Palladium-catalyzed hydroarylation, hydroalkenylation, and hydrobenzylation of ynol ethers with organohalides: A regio- and stereoselective entry to α,β- and β,β-disubstituted alkenyl ethers

Article abstract of DOI:10.1021/jo5002356

A Pd-catalyzed reductive addition of organohalides, including aryl, alkenyl, and benzyl halides, to ynol ethers has been realized in the presence of 2-propanol, giving α,β- and β,β-disubstituted olefinic ethers in satisfactory yields with excellent regio- and stereoselectivity. It represents the first highly regio- and stereoselective hydroarylation, hydroalkenylation, and hydrobenzylation of ynol ethers.

Full text of DOI:10.1021/jo5002356

Article
pubs.acs.org/joc
Palladium-Catalyzed Hydroarylation, Hydroalkenylation, and
Hydrobenzylation of Ynol Ethers with Organohalides: A Regio- and
Stereoselective Entry to α,β- and β,β-Disubstituted Alkenyl Ethers
Weijian Cui, Jing Yin, Renwei Zheng, Cungui Cheng, Yihui Bai, and Gangguo Zhu*
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
S
* Supporting Information
ABSTRACT: A Pd-catalyzed reductive addition of organohalides,
including aryl, alkenyl, and benzyl halides, to ynol ethers has been
realized in the presence of 2-propanol, giving α,β- and β,β-
disubstituted olefinic ethers in satisfactory yields with excellent
regio- and stereoselectivity. It represents the first highly regio- and
stereoselective hydroarylation, hydroalkenylation, and hydrobenzylation of ynol ethers.
which the regioselectivity is found to be determined by the
choice of organic halides. Indeed, it represents the first regio-
and stereoselective hydroarylation, hydroalkenylation, and
hydrobenzylation of ynol ethers.
INTRODUCTION
■
The development of operationally simple and general methods
for the preparation of alkenyl ethers is of importance in organic
chemistry, and consequently, a variety of protocols have been
described.1 However, there is still an urgent need for the
discovery of regio- and stereoselective approaches to this
framework, especially the catalytic versions. Recently, the
functionalization of ynol ethers has emerged as a straightfor-
ward and effective protocol for constructing stereodefined
vinylic ethers, including the hydrohalogenation,2 hydrobora-
tion,3 chloroallylation,4 reduction,5 carbometalation,6 cyclo-
addition,7 and radical reactions.8 In a previous work, we
reported a highly regio- and stereoselective approach to α,β-
disubstituted enol ethers featuring the Pd-catalyzed addition of
boronic acids to ynol ethers (Scheme 1).9a Compared with the
RESULTS AND DISCCUSION
■
Initially, we examined the hydroarylation reaction of ynol ether
1a with iodobenzene (2a) by employing isopropanol as the
hydride source in THF (Table 1). Screening of the base
revealed that Cs2CO3 was more effective than K2CO3,
NaHCO3, and other bases (Table 1, entries 1−5). Gratifyingly,
a better yield was obtained by utilizing PCy3 instead of PPh3 as
the ligand, giving α,β-disubstituted alkenyl ether 3aa9a in 72%
yield, and no other regio- and stereoisomers were detected by
NMR and GC−MS analysis (Table 1, entry 14). We then
decided to evaluate the solvent with PCy3 acting as the ligand,
and finally, the optimum reaction conditions were determined
as: ynol ether (0.5 mmol), organohalides (0.75 mmol),
Pd(OAc)2 (5 mol %), PCy3·HBF4 (10 mol %), Cs2CO3 (1.0
mmol), 2-propanol (0.75 mmol), and dioxane (2 mL) at 50 °C
for 10 h, which produced 94% of 3aa upon isolation (Table 1,
entry 16). In contrast, the reaction of PhBr only provided 3aa
in 68% yield under the reaction conditions.14
Scheme 1. Summary of Our Efforts to Access Alkenyl Ethers
The synthetic merit of this protocol was demonstrated by
varying the substrates, and the results are included in Table 2. A
wide range of organic halides were found to be compatible with
this transformation. In particular, 4-, 3-, and 2-iodotoluenes
(2b−2d) smoothly coupled with 1a to deliver enol ethers 3ab−
3ad in comparable yields (92, 91, and 91%), indicating that the
steric effects of organohalides have little influence on the yield
(Table 2, 3ab−3ad). Various substituents, including electron-
donating groups, such as methyl (2b−2d) and methoxy (2i and
2j), and electron-withdrawing groups, such as trifluoromethyl
(2f), chloride (2g), acetyl (2k), and ester (2n), were tolerated
prevalence of alkyne hydroarylation using boronic acids,10
surprisingly, transition-metal-catalyzed hydroarylation of al-
kynes with organohalides11 has received much less attention,
despite that the latter ones are more accessible. Recently,
alcohols stand out as a convenient reductant12 for the capture
of carbopalladation intermediates. Thus, we envisioned that
carbopalladation of ynol ethers, followed by reduction with 2-
propanol as the hydride source,12 would provide an expeditious
alternative to multisubstituted enol ethers. Herein, we wish to
demonstrate a highly regio- and stereoselective synthesis of α,β-
or β,β-disubstituted alkenyl ethers via the reductive addition of
organohalides to ynol ethers13 in the presence of 2-propanol, in
Received: January 29, 2014
Published: March 19, 2014
© 2014 American Chemical Society
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a
(Table 2, 3al). Notably, the hydroalkenylation of ynol ethers
could also be achieved by using olefinic halides as the coupling
partners. For example, 2-iodoundec-1-ene (2o) was converted
into dienyl ether 3ao in quite high yield (Table 2, 3ao). In
addition to alkenyl iodides, alkenyl bromides, such as (E)-styryl
bromide (2p) and (E)-p-chloro-β-bromostyrene (2q), also
furnished the corresponding products in high yields, albeit with
slightly reduced regioselectivity (Table 2, 3ap and 3aq).
Interestingly, when 2-iodobenzaldehyde (2s) was subjected
to the standard conditions, the cyclic products 4, instead of the
desired vinylic ethers 3, were obtained. As an example, the
reaction of 1d afforded 1H-inden-1-ones 4a in 74% yield, in the
presence or absence of 2-propanol, thus providing an efficient
and convenient access to 1H-inden-1-one derivatives (Scheme
2).15 Likewise, 4b was synthesized from 1e in a good yield.
Table 1. Optimization of the Reaction Parameters
b
entry
ligand
base
solvent
yield (%)
1
2
PPh3
PPh3
PPh3
PPh3
PPh3
K3PO4
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
toluene
dioxane
DMF
15
t-BuOK
NaHCO3
K2CO3
<10
<10
31
3
4
5
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
40
6
P(4-OMe-C6H4)3
P(2-furyl)3
P(C6F5)3
dppp
36
7
15
8
trace
<10
33
9
10
11
12
13
14
15
16
17
P(4-tol)3
P(3-tol)3
P(2-tol)3
Xphos
16
Scheme 2. Synthesis of 1H-Inden-1-one Derivatives
67
43
c
PCy3
72
c
PCy3
55
c
d
PCy3
94 (68)
38
c
PCy3
a
Unless otherwise noted, all reactions were carried out with 1a (0.5
mmol), 2a (0.75 mmol), Pd(OAc)2 (5 mol %), ligand (10 mol %),
base (1.0 mmol), 2-propanol (0.75 mmol), solvent (2 mL), 50 °C, 10
b
c
d
h. Isolated yield. Generated in situ from PCy3·HBF4. PhBr was used
These results indicated that the intramolecular insertion of the
C−Pd bond of intermediate B (see the proposed mechanism)
into the carbonyl group should be predominant over the
intermolecular reduction with isopropanol.
instead of PhI.
Table 2. Synthesis of α,β-Disubstituted Alkenyl Ethers via
the Hydroarylation or Hydroalkenylation of Ynol
Then, we briefly investigated the scope of this reaction with
regard to ynol ethers by using 2a as the substrate. Alkyl alkynyl
ethers, including the steric demanding 1e and 1f, turned out to
be effective substrates for this hydrophenylation reaction
(Table 2, 3ba−3fa). The reaction was also applicable to ether
ynol ethers, as demonstrated by the reaction of 1g−1j (Table 2,
3ga−3ja). In contrast, methyl ynol ether (1k), silyl ynol ether
(1l), and ethynyl phenyl ether (1m) all failed to provide the
desired products under the standard reaction conditions (Table
2, 3ka−3ma).
a b c d e
, , , ,
Ethers
On the other hand, subjection of BnBr (5a)16 to the
reductive addition process led to 89% yield of β,β-disubstituted
alkenyl ether 6aa as a single isomer, as evidenced by NMR and
NOE experiments (see the Supporting Information) (Table 3,
6aa). Notably, it represents a rare example of catalytic
hydrobenzylation of alkynes.17 As such, we further examined
the scope and limitations of this hydrobenzylation reaction.
Pleasingly, various benzyl bromides bearing F, Cl, OMe, alkyl,
and aryl groups were amenable to this reaction (Table 3, 6ab−
6ah). On the contrary, 4-nitrobenzyl bromide (5i) did not yield
the desired product under the reaction conditions (Table 3,
6ai). Reductive addition of benzyl chloride (5k) to 1a
proceeded as well, albeit in a prolonged reaction time (18 h)
and relatively decreased yield (Table 3, 6aa). Additionally, the
scope of this hydrobenzylation reaction with respect to ynol
ethers was investigated. For instance, the steric hindered
alkynyl ethers 1e and 1f delivered β,β-disubstituted vinylic
ethers 6ea and 6fa in high yields (Table 3, 6ea and 6fa).
Moreover, the transformation of ethyl ynol ether 1g with 5a
provided 60% yield of 6ga (Table 3, 6ga). Unfortunately, the
reaction of methyl ynol ether (1k), silyl ynol ether (1l), and
ethynyl phenyl ether (1m) all led to unsatisfactory results
(Table 3, 6ka−6ma).
a
Unless otherwise noted, all reactions were carried out with 1 (0.5
mmol), 2 (0.75 mmol), Pd(OAc)2 (5 mol %), PCy3·HBF4 (10 mol %),
2-propanol (0.75 mmol), Cs2CO3 (1.0 mmol), dioxane, 50 °C, 10 h.
b
c
d
e
Isolated yield. rr = 91:9. rr = 95:5. A complex mixture of products
was formed. ND = not detected. TIPS = Si(i-Pr)3. 2 = PhI (2a), 4-
MeC6H4I (2b), 3-MeC6H4I (2c), 2-MeC6H4I (2d), 4-FC6H4I (2e), 4-
CF3C6H4I (2f), 4-ClC6H4I (2g), 4-BrC6H4I (2h), 4-OMeC6H4I (2i),
2-OMeC6H4I (2j), 4-CH3COC6H4I (2k), 4-NH2C6H4I (2l), 4-
AcNHC6H4I (2m), 4-CO2EtC6H4Br (2n), CH2CI-n-C9H19 (2o),
(E)-styryl bromide (2p), or (E)-4−Cl-C6H4CHCHBr (2q).
under the reaction conditions. Furthermore, the free NH2
group proved to be tolerated, giving rise to 3al in good yield
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propanol might act as the hydride donor via the β-H
elimination reaction.
Table 3. Synthesis of β,β-Disubstituted Enol Ethers via the
Hydrobenzylation of Ynol Ethers
ab c d e
, , , ,
As such, a possible mechanism is proposed in Scheme 4 for
this regiocontrolled reductive addition of organohalides to ynol
ethers. First, the oxidative addition of Pd(0) with aryl or alkenyl
halides affords a species A, which is regio- and stereoselectively
converted into the intermediate B by cis-carbopalladation of
ynol ethers. The highly polarized C−C triple bonds of 1,
stemmed from the formation of a ketene-like mesomer 1′,7c
may account for the regioselective α-arylation or α-alkenylation.
Then, in the presence of Cs2CO3, the reaction of 2-propanol
with B gives the intermediate C, followed by a β-H
elimination/reductive elimination sequence to produce α,β-
disubstituted vinylic ethers 3 with concurrent formation of the
Pd(0) catalyst (Scheme 4, path a).
On the other hand, the benzylpalladium intermediate E,
generated by the oxidative addition of Pd(0) with benzyl
halides, may undergo the cis-carbopalladation with 1 to form an
alkenylpalladium intermediate F. The reversed regioselectivity
at this carbopalladation step is still unclear at the current stage.
A possible reason may be attributed to the unique properties of
benzylpalladium complexes, which usually act as electrophiles
rather than nucleophiles.18 As such, the external nucleophilic
attack of the β-carbon of ynol ethers leads to the regioselective
β-benzylation. Subsequently, reduction of the C−Pd bond of F
furnishes the β,β-disubstituted alkenyl ethers 6 with the
regeneration of Pd(0) species (Scheme 4, path b).
a
Unless otherwise noted, all reactions were carried out with 1 (0.5
mmol), 5 (1.1 mmol), Pd(OAc)2 (5 mol %), PCy3·HBF4 (10 mol %),
2-propanol (0.75 mmol), Cs2CO3 (1.0 mmol), dioxane, 50 °C, 10 h.
b
c
d
Isolated yield. BnCl (5k) was used instead of BnBr (5a). rr = 94:6.
e
A complex mixture of products was formed. NR = no reaction. 5 =
BnBr (5a), 4-MeC6H4CH2Br (5b), 3-MeC6H4CH2Br (5c), 2-
MeC6H4CH2Br (5d), 3,5-(Me)2C6H3CH2Br (5e), 4-FC6H4CH2Br
(5f), 4-ClC6H4CH2Br (5g), 3-OMeC6H4CH2Br (5h), 4-NO2C6H4-
CH2Br (5i), or 2-(bromomethyl)naphthalene (5j).
To gain some insight into the mechanism of this reductive
addition reaction, ynol ether 1a was treated with 1.5 equiv of
(CD3)2CDOD, 5 mol % of Pd(OAc)2, 10 mol % of PCy3·
HBF4, 2.0 equiv of Cs2CO3, and 1.5 equiv of 2a in 2 mL of
dioxane at 50 °C for 10 h, providing 3aa-d in 85% yield with
98% deuterium incorporation (Scheme 3, eq 1). In contrast, no
CONCLUSION
■
In summary, we have developed a highly effective Pd-catalyzed
reductive addition of organohalides, including aryl, alkenyl, and
benzyl halides, to ynol ethers for the first time. It proceeds
under mild reaction conditions with the use of readily available
2-propanol as the hydride source, giving α,β- and β,β-
disubstituted alkenyl ethers in satisfactory yields with excellent
regio- and stereoselectivity. The regioselectivity of this reaction
is found to be determined by the organic halides employed. It
constitutes a significant advance in the exploration of
regiocontrolled hydroarylation, hydroalkenylation, and hydro-
benzylation of internal alkynes using the readily accessible
organohalides as coupling partners, and we believe that it will
be of value for organic synthesis.
Scheme 3. The Deuteration and Related Experiments
EXPERIMENTAL SECTION
General. THF, dioxane, and toluene were distilled from sodium
prior to use. Unless otherwise noted, commercially available materials
■
1
and reagents were used directly without further purification. H and
13C NMR spectra were measured on 400 or 600 MHz NMR
spectrometers utilizing CDCl3 as the solvent and tetramethylsilane
(TMS) as the internal standard. Chemical shifts were given in δ
relative to TMS, while the coupling constants were given in Hz. High-
resolution mass spectra (HRMS) analyses were performed employing
a TOF MS instrument with an EI or ESI source. Column
chromatography was carried out using silica gel (300−400 mesh).
General Procedure for the Pd-Catalyzed Reductive Addition
of Organohalides to Ynol Ethers. To a mixture of Pd(OAc)2 (5.6
mg, 0.025 mmol), PCy3·HBF4 (18.4 mg, 0.05 mmol), and Cs2CO3
(326 mg, 1.0 mmol) was added a solution of 1a (94 mg, 0.5 mmol),
PhI (153 mg, 0.75 mmol), and 2-propanol (45 mg, 0.75 mmol) in 2
mL of dioxane under a nitrogen atmosphere. After stirring for 10 h at
50 °C, the reaction mixture was concentrated and purified by column
chromatography on silica (petroleum ether) to give 125 mg (94%
reaction occurred when (CD3)2CDOD was replaced by t-
BuOH (Scheme 3, eq 2), indicating that the protonolysis
mechanism might be less likely in this reaction. Furthermore,
when 4-heptanol was employed instead of 2-propanol as the
hydride source, the desired product 3aa was obtained in 77%
yield, together with the formation of a good yield of 4-
heptanone (Scheme 3, eq 3). Likewise, 6aa-d was isolated in
excellent yield with 91% deuterium incorporation by treating 1a
with (CD3)2CDOD under the hydrobenzylation conditions,
whereas the reaction did not proceed in the presence of t-
BuOH (Scheme 3, eqs 4 and 5). These results indicated that 2-
yield) of 3aa9a as a colorless oil. H NMR (600 MHz, CDCl3) δ 7.50
1
(d, J = 7.8 Hz, 2H), 7.32−7.15 (m, 3H), 7.09 (t, J = 7.9 Hz, 1H),
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Scheme 4. Proposed Mechanism
1
6.79−6.73 (m, 3H), 5.87 (t, J = 7.4 Hz, 1H), 2.31 (s, 3H), 2.22 (q, J =
7.3 Hz, 2H), 1.46−1.30 (m, 4H), 0.89 (t, J = 7.3 Hz, 3H).
Compound 3aj: 132 mg, 89% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.47 (d, J = 7.7 Hz, 1H), 7.24 (t, J = 7.8 Hz, 1H), 7.13
(t, J = 7.8 Hz, 1H), 6.95−6.91 (m, 2H), 6.87 (s, 1H), 6.83−6.76 (m,
2H), 6.05 (t, J = 7.3 Hz, 1H), 3.93 (s, 3H), 2.34−2.29 (m, 5H), 1.53−
1.41 (m, 4H), 0.96 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 157.4, 157.1, 145.1, 139.2, 128.9, 128.9, 128.6, 124.5, 122.4, 122.0,
120.4, 116.5, 112.6, 111.1, 55.4, 31.6, 25.7, 22.4, 21.4, 13.9; MS (EI,
m/z) 296 (M+, 43), 189 (95), 147 (68), 135 (64); HRMS (EI) calcd
for C20H24O2 (M+) 296.1776, found 296.1784.
Compound 3aa-d:9a The title compound was obtained by
replacing 2-propanol with (CD3)2CDOD under the standard
1
conditions, 113 mg, 85% yield, colorless oil; H NMR (600 MHz,
CDCl3) δ 7.48 (d, J = 7.8 Hz, 2H), 7.26 (t, J = 7.3 Hz, 2H), 7.20 (t, J =
7.4 Hz, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.79 (s, 1H), 6.73 (m, 2H), 2.27
(s, 3H), 2.20 (q, J = 7.3 Hz, 2H), 1.44−1.30 (m, 4H), 0.87 (t, J = 7.3
Hz, 3H).
Compound 3ab:9a 129 mg, 92% yield, colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.37 (d, J = 8.2 Hz, 2H), 7.10−7.03 (m, 3H), 6.79 (s,
1H), 6.72 (d, J = 7.9 Hz, 2H), 5.79 (t, J = 7.4 Hz, 1H), 2.29 (s, 3H),
2.27 (s, 3H), 2.18 (q, J = 7.3 Hz, 2H), 1.43−1.25 (m, 4H), 0.88 (t, J =
7.2 Hz, 3H).
Compound 3ak:9a 128 mg, 83% yield, yellow oil; H NMR (400
1
MHz, CDCl3) δ 7.89 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H),
7.12 (t, J = 7.9 Hz, 1H), 6.81−6.69 (m, 3H), 6.04 (t, J = 7.4 Hz, 1H),
2.58 (s, 3H), 2.31 (s, 3H), 2.26 (dd, J = 14.7, 7.4 Hz, 2H), 1.41 (m,
1.49−1.34, 4H), 0.91 (t, J = 7.2 Hz, 3H).
Compound 3ac:9a 127 mg, 91% yield, colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.31−7.24 (m, 2H), 7.15 (t, J = 7.6 Hz, 1H), 7.09 (t, J
= 7.8 Hz, 1H), 7.03 (d, J = 7.5 Hz, 1H), 6.79 (s, 1H), 6.73 (d, J = 8.0
Hz, 2H), 5.84 (t, J = 7.4 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 2.18 (q, J
= 7.3 Hz, 2H), 1.44−1.28 (m, 4H), 0.87 (t, J = 7.2 Hz, 3H).
Compound 3ad:9a 127 mg, 91% yield, colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.43−7.32 (m, 1H), 7.15−7.00 (m, 4H), 6.74 (s, 1H),
6.72−6.65 (m, 2H), 5.33 (t, J = 7.4 Hz, 1H), 2.42 (s, 3H), 2.30−2.19
(m, 5H), 1.49−1.33 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H).
Compound 3al: 96 mg, 68% yield, colorless oil; H NMR (600
1
MHz, CDCl3) δ 7.33−7.29 (m, 2H), 7.11 (t, J = 7.8 Hz, 1H), 6.81 (s,
1H), 6.76 (dd, J = 7.9, 1.8 Hz, 2H), 6.63−6.58 (m, 2H), 5.67 (t, J = 7.3
Hz, 1H), 3.70 (br, 2H), 2.31 (s, 3H), 2.21−2.16 (m, 2H), 1.44−1.34
(m, 4H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
157.6, 148.7, 146.0, 139.4, 129.1, 126.4, 126.1, 121.9, 116.2, 114.9,
114.8, 112.4, 31.6, 25.4, 22.4, 21.5, 13.9; MS (EI, m/z) 281 (M+, 43),
238 (18), 207 (10), 195 (2), 174 (100); HRMS (EI) calcd for
C19H23NO (M+) 281.1780, found 281.1778.
Compound 3ae:9a 126 mg, 89% yield, yellow oil; H NMR (600
Compound 3am: 115 mg, 71% yield, colorless oil; H NMR (600
1
1
MHz, CDCl3) δ 7.47−7.42 (m, 2H), 7.10 (t, J = 7.7 Hz, 1H), 6.97−
6.92 (m, 2H), 6.78−6.70 (m, 3H), 5.76 (t, J = 7.4 Hz, 1H), 2.29 (s,
3H), 2.18 (q, J = 7.4 Hz, 2H), 1.43−1.28 (m, 4H), 0.88 (t, J = 7.4 Hz,
3H).
MHz, CDCl3) δ 7.48−7.42 (m, 3H), 7.35−7.30 (m, 1H), 7.13−7.09
(m, 1H), 6.81−6.73 (m, 3H), 5.81 (t, J = 7.4 Hz, 1H), 2.30 (s, 3H),
2.23−2.19 (m, 2H), 2.15 (d, J = 7.0 Hz, 3H), 1.46−1.41 (m, 2H),
1.39−1.33 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 168.4, 157.4, 148.1, 139.5, 131.6, 129.1, 128.9, 125.8, 122.2,
119.7, 117.5, 116.1, 112.3, 31.4, 25.5, 24.5, 22.4, 21.4, 13.9; MS (EI,
m/z) 323 (M+, 32), 280 (18), 216 (100), 207 (8); HRMS (EI) calcd
for C21H25NO2 (M+) 323.1885, found 323.1884.
Compound 3af:9a 138 mg, 83% yield, yellow oil; H NMR (600
1
MHz, CDCl3) δ 7.62 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 8.3 Hz, 2H),
7.14 (t, J = 8.0 Hz, 1H), 6.79−6.74 (m, 2H), 6.75 (d, J = 7.0 Hz, 1H),
6.00 (t, J = 7.4 Hz, 1H), 2.32 (s, 3H), 2.27 (q, J = 7.4 Hz, 2H), 1.49−
1.39 (m, 2H), 1.38−1.31 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H).
Compound 3ag:9a 130 mg, 87% yield, colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.41 (d, J = 8.6 Hz, 2H), 7.26−7.17 (m, 2H), 7.09 (t,
J = 7.9 Hz, 1H), 6.76−6.65 (m, 3H), 5.83 (t, J = 7.4 Hz, 1H), 2.28 (s,
3H), 2.19 (q, J = 7.3 Hz, 2H), 1.45−1.27 (m, 4H), 0.87 (t, J = 7.2 Hz,
3H).
1
Compound 3an: 150 mg, 89% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H),
7.14−7.10 (m, 1H), 6.81−6.72 (m, 3H), 6.02 (t, J = 7.4 Hz, 1H), 4.37
(q, J = 7.1 Hz, 2H), 2.31 (s, 3H), 2.28−2.24 (m, 2H), 1.50−1.36 (m,
7H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 166.2,
157.2, 148.0, 139.9, 139.6, 129.7, 129.5, 129.2, 125.0, 122.4, 120.7,
116.1, 112.2, 60.8, 31.2, 25.7, 22.4, 21.4, 14.3, 13.8; MS (EI, m/z) 338
(M+, 17), 295 (19), 230 (38), 215 (13), 177 (47); HRMS (EI) calcd
for C22H26O3 (M+) 338.1882, found 338.1882.
1
Compound 3ah: 148 mg, 86% yield, colorless oil; H NMR (400
MHz, CDCl3) δ 7.45−7.35 (m, 4H), 7.16−7.10 (m, 1H), 6.83−6.71
(m, 3H), 5.88 (t, J = 7.4 Hz, 1H), 2.32 (s, 3H), 2.23 (td, J = 7.3, 7.3
Hz, 2H), 1.49−1.34 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 157.2, 147.8, 139.7, 134.6, 131.5, 129.2, 126.8, 122.4,
121.6, 118.9, 116.1, 112.2, 31.3, 25.6, 22.4, 21.5, 13.9; MS (EI, m/z)
346 (14), 344 (M+, 17), 303 (10), 301 (10), 238 (21); HRMS (EI)
calcd for C19H21BrO (M+) 344.0776, found 344.0773.
1
Compound 3ao: 147 mg, 86% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.16 (t, J = 7.8 Hz, 1H), 6.82−6.72 (m, 3H), 5.53 (t, J
= 7.3 Hz, 1H), 5.19 (s, 1H), 4.92 (s, 1H), 2.35 (s, 3H), 2.30−2.26 (m,
2H), 2.15−2.09 (m, 2H), 1.59 (t, J = 7.1 Hz, 2H), 1.41−1.31 (m,
16H), 0.94 (t, J = 6.9 Hz, 3H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 157.9, 149.2, 141.7, 139.4, 129.1, 121.8, 118.8,
115.6, 112.4, 111.7, 32.9, 31.9, 31.3, 29.6, 29.5, 29.5, 29.3, 28.5, 25.5,
22.7, 22.4, 21.5, 14.1, 13.9; MS (EI, m/z) 342 (M+, 21), 229 (16), 215
(13), 187 (14), 173 (19); HRMS (EI) calcd for C24H38O (M+)
342.2923, found 342.2925.
Compound 3ai:9a 132 mg, 89% yield, yellow oil; H NMR (400
1
MHz, CDCl3) δ 7.43 (d, J = 8.7 Hz, 2H), 7.10 (t, J = 7.8 Hz, 1H),
6.84−6.76 (m, 3H), 6.75−6.70 (m, 2H), 5.75 (t, J = 7.4 Hz, 1H), 3.80
(s, 3H), 2.28 (s, 3H), 2.17 (q, J = 7.1 Hz, 2H), 1.44−1.28 (m, 4H),
0.87 (t, J = 7.3 Hz, 3H).
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1
Compound 3ap: 123 mg, 84% yield, colorless oil; rr = 91:9; H
NMR (600 MHz, CDCl3) δ 7.38 (d, J = 7.4 Hz, 2H), 7.31 (t, J = 7.7
Hz, 2H), 7.26−7.17 (m, 2H), 6.88−6.81 (m, 3H), 6.72 (d, J = 15.9
Hz, 1H), 6.59 (d, J = 15.9 Hz, 1H), 5.51 (t, J = 7.5 Hz, 1H), 2.36 (s,
3H), 2.14 (td, J = 7.3, 7.3 Hz, 2H), 1.43−1.31 (m, 4H), 0.90 (t, J = 7.2
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 157.7, 148.9, 139.6, 136.8,
129.2, 128.5, 128.2, 127.5, 126.5, 123.9, 123.5, 122.1, 115.6, 111.9,
31.2, 25.7, 22.3, 21.5, 13.8; MS (EI, m/z) 292 (M+, 23), 263 (7), 249
(100), 221 (76); HRMS (EI) calcd for C21H24O (M+) 292.1827,
found 292.1824.
Compound 4b: 111 mg, 70% yield, yellow oil; 1H NMR (600 MHz,
CDCl3) δ 7.39 (d, J = 7.0 Hz, 1H), 7.23 (t, J = 7.8 Hz, 1H), 7.14 (t, J =
7.3 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.95 (s,
1H), 6.92−6.89 (m, 1H), 6.38 (d, J = 7.2 Hz, 1H), 2.47−2.41 (m,
1H), 2.36 (s, 3H), 1.72−1.63 (m, 6H), 1.24 (d, J = 14.2 Hz, 4H); 13C
NMR (150 MHz, CDCl3) δ 195.3, 168.1, 155.2, 140.1, 139.1, 132.2,
129.5, 128.6, 125.6, 125.1, 121.2, 120.0, 118.7, 115.0, 33.2, 30.7, 26.6,
25.8, 21.4; MS (EI, m/z) 318 (M+, 100), 275 (26), 262 (15), 249 (37),
181 (46); HRMS (EI) calcd for C22H22O2 (M+) 318.1620, found
318.1624.
1
Compound 6aa: The title compound was prepared from 1a and 5a
according to the general procedure except that 2.2 equiv of 5a was
used, 124 mg, 89% yield, colorless oil; 1H NMR (600 MHz, CDCl3) δ
7.30 (t, J = 7.5 Hz, 2H), 7.26−7.16 (m, 4H), 6.83 (d, J = 7.5 Hz, 1H),
6.81−6.77 (m, 2H), 6.28 (s, 1H), 3.32 (s, 2H), 2.34 (s, 3H), 2.12−
2.08 (m, 2H), 1.40−1.35 (m, 2H), 1.34−1.28 (m, 2H), 0.86 (t, J = 7.3
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 157.8, 139.8, 139.6, 137.4,
129.2, 128.9, 128.3, 126.1, 124.6, 122.9, 116.8, 112.9, 37.9, 29.7, 26.5,
22.5, 21.4, 13.9; MS (EI, m/z) 280 (M+, 31), 223 (7), 181 (10), 159
(8), 129 (100); HRMS (EI) calcd for C20H24O (M+) 280.1827, found
280.1825.
Compound 3aq: 140 mg, 86% yield, colorless oil; rr = 95:5; H
NMR (600 MHz, CDCl3) δ 7.31−7.25 (m, 4H), 7.18 (t, J = 7.8 Hz,
1H), 6.87−6.80 (m, 3H), 6.67 (d, J = 15.9 Hz, 1H), 6.52 (d, J = 15.9
Hz, 1H), 5.52 (t, J = 7.5 Hz, 1H), 2.36 (s, 3H), 2.13 (td, J = 7.4 Hz, J =
7.4 Hz, 2H), 1.42−1.30 (m, 4H), 0.89 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 157.6, 148.7, 139.6, 133.0, 129.2, 128.7, 127.6,
127.5, 126.8, 124.6, 124.2, 122.2, 115.5, 111.8, 31.1, 25.7, 22.3, 21.5,
13.8; MS (EI, m/z) 328 (11), 326 (M+, 36), 283 (39), 271 (26), 239
(25); HRMS (EI) calcd for C21H23ClO (M+) 326.1437, found
326.1435.
Compound 3ba:9a 128 mg, 90% yield, yellow oil; H NMR (600
1
Compound 6aa-d: 123 mg, 88% yield, colorless oil; 1H NMR (600
MHz, CDCl3) δ 7.30 (t, J = 7.5 Hz, 2H), 7.27−7.16 (m, 4H), 6.86−
6.76 (m, 3H), 6.28 (s, 0.09H), 3.32 (s, 2H), 2.34 (s, 3H), 2.10 (t, J =
7.6 Hz, 2H), 1.42−1.35 (m, 2H), 1.33−1.25 (m, 2H), 0.86 (t, J = 7.3
Hz, 3H); MS (EI, m/z) 282 (11), 281 (M+, 59), 224 (11), 190 (3),
130 (100).
MHz, CDCl3) δ 7.48−7.40 (m, 2H), 7.31−7.23 (m, 3H), 7.20−7.15
(m, 2H), 6.95−6.82 (m, 2H), 5.87 (t, J = 7.4 Hz, 1H), 2.19 (q, J = 7.4
Hz, 2H), 1.47−1.31 (m, 4H), 0.90 (t, J = 7.3 Hz, 3H).
Compound 3ca:9a 116 mg, 92% yield, colorless oil; 1H NMR (600
MHz, CDCl3) δ 7.56−7.52 (m, 2H), 7.36−7.24 (m, 5H), 7.05−6.93
(m, 3H), 5.92 (t, J = 7.4 Hz, 1H), 2.27 (q, J = 7.4 Hz, 2H), 1.51−1.37
(m, 4H), 0.94 (t, J = 7.3 Hz, 3H).
1
Compound 6ab: 121 mg, 82% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.19−7.17 (m, 1H), 7.16−7.12 (m, 4H), 6.80 (d, J =
7.5 Hz, 1H), 6.74 (s, 1H), 6.70 (dd, J = 8.1, 2.2 Hz, 1H), 6.00 (s, 1H),
3.32 (s, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 2.18−2.14 (m, 2H), 1.46−
1.42 (m, 2H), 1.34−1.30 (m, 2H), 0.89 (t, J = 7.3 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 157.8, 139.6, 137.6, 136.6, 130.2, 129.7, 129.2,
126.3, 125.9, 122.8, 116.7, 112.7, 35.4, 29.9, 27.3, 22.5, 21.4, 19.4, 14.0;
MS (EI, m/z) 294 (M+, 20), 237 (4), 207 (6), 195 (8), 143 (100);
HRMS (EI) calcd for C21H26O (M+) 294.1984, found 294.1985.
Compound 3da:9a 130 mg, 83% yield, colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.45 (d, J = 7.0 Hz, 2H), 7.27−7.14 (m, 8H), 7.05 (t,
J = 7.8 Hz, 1H), 6.76−6.64 (m, 3H), 5.85 (t, J = 7.3 Hz, 1H), 2.73 (t, J
= 7.7 Hz, 2H), 2.52 (q, J = 7.6 Hz, 2H), 2.25 (s, 3H).
Compound 3ea:9a 124 mg, 85% yield, colorless oil; 1H NMR (600
MHz, CDCl3) δ 7.46 (d, J = 7.4 Hz, 2H), 7.26−7.14 (m, 3H), 7.10−
7.04 (m, 1H), 6.80 (s, 1H), 6.73−6.71 (m, 2H), 5.67 (d, J = 9.4 Hz,
1H), 2.56−2.48 (m, 1H), 2.26 (s, 3H), 1.74−1.65 (m, 4H), 1.29−1.12
(m, 6H).
1
Compound 6ac: 112 mg, 76% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.24−7.20 (m, 2H), 7.11−7.04 (m, 3H), 6.89−6.80
(m, 3H), 6.31 (s, 1H), 3.32 (s, 2H), 2.38 (m, 6H), 2.16−2.11 (m, 2H),
1.32−1.42 (m, 4H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 157.8, 139.7, 139.6, 137.9, 137.3, 129.6, 129.2, 128.2, 126.9,
125.9, 124.7, 122.8, 116.7, 112.9, 37.8, 29.7, 26.5, 22.5, 21.5, 21.4, 13.9;
MS (EI, m/z) 294 (M+, 12), 237 (32), 207 (7), 195 (12), 143 (100);
HRMS (EI) calcd for C21H26O (M+) 294.1984, found 294.1986.
Compound 3fa:9a 136 mg, 87% yield, yellow oil; H NMR (400
1
MHz, CDCl3) δ 7.43−7.41 (m, 2H), 7.27−7.13 (m, 5H), 6.89−6.85
(m, 2H), 5.69 (d, J = 9.4 Hz, 1H), 2.51−2.43 (m, 1H), 1.70−1.67 (m,
4H), 1.26−1.11 (m, 6H).
Compound 3ga:9a 92 mg, 82% yield, colorless oil; H NMR (600
1
MHz, CDCl3) δ 7.78 (d, J = 7.4 Hz, 2H), 7.58 (d, J = 7.4 Hz, 2H),
7.45−7.29 (m, 5H), 7.23 (t, J = 7.4 Hz, 1H), 6.18 (s, 1H), 3.90 (q, J =
7.1 Hz, 2H), 1.40 (t, J = 7.0 Hz, 3H).
1
Compound 6ad: 107 mg, 73% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.17 (t, J = 7.8 Hz, 1H), 7.19−7.14 (m, 4H), 6.83 (d,
J = 7.5 Hz, 1H), 6.80 (s, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.26 (s, 1H),
3.28 (s, 2H), 2.33 (s, 3H), 2.32 (s, 3H), 2.11−2.06 (m, 2H), 1.40−
1.34 (m, 2H), 1.32−1.24 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 157.8, 139.6, 137.2, 136.6, 135.6, 129.2, 129.0,
128.7, 128.3, 124.8, 122.8, 116.8, 112.9, 37.4, 29.7, 26.4, 22.5, 21.4,
21.0, 13.9; MS (EI, m/z) 294 (M+, 8), 237 (23), 207 (8), 195 (10),
143 (100); HRMS (EI) calcd for C21H26O (M+) 294.1984, found
294.1983.
Compound 3ha:9a 110 mg, 85% yield, yellow oil; H NMR (400
1
MHz, CDCl3) δ 7.69 (d, J = 8.6 Hz, 2H), 7.55 (m, J = 8.4 Hz, 2H),
7.43−7.35 (m, 3H), 7.29 (d, J = 8.6 Hz, 2H), 6.01 (s, 1H), 3.86 (q, J =
7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H).
Compound 3ia:9a 102 mg, 86% yield, colorless oil; H NMR (400
1
MHz, CDCl3) δ 7.70 (d, J = 8.1 Hz, 2H), 7.63−7.58 (m, 2H), 7.43 (t,
J = 7.4 Hz, 2H), 7.37 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H),
6.15 (s, 1H), 3.87 (q, J = 7.0 Hz, 2H), 2.40 (s, 3H), 1.39 (t, J = 7.0 Hz,
3H).
1
Compound 6ae: 100 mg, 65% yield, colorless oil; H NMR (600
Compound 3ja:9a 90 mg, 71% yield, yellow oil; H NMR (600
1
MHz, CDCl3) δ 7.22 (t, J = 7.8 Hz, 1H), 6.91−6.83 (m, 6H), 6.31 (s,
1H), 3.29 (s, 2H), 2.38 (s, 3H), 2.34 (s, 6H), 2.17−2.12 (m, 2H),
1.46−1.40 (m, 2H), 1.36−1.30 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 157.8, 139.6, 137.7, 137.3, 129.2, 127.8,
126.7, 126.2, 124.8, 122.8, 116.7, 112.9, 37.7, 29.7, 26.5, 22.4, 21.4,
21.3, 13.9; MS (EI, m/z) 308 (M+, 12), 251 (32), 221 (24), 207 (45),
143 (100); HRMS (EI) calcd for C22H28O (M+) 308.2140, found
308.2135.
MHz, CDCl3) δ 7.68 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 7.5 Hz, 2H),
7.35 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.3 Hz, 1H), 6.87 (d, J = 8.8 Hz,
2H), 6.06 (s, 1H), 3.82−3.77 (m, 5H), 1.33 (t, J = 7.0 Hz, 3H).
Compound 4a: The title compound was obtained by replacing PhI
with o-iodobenzaldehyde under the standard conditions with or
1
without 2-propanol, 125 mg, 74% yield, yellow oil; H NMR (600
MHz, CDCl3) δ 7.48−7.44 (m, 1H), 7.29−7.22 (m, 5H), 7.18 (d, J =
7.4 Hz, 1H), 7.08 (d, J = 7.3 Hz, 3H), 6.88 (d, J = 6.3 Hz, 2H), 6.74−
6.70 (m, 1H), 2.74−2.68 (m, 2H), 2.40−2.36 (m, 5H); 13C NMR
(150 MHz, CDCl3) δ 195.5, 169.6, 154.8, 141.5, 140.0, 139.6, 132.4,
132.1, 129.4, 129.0, 128.4, 128.2, 125.9, 125.8, 121.2, 119.8, 119.5,
116.2, 34.6, 23.6, 21.3; MS (EI, m/z) 340 (M+, 2), 250 (16), 249
(100), 221 (38), 193 (7); HRMS (EI) calcd for C24H20O2 (M+)
340.1463, found 340.1464.
1
Compound 6af: 118 mg, 79% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.26−7.20 (m, 3H), 7.07−7.01 (m, 2H), 6.89 (d, J =
7.5 Hz, 1H), 6.83−6.81 (m, 2H), 6.31 (s, 1H), 3.33 (s, 2H), 2.39 (s,
3H), 2.18−2.10 (m, 2H), 1.47−1.28 (m, 4H), 0.91 (t, J = 7.3 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 161.5 (d, J = 242.3 Hz), 157.7, 139.7,
137.5, 135.3 (d, J = 3.1 Hz), 130.2 (d, J = 7.8 Hz), 129.3, 124.3, 123.0,
116.8, 115.1 (d, J = 21.0 Hz), 112.9, 37.1, 29.6, 26.4, 22.4, 21.4, 13.9;
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Article
MS (EI, m/z) 298 (M+, 42), 255 (8), 241 (11), 199 (13), 147 (60);
Compound 6ga: 71 mg, 60% yield, yellow oil; 1H NMR (600 MHz,
CDCl3) δ 7.54−7.32 (m, 2H), 7.30−7.20 (m, 8H), 6.22 (s, 1H), 3.92
(q, J = 7.1 Hz, 2H), 3.65 (s, 2H), 1.32 (t, J = 7.0 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 145.5, 141.8, 140.7, 129.7, 128.4, 128.4, 128.3,
128.0, 127.8, 125.5, 68.6, 38.6, 15.4; MS (EI, m/z) 238 (M+, 100), 209
(15), 193 (12), 181 (30), 131 (20); HRMS (EI) calcd for C17H18O
(M+) 238.1358, found 238.1361.
HRMS (EI) calcd for C20H23FO (M+) 298.1733, found 298.1731.
1
Compound 6ag: 113 mg, 72% yield, colorless oil; rr = 94:6; H
NMR (600 MHz, CDCl3) δ 7.30 (t, J = 7.7 Hz, 2H), 7.24−7.19 (m,
3H), 6.90−6.80 (m, 3H), 6.31 (s, 1H), 3.32 (s, 2H), 2.38 (s, 3H),
2.14−2.09 (m, 2H), 1.43−1.29 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 157.6, 139.7, 138.3, 137.7, 131.9, 130.2,
129.3, 128.4, 123.9, 123.0, 116.8, 112.9, 37.3, 29.6, 26.4, 22.4, 21.5,
13.9; MS (EI, m/z) 316 (14), 314 (M+, 42), 271 (9), 257 (12), 214
(14); HRMS (EI) calcd for C20H23ClO (M+) 314.1437, found
314.1431.
ASSOCIATED CONTENT
* Supporting Information
Spectroscopic data of compounds 3, 4, and 6. This material is
■
S
1
Compound 6ah: 118 mg, 76% yield, colorless oil; H NMR (600
available free of charge via the Internet at http://pubs.acs.org.
MHz, CDCl3) δ 7.26 (t, J = 7.9 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H),
6.90−6.87 (m, 2H), 6.85−6.79 (m, 4H), 6.33 (s, 1H), 3.85 (s, 3H),
3.34 (s, 2H), 2.38 (s, 3H), 2.16−2.12 (m, 2H), 1.44−1.32 (m, 4H),
0.91 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 159.6, 157.7,
141.5, 139.6, 137.4, 129.3, 129.2, 124.3, 122.9, 121.3, 116.7, 114.6,
112.9, 111.4, 55.1, 37.9, 29.7, 26.4, 22.5, 21.4, 13.9; MS (EI, m/z) 310
(M+, 17), 203 (7), 173 (16), 159 (100), 147 (21); HRMS (EI) calcd
for C21H26O2 (M+) 310.1933, found 310.1935.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gangguo@zjnu.cn.
■
Notes
The authors declare no competing financial interest.
1
Compound 6aj: 114 mg, 69% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.87−7.83 (m, 3H), 7.73 (s, 1H), 7.52−7.44 (m, 3H),
7.24 (t, J = 7.8 Hz, 1H), 6.92−6.84 (m, 3H), 6.40 (s, 1H), 3.54 (s,
2H), 2.40 (s, 3H), 2.22−2.17 (m, 2H), 1.50−1.44 (m, 2H), 1.38−1.32
(m, 2H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
157.8, 139.6, 137.7, 137.3, 133.6, 132.2, 129.2, 127.9, 127.6, 127.5,
127.4, 127.1, 125.9, 125.3, 124.4, 122.9, 116.8, 112.9, 38.1, 29.7, 26.6,
22.5, 21.4, 13.9; MS (EI, m/z) 330 (M+, 25), 193 (11), 179 (100), 167
(52); HRMS (EI) calcd for C24H26O (M+) 330.1984, found 330.1987.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
of China (21172199), the Natural Science Foundation of
Zhejiang Province (LR12B02001), Education of Zhejiang
Province (Y200805842), and the Open Research Fund of
Key Laboratory of the Ministry of Education for Advanced
Catalysis Materials (ZJHX201310).
1
Compound 6ba: 123 mg, 82% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.36−7.24 (m, 7H), 6.95 (d, J = 8.8 Hz, 2H), 6.26 (s,
1H), 3.37 (s, 2H), 2.15 (t, J = 7.6 Hz, 2H), 1.46−1.38 (m, 2H), 1.36−
1.30 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 156.3, 139.4, 137.0, 129.4, 128.8, 128.5, 128.4, 128.3, 126.2, 117.1,
37.8, 29.6, 26.5, 22.4, 13.9; MS (EI, m/z) 302 (5), 300 (M+, 16), 243
(2), 179 (3), 129 (100); HRMS (EI) calcd for C19H21ClO (M+)
300.1281, found 300.1284.
REFERENCES
■
(1) For recent reviews, see: (a) Winternheimer, D. J.; Shade, R. E.;
Merlic, C. A. Synthesis 2010, 2497. (b) Evano, G.; Gaumont, A.-C.;
Alayrac, C.; Wrona, I. E.; Giguere, J. R.; Delacroix, O.; Bayle, A.;
Jouvin, K.; Theunissen, C.; Gatignol, J.; Silvanus, A. C. Tetrahedron
2014, 70, 1529 and references therein. For some recent examples of
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Am. Chem. Soc. 2013, 135, 18327. (d) Lin, X.; Ye, X.; Sun, X.; Zhang,
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1
Compound 6ca: 109 mg, 82% yield, colorless oil; H NMR (400
MHz, CDCl3) δ 7.42−7.26 (m, 7H), 7.09−7.00 (m, 3H), 6.33 (s, 1H),
3.38 (s, 2H), 2.20−2.12 (m, 2H), 1.46−1.31 (m, 4H), 0.91 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.8, 139.7, 137.3, 129.5,
128.9, 128.3, 126.2, 124.9, 122.0, 116.0, 37.9, 29.7, 26.5, 22.4, 13.9; MS
(EI, m/z) 266 (M+, 26), 244 (11), 207 (7), 185 (14), 129 (100);
HRMS (EI) calcd for C19H22O (M+) 266.1671, found 266.1669.
Compound 6da: 123 mg, 75% yield, colorless oil; H NMR (400
MHz, CDCl3) δ 7.39−7.33 (m, 2H), 7.32−7.18 (m, 9H), 6.91−6.78
(m, 3H), 6.35 (s, 1H), 3.35 (s, 2H), 2.79−2.71 (m, 2H), 2.51−2.44
(m, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6, 142.1,
139.6, 139.5, 138.0, 129.2, 128.9, 128.4, 128.4, 128.2, 126.2, 125.7,
123.5, 123.0, 116.9, 113.0, 38.2, 34.0, 28.9, 21.4; MS (EI, m/z) 328
(M+, 3), 237 (8), 207 (4), 159 (4), 129 (100); HRMS (EI) calcd for
C24H24O (M+) 328.1827, found 328.1823.
̈
̈
1
Compound 6ea: 132 mg, 86% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.37−7.30 (m, 4H), 7.26−7.20 (m, 2H), 6.88 (d, J =
7.5 Hz, 1H), 6.84 (s, 1H), 6.82−6.79 (m, 1H), 6.05 (s, 1H), 3.36 (s,
2H), 2.62 (tt, J = 12.1, 3.3 Hz, 1H), 2.38 (s, 3H), 1.75−1.70 (m, 2H),
1.68−1.64 (m, 1H), 1.63−1.59 (m, 2H), 1.41 (qd, J = 12.6, 3.1 Hz,
2H), 1.32−1.25 (m, 2H), 1.15 (tt, J = 12.9, 3.5 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 157.8, 140.3, 139.6, 137.7, 129.2, 129.2, 129.0,
128.2, 126.0, 122.8, 116.8, 112.9, 38.2, 36.2, 31.1, 26.7, 26.2, 21.4; MS
(EI, m/z) 306 (M+, 100), 223 (26), 155 (65), 129 (64); HRMS (EI)
calcd for C22H26O (M+) 306.1984, found 306.1982.
́
Huck, J.; Frey, W.; Bats, J. W.; Hamzic, M. Angew. Chem., Int. Ed. 2009,
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Tanaka, K. Angew. Chem., Int. Ed. 2011, 50, 10922. (f) Miyauchi, Y.;
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1
(9) (a) Bai, Y.; Yin, J.; Kong, W.; Mao, M.; Zhu, G. Chem. Commun.
2013, 49, 7650. For another approach to α,β-disubstituted enol
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(10) For selected reports, see: (a) Oh, C. H.; Jung, H. H.; Kim, K. S.;
Kim, N. Angew. Chem., Int. Ed. 2003, 42, 805. (b) Kim, N.; Kim, K. S.;
Gupta, A. K.; Oh, C. H. Chem. Commun. 2004, 618. (c) Zeng, H.; Hua,
R. J. Org. Chem. 2008, 73, 558. (d) Hayashi, T.; Inoue, K.; Taniguchi,
Compound 6fa: 138 mg, 71% yield, colorless oil; H NMR (600
MHz, CDCl3) δ 7.36−7.21 (m, 7H), 6.92−6.88 (m, 2H), 5.94 (s, 1H),
3.34 (s, 2H), 2.60−2.56 (m, 1H), 1.75−1.68 (m, 3H), 1.62−1.53 (m,
2H), 1.41−1.34 (m, 2H), 1.30−1.24 (m, 2H), 1.15−1.10 (m, 1H); 13C
NMR (150 MHz, CDCl3) δ 156.4, 139.9, 137.3, 130.5, 129.4, 129.0,
128.3, 126.9, 126.1, 117.2, 38.2, 36.1, 31.0, 26.7, 26.1; MS (EI, m/z)
328 (16), 326 (M+, 51), 235 (54), 207 (14), 147 (32); HRMS (EI)
calcd for C21H23ClO (M+) 326.1437, found 326.1436.
3492
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The Journal of Organic Chemistry
Article
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̈
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