthesis of
3‑Acylspiro[4,5]trienones from N‑Arylpropiolamides and Aldehydes
Xuan-Hui Ouyang, Ren-Jie Song,* Yang Li, Bang Liu, and Jin-Heng Li*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, China
S
* Supporting Information
ABSTRACT: A general and metal-free radical route to
synthesis of 3-acylspiro[4,5]trienones is established that
utilizes TBHP (tert-butyl hydrogenperoxide) as an oxidation
and a reaction partner to trigger the oxidative ipso-
carboacylation of N-arylpropiolamides with aldehydes. This
method offers a new difunctionalization of alkynes through
oxidative cross coupling of the aldehyde C(sp2)−H bond with
an ipso-aromatic carbon.
Scheme 1. Ipso-Carboacylation of Alkynes with Aldehydes
INTRODUCTION
■
The introduction of a carbonyl group into the organic
frameworks is one of the most popularly fundamental
processes in organic synthesis and chemical industries.
Traditionally, the frequently utilized method for the carbonyl
introduction purpose is the carbonylation reaction that
employs the toxic CO gas as the carbonyl resource.1 However,
the reaction suffers from the storage and transport of the toxic
CO gas, thereby limiting their wide application in fine
chemistry research and industry. Alternatively, the acylation
reaction is becoming a major topic of research in the carbonyl
introduction by direct functionalization of the carbonyl C−H
bond.2−5 In this field, acylation of alkynes with aldehydes to
versatile α-alkenyl ketones as one of the most elegant
examples has received considerable attention in recent years
with the inherent advantages: high atom economy and
avoidance of using the toxic CO gas. Generally, the method
is initially performed via the addition of the metal catalyst into
the carbonyl C−H bond leading to an acylmetal hydride
intermediate, followed by 1,2-hydroacylation of an alkyne with
the acylmetal hydride intermediate that furnishes an α-alkenyl
ketone.2,3 To our knowledge, however, difunctionalization of
alkynes using the acylation strategy to simultaneously
introduce an acyl group and another non-hydrogen group
remains an unexplored area. Herein, we report a novel metal-
free TBHP-mediated oxidative ipso-carboacylation of alkynes
with aldehydes to synthesize 3-acylspiro[4,5]trienones
(Scheme 1); this new oxidative tandem method is achieved
by sequential acylation, ipso-carbocylation, dearomatization,
and hydration, thus providing the first example of alkyne
difunctionalization for the simultaneous formation of two new
carbon−carbon bonds through an oxidative cross coupling
strategy.4a−g,5 Notably, the spirocycle unit is the common core
structure in many natural products and pharmaceuticals as
well as a versatile building block in organic synthesis.6
Recently, oxidative cross coupling involving a C−H
functionalization process has attracted increasing interest
because it offers an ideal process to overcome the
disadvantages of the classical cross-coupling reactions,
particularly avoiding prefunctionalization of the coupling
partners.4,5 Among them, oxidative coupling with an aldehyde
C(sp2)−H bond holds a particular fascination to organic
synthesis because it provides an efficient way to both form
new carbon−carbon bonds and incorporate an acyl group into
the products.4 In light of these findings, we reason that the
oxidative coupling reactions between alkynes and aldehydes
can be realized under metal-free conditions using a single-
electron-transfer (SET) strategy because the reported
transition-metal-free cross-coupling7 and some transition-
metal-catalyzed oxidative coupling have been proven to
include a radical process.4,5
RESULTS AND DISCUSSION
■
To test our hypothesis, the reaction between N-methyl-N,3-
diphenylpropiolamide (1a) and 4-methoxybenzaldehyde (2a)
was initially selected (Table 1).8 As expected, treatment of
substrate 1a with aldehyde 2a and TBHP (tert-butyl hydrogen
peroxide, anhydrous, 5 M in decane) at 110 °C for 36 h
afforded the desired 3-acylspiro[4,5]trienone 3aa in 68% yield
(entry 1). However, the yield was lowered slightly using
Received: March 13, 2014
Published: April 25, 2014
© 2014 American Chemical Society
4582
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
a
aqueous TBHP (entry 2). We found that the reaction
temperature played an important role in the reaction, and the
reaction at 110 °C gave the best results (entries 1, 3, and 4).
Subsequently, a series of other oxidants, including TAHP
(tert-amyl hydroperoxide), CHP (cumene hydroperoxide),
DTBP (di-tert-butyl peroxide), DCP (dicumyl peroxide), and
BPO (benzoyl peroxide), were investigated (entries 5−10).
We were surprised to find that only hydroperoxides, TAHP
and CHP, effected the reaction (entries 5 and 6), and the
other oxidants, DTBP, DCP, and BPO, have no reactivity for
the reaction (entries 7−10). Notably, aldehyde 2a was
completely transferred into 4-methoxybenzoic acid using
DTBP combined with 2 equiv of H2O, resulting in no
detectable 3-acylspiro[4,5]trienone 3aa (entry 8). Among the
Table 1. Screening Optimal Conditions
b
entry
1
[O]
solvent
T (°C)
yield (%)
TBHP
TBHP
TBHP
TBHP
TAHP
CHP
neat
110
110
80
68
63
15
65
38
18
0
c
2
neat
3
4
5
6
neat
neat
130
110
110
110
110
110
110
110
110
110
110
neat
neat
n
d
effect of solvents examined, it turned out that BuOAc was
7
DTBP
DTBP
DCP
neat
the most efficient, increasing the yield to 86% (entry 11).8
However, the reaction was suppressed under either O2 or air
atmosphere (entry 12 and 13). The reason is that aldehyde 2a
is readily converted to acid under the conditions. Noteworthy
is that the reaction can be performed on gram scale of
propiolamide 1a (5 mmol), and good yield is still achieved
(entry 14).
e
8
f
neat
0
9
neat
0
g
10
BPO
neat
0
11
TBHP
TBHP
TBHP
TBHP
nBuOAc
nBuOAc
nBuOAc
nBuOAc
86
57
68
83
g
12
h
13
i
14
With the optimal conditions in hand, we first investigated
the scope of N-arylacrylamides 1 with respect to 4-
methoxybenzaldehyde (2a) for this new ipso-carboacylation
process (Table 2). We were pleased to find that analogous
amide with N-Bn was a viable substrate for the reaction
(product 3ba), but changing to N-H resulted in a lower
reactivity (product 3ca). Subsequently, the substitution effect
of the N-aryl moiety was tested (products 3da−ha). For
example, substrates 1d or 1e, bearing a o-Me group or a m-
Me group on the aromatic ring of the N-aryl moiety, were
a
Reaction conditions: 1a (0.3 mmol), 2a (2 equiv), [O] (2 equiv), and
solvent (2 mL) under argon atmosphere for 36 h. Some byproducts,
including 4-methoxybenzoic acid, C−N bond decomposition products,
and hydroacylation product, were observed by GC−MS analysis.
b
c
d
Isolated yield. TBHP (70% in water) was added. >90% of both 1a
e
and 2a were recovered. 2 equiv of H2O was added: >90% of 1a was
recovered, and aldehyde 2a was completely converted to acid. An
unidentified product was isolated in 52% yield. Under oxygen
atmosphere. Under air atmosphere. 1a (5 mmol, 1.175 g).
f
g
h
i
a
Table 2. Screening Scope of N-Arylacrylamides (1)
a
n
Reaction conditions: 1 (0.3 mmol), 2a (2 equiv), TBHP (2 equiv), and BuOAc (2 mL) at 110 °C under argon atmosphere for 36 h.
4583
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
a
Table 3. Screening Scope of Aldehydes (2)
a
n
Reaction conditions: 1a (0.3 mmol), 2 (2 equiv), TBHP (2 equiv), and BuOAc (2 mL) at 110 °C under argon atmosphere for 36 h.
successfully reacted with aldehyde 2a and TBHP in good
yields (products 3da and 3ea). Importantly, the iodo group
was found to be well tolerated (product 3fa). Substrate 1g
with two MeO groups was also consistent with the optimal
conditions (product 3ga). Extensive screening revealed that
several substituents, including MeO, Me, and CN groups, on
the aromatic ring at the terminal alkyne were tolerated well,
and the electron-donating groups displayed higher reactivity
than the electron-withdrawing groups in terms of the yields
(products 3ha−ka). Using pyridin-2-yl-susbtituted substrate
1l, a good yield of the desired 3-acylspiro[4,5]trienones 3la
was still isolated. Notably, the ipso-carboacylation process
could toleratethe iodo group: N-(2-iodobenzyl)-N,3-diphenyl-
propiolamide (1m) delivered iodo-substituted spiro[4,5]-
trienone 2ma in 80% yield. Unfortunately, both N-methyl-
N-(naphthalen-1-yl)-3-phenylpropiolamide and N-methyl-N-
(naphthalen-2-yl)-3-phenylpropiolamide were not suitable
substrates for the reaction.
To our surprise, substrates 1 with a substituent, MeO or F,
at the para-position of the N-phenyl moiety furnished 3-
acylspiro[4,5]trienone 3aa in good yield by releasing para-
substituents (eq 1). However, aliphatic alkyne 1o was not a
suitable substrate (product 3oa).
As shown in Table 3, we next set out to explore the scope
of alkyl 2 in the presence of N-methyl-N,3-diphenylpropio-
lamide (1a) and TBHP. The results demonstrated that this
process could be applied to ipso-carboacylation of a wide
range of aldehydes 2b−o, including functionalized aryl and
aliphatic aldehydes. Using fresh benzaldehyde 2b, for instance,
the desired 3-benzoyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione 3ab was obtained in 94% yield. The optimal conditions
were compatible with various arylaldehydes having substitu-
ents, such as Br, OH, MeO, Me, CN, and CO2Me, on the aryl
ring, and the reactivity order is para > meta > ortho (products
3ac−ai). To our delight, aliphatic aldehydes 2j−o, even with a
MeO group or an olefin group, were viable for the reaction
with substrate 1a and TBHP, offering 3-acylspiro[4,5]-
trienones 3aj−ao in good yields. Notably, aldehydes 2m−o,
important components in flavors and fragrances as well as
having strong antifungal qualities,9 could be easily introduced
into the spiro[4,5]trienone frameworks (products 3am−ao),
4584
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
Scheme 2. Control Experiments and Utilization of Product 3ma
Scheme 3. Possible Mechanisms
thereby making this methodology more useful in organic
synthesis.
metric amount of radical inhibitor (2 equiv), TEMPO or 2,6-
di-tert-butylphenol, resulted in no conversion of substrate 1a;
moreover, aldehyde 2a was converted into 2,2,6,6-tetrame-
thylpiperidin-1-yl 4-methoxybenzoate by reacting with
TEMPO (eq 3, Scheme 2). It was noted that substrate 5aa,
a hydroacylation product, is inert for the reaction (eq 4,
Scheme 2). Interestingly, treatment of product 3ma with
Pd(OAc)2, PPh3 and NaHCO3 delivered anthor polycyclic
compound 6ma in 85% yield (eq 5, Scheme 2).6n
Consequently, a work mechanism outlined in Scheme 3 is
proposed on the basis of the present results and the literature
reports.2−5,7 Initially, carbonyl radical A is formed from
aldehyde 1a by a single-electron transfer (SET) with TBHP.5
Subsequently, acylation of alkyne 2a with carbonyl radical A
yields vinyl radical intermediate B, followed by selective ipso-
The results in Table 1 showed that the presence of either
H2O or O2 disfavored the reaction (entries 1, 2, 12, and 13).
Thus, some control experiments in the presence of 2 equiv of
H218O or 1 atm of 18O2 were performed, and the results
indicated that the amount of 18O in 3-acylspiro[4,5]trienones
3aa did not increase obviously (eq 2, Scheme 2). These
suggest that the oxygen atom of the new formed carbonyl
group is not from either H2O or O2. We carefully checked the
results in Table 1 again, and we found that only hydro-
peroxides displayed catalytic activity for the current reaction
(entries 1−2, 5, 6 vs entries 7−10). In light of these, we
deduce that the oxygen atom of the new formed carbonyl
group is from TBHP. Screening disclosed that a stoichio-
4585
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
10.0 Hz, 1H), 6.54 (d, J = 10.0 Hz, 1H), 6.45 (s, 1H), 3.82 (s, 3H),
2.89 (s, 3H), 1.90 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 189.8,
184.6, 167.3, 164.4, 154.0, 144.7, 140.6, 139.5, 136.1, 133.1, 131.9,
130.3, 130.2, 128.8, 128.6, 127.7, 113.9; IR (KBr, cm−1) 1632, 1668,
1699; LRMS (EI, 70 eV) m/z 399 (M+, 21), 384 (8), 263 (18), 135
(100); HRMS m/z (ESI) calcd for C25H21NO4 ([M + H]+)
400.1543, found 400.1558.
3-(4-Methoxybenzoyl)-1,7-dimethyl-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (3ea): 89.8 mg, 75%; yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.8 Hz, 2H), 7.25 (d, J =
7.2 Hz, 3H), 7.20 (d, J = 6.4 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H),
6.66−6.63 (m, 1H), 6.56−6.45 (m, 1H), 6.45 (d, J = 1.6 Hz, 1H),
3.83 (s, 3H), 2.90 (s, 3H), 2.00 (d, J = 1.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 189.8, 184.7, 167.4, 164.4, 154.1, 144.7, 140.7,
139.5, 136.0, 133.1, 131.9, 130.3, 128.8, 128.7, 128.2, 127.7, 114.0,
67.7, 55.5, 25.8, 15.9; IR (KBr, cm−1) 1628, 1679, 1699; LRMS (EI,
70 eV) m/z 399 (M+, 13), 398 (5), 263 (23), 135 (100); HRMS m/
z (ESI) calcd for C25H21NO4 ([M + H]+) 400.1543, found 400.1556.
6-Iodo-3-(4-methoxybenzoyl)-1-methyl-4-phenyl-1-azaspiro-
[4.5]deca-3,6,9-triene-2,8-dione (3fa): 104.3 mg, 68%; yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.8 Hz, 2H), 7.35 (d, J
carbocyclization to give intermediate C. Intermediate C
selectively undergoes the addition with •OH to afford
intermediate D. Finally, oxidation of intermediate D by
TBHP results in the desired 3-acylspiro[4,5]trienone 3aa.
CONCLUSIONS
■
In summary, we have illustrated an unprecedented metal-free
TBHP-mediated ipso-carboacylation of alkynes with aldehydes
through sequential aldehyde C(sp2)−H oxidation, acylation,
ipso-carbocyclization, dearomatization, hydration, and hydroxyl
group oxidation processes. This method is the first example of
alkyne difunctionalization to simultaneously form two
carbon−carbon bonds using the oxidative cross-coupling
strategy and provides valuable access to 3-acylspiro[4,5]-
trienones. Applications of this oxidative cross-coupling
method in organic synthesis are currently underway in our
laboratory.
EXPERIMENTAL SECTION
■
= 1.2 Hz, 1H), 7.32−7.00 (m, 5H), 6.93−6.87 (m, 3H), 6.64−6.61
(m, 1H), 3.84 (s, 3H), 2.88 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 189.2, 180.8, 167.3, 164.5, 153.7, 145.2, 144.2, 138.2, 132.3, 132.2,
130.6, 129.5, 128.9, 128.8, 127.9, 124.3, 114.0, 71.9, 55.5, 25.6; IR
(KBr, cm−1) 1630, 1672, 1708; LRMS (EI, 70 eV) m/z 511 (M+,
12), 385 (87), 135 (100); HRMS m/z (ESI) calcd for C24H19INO4
([M + H]+) 512.0359, found 512.0363.
1
General Considerations. The H and 13C NMR spectra were
recorded in CDCl3 solvent on a NMR spectrometer using TMS as
internal standard. LRMS was performed on a GC−MS instrument
and HRMS was measured on an electrospray ionization (ESI)
apparatus using time-of-flight (TOF) mass spectrometry. Melting
points are uncorrected.
Caution. Organic peroxides are dangerous under heating because
6,9-Dimethoxy-3-(4-methoxybenzoyl)-1-methyl-4-phenyl-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (3ga): 121.5 mg, 91%;
yellow solid; mp 204.5−205.7 °C (uncorrected); 1H NMR (400
MHz, CDCl3) δ 7.87 (d, J = 8.8 Hz, 2H), 7.28−7.18 (m, 5H), 6.86
(d, J = 8.8 Hz, 2H), 5.91 (s, 1H), 5.26 (s, 1H), 3.86 (s, 3H), 3.83 (s,
3H), 3.67 (s, 3H), 2.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
190.1, 180.9, 168.9, 167.8, 164.3, 154.0, 153.2, 136.1, 132.0, 130.2,
130.0, 128.9, 128.7, 127.5, 113.9, 106.6, 105.8, 69.5, 55.9, 55.8, 55.4,
25.2; IR (KBr, cm−1) 1611, 1646, 1663, 1689; LRMS (EI, 70 eV) m/
z 445 (M+, 12), 430 (3), 263 (15), 135 (100); HRMS m/z (ESI)
calcd for C26H23NO6 ([M + H]+) 446.1598, found 446.1593.
3-(4-Methoxybenzoyl)-4-(2-methoxyphenyl)-1-methyl-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (3ha): 103.3, 83%; yellow
solid; mp 127.5−128.7 °C (uncorrected); 1H NMR (400 MHz,
CDCl3) δ 7.84 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 1H), 7.13−
7.11 (m, 1H), 6.86 (d, J = 9.2 Hz, 2H), 6.84−6.80 (m, 1H), 6.71−
6.66 (m, 3H), 6.46 (d, J = 10.4 Hz, 2H), 3.84 (s, 3H), 3.45 (s, 3H),
2.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.5, 184.1, 167.6,
164.0, 155.9, 152.6, 144.9, 138.1, 132.8, 131.9, 131.4, 129.0, 128.9,
120.2, 118.7, 113.5, 111.0, 68.2, 55.5, 54.7, 26.2; IR (KBr, cm−1)
1658, 1663, 1699; LRMS (EI, 70 eV) m/z 415 (M+, 7), 385 (12),
263 (21), 135 (100); HRMS m/z (ESI) calcd for C25H22NO5 ([M +
H]+) 416.1492, found 416.1496.
3-(4-Methoxybenzoyl)-4-(4-methoxyphenyl)-1-methyl-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (3ia): 109.6 mg, 88%;
yellow solid; mp 121.4−123.2 °C (uncorrected); 1H NMR (400
MHz, CDCl3) δ 7.84 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H),
6.87 (d, J = 8.8 Hz, 2H), 6.71−6.68 (m, 4H), 6.59 (d, J = 10.0 Hz,
2H), 3.83 (s, 3H), 3.72 (s, 3H), 2.89 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 190.3, 183.9, 167.6, 164.4, 161.2, 153.0, 145.4, 134.3,
133.2, 131.9, 129.4, 128.8, 122.5, 114.3, 114.0, 66.8, 55.5, 55.2, 25.7;
IR (KBr, cm−1) 1658, 1672, 1708; LRMS (EI, 70 eV) m/z 415 (M+,
31), 263 (18), 135 (100); HRMS m/z (ESI) calcd for C25H22NO5
([M + H]+) 416.1492, found 416.1477.
they may cause a fire or explosion.
Preparation of N-Arylpropiolamides (1). All N-arylpropiola-
mides (1) were synthesized according to the known methods.10
Typical Experimental Procedure for the TBHP-Mediated
Synthesis of 3-Acylspiro[4,5]trienone from N-Arylpropiola-
mides with Aldehydes. To a Schlenk tube were added N-
arylpropiolamides 1 (0.3 mmol), aldehydes 2 (2 equiv), TBHP
(anhydrous, 2 equiv) and nBuOAc (2 mL). Then the tube was
charged with argon, and was stirred at 110 °C for 36 h until
complete consumption of starting material as monitored by TLC
and/or GC-MS analysis. After the reaction was finished, the reaction
mixture was washed with brine. The aqueous phase was re-extracted
with ethyl acetate. The combined organic extracts were dried over
Na2SO4, concentrated in vacuum, and the resulting residue was
purified by silica gel column chromatography (hexane/ethyl acetate)
to afford the desired product.
3-(4-Methoxybenzoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3aa): 99.3 mg, 86%; yellow solid; mp 171.2−
1
172.3 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.82 (d, J =
8.8 Hz, 2H), 7.230−7.25 (m, 3H), 7.21−7.20 (m, 2H), 6.86 (d, J =
8.8 Hz, 2H), 6.90 (d, J = 10.0 Hz, 2H), 6.58 (d, J = 10.0 Hz, 2H),
3.82 (s, 3H), 2.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.6,
183.8, 167.3, 164.4, 153.6, 144.8, 136.3, 133.4, 131.9, 130.4, 130.1,
128.7 (2C), 127.7, 114.0, 67.1, 55.5, 25.8; IR (KBr, cm−1) 1628,
1658, 1699; LRMS (EI, 70 eV) m/z 385 (M+, 13), 384 (8), 263
(25), 135 (100); HRMS m/z (ESI) calcd for C24H20NO4 ([M +
H]+) 386.1387, found 386.1403.
1-Benzyl-3-(4-methoxybenzoyl)-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3ba): 117.6 mg, 85%; yellow solid; mp
1
133.5−135.7 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.82
(d, J = 8.8 Hz, 2H), 7.27−7.16 (m, 10H), 6.87 (d, J = 8.8 Hz, 2H),
6.51 (d, J = 10.0 Hz, 2H), 6.34 (d, J = 10.0 Hz, 2H), 4.58 (s, 2H),
3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.5, 184.0, 167.5,
164.4, 154.2, 145.0, 137.2, 136.2, 132.6, 131.9, 130.4, 130.0, 128.9,
128.8, 128.6 (2C), 127.9, 127.8, 114.0, 67.6, 55.5, 44.6; IR (KBr,
cm−1) 1629, 1678, 1708; LRMS (EI, 70 eV) m/z 461 (M+, 13), 135
(100); HRMS m/z (ESI) calcd for C30H24NO4 ([M + H]+)
462.1700, found 462.1720.
3-(4-Methoxybenzoyl)-1-methyl-4-p-tolyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3ja): 97 mg, 81%; yellow solid; mp 119.6−
1
121.0 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
8.8 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.86
(d, J = 8.8 Hz, 2H), 6.69 (d, J = 10.0 Hz, 2H), 6.58 (d, J = 10.0 Hz,
2H), 3.83 (s, 3H), 2.90 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 189.9, 183.9, 167.5, 164.4, 153.6, 145.1, 140.9, 135.5,
133.2, 131.9, 129.5, 128.8, 127.6, 127.3, 114.0, 67.0, 55.5, 25.8, 21.2;
3-(4-Methoxybenzoyl)-1,6-dimethyl-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (3da): 87.4 mg, 73%; yellow oil; 1H
NMR (500 MHz, CDCl3) δ 7.83 (d, J = 9.0 Hz, 2H), 7.27−7.25 (m,
3H), 7.18 (t, J = 7.5 Hz, 2H), 6.86 (d, J = 9.0 Hz, 2H), 6.64 (d, J =
4586
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
IR (KBr, cm−1) 1628, 1664, 1699; LRMS (EI, 70 eV) m/z 399 (M+,
12), 135 (100); HRMS m/z (ESI) calcd for C25H22NO4 ([M + H]+)
400.1543, found 400.1563.
7.29−7.18 (m, 5H), 7.01 (t, J = 8.4 Hz, 1H), 6.93 (d, J = 8.4 Hz,
1H), 6.61 (d, J = 10.4 Hz, 2H), 6.53 (d, J = 10.0 Hz, 2H), 3.85 (s,
3H), 2.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.6, 183.9,
167.3, 159.6, 152.3, 144.9, 139.5, 135.2, 133.3, 131.1, 130.4, 129.9,
128.5, 127.8, 126.78, 121.1, 111.9, 66.9, 55.8, 25.7; IR (KBr, cm−1)
1570, 1608, 1660, 1698; LRMS (EI, 70 eV) m/z 385 (M+, 3), 367
(14), 354 (41), 135 (100); HRMS m/z (ESI) calcd for C24H20NO4
([M + H]+) 386.1387, found 386.1400.
4-(3-(4-Methoxybenzoyl)-1-methyl-2,8-dioxo-1-azaspiro[4.5]-
deca-3,6,9-trien-4-yl)benzonitrile (3ka): 88.6 mg, 72%; yellow solid;
1
mp 179.6−181.0 °C (uncorrected); H NMR (400 MHz, CDCl3) δ
7.80 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4
Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.67 (d, J = 10.0 Hz, 2H), 6.60
(d, J = 10.40 Hz, 2H), 3.86 (s, 3H), 2.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 188.7, 183.2, 166.7, 164.9, 151.5, 144.0, 138.8,
134.5, 133.9, 132.4, 132.0, 128.5, 128.4, 117.6, 114.2, 114.1, 67.1,
55.6, 26.0; IR (KBr, cm−1) 1639, 1678, 1702; LRMS (EI, 70 eV) m/
z 410 (M+, 17), 288 (37), 135 (100); HRMS m/z (ESI) calcd for
C25H19N2O4 ([M + H]+) 411.1339, found 411.1349.
3-(3-Methoxybenzoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
1
3,6,9-triene-2,8-dione (3af): 93.6, 81%; yellow oil; H NMR (400
MHz, CDCl3) δ 7.44 (s, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.30−7.26
(m, 4H), 7.22−7.18 (m, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.69 (d, J =
10.0 Hz, 2H), 6.58 (d, J = 10.0 Hz, 2H), 3.81 (s, 3H), 2.92 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 191.2, 183.7, 167.1, 159.9, 154.2,
144.7, 136.8, 136.2, 133.5, 130.5, 130.1, 129.7, 128.8, 127.8, 122.7,
121.0, 112.9, 67.2, 55.4, 25.9; IR (KBr, cm−1) 1582, 1599, 1663,
1697; LRMS (EI, 70 eV) m/z 385 (M+, 22), 263 (45), 135 (100);
HRMS m/z (ESI) calcd for C24H20NO4 ([M + H]+) 386.1387,
found 386.1403.
3-(4-Methoxybenzoyl)-1-methyl-4-(pyridin-4-yl)-1-azaspiro[4.5]-
1
deca-3,6,9-triene-2,8-dione (3la): 95 mg, 82%; yellow oil; H NMR
(500 MHz, CDCl3) δ 8.49 (d, J = 4.5 Hz, 2H), 7.81 (d, J = 7.0 Hz,
2H), 7.17 (d, J = 5.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 6.67 (d, J =
11.0 Hz, 2H), 6.61 (d, J = 10.5 Hz, 2H), 3.85 (s, 3H), 2.93 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 188.6, 183.2, 166.5, 164.8, 150.5,
1-Methyl-3-(4-methylbenzoyl)-4-phenyl-1-azaspiro[4.5]deca-
150.2, 143.8, 138.9, 137.7, 133.8, 131.9, 128.4, 121.8, 114.2, 66.9,
55.5, 25.9; IR (KBr, cm−1) 1634, 1662, 1698; LRMS (EI, 70 eV) m/
z 386 (M+, 26), 385 (30), 264 (23), 135 (100); HRMS m/z (ESI)
calcd for C23H19N2O4 ([M + H]+) 387.1345, found 387.1336.
1-(2-Iodobenzyl)-3-(4-methoxybenzoyl)-4-phenyl-1-azaspiro-
[4.5]deca-3,6,9-triene-2,8-dione (3ma): 140.9 mg, 80%; yellow
solid; mp 233.1−234.6 °C (uncorrected); 1H NMR (400 MHz,
CDCl3) δ 7.85 (d, J = 9.2 Hz, 2H), 7.78 (d, J = 8.0 Hz, 1H), 7.42
(d, J = 8.0 Hz, 1H), 7.29−7.16 (m, 6H), 7.00 (t, J = 8.0 Hz, 1H),
6.88 (d, J = 8.8 Hz, 2H), 6.51 (d, J = 8.0 Hz, 2H), 6.32 (d, J = 10.0
Hz, 2H), 4.75 (s, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 189.3, 184.0, 167.4, 164.4, 154.6, 144.1, 139.5, 139.4, 136.0, 132.9,
131.9, 130.3, 130.2, 129.9, 129.6, 128.7, 128.6 (2C), 127.7, 114.0,
99.4, 67.5, 55.5, 48.9; IR (KBr, cm−1) 1630, 1669, 1697, 1703;
HRMS m/z (ESI) calcd for C30H23INO4 ([M + H]+) 588.0666,
found 588.0657.
3,6,9-triene-2,8-dione (3ag): 101.8 mg, 92%; yellow solid; mp
1
123.1−124.9 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.74
(d, J = 7.6 Hz, 2H), 7.28 (d, J = 7.6 Hz, 3H), 7.20 (t, J = 7.6 Hz,
4H), 6.69 (d, J = 9.6 Hz, 2H), 6.58 (d, J = 9.6 Hz, 2H), 2.92 (s,
3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.9, 183.8,
167.3, 154.0, 145.4, 144.8, 136.3, 133.4, 133.2, 130.5, 130.1, 129.6,
129.4, 128.8, 127.8, 67.2, 25.9, 21.8; IR (KBr, cm−1) 1589, 1645,
1668, 1697; LRMS (EI, 70 eV) m/z 369 (M+, 20), 247 (25), 119
(100); HRMS m/z (ESI) calcd for C24H20NO3 ([M + H]+)
370.1438, found 370.1427.
4-(1-Methyl-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-
trienecarbonyl)benzonitrile (3ah): 93.5 mg, 82%; yellow solid; mp
1
183.4−184.6 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.90
(d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H), 7.31 (t, J = 4.4 Hz,
1H), 7.22 (d, J = 4.0 Hz, 4H), 6.69−6.65 (m, 2H), 6.62−6.59 (m,
2H), 2.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.7, 183.5,
166.7, 156.8, 144.0, 138.4, 135.0, 133.8, 132.5, 131.0, 129.7, 129.0,
127.7, 117.7, 117.21, 67.4, 26.0; IR (KBr, cm−1) 1575, 1602, 1669,
1694; LRMS (EI, 70 eV) m/z 380 (M+, 43), 252 (24), 102 (49),
129 (100); HRMS m/z (ESI) calcd for C24H17N2O3 ([M + H]+)
381.1239, found 381.1230.
3-Benzoyl-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3ab): 100.1 mg, 94%; yellow solid; mp 108.2−110.0 °C
1
(uncorrected); H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.8 Hz,
2H), 7.51−7.50 (m, 1H), 7.40−7.39 (m, 2H), 7.27 (t, J = 3.6 Hz,
3H), 7.26−7.20 (m, 2H), 6.70 (d, J = 10.0 Hz, 2H), 6.59 (d, J =
10.8 Hz, 2H), 2.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 191.3,
183.7, 167.2, 154.5, 144.6, 136.0, 135.5, 134.2, 133.5, 130.5, 130.0,
129.4, 128.7 (2C), 127.7, 67.2, 25.9; IR (KBr, cm−1) 1573, 1597,
1669, 1699; LRMS (EI, 70 eV) m/z 355 (M+, 27), 233 (17), 105
(100); HRMS m/z (ESI) calcd for C23H18NO3 ([M + H]+)
356.1281, found 356.1272.
3-(2-Bromobenzoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3ac): 97.9 mg, 75%; yellow oil; 1H NMR
(400 MHz, CDCl3) δ 7.49−7.41 (m, 2H), 7.26−7.15 (m, 7H), 6.64
(d, J = 10.4 Hz, 2H), 6.51 (d, J = 10.4 Hz, 2H), 2.92 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 190.7, 183.6, 166.5, 157.3, 143.7, 139.0,
135.8, 133.7, 133.3, 132.9, 131.3, 130.2, 129.8, 128.3, 127.7, 127.4,
120.6, 67.4, 26.0; IR (KBr, cm−1) 1568, 1603, 1688, 1701; LRMS
(EI, 70 eV) m/z 435 (M++2, 13), 433 (M+, 13), 354 (100), 326
(70); HRMS m/z (ESI) calcd for C23H17BrNO3 ([M + H]+)
434.0392, found 434.0383.
Methyl 4-(1-methyl-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-trienecarbonyl)benzoate (3ai): 104.1 mg, 84%; yellow oil;
1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.4 Hz, 2H), 7.88 (d, J
= 8.0 Hz, 2H), 7.26−7.17 (m, 5H), 6.70 (d, J = 10.0 Hz, 2H), 6.60
(d, J = 9.6 Hz, 2H), 3.92 (s, 3H), 2.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 190.7, 183.6, 166.9, 165.9, 155.6, 144.3, 138.6,
135.5, 134.6, 133.6, 130.8, 129.8, 129.3, 128.9, 127.7, 67.3, 52.5, 25.9;
IR (KBr, cm−1) 1499, 1572, 1631, 1669, 1706; LRMS (EI, 70 eV)
m/z 413 (M+, 32), 384 (11), 291 (16), 163 (100); HRMS m/z
(ESI) calcd for C25H20NO5 ([M + H]+) 414.1336, found 414.1314.
3-Butyryl-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3aj): 82.8 mg, 86%; yellow oil; 1H NMR (400 MHz,
CDCl3) δ 7.39−7.18 (m, 3H), 7.19 (d, J = 8.8 Hz, 2H), 6.55−6.48
(m, 4H), 2.90 (s, 3H), 2.72 (t, J = 7.2 Hz, 2H), 1.63−1.57 (m, 2H),
0.87 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.0,
183.6, 167.1, 157.0, 144.0, 136.2, 133.6, 130.3, 130.2, 128.5, 127.7,
67.3, 45.0, 26.0, 16.7, 13.5; IR (KBr, cm−1) 1633, 1670, 1697; LRMS
(EI, 70 eV) m/z 321 (M+, 57), 251 (65), 129 (100); HRMS m/z
(ESI) calcd for C20H20NO3 ([M + H]+) 322.1443, found 322.1434.
3-Heptanoyl-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-tri-
3-(2-Hydroxybenzoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
1
3,6,9-triene-2,8-dione (3ad): 79.0, 71%; yellow oil; H NMR (400
MHz, CDCl3) δ 8.13 (d, J = 7.6 Hz, 1H), 7.67−7.62 (m, 2H), 7.56
(d, J = 6.4 Hz, 1H), 7.51−7.47 (m, 2H), 7.39−7.33 (m, 3H), 6.45
(d, J = 8.8 Hz, 2H), 6.31 (d, J = 7.6 Hz, 2H), 3.19 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 176.3, 165.5, 160.5, 155.8, 134.1, 132.1,
131.5, 129.0, 128.6, 128.4, 126.6, 125.9, 125.4, 122.5, 120.6, 118.0,
115.6, 60.5, 37.3; IR (KBr, cm−1) 1572, 1600, 1682, 1700; LRMS
(EI, 70 eV) m/z 371 (M+, 14), 261 (12), 135 (100); HRMS m/z
(ESI) calcd for C23H18NO4 ([M + H]+) 372.1230, found 372.1220.
3-(2-Methoxybenzoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3ae): 90.1 mg, 78%; yellow oil; 1H NMR
(400 MHz, CDCl3) δ 7.80−7.77 (m, 1H), 7.51−7.47 (m, 1H),
1
ene-2,8-dione (3ak): 84.9 mg, 78%; yellow oil; H NMR (400 MHz,
CDCl3) δ 7.38 (t, J = 7.2 Hz, 1H), 7.34−7.29 (m, 2H), 7.19 (d, J =
7.6 Hz, 2H), 6.54 (d, J = 10.0 Hz, 2H), 6.49 (d, J = 10.0 Hz, 2H),
2.89 (s, 3H), 2.73 (t, J = 7.2 Hz, 2H), 1.57−1.52 (m, 2H), 1.21 (s,
6H), 0.84 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
199.1, 183.5, 167.0, 156.8, 143.9, 136.2, 133.6, 130.2, 130.1, 128.4,
127.7, 67.3, 43.0, 31.4, 28.5, 25.9, 23.1, 22.3, 13.9; IR (KBr, cm−1)
1460, 1631, 1670, 1697; LRMS (EI, 70 eV) m/z 363 (M+, 34), 292
4587
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
(58), 207 (100); HRMS m/z (ESI) calcd for C23H26NO3 ([M +
H]+) 364.1913, found 364.1904.
ASSOCIATED CONTENT
* Supporting Information
Screening of the optimal conditions (Table S1) and copies of
1H and 13C spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
S
3-Dodecanoyl-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-tri-
1
ene-2,8-dione (3al): 93.5 mg, 72%; yellow oil; H NMR (400 MHz,
CDCl3) δ 7.40−7.28 (m, 3H), 7.19 (d, J = 8.0 Hz, 2H), 6.55−6.48
(m, 4H), 2.89 (s, 3H), 2.75−2.71 (m, 2H), 1.55 (t, J = 7.2 Hz, 2H),
1.24−1.21 (m, 16H), 0.88 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 199.1, 183.5, 167.0, 156.8, 144.0, 136.2, 133.6, 130.2,
130.1, 128.5, 127.7, 67.3, 43.0, 31.8, 29.5 (2C), 29.3, 29.2, 28.9, 25.9,
23.1, 22.6, 14.0; IR (KBr, cm−1) 1638, 1671, 1697; LRMS (EI, 70
eV) m/z 433 (M+, 38), 207 (100); HRMS m/z (ESI) calcd for
C28H36NO3 ([M + H]+) 434.2695, found 434.2687.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: srj0731@hnu.edu.cn.
*E-mail: jhli@hnu.edu.cn.
Notes
3-(7-Methoxy-3,7-dimethyloctanoyl)-1-methyl-4-phenyl-1-
azaspiro[4.5]deca-3,6,9-triene-2,8-dione (3am): 79.8 mg, 66%;
yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.2 Hz,
1H), 7.33 (t, J = 7.2 Hz, 2H), 7.19 (d, J = 7.2 Hz, 2H), 6.56−6.47
(m, 4H), 3.15 (s, 3H), 2.89 (s, 3H), 2.74−2.68 (m, 1H), 2.56−2.52
(m, 1H), 2.05−1.98 (m, 1H), 1.26−1.17 (m, 2H), 1.13−1.10 (m,
4H), 1.10 (s, 6H), 0.84 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 198.9, 183.6, 167.0, 156.7, 144.0 (2C), 136.5, 133.7 (2C),
130.3, 130.1, 128.5, 127.8, 67.4, 50.3, 49.0, 39.9, 37.2, 28.8, 26.0, 24.9
(2C), 21.1, 19.7; IR (KBr, cm−1) 1630, 1678, 1699; LRMS (EI, 70
eV) m/z 403 (M+, 14), 363 (5), 320 (16), 73 (100); HRMS m/z
(ESI) calcd for C27H34NO4 ([M + H]+) 436.2488, found 436.2480.
1-Methyl-4-phenyl-3-undec-10-enoyl-1-azaspiro[4.5]deca-3,6,9-
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Natural Science Foundation of China (No.
21172060), Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20120161110041), and
Hunan Provincial Natural Science Foundation of China (No.
13JJ2018) for financial support. Dr. R.-J. Song also thanks the
China Postdoctoral Science Foundation (No. 2012M511716)
and Hunan Province Science and Technology Project (No.
2013RS4026)
REFERENCES
■
1
triene-2,8-dione (3an): 102.6 mg, 82%; yellow oil; H NMR (400
(1) For reviews on the carbonylation reaction, see: (a)
Carbonylation: Direct Synthesis of Carbonyl Compounds; Colquhoun,
H. M., Thompson, D. J., Twigg, M. V., Eds.; Springer: New York,
MHz, CDCl3) δ 7.39 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 7.2 Hz, 2H),
7.18 (t, J = 7.2 Hz, 2H), 6.55−6.51 (m, 4H), 5.83−5.77 (m, 1H),
5.01−4.91 (m, 2H), 2.90 (s, 3H), 2.73 (t, J = 7.2 Hz, 2H), 2.05−
1.99 (m, 2H), 1.56 (t, J = 7.2 Hz, 2H), 1.36−1.22 (m, 10H); 13C
NMR (100 MHz, CDCl3) δ 199.1, 183.6, 167.1, 156.9, 144.0, 139.1,
136.2, 133.6, 130.3, 130.1, 128.5, 127.8, 114.1, 67.3, 43.1, 33.7, 29.2,
29.0, 28.9, 28.8, 26.0, 23.2; IR (KBr, cm−1) 1635, 1678, 1697; LRMS
(EI, 70 eV) m/z 417 (M+, 48), 292 (99), 129 (100), 55 (71);
HRMS m/z (ESI) calcd for C27H32NO3 ([M + H]+) 418.2378,
found 418.2371.
́
1991. (b) Modern Carbonylation Methods; Kollar, L., Ed.; Wiley-
VCH: Weinheim, 2008. (c) Catalytic Carbonylation Reactions; Beller,
M., Ed.; Springer-Verlag: Berlin, 2006. (d) Liu, Q.; Zhang, H.; Lei, A.
Angew. Chem., Int. Ed. 2011, 50, 10788. (e) Wu, X.-F.; Neumann, H.;
Beller, M. Chem. Rev. 2013, 113, 1.
(2) For special reviews on the hydroacylation reaction, see:
(a) Bosnich, B. Acc. Chem. Res. 1998, 31, 667. (b) Jun, C.-H.;
Hong, J.-B.; Lee, D. L. Synlett 1999, 1. (c) Jun, C.-H.; Park, Y. J. In
Handbook of C−H Transformations: Applications in Organic Synthesis;
Dyker, G., Ed.; Wiley-VCH: Weinheim, 2005; p 303. (d) Fu, G. C.
In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.;
Wiley-VCH: Weinheim, 2005; p 79. (e) Jun, C.-H.; Jo, E.-A.; Park,
J.-W. Eur. J. Org. Chem. 2007, 1869. (f) Willis, M. C. Chem. Rev.
2010, 110, 725. (g) Gonzalez-Rodriguez, C.; Willis, M. C. Pure Appl.
Chem. 2011, 83, 577. (h) Leung, J. C.; Krische, M. J. Chem. Sci.
2012, 3, 2202.
(3) For pioneering papers on hydroacylation of alkynes, see:
(a) Tsuda, T.; Kiyoi, T.; Saegusa, T. J. Org. Chem. 1990, 55, 2554.
(b) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 11492.
(c) Fu, G. C.; Tanaka, K. Angew. Chem., Int. Ed. 2002, 41, 1607.
(d) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 10296.
(e) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 8078.
(f) Takeishi, K.; Sugishama, K.; Sasaki, K.; Tanaka, K. Chem.Eur. J.
2004, 10, 5681. (g) Tanaka, K.; Sasaki, K.; Takeishi, K.; Hirano, M.
Eur. J. Org. Chem. 2007, 5675. (h) Kokubo, K.; Matsumasa, K.;
Miura, M.; Nomura, M. J. Org. Chem. 1997, 62, 4564. (i) Jun, C.-H.;
Lee, H.; Hong, J.-B.; Kwon, B.-I. Angew. Chem., Int. Ed. 2002, 41,
2146. (j) Willis, M. C.; Randell-Sly, H. E.; Woodward, R. L.; Currie,
G. S. Org. Lett. 2005, 7, 2249. (k) Moxham, G. L.; Randell-Sly, H.
E.; Brayshaw, S. K.; Woodward, R. L.; Weller, A. S.; Willis, M. C.
Angew. Chem., Int. Ed. 2006, 45, 7618. (l) Willis, M. C.; Randell-Sly,
H. E.; Woodward, R. L.; McNally, S.; Currie, G. S. J. Org. Chem.
2006, 71, 5291. (m) Rueda, X. Y.; Castillon, S. J. Organomet. Chem.
2007, 692, 1628. (n) Moxham, G. L.; Randell-Sly, H. E.; Brayshaw,
S. K.; Weller, A. S.; Willis, M. C. Chem.Eur. J. 2008, 14, 8383.
(o) Biju, A. T.; Wurz, N. E.; Glorius, F. J. Am. Chem. Soc. 2010, 132,
3-(3,7-Dimethyloct-6-enoyl)-1-methyl-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (3ao): 95.5 mg, 79%; yellow oil; the
1
ratio of two diastereomers is 2:1; H NMR (400 MHz, CDCl3) δ
7.40 (t, J = 7.2 Hz, 2H), 7.32 (t, J = 7.2 Hz, 2H), 7.28 (s, 1.6H),
7.19 (d, J = 7.6 Hz, 2H), 6.54−6.47 (m, 5H), 6.30 (d, J = 10.0 Hz,
1H), 5.02 (S, 1H), 3.88−3.85 (m, 0.5H), 2.89 (s, 3H), 2.83 (m,
1.5H), 2.73−2.68 (m, 1.5H), 2.58−2.52 (m, 1.5H), 2.01−1.99 (m,
1.5H), 1.91−1.88 (m, 3H), 1.66 (s, 4.5H), 1.56 (s, 3H), 1.42−1.40
(m, 1.5H), 1.16−1.10 (m, 2H), 0.99 (d, J = 6.4 Hz, 1.5H), 0.85 (d, J
= 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 211.9, 198.8, 183.6,
166.8, 156.7, 146.7, 146.3, 145.7, 144.0, 136.5, 133.6, 133.0, 132.7,
131.4, 130.3, 130.1, 128.5, 128.1, 128.0, 124.2, 99.9, 67.9, 67.3, 54.1,
51.4, 50.3, 38.2, 36.7, 35.5, 34.2, 28.5, 27.2, 26.7, 26.2, 26.0, 25.6,
25.3, 22.9, 22.3, 19.6, 17.6; IR (KBr, cm−1) 1633, 1673, 1697; LRMS
(EI, 70 eV) m/z 403 (M+, 72), 292 (100), 265 (65); HRMS m/z
(ESI) calcd for C26H30NO3 ([M + H]+) 404.2220, found 404.2201.
6-(4-Methoxybenzoyl)-5-phenyl-2H-pyrrolo[2,1-e]phenanthri-
dine-2,7(9H)-dione (6ma): 78.0 mg, 85%; yellow solid; mp 193.7−
1
196.1 °C (uncorrected); H NMR (400 MHz, CDCl3) δ 7.62 (d, J =
1.6 Hz, 1H), 7.49 (t, J = 2.8 Hz, 2H), 7.39−7.37 (m, 3H), 7.29−
7.20 (m, 3H), 7.03 (d, J = 2.8 Hz, 2H), 6.87 (d, J = 4.8 Hz, 1H),
6.69 (d, J = 4 Hz, 2H), 6.49 (s, 1H), 6.26 (d, J = 4.8 Hz, 1H), 5.18
(d, J = 7.2 Hz, 1H), 4.15 (d, J = 7.6 Hz, 1H), 3.77 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 188.4, 184.3, 173.7, 164.2, 159.7, 151.1,
146.5, 138.5, 136.4, 132.9, 131.7, 131.5, 130.9, 129.9, 129.0,
128.7(2C), 128.6, 128.1, 126.3, 125.0, 113.7, 72.0, 55.45, 44.5;
HRMS m/z (ESI) calcd for C30H22NO4 ([M + H]+) 460.1543,
found 460.1533.
5970. (p) Gonzal
Willis, M. C. Chem.Eur. J. 2010, 16, 10950. (q) Parsons, S. R.;
Hooper, J. F.; Willis, M. C. Org. Lett. 2011, 13, 998. (r) Gonzalez-
́
ez-Rodríguez, C.; Parsons, S. R.; Thompson, A. L.;
́
4588
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589

The Journal of Organic Chemistry
Article
Rodríguez, C.; Pawley, R. J.; Chaplin, A. B.; Thompson, A. L.;
Weller, A. S.; Willis, M. C. Angew. Chem., Int. Ed. 2011, 50, 5134.
(s) Lenden, P.; Entwistle, D. A.; Willis, M. C. Angew. Chem., Int. Ed.
2011, 50, 10657. (t) Pawley, R. J.; Huertos, M. A.; Lloyd-Jones, G.
C.; Weller, A. S.; Willis, M. C. Organometallics 2012, 31, 5650.
(u) Poingdestre, S.-J.; Goodacre, J. D.; Wellera, A. S.; Willis, M. C.
Chem. Commun. 2012, 48, 6354. (v) Vedachalam, S.; Wong, Q.-L.;
Maji, B.; Zeng, J.; Ma, J.; Liu, X.-W. Adv. Synth. Catal. 2011, 353,
219. (w) Chaplin, A. B.; Hooper, J. F.; Weller, A. S.; Willis, M. C. J.
Am. Chem. Soc. 2012, 134, 4885. For papers on NHC-catalyzed
benzoin reactions and Steeer reactions, see: (x) Zhang, J.-M.; Xing,
C.; Tiwari, B.; Robin Chi, Y.-G. J. Am. Chem. Soc. 2013, 135, 8113.
(y) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107,
5606. (z) DiRocco, D. A.; Noey, E. L.; Houk, K. N.; Rovi, T. Angew.
Chem., Int. Ed. 2012, 51, 2391.
X.-H.; Li, Y.; Li, H.-B.; Li, J.-H. Org. Chem. Front. 2014,
DOI: 10.1039/c4qo00006d.
(7) For reviews, see: (a) Ouyang, K.; Xi, Z. Acta Chim. Sinica 2013,
71, 13. (b) Shirakawa, E.; Hayashi, R. Chem. Lett. 2012, 41, 130.
(c) Yanigasawa, S.; Itami, K. Chem. Catal. Chem. 2011, 3, 827.
(d) Wang, Y. Synlett 2011, 2901.
(8) The detailed optimal conditons are summaried in Table S1 of
the Supporting Information.
(9) (a) Mahalwal, V. S.; Ali, M. Flav. Fragr. J. 2003, 18, 73.
(b) Kim, J.-K.; Kang, C.-S.; Lee, J.-K.; Kim, Y.-R.; Han, H.-Y.; Yun,
H. K. Entomol. Res. 2005, 35, 117.
(10) Tang, S.; Peng, P.; Pi, S.-F.; Liang, Y.; Wang, N.-X.; Li, J.-H.
Org. Lett. 2008, 10, 1179.
(4) (a) Mcglacken, G. P.; Bateman, L. M.; Bateman, L. Chem. Soc.
Rev. 2009, 38, 2447. (b) Shabashov, D. Acc. Chem. Res. 2009, 42,
1074. (c) Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39, 540. (d) Cho,
S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068.
(e) Le Bras, J.; Muzart, J. Chem. Rev. 2011, 111, 1170. (f) Liu, C.;
Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780. (g) Xie, Y.-
X.; Song, R.-J.; Xiang, J.-N.; Li, J.-H. Chin. J. Org. Chem. 2012, 32,
1555. For papers on metal-catalyzed carboformylation of alkenes:
(h) Brown, S.; Clarkson, S.; Grigg, R.; Thomas, W. A.; Sridharan, V.;
Wilson, D. M. Tetrahedron 2001, 57, 1347. (i) Okazaki, E.;
Okamoto, R.; Shibata, Y.; Noguchi, K.; Tanaka, K. Angew. Chem.,
Int. Ed. 2012, 51, 6722.
(5) For pioneering papers on the oxidative cross-coupling
transformations of aldehydes with aryl C(sp2)−H bond: (a) Chan,
C.-W.; Zhou, Z.; Chan, A. S. C.; Yu, W.-Y. Org. Lett. 2010, 12, 3296.
(b) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009,
11, 3120. (c) Al-Masum, M.; Ng, E.; Wai, M. C. Tetrahedron Lett.
2011, 52, 1008. (d) Tang, B.-X.; Song, R.-J.; Li, J.-H. J. Am. Chem.
Soc. 2010, 132, 8900. (e) Wu, Y.; Li, B.; Mao, F.; Li, X.; Kwong, F.
́
Y. Org. Lett. 2011, 13, 3258. (f) Basle, O.; Bidange, J.; Shuai, Q.; Li,
C.-J. Adv. Synth. Catal. 2010, 352, 1145. With the C−C double
bond: (g) Chudasama, V.; Fitzmaurice, R. J.; Caddick, S. Nat. Chem.
2010, 2, 592. (h) Tsujimoto, S.; Iwahama, T.; Sakaguchi, S.; Ishii, Y.
Chem. Commun. 2001, 2352. (i) Tsujimoto, S.; Sakaguchi, S.; Ishii, Y.
Tetrahedron Lett. 2003, 44, 5601. (j) Liu, W.; Li, Y.; Liu, K.; Li, Z. J.
Am. Chem. Soc. 2011, 133, 10756. (k) Zhou, M.-B.; Song, R.-J.;
Ouyang, X.-H.; Liu, Y.; Wei, W.-T.; Deng, G.-B.; Li, J.-H. Chem. Sci.
2013, 4, 2690. (l) Wang, J.; Liu, C.; Yuan, J.; Lei, A. Angew. Chem.,
Int. Ed. 2013, 52, 2256.
(6) (a) Heathcock, C. H.; Graham, S. L.; Pirrung, M. C.; Plavac, F.;
White, C. T. The Total Synthesis of Natural Products; Apsimon, J.,
Ed.; Wiley-Interscience: New York, 1983; Vol. 5, p 264. (b) Yoneda,
K.; Yamagata, E.; Nakanishi, T.; Nagashima, T.; Kawasaki, I.;
Yoshida, T.; Mori, H.; Miura, I. Phytochemistry 1984, 23, 2068.
(c) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46,
8748. (d) Chawla, A. S.; Kapoor, V. K. In The Alkaloids: Chemical
and Biological Perspectives; Pelletier, S. W., Ed.; Pergamon: New York,
1995; Vol. 9, p 86. (e) Tsuda, Y.; Sano, T. In The Alkaloids; Cordell,
G. A., Ed.; Academic Press: San Diego, 1996; Vol. 48, p 249. For a
special review and papers on the ipso-cyclization of N-arylalkynes to
construct spiro-cyclic compounds, see: (f) Godoi, B.; Schumacher, R.
F.; Zeni, G. Chem. Rev. 2011, 111, 2937. (g) Zhang, X.; Larock, R.
C. J. Am. Chem. Soc. 2005, 127, 12230. (h) Li, C.-W.; Wang, C.-I.;
Liao, H.-Y.; Chaudhuri, R.; Liu, R.-S. J. Org. Chem. 2007, 72, 9203.
(i) Okitsu, T.; Nakazawa, D.; Kobayashi, A.; Mizohata, M.; In, Y.;
Ishida, T.; Wada, A. Synlett 2010, 203. (j) Tang, B.-X.; Yin, Q.; Tang,
R.-Y.; Li, J.-H. J. Org. Chem. 2008, 73, 9008. (k) Yu, Q.-F.; Zhang,
Y.-H.; Yin, Q.; Tang, B.-X.; Tang, R.-Y.; Zhong, P.; Li, J.-H. J. Org.
Chem. 2008, 73, 3658. (l) Tang, B.-X.; Tang, D.-J.; Tang, S.; Yu, Q.-
F.; Zhang, Y.-H.; Liang, Y.; Zhong, P.; Li, J.-H. Org. Lett. 2008, 10,
1063. (m) Wang, Z.-Q.; Tang, B.-X.; Zhang, H.-P.; Wang, F.; Li, J.-
H. Synthesis 2009, 891. (n) Tang, B.-X.; Zhang, Y.-H.; Song, R.-J.;
Tang, D.-J.; Deng, G.-B.; Wang, Z.-Q.; Xie, Y.-X.; Xia, Y.-Z.; Li, J.-H.
J. Org. Chem. 2012, 77, 2837. (o) Wei, W.-T.; Song, R.-J.; Ouyang,
4589
dx.doi.org/10.1021/jo5005982 | J. Org. Chem. 2014, 79, 4582−4589