N-Heterocyclic Carbene/Lewis Acid Catalyzed Enantioselective Aerobic Annulation of α,β-Unsaturated Aldehydes with 1,3-Dicarbonyl Compounds

Article abstract of DOI:10.1021/acs.joc.6b01152

A novel and efficient aerobic asymmetric cyclization reaction of cinnamaldehydes and 1,3-dicarbonyl compounds through oxidative NHC-catalysis has been developed, and it allows the synthesis of a wide range of enantiomeric enriched dihydropyranone derivatives in good yields with good to excellent enantioselectivities. Various α,β-unsaturated aldehydes with aliphatic and aromatic substitution groups and 1,3-dicarbonyl compounds were well tolerated. The air was directly used as the oxidant, which made this asymmetric cyclization reaction in a highly efficient, cheap, and green manner.

Full text of DOI:10.1021/acs.joc.6b01152

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Note
N-Heterocyclic Carbene/Lewis Acid Catalyzed
Enantioselective Aerobic Annulation of alpha,beta-
Unsaturated Aldehydes with 1,3-Dicarbonyl Compounds
Danbo Xie, Dan Shen, Qiliang Chen, Jiaqi Zhou, Xiaofei Zeng, and Guofu Zhong
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01152 • Publication Date (Web): 23 Jun 2016
Downloaded from http://pubs.acs.org on June 27, 2016
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NꢀHeterocyclic Carbene/Lewis Acid Catalyzed
Enantioselective Aerobic Annulation of α,βꢀUnsaturated
Aldehydes with 1,3ꢀDicarbonyl Compounds
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Danbo Xie, Dan Shen, Qiliang Chen, Jiaqi Zhou, Xiaofei Zeng,* and Guofu Zhong*
College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou
310036, China.
Eꢀmail: chemzxf@hznu.edu.cn ; zgf@hznu.edu.cn
Abstract: A novel and efficient aerobic asymmetric cyclization reaction of cinnamaldehydes and
1,3ꢀdicarbonyl compounds through oxidative NHCꢀcatalysis has been developed, and allows the
synthesis of a wide range of enantiomeric enriched dihydropyranone derivatives in good yields
with good to excellent enantioselectivities. Various α,βꢀunsaturated aldehydes with aliphatic and
aromatic substitution groups and 1,3ꢀdicarbonyl compounds were well tolerated. The air was
directly used as the oxidant, which make this asymmetric cyclization reaction in highly efficient,
cheap and green manner.
Over the past two decades, NꢀHeterocyclic carbene (NHC) catalysis has emerged as a
powerful and useful methodology in organic synthesis by providing an assortment of new
scaffolds as well as enantiomerically enriched compounds.1 In this synthetic strategy, aldehydes
and their derivatives are activated by NHCs a through the formation of acyl anion equivalent b
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and b’ (so called Breslow intermediate2), which can react as enolate or homoenolate with various
electrophiles to undergo the nucleophilic addition process (Scheme 1). With this unique
chemistry termed umpolung, dozens of reactivity manifolds have been developed across a range
of reaction subtypes for the formation of CꢀC, CꢀN and CꢀO bonds and corresponding
compounds with significantly importance.
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While the activation modes of NHC catalysis have been well established, chemists realized that
the Breslow intermediate could be readily oxidized by mild inorganic and organic oxidants to
acylazolium ion species c and c’, which could undergo subsequent esterification reaction through
O acylation with different O nucleophiles.3 Moreover, the oxidative generated α,βꢀunsaturated
acylazolium intermediate c could serve as unique and efficient Michael acceptors. which has
been succefully employed in the 1,4ꢀaddition by reacting with soft carbon nucleophiles. In this
strategy the intermediate c is typically generated from the nucleophilic addition of NHC with
α,βꢀunsaturated acyl fluoride,4 esters,5 acids6 or anhydrides7, the internal redox reaction
generated ynals8, or enals in the presence of the high cost 3,3',5,5'ꢀtetraꢀtertꢀ
butyldiphenoquinone9 (DPQ, $125/50mg from Sigmaaldrich Pte. Ltd.) as external oxidant. which
is greatly limited the large scale synthesis.
Scheme 1. Activation of carbonyl compounds through enolate/homoenolate and oxidative
acylazolium salt intermediates in NHC catalysis
O
O
OH
OH
N
N
N
R
H
R
H
R
R
N
N
umplong
umplong
N
N
N
N
b
b'
a
[O]
[O]
O
O
O
N
R
OR1
R1 OH
R2 NH2
N
R
R
O
Michael
acceptor
N
N
N
N
R
NHR1
c'
c
The incorporation of atmosphere molecular oxygen (O2) into an organic oxidation
reaction offers one of the most ideal processes in organic synthesis.10 The activation of O2
by NHC catalysts was succeeded by several research groups in NHCꢀcatalyzed oxidation
of aldehydes, the corresponding carboxylic acids11 and esters12 could be obtained in
moderate to good yields. In these approaches, the Breslow intermediates generated from
aldehydes and NHC catalyst could be oxidized to acylazolium ions by O2, which can
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undergo the next
Oꢀacylation reactions. We therefore envisioned that this chemistry could
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be more attractive if O2 could be directly used as oxidant in NHCꢀcatalyzed
enantioselective reactions. However, to the best of our knowledge, there is no successful
example concerning an NHCꢀcatalyzed asymmetric reaction with O2 as oxidant. Given
the fact that, 3,4ꢀdihydroꢀαꢀpyranones are important intermediate for the construction of
pyridones, γꢀlactones, benzenoid derivatives etc.,13 some successful examples in the
synthesis of 3,4ꢀdihydroꢀαꢀpyranones were reported by several groups.14 To make the
synthesis of this kind of compounds in a more efficient and green manner, we decided to
contribute a catalytically asymmetric synthesis of 3,4ꢀdihydroꢀαꢀpyranones through a
chiral NHCꢀcatalyzed reaction of cinnamaldehyde with 1,3ꢀdicarbonyl compounds by
using air as the oxidant.
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Table 1. Reaction condition optimizationa
entry NHC
base
solvent
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Tol
additives
—
yield (%)b
80
ee (%)c
60
87
89
94
91
77
85
62
80
85
—
83
89
89
92
1
2
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
K2CO3
A
A
A
A
A
B
C
D
A
A
A
A
A
A
A
A
LiCld
LiCle
LiClf
79
80
82
81
65
75
82
70
78
N.R.
65
78
65
3
4
5
6
LiClg
LiCl f
LiCl f
LiCl f
LiOTf
LiBF3
Sc(OTf)3
LiCl f
LiCl f
LiCl f
LiCl f
LiCl f
7
8
9
10
11
12
13
14
15
16
Cs2CO3
DMAP
DABCO
DABCO
80
27
DCM
91
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a General conditions: 1a (0.2 mmol), 2a (0.1 mmol), A (0.02 mmol), solvent
(1 mL), 14h. b Yields of isolated products based on 2a. c Enantiomeric excess
of 3a, determined by HPLC on a chiral stationary phase; absolute
configuration of the major enantiomer was assigned based on optical rotation
d
e
of 3a (see the Supporting Information). 0.1 mmol LiCl. LiCl (0.1 mmol)
f
and 3Å M.S. powder (20 mg). LiCl (0.1 mmol) and 4Å M.S. powder (20
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mg). g LiCl (0.1 mmol) and 5Å M.S. powder (20 mg).
As a starting point, we examined the reaction of cinnamaldehyde (1a, 2.0 equiv.) with
acetylacetone (2a, 1.0 equiv.) in the presence of NHC catalyst A (20 mol%) and DABCO (1.5
equiv.) in THF under air without any external oxidant. To our delight, the reaction proceeded
well and the desired dihydropyranone 3a was obtained with 80% yield and 60% ee, the cinnamic
acid 4a was found to be the side product. Next, we started to optimize the reaction conditions. It
was reported that Lewis acids can be good cooperative catalyst in NHC catalysis due to the
complexation of the Oꢀatom of the acylazolium ion with the metal cation, which should lower
the LUMO hence activate the Michael acceptor.15 Therefore, a series of Lewis acids were tested
in this reaction, and LiCl was found to be the best, the ee value of 3a could be improved to 87%.
(Table 1, entries 2, 9ꢀ11; LiBr, Mg(OTf)2, MgI2 et. al. see the Supporting Information) A slight
increase of the ee value was achieved when molecular sieves (M.S.) were used, and 4Å M.S.
exhibited most superiority (3a: 82% yield and 94% ee). (Table 1, entries 3ꢀ5) Catalyst A remains
the best catalyst among several catalysts that were studied under this condition. (Table 1, entries
5ꢀ8) After further screening of bases and solvents in the reaction, (Table 1, entries 12ꢀ16) the
best results could be achieved in the presence of catalyst A (20 mmol%), LiCl (1.0 equiv.) and
4Å M.S. (20 mg) in THF under air at r.t..
With the optimal reaction conditions in hand, we started to explore the substrate scope through
the variation of enals. A range of enals were examined and found to react well with
acetylacetone in this study. (Table 2, products 3a-j) The ones that bearing electronꢀwithdrawing
and electronꢀdonating groups on the paraꢀ and orthoꢀ positions can provide the corresponding
dihydropyraones (3bꢀ3g) in good yields (64ꢀ81%) and with good to excellent enantioselectivities
(85ꢀ94% ee). When the (E)ꢀ3ꢀ(furanꢀ2ꢀyl)acrylaldehyde was used, the product 3h was afforded
in 73% yield and with slightly lower enantioselectivity (87% ee). Surprisingly, the βꢀalkyl
substituted aldehydes in this aerobic annulation reaction also worked well with good yields and
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relatively lower ee values (3i: 71% yield and 77% ee; 3j: 71% yield and 80% ee), which were
usually difficult to succeed in such kind of NHCꢀcatalyzed oxidative asymmetric reaction.
Table 2. The exploration of substrate scopea
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Further investigation of different 1,3ꢀdicarbonyls were also conducted, the heptaneꢀ3,5ꢀ
dione could offer the product 3m in high yield (74%) and ee (90%); unfortunately, the 1ꢀ
phenylbutaneꢀ1,3ꢀdione only gave 3k in 69% ee probably due to the steric reason. We
found that βꢀketo esters are also good nucleophiles for this NHCꢀcatalyzed aerobic
oxidative annulation reaction (3l and 3n-q). All βꢀketo esters used can offer the desired
products in good yields (65ꢀ81%) and excellent enantioselectivities (89ꢀ92%); however, a
noticeable steric effect of the ester groups on these substrates was not observed in this
reaction.
The suggested catalytic cycle is depicted below (Scheme 2). First, the enaminol II could be
generated through the reaction of carbene I and enal 1a. Next, in the presence of O2, the
enaminol II will be oxidized to α,βꢀunsaturated acyl triazolium species III, which could act as
good Michael acceptor; further formation of the product 3a and liberation of the carbene catalyst
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I are similar to the literature reported by Studer and coꢀworkers. We suppose that, in this aerobic
oxidative strategy, a hydroperoxide anion will be gernerated in the oxidation process, which will
greatly facilitate the formation of the side product cinnamic acid 4. Indeed, we observed the
cinnamic acid as main side product in this reaction.
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Scheme 2. The proposed catalytic cycle
To verify our hypothesis, some control experiments were conducted. When the reaction
of cinnamaldehyde 1a and acetylacetone 2a in the presence of
A was carried out under N2
without any external oxidant, nearly no reaction happened; when O2 gas was used instead
of N2, the reaction went smoothly and afforded the desired product 3a in 77% yield,
however, the ee value dropped to 58% (Scheme 3, exp. 1). An 18O isotope labeling
experiment of NHCꢀcatalyzed oxidation of cinnamaldehyde was also taken out by using
18O2 as the oxidant, and the product yielded in 85% was found to be cinnamicꢀ18O acid
(Scheme 3, exp. 2). This implied that O2 can successfully promote the oxidation of
homoenolate II to the α,βꢀunsaturated acyl triazolium intermediate III, which facilitated
the consequence Michael addition reaction with 1,3ꢀdicarbonyl compounds. Next,
hydrogen peroxide was used as oxidant instead of O2 under N2 atmosphere in the
cyclization reaction; we found that only trace amount of desired 3a was detected, and the
side product cinnamic acid
4 was isolated in 83% yield (Scheme 3, exp. 3), which
indicated that the hydroperoxide anion generated facilitated the formation of cinnamic
acid.
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Scheme 3. Control experiments
O
A
1)
DABCO
CHO
O
O
O
+
THF, RT
O
R
1a
1) N2, 24 h, no reaction
2a
3a
2) O2, 4 h, yield: 77%, 58% ee
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2)
3)
A
CHO
CO18OH
DABCO
THF, 18O2, RT
1a
4: 85% yield
4 h
O
A, LiCl
DABCO
H2O2
O
CHO
+
O
O
cinnamic acid
+
O
THF, N2, RT
4 h
1a
2a
3a: trace
4: 83% yield
Conclusions
In conclusion, we have developed an aerobic asymmetric annulation reaction of
cinnamaldehydes and 1,3ꢀdicarbonyl compounds through oxidative NHCꢀcatalysis, the desired
dihydropyranones were obtained in good yields and good to excellent enantioselectivities. The
air was directly used as the oxidant, which make this asymmetric annulation reaction in highly
efficient, cheap and green manner. We expect air to offer alternative, concise and low cost
strategy for oxidative NHCꢀcatalysis.
■ EXPERIMENTAL SECTION
Analytical thin layer chromatography (TLC) was performed using precoated silica gel plate (0.2
mm thickness). Further visualization was possible by staining with basic solution of potassium
permanganate or acidic solution of ceric molybdate. Proton nuclear magnetic resonance spectra
(1H NMR) were recorded by using CDCl3 as solvent. Chemical shifts for H NMR spectra are
1
reported as δ in units of parts per million (ppm) downfield from SiMe4 (0.0) and relative to the
signal of chloroformꢀd (7.26, singlet). Multiplicities were given as: s (singlet), d (doublet), t
(triplet), dd (doublets of doublet) or m (multiplets). The number of protons (n) for a given
resonance is indicated by nH. Coupling constants are reported as a J value in Hz. Carbon nuclear
magnetic resonance spectra (13C NMR) are reported as δ in units of parts per million (ppm)
downfield from SiMe4 (0.0) and relative to the signal of chloroformꢀd (77.0, triplet).
Enantiomeric excesses were determined by high performance liquid chromatography (HPLC)
analysis on a chiral stationary phase. Optical rotations were measured in CHCl3 with a 10 cm cell
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(c given in g/100 mL). Absolute configuration of the products was determined by comparing the
optical rotation with the known compounds. High resolution mass spectrometry (HRMS) was
recorded on QTOF perimer for ESI+. The NHCꢀcatalysts were prepared according to the
literatures reported.16 Enals which are not commercially available were prepared following the
literatures procedures.17 The racemic products used to determine the ee values were synthesized
by using cisꢀmixture catalyst as racemic catalyst to generate racemic products. It was prepared
by mixing the following two catalysts in 1:1 ration.
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General procedure for the synthesis of 3: To an oven dried 5 mL vial was added aldehyde (1, 0.4
mmol, 2.0 equiv.), 1,3ꢀdicarbonyl compounds (2, 0.2 mmol, 1.0 equiv.) and NHCꢀcatalyst A
(0.04 mmol, 0.2 equiv.) in 1 mL solvent, followed by addition of base and additive, the resulting
reaction mixture was stirred under air at rt. After the reaction was complete, (monitored by TLC)
water was added to the vial, extracted with dichloromethane, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The resulting residue was purified by flash
chromatography (EtOAc/hexane) to provide 3.
(R)-5-Acetyl-6-methyl-4-phenyl-3,4-dihydro-2H-pyran-2-one (3a). Reaction time: 14 h.
Colourless oil, yield: 19 mg (82%); [α]D20 = ꢀ116.4 (c 0.7, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.34 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 7.4 Hz, 1H), 7.14 (d, J = 7.5 Hz, 2H), 4.14 (d, J = 6.7 Hz,
1H), 2.97 (dd, J = 15.7, 7.2 Hz, 1H), 2.84 (dd, J = 15.7, 2.5 Hz, 1H), 2.43 (s, 3H), 2.12 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 197.9, 165.5, 160.2, 139.8, 129.5, 128.0, 126.7, 117.4, 38.9, 37.2,
29.8, 19.1; HRMS (ESI) calcd for C14H14O3 (M+H)+: 231.1016, Found: 231.1043; 94% ee as
determined by HPLC (Chiralcel IB, 80:20 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 9.5 min, tr
(minor) = 8.2 min.
(R)-5-Acetyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydro-2H-pyran-2-one (3b). Reaction
time: 14 h. Yellow solid, yield: 21 mg (81%); mp: 92.1ꢀ93.5 oC; [α]D20 = ꢀ91.0 (c 0.7, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.06 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 4.09 (d, J = 5.9 Hz,
1H), 3.78 (s, 3H), 2.93 (dd, J = 15.6, 7.1 Hz, 1H), 2.80 (dd, J = 15.6, 1.6 Hz, 1H), 2.41 (s, 3H),
2.12 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 198.0, 165.7, 160.0, 159.2, 131.6, 127.8, 117.6,
114.8, 55.3, 38.1, 37.4, 29.6, 19.0; HRMS(ESI) calcd for C15H16O4 (M+H)+: 261.1121, Found:
261.1130; 85% ee as determined by HPLC (Chiralcel IB, 85:15 hexanes/iꢀPrOH, 1 mL/min), tr
(major) = 12.6 min, tr (minor) = 11.6 min.
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(R)-5-Acetyl-4-(4-fluorophenyl)-6-methyl-3,4-dihydro-2H-pyran-2-one (3c). Reaction time:
o
1
18 h.Yellow solid, yield: 18 mg (73%); mp: 111.8ꢀ112.6 C; [α]D20 = ꢀ72.0 (c 0.6, CHCl3); H
NMR (500 MHz, CDCl3) δ 7.12 (dd, J = 8.7, 5.2 Hz, 2H), 7.03 (t, J = 8.6 Hz, 2H), 4.16 (d, J =
6.2 Hz, 1H), 2.95 (dd, J = 15.7, 7.2 Hz, 1H), 2.81 (dd, J = 15.7, 2.5 Hz, 1H), 2.43 (d, J = 0.8 Hz,
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13
3H), 2.14 (s, 3H); C NMR (125 MHz, CDCl3) δ 197.6, 165.4, 162.5 (d, 1JC-F = 246.8 Hz),
160.4, 135.4, 128.4 (d, 3JC-F = 8.7 Hz), 117.5, 116.5 (d, 2JC-F = 21.3 Hz), 38.1, 37.2, 29.8,
19.1; HRMS (ESI) calcd for C14H13 FO3 (M+H)+: 249.0921, Found: 249.0920; 91% ee as
determined by HPLC (Chiralcel IB, 85:15 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 12.4 min, tr
(minor) = 10.4 min
(R)-5-Acetyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydro-2H-pyran-2-one (3d). Reaction time:
14 h. Yellow oil, yield: 17 mg (64%); [α]D20 = ꢀ21.5 (c 0.5, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.31 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 4.15 (d, J = 6.6 Hz, 1H), 2.96 (dd, J = 15.7,
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7.3 Hz, 1H), 2.80 (dd, J = 15.7, 2.5 Hz, 1H), 2.43 (d, J = 0.8 Hz, 3H), 2.14 (s, 3H); C NMR
(125 MHz, CDCl3) δ 197.4, 165.3, 160.6, 138.2, 133.8, 129.6, 128.1, 117.2, 38.1, 36.9, 29.8,
19.2; HRMS (ESI) calcd for C14H13ClO3 (M+H)+: 265.0626, Found: 265.0536; 94% ee as
determined by HPLC (Chiralcel IB, 95:5 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 29.9 min, tr
(minor) = 23.5 min.
(R)-5-Acetyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydro-2H-pyran-2-one (3e). Reaction time:
12 h. Yellow oil, yield: 21 mg (77%); [α]D20 = ꢀ74.0 (c 0.5, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 8.20 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 4.34 (d, J = 6.7 Hz, 1H), 3.02 (dd, J = 15.9,
7.5 Hz, 1H), 2.85 (dd, J = 15.9, 2.3 Hz, 1H), 2.47 (s, 3H), 2.21 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 196.6, 164.7, 161.2, 147.6, 147.3, 127.8, 124.6, 117.2, 38.3, 36.3, 30.2, 19.5; HRMS
(ESI) calcd for C14H13NO5 (M+H)+: 276.0866, Found: 276.0877; 90% ee as determined by
HPLC (Chiralcel AD, 90:10 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 26.9 min, tr (minor) = 29.2
min.
(R)-5-Acetyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydro-2H-pyran-2-one (3f). Reaction
time: 14 h. White solid, yield: 21 mg (80%); mp: 90.5ꢀ92.0 oC; [α]D20 = ꢀ35.6 (c 0.8, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.26 (td, J = 8.1, 1.7 Hz, 1H), 6.97 (dd, J = 7.4, 1.5 Hz, 1H), 6.89 (dd,
J = 11.5, 4.3 Hz, 2H), 4.54–4.46 (m, 1H), 3.86 (s, 3H), 2.91–2.82 (m, 2H), 2.42 (d, J = 0.9 Hz,
3H), 2.08 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 198.3, 166.2, 160.4, 156.5, 129.1, 127.2,127.1,
121.1, 116.4, 110.9, 55.2, 35.0, 32.9, 29.3, 19.0; HRMS (ESI) calcd for C15H16O4 (M+H)+:
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261.1120, Found: 261.1109; 93% ee as determined by HPLC (Chiralcel AD, 98:2 hexanes/iꢀ
PrOH, 1 mL/min), tr (major) = 18.5 min, tr (minor) = 21.1 min.
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(R)-5-Acetyl-6-methyl-4-(2-nitrophenyl)-3,4-dihydro-2H-pyran-2-one (3g). Reaction time:
20 h. Yellow oil, yield: 19 mg (70%); [α]D20 = ꢀ143.2 (c 0.5, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.99 (dd, J = 8.1, 1.2 Hz, 1H), 7.60–7.56 (m, 1H), 7.48 (td, J = 8.1, 1.3 Hz, 1H), 7.22 (dd, J =
7.8, 1.2 Hz, 1H), 4.86 (d, J = 6.7 Hz, 1H), 3.07 (dd, J = 16.1, 7.7 Hz, 1H), 3.00 (dd, J = 16.1, 2.4
Hz, 1H), 2.48 (d, J = 0.9 Hz, 3H), 2.09 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.7, 165.0,
162.0, 148.7, 134.3, 134.1, 129.1, 128.2, 125.7, 116.4, 35.8, 34.2, 29.7, 19.3; HRMS (ESI) calcd
for C14H13NO5 (M+H)+: 276.0866, Found: 276.0866; 92% ee as determined by HPLC (Chiralcel
AD, 95:5 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 18.7 min, tr (minor) = 20.6 min.
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(S)-5-Acetyl-4-(furan-2-yl)-6-methyl-3,4-dihydro-2H-pyran-2-one (3h). Reaction time: 14h.
Yellow oil, yield: 16 mg (73%); [α]D20 = ꢀ35.7 (c 0.7, CHCl3); 1H NMR (500 MHz, CDCl3) δ
7.34 (d, J = 1.2 Hz, 1H), 6.28 (dd, J = 3.2, 1.9 Hz, 1H), 6.09 (d, J = 3.2 Hz, 1H), 4.26 (d, J = 6.6
Hz, 1H), 3.04 (dd, J = 15.9, 2.1 Hz, 1H), 2.84 (dd, J = 15.9, 6.8 Hz, 1H), 2.37 (s, 3H), 2.31 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 197.1, 165.5, 161.0, 152.5, 142.8, 115.7, 110.4, 106.6, 33.8,
32.3, 29.8, 19.4; HRMS (ESI) calcd for C12H12O4 (M+H)+: 221.0808, Found: 221.0834; 87% ee
as determined by HPLC (Chiralcel IB, 90:10 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 11.0 min,
tr (minor) = 9.4 min.
(S)-5-Acetyl-6-methyl-4-propyl-3,4-dihydro-2H-pyran-2-one (3i). Reaction time: 14 h.
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Yellow oil, yield: 14 mg (71%); [α]D20 = ꢀ4.3 (c 0.7, CHCl3); H NMR (500 MHz, CDCl3) δ
2.98–2.90 (m, 1H), 2.73 (dd, J = 15.9, 1.9 Hz, 1H), 2.59 (dd, J = 15.9, 6.4 Hz, 1H), 2.35 (s, 3H),
2.27 (s, 3H), 1.53–1.39 (m, 2H), 1.33 (dd, J = 8.1, 4.2 Hz, 2H), 0.91 (t, J = 7.0 Hz, 3H); 13C
NMR (125 MHz, CDCl3) δ 197.7, 167.0, 158.8, 120.4, 35.6, 33.1, 32.1, 30.2, 19.8, 19.3, 13.8;
HRMS (ESI) calcd for C11H16O3 (M+Na)+: 219.0992, Found: 219.0990; 77% ee as determined
by HPLC (Chiralcel IB, 90:10 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 8.0 min, tr (minor) = 7.5
min.
(S)-5-Acetyl-6-methyl-4-pentyl-3,4-dihydro-2H-pyran-2-one (3j). Reaction time: 14 h.
Yellow oil, yield: 16 mg (71%); [α]D20 = ꢀ2.1 (c 0.7, CHCl3); 1H NMR (500 MHz, CDCl3) δ
2.95–2.87 (m, 1H), 2.73 (dd, J = 15.9, 1.8 Hz, 1H), 2.58 (dd, J = 15.9, 6.4 Hz, 1H), 2.35 (s, 3H),
2.27 (s, 3H), 1.30 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 197.8, 167.02,
158.7, 120.4, 33.4, 33.1, 32.3, 31.5, 30.2, 26.2, 22.4, 19.3, 13.9; HRMS (ESI) calcd for C13H20O3
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(M+H)+: 225.1485, Found: 225.1480; 80% ee as determined by HPLC (Chiralcel IB, 95:5
hexanes/iꢀPrOH, 1 mL/min), tr (major) = 8.6 min, tr (minor) = 8.2 min.
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(R)-5-Acetyl-4,6-diphenyl-3,4-dihydro-2H-pyran-2-one (3k). Reaction time: 14 h.
Colourless oil, yield: 20 mg (69%); mp: 76.5ꢀ77.6 oC; [α]D20 = ꢀ1.8 (c 0.8, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.58–7.53 (m, 2H), 7.46–7.43 (m, 1H), 7.32 (t, J = 7.7 Hz, 2H), 7.19 (t, J = 7.3
Hz, 3H), 7.15–7.11 (m, 1H), 7.08–7.04 (m, 2H), 4.24 (dd, J = 7.1, 3.1 Hz, 1H), 2.99 (dd, J = 16.0,
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7.6 Hz, 1H), 2.86 (dd, J = 16.0, 3.6 Hz, 1H), 1.83 (d, J = 1.0 Hz, 3H). C NMR (125 MHz,
CDCl3) δ 195.8, 166.5, 154.7, 140.0, 138.4, 133.1, 129.1, 128.8, 128.7, 127.6, 126.8, 117.8, 39.5,
36.2, 19.0; HRMS (ESI) calcd for C19H16O3 (M+H)+: 293.1172, Found: 293.1146; 74% ee as
determined by HPLC (Chiralcel IB, 90:10 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 10.4 min, tr
(minor) = 9.6 min.
Ethyl (R)-6-ethyl-2-oxo-4-phenyl-3,4-dihydro-2H-pyran-5-carboxylate (3l). Reaction time:
14 h. Yellow oil, yield: 19 mg (69%); [α]D20 = ꢀ71.0 (c 0.6, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.29 (t, J = 7.4 Hz, 2H), 7.23 (dd, J = 10.5, 4.2 Hz, 1H), 7.13 (d, J = 7.3 Hz, 2H), 4.27–4.22 (m,
1H), 4.12 (q, J = 7.1 Hz, 2H), 2.92 (ddd, J = 13.7, 12.1, 7.5 Hz, 2H), 2.87 – 2.77 (m, 2H), 1.27 (t,
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J = 7.5 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); C NMR (125 MHz, CDCl3) δ 166.3, 165.9, 165.8,
140.6, 129.0, 127.4, 126.5, 109.3, 60.8, 37.8, 36.4, 25.4, 14.0, 11.7; HRMS (ESI) calcd for
C16H18O4 (M+H)+: 275.1278 , Found: 275.1265; 92% ee as determined by HPLC (Chiralcel IB,
95:5 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 6.9 min, tr (minor) = 6.1 min.
(R)-6-Ethyl-4-phenyl-5-propionyl-3,4-dihydro-2H-pyran-2-one (3m). Reaction time: 14 h.
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Yellow oil, yield: 19 mg (74%); [α]D20 = ꢀ54.2 (c 0.8, CHCl3); H NMR (500 MHz, CDCl3) δ
7.34 (t, J = 7.4 Hz, 2H), 7.28 (d, J = 7.4 Hz, 1H), 7.14 (d, J = 7.3 Hz, 2H), 4.11 (dd, J = 7.1, 2.8
Hz, 1H), 2.95 (dd, J = 15.7, 7.2 Hz, 1H), 2.81 (dd, J = 15.7, 3.0 Hz, 1H), 2.73 (qd, J = 13.8, 7.1
Hz, 2H), 2.49 (dq, J = 17.8, 7.2 Hz, 1H), 2.23 (dq, J = 17.8, 7.2 Hz, 1H), 1.28 (t, J = 7.4 Hz, 3H),
0.94 (t, J = 7.2 Hz, 3H).13C NMR (126 MHz, CDCl3) 13C NMR (125 MHz, CDCl3) δ 201.1,
165.9, 163.7, 139.7, 129.5, 127.9, 126.7, 116.5, 38.7, 37.4, 34.7, 25. 3, 11.9, 7.9; HRMS (ESI)
calcd for C16H18O3 (M+H)+: 259.1329, Found: 259.1298; 90% ee as determined by HPLC
(Chiralcel IB, 80:20 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 6.5 min, tr (minor) = 5.5 min.
Methyl (R)-6-methyl-2-oxo-4-phenyl-3,4-dihydro-2H-pyran-5-carboxylate (3n). Reaction
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time: 14 h. Yellow oil, yield: 20 mg (81%); [α]D20 = ꢀ46.0 (c 0.8, CHCl3); H NMR (500 MHz,
CDCl3) δ 7.30 (t, J = 7.4 Hz, 2H), 7.24 (t, J = 7.4 Hz, 1H), 7.13 (d, J = 7.3 Hz, 2H), 4.26 (d, J =
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7.2 Hz, 1H), 3.68 (s, 3H), 2.94 (dd, J = 15.8, 7.5 Hz, 1H), 2.83 (dd, J = 15.8, 2.1 Hz, 1H), 2.48 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 166.4, 166.0, 161.7, 140.4, 129.1, 127.5, 126.6, 109.7, 51.9,
37.8, 36.5, 18.9; HRMS (ESI) calcd for C14H14O4 (M+H)+: 247.0965, Found: 247.0932; 90% ee
as determined by HPLC (Chiralcel IB, 80:20 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 8.8 min, tr
(minor) = 6.3 min.
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Ethyl (R)-6-methyl-2-oxo-4-phenyl-3,4-dihydro-2H-pyran-5-carboxylate (3o). Reaction
time: 14 h. Yellow oil, yield: 20 mg (77%); mp: 78.2ꢀ79.5 oC; [α]D20 = ꢀ115.0 (c 0.8, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.29 (dd, J = 10.1, 4.6 Hz, 2H), 7.26–7.23 (m, 1H), 7.15–7.12 (m,
2H), 4.25 (d, J = 7.4 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 2.94 (dd, J = 15.9, 7.6 Hz, 1H), 2.82 (dd,
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J = 15.9, 2.3 Hz, 1H), 2.47 (d, J = 0.8 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H). C NMR (125 MHz,
CDCl3) δ 166.0, 165.9, 161.2, 140.6, 129.0, 127.4, 126.6, 110.0, 60.8, 37.8, 36.3, 18.8, 14.0;
HRMS (ESI) calcd for C15H16O4 (M+H)+: 261.1121 , Found: 261.1121; 90% ee as determined by
HPLC (Chiralcel IB, 80:20 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 9.1 min, tr (minor) = 6.5
min.
Isopropyl
(R)-6-methyl-2-oxo-4-phenyl-3,4-dihydro-2H-pyran-5-carboxylate
(3p).
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Reaction time: 14 h. Yellow oil, yield: 19 mg (69%); [α]D20 = ꢀ135.0 (c 0.5, CHCl3); H NMR
(500 MHz, CDCl3) δ 7.31–7.27 (m, 2H), 7.25–7.21 (m, 1H), 7.15–7.11 (m, 2H), 4.98 (dt, J =
12.5, 6.2 Hz, 1H), 4.23 (d, J = 6.7 Hz, 1H), 2.95 (dd, J = 15.9, 7.7 Hz, 1H), 2.82 (dd, J = 15.9,
2.5 Hz, 1H), 2.46 (d, J = 0.9 Hz, 3H), 1.23 (d, J = 6.2 Hz, 3H), 1.06 (d, J = 6.2 Hz, 3H);13C
NMR (125 MHz, CDCl3) δ 166.2, 165.4, 160.9, 140.8, 128.9, 127.4, 126.6, 110.3, 68.4, 37.9,
36.3, 21.9, 21.5, 18.8; HRMS (ESI) calcd for C16H18O4 (M+H)+: 275.1278, Found: 275.1258;
90% ee as determined by HPLC (Chiralcel IB, 95:5 hexanes/iꢀPrOH, 1 mL/min), tr (major) = 8.2
min, tr (minor) = 6.4 min.
Benzyl (R)-6-methyl-2-oxo-4-phenyl-3,4-dihydro-2H-pyran-5-carboxylate (3q). Reaction
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time: 14 h. Yellow oil, yield: 22 mg (65%); [α]D20 = ꢀ56.4 (c 0.5, CHCl3); H NMR (500 MHz,
CDCl3) δ 7.31 (dd, J = 25.2, 17.2 Hz, 6H), 7.12 (t, J = 7.2 Hz, 4H), 5.11 (q, J = 12.5 Hz, 2H),
4.27 (d, J = 7.4 Hz, 1H), 2.95 (dd, J = 15.9, 7.7 Hz, 1H), 2.82 (d, J = 15.8 Hz, 1H), 2.49 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 165.9, 165.7, 162.0, 140.5, 135.6, 129.1, 128.5, 128.2, 127.9,
127.6, 126.6, 109.6, 66.6, 37.9, 36.4, 18.9; HRMS (ESI) calcd for C20H18O4 (M+H)+: 323.1278,
Found: 323.1269; 89% ee as determined by HPLC (Chiralcel IB, 95:5 hexanes/iꢀPrOH, 1
mL/min), tr (major) = 14.8 min, tr (minor) = 11.0 min.
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■ASSOCIATED CONTENT
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Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.
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Copies of 1H, 13C NMR and chiral HPLC spectra for compounds 3a-q and MS spectra of 4 (PDF)
■AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: chemzxf@hznu.edu.cn; zgf@hznu.edu.cn
Notes
The authors declare no competing financial interest.
■ACKNOWLEDGMENTS
This paper is dedicated to professor Dieter Enders on the occasion of his 70th birthday.
We gratefully acknowledge the Natural Science Foundation of China (No. 21373073), the
Young National Natural Science Foundation of China (No. 21302033), the PCSIRT (IRT
1231) and Hangzhou Normal University for financial support. G.Z. appreciated a
Qianjiang Scholar from Zhejiang Province in China.
■REFERENCES
1 For reviews on NHC catalysis, see: (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007
5606. (b) Cohen, D. T.; Scheidt, K. A. Chem. Sci 2012 , 53. (c) Biju, A. T.; Kuhl, N.; Glorius, F.
Acc. Chem. Res. 2011 44, 1182.(d) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.; Paul, R. R.; Jose,
A.; Sreekumar, V. Chem. Soc. Rev. 2011 40, 5336.(e) Grossmann, A.; Enders, D. Angew. Chem. Int.
Ed 2012 51, 314. (f) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012 41, 3511. (g) Izquierdo, J.;
Hutson, G. E.; Cohen, D. T.; Scheidt, K. A. Angew. Chem. Int. Ed. 2012 51, 11686. (h) Ryan, S. J.;
Candish, L.; Lupton, D. W. Chem. Soc. Rev. 2013 42, 4906. (i) Hopkinson, M. N.; Richter, C.;
, 107,
.
, 3
,
,
.
,
,
,
,
Schedler, M.; Glorius, F. Nature
Res. 2014 47, 696.
,
2014
,
510, 585. (j) Mahatthananchai, J.; Bode, J. W. Acc. Chem.
,
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2 Breslow, R. J. J. Am. Chem. Soc.
3 (a) De Sarkar, S.; Studer, A. Angew. Chem. Int. Ed. 2010
Studer, A. J. Am. Chem. Soc 2010 132, 1190. (c) Gu, L.; Zhang, Y. J. Am. Chem. Soc. 2010
, 1958, 80, 3719.
,
49, 9266. (b) DeSarkar, S.; Grimme, S.;
.
,
,
132
12
,
,
914. (d) Nair, V.; Varghese, V.; Paul, R. R.; Jose, A.; Sinu, C. R.; Menon, R. S. Org. Lett. 2010
,
9
2653.
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4 (a) Ryan, S. J.; Candish, L.; Lupton, D. W. J. Am. Chem. Soc. 2009
J.; Candish L.; Lupton, D. W. J. Am. Chem. Soc. 2011 133, 4694. (c) Candish
Am. Chem. Soc 2013 135, 58.
5 (a) Cheng, J.ꢀJ.; Huang, Z.ꢀJ.; Chi, Y.ꢀG. Angew. Chem. Int. Ed. 2013
L.; Zhang, Y.ꢀX.; Tiwari, B.; Chi, Y.ꢀG. Org. Lett. 2013 15, 5822. (c) Fu, Z.ꢀQ.; Jiang, K.; Zhu, T.ꢀS.;
Torres, J.; Chi, Y.ꢀG. Angew. Chem. Int. Ed 2014 53, 6506. (d) Lin, Y.ꢀQ.; Yang, L.ꢀM.; Deng, Y.;
Zhong, G.ꢀF. Chem. Commun. 2015 51, 8330. (e) Xie, D.ꢀB.; Yang, L.ꢀM.; Lin, Y.ꢀQ.; Zhang, Z.ꢀM.;
Chen, D.ꢀD.; Zeng, X.ꢀF.; Zhong, G.ꢀF. Org. Lett 2015 17, 2318.
,
131, 14176. (b) Ryan, S.
,
,
,
L.; Lupton, D. W. J.
.
,
,
52, 8592. (b) Chen, S.ꢀJ.; Hao,
,
.
,
,
.
,
6 (a) A. Lee, A. Younai, C. K. Price, J. Izquierdo, R. K. Mishra and K. A. Scheidt, J. Am. Chem. Soc.
2014, 136, 10589. (b) X.ꢀY. Chen, Z.ꢀH. Gao, C.ꢀY. Song, C.ꢀL. Zhang, Z.ꢀX. Wang and S. Ye,
Angew. Chem. Int. Ed. 2014, 53, 11611. (c) Xie, Y.ꢀW.; Yu, C.ꢀX.; Li, T.ꢀJ.; Tu, S.ꢀJ.; Yao, C.ꢀS.
Chem. Eur. J. 2015
C.ꢀS. Chem. Asian J. 2016
W.ꢀJ.; Yao, C.ꢀS. Org. Biomol. Chem. 2016
7 Jin, Z.ꢀC.; Chen, S.ꢀJ.; Wang, Y.ꢀH.; Zheng, P.ꢀC.; Yang, S.; Chi, Y.ꢀG. Angew. Chem. Int.
Ed 2014, 53, 13506.
8 (a) Kaeobamrung, J.; Mahatthananchai, J.; Zheng
8810. (b) Zhu, Z.ꢀQ.; Zheng, X.ꢀL.; Jiang, N.ꢀF.; Wan, X.; Xiao, J.ꢀC. Chem. Commun
(c) Du, D.; Hu, Z.; Jin, J.; Lu, Y.; Tang, W.; Wang, B.; Lu, T. Org. Lett. 2012 14, 1274. (d) Zhou, B.;
Luo, Z.; Li, Y.ꢀC. Chem. Eur. J. 2013 19, 4428. (e) Sun, L.ꢀH.; Liang, Z.ꢀQ.; Jia, W.ꢀQ.; Ye, S.
Angew. Chem. Int. Ed. 2013 52, 5803. (f) Lu, Y.ꢀY.; Tang, W.ꢀF.; Zhang, Y.; Du, D.; Lu, T. Adv.
Synth. Catal 2013 355, 321.
9 (a) DeSarkar, S.; Grimme, S.; Studer, A. J. Am. Chem. Soc
Q.; You, S.ꢀL. Org. Lett. 2011 13, 4080. (c) Biswas, A.; DeSarkar, S.; Tebben, L.; Studer, A. Chem.
Commun. 2012 48, 5190. (d) Chen, X.ꢀK.; Yang, S.; Song, B.ꢀA.; Chi, Y.ꢀG. Angew. Chem. Int.
Ed 2013 52, 11134. (e) Guo, C.; Schedler, M.; Daniliuc, C. G.; Glorius, F. Angew. Chem. Int. Ed
2014 53, 10232. (f) Wang, M.; Huang, Z.ꢀJ.; Xu, J.ꢀF.; Chi, Y.ꢀG. J. Am. Chem. Soc 2014, 136
1214. (g) Zhu, T.ꢀS.; Zheng, P.ꢀC.; Mou, C.ꢀL.; Yang, S.; Song, B.ꢀA.; Chi, Y.ꢀG. Nature Commun
2014 5, 5027.
,
21, 5355. (d) Que, Y.ꢀL.; Lu, Y.ꢀN.; Wang, W.ꢀJ.; Wang, X.ꢀS.; Shen, S.ꢀD.; Yao,
11, 626. (e) Zhu, L.; Yu, C.ꢀX.; Li, T.ꢀJ.; Wang, Y.ꢀH.; Lu, Y.ꢀN.; Wang,
14, 1485.
,
,
.
,
P.ꢀG.; Bode, J. W. J. Am. Chem. Soc
.
2010
, 132,
.
2011
,
47, 8670.
,
,
,
.
,
.
2010, 132, 1190. (b) Rong, Z.ꢀQ.; Jia, M.ꢀ
,
,
.
,
.
,
.
,
.
,
14
ACS Paragon Plus Environment

Page 15 of 15
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10 For reviews, see: (a) Solomon, E. L.; Sundaram, U. M.; Machonkin, T. E. Chem. Rev
.
1996
,
96, 2563.
40
105, 2329. (d) Shi, Z.ꢀZ.;
(b) Solomon, E. I.; Chen, P.; Metz, M.; Lee, S.ꢀK.; Palmer, A. E. Angew. Chem. Int. Ed. 2001
4570. (c) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. Rev. 2005
Zhang, C.; Tang, C.ꢀH.; Jiao, N. Chem. Soc. Rev. 2012 41, 3381.
11 (a) Yoshida, M.; Katagiri, Y.; Zhu, W.ꢀB.; Shishido, K. Org. Biomol. Chem
Möhlmann, L.; Ludwig, S.; Blechert, S. Beilstein J. Org. Chem. 2013 , 602. (c) Yang, W.; Gou, G.ꢀ
,
,
,
,
.
2009, 7, 4062. (b)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
,
9
Z.; Wang, Y.; Fu, W.ꢀF. RSC Adv. 2013
,
3
, 6334. (d) Chiang, P.ꢀC.; Bode, J. W. Org. Lett. 2011
,
13
,
2422.
12 (a) Reddy, R. S.; Rosa, J. N.; Veiros, L. F.; Caddick, S.; Gois, P. M. P. Org. Biomol. Chem
3126. (b) Meng, J.ꢀJ.; Gao, M.; Wei, Y.ꢀP.; Zhang, W.ꢀQ. Chem. Asian J. 2012
G.; Fagan, C.ꢀL.; Gundala, S.; Mari, A.; Broja, T.; Zeitler, K.; Connon, S. J. Chem. Commun. 2013
49, 6510. (d) Delany, E. G.; Fagan, C.ꢀL.; Gundala, S.; Zeitler, K.; Connon, S. J. Chem. Commun.
2013 49, 6513.
13 (a) Rosenthal, D.; Grabowich, P.; Sabo, E. F.; Fried, J. J. Am. Chem. Soc. 1963
A. K.; Jawalker, D. G. Tetrahedron Lett 1986 27, 99. (c) Kume, T.; Iwasaki, H.; Yamamoto, Y.;
Akiba, K. Tetrahedron Lett. 1988 29, 3825. (d) Mandal, A. K.; Jawalker, D. J. J. Org. Chem. 1989
54, 2364. (e) Robl, J. A. Tetrahedron Lett. 1990 31, 3421. (f) Thang, S. H.; Rigg, D. J. Synth.
Commun 1993 23, 2355. (g) Harrowven, D. C.; Hannam, J. C. Tetrahedron 1999 55, 9333. (h)
Zhang, F.ꢀY.; Corey, E. J. Org. Lett. 2000 , 1097.
14 (a) Itoh, K.; Hasegawa, M.; Tanaka, J.; Kanemasa, S. Org. Lett
A. Angew. Chem. Int. Ed. 2010 49, 9266. (c) Fang, X.ꢀQ.; Chen, X.ꢀK.; Chi, Y.ꢀG. Org. Lett. 2011
13, 4708. (d) Rong, Z.ꢀQ.; Jia, M.ꢀQ.; You, S.ꢀL. Org. Lett. 2011 13, 4080. (e) Zhu, Z.ꢀQ.; Zheng, X.ꢀ
L.; Jiang, N.ꢀF.; Wan, X.ꢀL.; Xiao, J.ꢀC. Chem. Commun. 2011 47, 8670. (f) Yao, C.ꢀS.; Wang, D.ꢀL.;
Lu, J.; Li, T.ꢀJ.; Jiao, W.ꢀH.; Yu, C.ꢀX. Chem. Eur. J 2012 18, 1914. (g) Wang, G.; Chen, X.; Miao,
G.ꢀH.; Yao, W.ꢀJ.; Ma, C. J. Org. Chem 2013 78, 6223. (h) Mo, J.ꢀM.; Shen, L.; Chi, Y.ꢀG. Angew.
Chem. Int. Ed. 2013 52, 8588.
15 (a) Bera. S.; Samanta, R. C.; Daniluic, C. G.; Studer, A. Angew. Chem. Int. Ed. 2014
Que, Y.ꢀL.; Lu, Y.ꢀN.; Wang, W.ꢀJ.; Wang, Y.ꢀH.; Wang, H.ꢀT.; Yu, C.ꢀX.; Li, T.ꢀJ.; Wang, X.ꢀS.;
Shen, S.ꢀD.; Yao, C.ꢀS. Chem. Asian J. 2016 11, 678.
16 Struble, J. R.; Bode, J. W. Org. Synth. 2010 87, 362.
17 (a) Schmidt, A.; Hilt, G. Org. Lett. 2013
Chem. Soc. 2012 134, 8810.
.
2011
, 9
,
, 7, 872. (c) Delany, E.
,
,
,
85, 3971. (b) Mandal,
.
,
,
,
,
.
,
,
,
2
.
2005, 7, 979. (b) Sarkar, S. D.; Studer,
,
,
,
,
.
,
.
,
,
,
53, 9622. (b)
,
,
,
15, 2708. (b) Mo, J. M.; Chen, X. K.; Chi, Y. G. J. Am.
,
15
ACS Paragon Plus Environment