Regioselective and stereoselective entry to β,β-disubstituted vinyl ethers via the sequential hydroboration/Suzuki-Miyaura coupling of ynol ethers

Article abstract of DOI:10.1021/jo401523m

A highly regio- and stereoselective synthesis of stereodefined β,β-disubstituted alkenyl ethers featuring the sequential hydroboration/Suzuki-Miyaura coupling of ynol ethers has been described. A number of functional groups, including OMe, Ac, CO₂Et, CN, halides, and alkyl, (hetero)aryl, and alkenyl groups, are well-tolerated under the reaction conditions. Furthermore, it allows a facile entry to the labile diarylacetaldehydes by TFA-mediated hydrolysis of β,β-disubstituted vinyl ethers.

Full text of DOI:10.1021/jo401523m

Article
pubs.acs.org/joc
Regioselective and Stereoselective Entry to β,β-Disubstituted Vinyl
Ethers via the Sequential Hydroboration/Suzuki−Miyaura Coupling
of Ynol Ethers
Weijian Cui, Mengyi Mao, Zuying He, and Gangguo Zhu*
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
S
* Supporting Information
ABSTRACT: A highly regio- and stereoselective synthesis of stereodefined
β,β-disubstituted alkenyl ethers featuring the sequential hydroboration/
Suzuki−Miyaura coupling of ynol ethers has been described. A number of
functional groups, including OMe, Ac, CO2Et, CN, halides, and alkyl,
(hetero)aryl, and alkenyl groups, are well-tolerated under the reaction
conditions. Furthermore, it allows a facile entry to the labile diary-
lacetaldehydes by TFA-mediated hydrolysis of β,β-disubstituted vinyl ethers.
catalyzed stereospecific addition of boronic acids to ynol
ethers.37 Despite the significant success in assembling α,β-
disubstituted vinyl ethers, the regio- and stereoselective
synthesis of β,β-disubstituted vinyl ethers constitutes a
formidable challenge. Indeed, in 1987, a seminal work done
by Suzuki and co-workers38 disclosed a two-step procedure for
the synthesis of β,β-disubstituted vinyl ethers involving a
regioselective hydroboration of ynol ethers using catecholbor-
ane (HBcat) followed by a Pd-catalyzed Suzuki−Miyaura
coupling39,40 with aryl halides (Scheme 1). However, it was
INTRODUCTION
■
Alkenyl ethers possess versatile reactivity in organic chemistry,1
and there are a diverse array of methods that exist for the
assembly of these motifs, such as the olefination of carbonyl
compounds, elimination reaction, hydroalkoxylation of acety-
lenes, C−O bond formation, and other transformations.2−10 In
particular, the C−O bond coupling strategy2−6 provides a
highly regio- and stereoselective approach to prepare vinyl
ethers; however, the construction of stereodefined alkenyl
coupling precursors, especially the thermodynamically unfav-
orable Z-isomers, is difficult to achieve in many cases. Hence,
the development of a simple and general method for the access
of stereodefined multisubstituted vinyl ethers is still highly
desirable.
Scheme 1. Complementary Approaches to Vinyl Ethers
On the other hand, the functionalization of ynol ethers11−19
has attracted considerable attention over the past decades and
provides a straightforward and effective alternative to access
alkenyl ethers.20−28 As an example, Greene and co-workers20
reported that (Z)- or (E)-vinyl ethers could be synthesized via
the reduction of ynol ethers by Lindlar catalyst or LiAlH4,
respectively. Marek21 described an effective regiodivergent
synthesis of vinyl ethers featuring the carbocupration of ynol
ethers, in which the regioselectivity was determined by the
nature of heteroatom substituents. Remarkably, a range of
densely substituted vinyl ethers were found to be assembled by
the Al-catalyzed,22 Au-catalyzed,23 Ni-catalyzed,24 or Rh-
catalyzed25,26 cycloaddition of ynol ethers, respectively reported
by Ready,22 Hashimi,23 Saito,24 and Tanaka.25,26 In addition,
Daoust et al.27,28 demonstrated that either intermolecular or
intramolecular radical addition to ynol ethers proceeded
regioselectively, providing α-iodovinyl ethers in good yields.
As part of our ongoing interest in the functionalization of
heteroatom-substituted alkynes,29−35 we have reported a regio-
and stereoselective protocol for the preparation of (1E)-α-
chloroenol ethers via Pd-catalyzed chloroallyaltion of aromatic
alkynyl ethers.36 Quite recently, we implemented a facile and
concise synthesis of α,β-disubstituted vinyl ethers by the Pd-
reported that alkenylboronates I obtained by the hydroboration
of ynol ethers with HBcat were air-sensitive,41 therefore
significantly limiting the synthetic utility of this protocol.
Meanwhile, since the report by Knochel,42 pinacolborane
(HBpin) has been widely employed in acetylenic hydroboration
reaction43−54 due to the improved reactivity and stability. For
example, the regioselective hydroboration of ynol ethers with
HBpin was realized by Hoffman,48 including the catalytic
Received: July 13, 2013
© XXXX American Chemical Society
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reaction using Cp2ZrHCl as the catalyst and the noncatalytic
version, although only one example was reported in the latter
case. In light of these advances, we envisioned that the
regioselective hydroboration of ynol ethers with HBpin48
followed by a subsequent Suzuki−Miyaura coupling reac-
tion39,40 would provide an operationally simple, highly efficient,
and one-pot method for the synthesis of β,β-disubstituted vinyl
ethers (Scheme 1). Clearly, compared with our previous
report,37 it may provide a complementary method to assemble
polysubstituted vinyl ethers.
lower regioselectivity (92:8) (Table 1, entry 6), indicating that
an uncatalyzed hydroboration56 followed a subsequent Suzuki−
Miyaura coupling appeared to be the most suitable procedure.
Next we employed Pd(dba)2 together with PPh3 to perform
further optimization. Of the bases we examined, Cs2CO3
seemed to be the most effective, although other bases such as
K2CO3, K3PO4, and t-BuOK also produced 3aa in good yields
(Table 1, entries 3 and 9−14). Additionally, the reaction
performed in other solvents, including dioxane and toluene, just
led to decreased yields (Table 1, entries 15 and 16). Therefore,
further substrate screening was carried out using 5 mol %
Pd(dba)2, 10 mol % PPh3, and 2 equiv of Cs2CO3 in THF at
reflux for 4 h.
As shown in Table 2, the scope of this reaction with respect
to halide electrophiles (R3X) was found to be quite satisfactory.
Both electron-rich and electron-poor organic halides proved to
be effective coupling partners, giving desired β,β-disubstituted
vinyl ethers in good yields (Table 2). In particular, the reaction
of 4-MeC6H4I (2b), 3-MeC6H4I (2c), and 2-MeC6H4I (2d)
afforded the desired products 3ab−ad in 84%, 82%, and 78%
yield, respectively, indicating that the steric effect had little
influence on this sequential reaction (Table 2, entries 2−4). A
number of functional groups, including Me, OMe, Ac, CO2Et,
CN, halides, and heteroaryl and alkenyl groups, were found to
be very compatible under the reaction conditions. It should be
noted that, as for 4-BrC6H4I (2g), the competitive coupling of
the C−Br bond was also observed (<20%), thereby leading to a
slight decrease of the yield of 3ag (Table 2, entry 7).
Besides that of iodobenzenes, the reaction of bromobenzenes
and bromoalkenes proceeded smoothly as well and generated
β,β-disubstituted vinyl ethers in excellent regioselectivity. In
particular, the reaction of 3-thienyl bromide (2p) led to 3ap in
reasonable yield (Table 2, entry 16). Notably, the coupling of
1a with vinyl bromides 2q−s furnished the stereodefined dienyl
ethers 3aq−as in good yields (Table 2, entries 17−19). On the
other hand, the ynol ether component was varied, and as a
result, ynol ether (1d) coupled successfully with 2a to form 3da
in an excellent yield (Table 2, entry 22). In contrast, ynol ethers
1e and 1f, bearing a terminal alkene functionality, gave the
corresponding vinyl ethers 3ea and 3fa in respective yields of
65% and 64%, together with formation of some (<15%)
byproducts resulting from the competitive alkenyl hydro-
boration followed by the Suzuki−Miyaura coupling reaction
(Table 2, entries 23 and 24). Interestingly, the sequential
reaction of sterically demanding substrate 1g with 2a produced
86% 3ga as a mixture of two regioisomers at a ratio of 5:1. This
implied that the sterically demanding Cy group might disfavor
the β-phenylation of ynol ethers, therefore resulting in
decreased regioselectivity (Table 2, entry 25).
RESULTS AND DISCUSSION
■
At the outset, the ynol ether 1a, which was easily prepared by
Evano’s method,55 was chosen for examining the reaction. By
treating a solution of 1a in THF with 1.1 equiv of neat HBpin
at room temperature for 1 h, 5 mol % Pd(PPh3)2Cl2, 2.0 equiv
of Cs2CO3, and 1.2 equiv of PhI (2a) were added. To our
delight, the β,β-disubstituted vinyl ether 3aa was obtained in
45% yield (Table 1, entry 1), and no other regio- and
a
Table 1. Screening of the Reaction Conditions
b
entry
PdXn
base
solvent
yield (%)
1
2
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(dba)2
Pd(PPh3)4
Pd2(dba)3
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
t-BuOK
Na2CO3
KF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
dioxane
toluene
45
78
3
92
4
86
5
85
cd
,
6
89 (92:8)
e
7
84
f
8
5
9
84
76
74
67
76
69
55
67
10
11
12
13
14
15
16
CsF
Cs2CO3
Cs2CO3
a
Reaction conditions: (i) 1a (0.5 mmol), HBPin (0.55 mmol), rt, 1−2
h; (ii) 2a (0.6 mmol), PdXn (5 mol %), PPh3 (10 mol %), base (1.0
b
c
d
mmol), reflux, 4 h. Isolated yield. PdLn was added in step i. The
regioisomeric ratio (rr = 92:8) was determined by GC. A 1 equiv
portion of Cs2CO3 was used. Without PPh3.
e
f
Additionally, the reaction of aryl ynol ethers occurred
uneventfully and generated the desired products in good
yields. For instance, 1-ethoxy-2-phenylacetylene (1h) coupled
with 2a, 2b, and 2f smoothly to provide the corresponding β,β-
disubstituted vinyl ethers in good yields and perfect
regioselectivity (Table 2, entries 26−28). Notably, the reaction
of 1j afforded 3ja in 78% yield with a slightly decreased
regioselectivity (rr = 9:1), whereas 1k furnished an 88% yield of
3ka in a single β-regioisomer (Table 2, entries 30 and 31),
indicating that the utilization of sterically hindered R2 group
could increase the regioselectivity of β-substitution of ynol
ethers, probably owing to the steric interaction in the
hydroboration step. Furthermore, we were pleased to find
that the hydroxy group was well tolerated, although only a
stereoisomers were observed by NMR and GC−MS analysis.
Encouraged by this result, we further investigated other
conditions for this sequential reaction.
Pleasingly, the combination of 5 mol % Pd(dba)2 and 10 mol
% PPh3 worked better and resulted in 3aa in 92% yield, while
the omission of PPh3 ligand furnished only a very low (5%)
yield (Table 1, entries 3 and 8). Other palladium catalysts,
including Pd(PPh3)4 and Pd2(dba)3, led to 3aa in slightly
reduced yields (Table 1, entries 4 and 5). Noteworthy, it was
reported by Miyaura and Suzuki40 that palladium complexes
could catalyze the hydroboration of alkynes. As such, we tried
the reaction utilizing Pd(dba)2 and PPh3 as the catalyst for both
the hydroboration and coupling reaction; however, the
hydroboration/coupling sequence produced 89% 3aa with a
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a
Table 2. Scope and Limitations
b
entry
R1/R2 (1)
R3X (2)
yield (%)
1
2
n-Bu/3-tol (1a)
PhI (2a)
92 (3aa)
84 (3ab)
82 (3ac)
78 (3ad)
90 (3ae)
85 (3af)
55 (3ag)
75 (3ah)
70 (3ai)
86 (3aa)
80 (3ab)
88 (3ae)
67 (3ah)
73 (3an)
81 (3ao)
60 (3ap)
71 (3aq)
70 (3ar)
62 (3as)
86 (3ba)
88 (3ca)
92 (3da)
65 (3ea)
64 (3fa)
1a
4-MeC6H4I (2b)
3
1a
3-MeC6H4I (2c)
4
1a
2-MeC6H4I (2d)
5
1a
4-FC6H4I (2e)
6
1a
4-ClC6H4I (2f)
7
1a
4-BrC6H4I (2g)
8
1a
4-OMeC6H4I (2h)
9
1a
4-CH3COC6H4I (2i)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
1a
PhBr (2j)
1a
4-MeC6H4Br (2k)
1a
4-FC6H4Br (2l)
1a
4-OMeC6H4Br (2m)
1a
4-CO2EtC6H4Br (2n)
1a
3-CNC6H4Br (2o)
1a
3-thienyl bromide (2p)
1a
(E)-styryl bromide (2q)
1a
(E)-4-ClC6H4CHCHBr (2r)
1a
(E)-4-OMeC6H4CHCHBr (2s)
n-Bu/Ph (1b)
n-Bu/4-ClC6H4 (1c)
PhCH2CH2/3-tol (1d)
CH2CHCH2/Ph (1e)
CH2CHCH2/3-tol (1f)
Cy/3-tol (1g)
Ph/Et (1h)
2a
2a
2a
2a
2a
2a
2a
2b
2f
c
86 (3ga)
81 (3ha)
80 (3hb)
84 (3hf)
87 (3ia)
Ph/Et (1h)
Ph/Et (1h)
4-OMeC6H4/Et (1i)
4-ClC6H4/Et (1j)
4-ClC6H4/t-Bu (1k)
CH2OH/t-Bu (1l)
H/Ph (1m)
2a
2a
2a
2a
d
78 (3ja)
88 (3ka)
55 (3la)
62 (3ma)
2a
a
b
c
d
Reaction conditions: see Table 1. Isolated yield. Combined yield of two regioisomers at a ratio of 5:1. Combined yield of two regioisomers at a
ratio of 9:1.
moderate yield was observed (Table 2, entry 32). Finally, the
terminal alkynyl ether 1m also underwent the sequential
hydroboration/Suzuki−Miyaura coupling reaction smoothly
and gave 3ma in a reasonable yield (Table 2, entry 33). The
regio- and stereochemistry of β,β-disubstituted vinyl ethers 3
was determined by NOE measurements.57 Therefore, we have
realized an operationally simple and effective protocol for the
elaboration of stereodefined β,β-disubstituted vinyl ethers from
the readily available ynol ethers,20,55,58 which is highlighted by
the broad substrate scope, mild reaction conditions, and
excellent regio- and stereocontrol.
Next the synthetic utility of this method was explored by
treating vinyl ether 3ha with 5 equiv of CF3CO2H (TFA) in
CH2Cl2 at room temperature. After being stirred for 1 h, the
reaction mixture was quenched with saturated NaHCO3
solution, followed by extraction and concentration to give
2,2-diphenylacetaldehyde (4a)59 in 85% yield (note that 4a will
decompose in the presence of silica gel) (Scheme 2).
Furthermore, the reaction worked well for other β,β-
disubstituted vinyl ethers, including 3hb and 3hf, producing
Scheme 2. Preparation of Diarylacetaldehydes from 3
α-branched aldehydes 4b60 and 4c in excellent yields. It is
worth mentioning that diarylacetaldehydes are usually a class of
air- and light-sensitive compounds in organic chemistry.61 As
such, the method developed here provides an effective and mild
protocol for the synthesis of diarylacetaldehydes in excellent
yields with satisfactory purity.
CONCLUSION
■
In summary, we have realized a novel method for the highly
regio- and stereoselective synthesis of β,β-disubstituted vinyl
ethers from the readily accessible ynol ethers via a hydro-
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(t, J = 7.3 Hz, 2 H), 2.43 (s, 3 H), 1.53−1.38 (m, 4 H), 0.98 (t, J = 7.2
Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ 161.9 (d, J = 245.4 Hz),
157.6, 139.8, 138.8, 135.1, 129.3, 127.8 (d, J = 7.7 Hz), 124.8, 123.6,
117.0, 115.3 (d, J = 21.3 Hz), 113.3, 30.2, 27.0, 22.4, 21.4, 13.9; 19F
NMR (565 MHz, CDCl3) δ −116.18; MS (EI, m/z) 284 (M+, 100),
265 (69), 293 (47), 207 (37); HRMS (EI, m/z) calcd for C19H21FO
(M+) 284.1576, found 284.1570.
boration/Suzuki−Miyaura coupling sequence. The notable
features of this reaction include the readily available catalytic
system, broad substrate scope, high efficiency, and excellent
regio- and stereoselectivity. Moreover, it offers a very effective
access to the labile diarylacetaldehydes via the hydrolysis of β,β-
disubstituted vinyl ethers promoted by TFA. As such, we
believe that it will contribute to the progress of synthetic
chemistry.
1
Data for compound 3af: 128 mg, 85% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.37−7.31 (m, 4 H), 7.30−7.22 (m, 1 H),
6.97−6.87 (m, 3 H), 6.76 (s, 1 H), 2.68 (t, J = 7.2 Hz, 2 H), 2.40 (s, 3
H), 1.52−1.35 (m, 4 H), 0.95 (t, J = 7.1 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 157.5, 139.8, 139.4, 137.6, 132.3, 129.4, 128.6, 127.5,
124.5, 123.6, 117.1, 113.4, 30.2, 26.7, 22.4, 21.4, 13.9; MS (EI, m/z)
302 (15), 300 (M+, 48), 194 (59), 151 (49), 125 (100); HRMS (EI,
m/z) calcd for C19H21ClO (M+) 300.1281, found 300.1278.
EXPERIMENTAL SECTION
■
General Procedures. Toluene, THF, and dioxane were distilled
from sodium prior to use. Unless otherwise noted, materials obtained
from commercial suppliers were used without further purification.
Commercial available neat pinacolborane (HBpin) was employed as
the hydroborating reagent. 13C{1H} NMR spectra were measured on a
400 or 600 MHz NMR spectrometer using CDCl3 as the solvent with
tetramethylsilane (TMS) as the internal standard. Chemical shifts are
given in δ relative to TMS, and the coupling constants are given in
hertz. Column chromatography was performed using silica gel (300−
400 mesh). High-resolution mass spectral (HRMS) analyses were
carried out using a TOF MS instrument with an EI or ESI source.
General Procedure for the Sequential Hydroboration/
Suzuki−Miyaura Coupling of Ynol Ethers. To a solution of 1a
(94 mg, 0.5 mmol) in 1 mL of THF was added neat HBpin (71 mg,
0.55 mmol) under a nitrogen atmosphere. After the resulting mixture
was stirred at rt for around 1.5 h (determined by GC), Pd(dba)2 (14
mg, 0.025 mmol), PPh3 (13 mg, 0.05 mmol), Cs2CO3 (326 mg, 1.0
mmol), and PhI (123 mg, 0.6 mmol) were added. After being stirred at
reflux for 4 h, the reaction mixture was concentrated and purified by
column chromatography on silica gel (petroleum ethers:EtOAc =
50:1) to give 122 mg (92% yield) of 3aa as a colorless oil. Compound
3aa was also prepared from 2j in 86% yield (114 mg): 1H NMR (400
MHz, CDCl3) δ 7.45−7.34 (m, 4 H), 7.33−7.21 (m, 2 H), 6.94−6.87
(m, 3 H), 6.76 (s, 1 H), 2.70 (t, J = 7.4 Hz, 2 H), 2.39 (s, 3 H), 1.52−
1.34 (m, 4 H), 0.94 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3)
δ 157.7, 139.8, 139.1, 139.0, 129.3, 128.4, 126.6, 126.3, 125.7, 123.4,
117.0, 113.3, 30.3, 26.8, 22.5, 21.4, 13.9; MS (EI, m/z) 266 (M+, 53),
223 (23), 195 (88), 180 (54), 117 (100); HRMS (EI, m/z) calcd for
C19H22O (M+) 266.1671, found 266.1673.
Data for compound 3ag: 95 mg, 55% yield, colorless oil; 1H NMR
(600 MHz, CDCl3) δ 7.50−7.44 (m, 2 H), 7.29−7.20 (m, 3 H), 6.93−
6.85 (m, 3 H), 6.73 (s, 1 H), 2.64 (t, J = 7.2 Hz, 2 H), 2.37 (s, 3 H),
1.46−1.31 (m, 4 H), 0.91 (t, J = 7.2 Hz, 3 H); 13C NMR (150 MHz,
CDCl3) δ 157.5, 139.8, 139.4, 138.1, 131.5, 129.4, 127.8, 124.5, 123.6,
120.3, 117.1, 113.4, 30.2, 26.7, 22.4, 21.4, 13.9; MS (EI, m/z) 346 (4),
344 (M+, 4), 221 (5), 194 (100), 179 (61); HRMS (EI, m/z) calcd for
C19H21BrO (M+) 344.0776, found 344.0778.
Data for compound 3ah: 111 mg, 75% yield from 2h, colorless oil;
it was prepared from 2m in 67% yield (99 mg); 1H NMR (400 MHz,
CDCl3) δ 7.39−7.31 (m, 2 H), 7.28−7.20 (m, 1 H), 6.98−6.86 (m, 5
H), 6.69 (s, 1 H), 3.86 (s, 3 H), 2.67 (t, J = 7.2 Hz, 2 H), 2.39 (s, 3 H),
1.51−1.34 (m, 4 H), 0.94 (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz,
CDCl3) δ 158.6, 157.7, 139.7, 137.9, 131.5, 129.3, 127.3, 125.5, 123.2,
116.9, 113.9, 113.2, 55.2, 30.3, 27.0, 22.5, 21.4, 13.9; MS (EI, m/z) 296
(M+, 100), 253 (8), 239 (13), 145 (37), 121 (72); HRMS (EI, m/z)
calcd for C20H24O2 (M+) 296.1776, found 296.1780.
Data for compound 3ai: 108 mg, 70% yield, colorless oil; 1H
NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 2 H), 7.53 (d, J = 8.4
Hz, 2 H), 7.26−7.20 (m, 1 H), 6.94−6.83 (m, 4 H), 2.70 (t, J = 7.4
Hz, 2 H), 2.62 (s, 3 H), 2.37 (s, 3 H), 1.50−1.32 (m, 4 H), 0.91 (t, J =
7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 197.6, 157.4, 144.2,
140.9, 139.9, 135.2, 129.4, 128.7, 125.9, 124.2, 123.9, 117.3, 113.5,
30.3, 26.5, 26.4, 22.4, 21.4, 13.9; MS (EI, m/z) 308 (M+, 10), 265
(87), 250 (13), 175 (43), 117 (100); HRMS (EI, m/z) calcd for
C21H24O2 (M+) 308.1776, found 308.1777.
Data for compound 3ab: 117 mg, 84% yield from 2b, colorless oil;
1
it was also prepared from 2k in 80% yield (112 mg); H NMR (400
1
Data for compound 3an: 123 mg, 73% yield, colorless oil; H
MHz, CDCl3) δ 7.36−7.28 (m, 2 H), 7.28−7.17 (m, 3 H), 6.95−6.85
(m, 3 H), 6.73 (s, 1 H), 2.68 (t, J = 6.4 Hz, 2 H), 2.40 (s, 3 H), 2.39 (s,
3 H), 1.53−1.34 (m, 4 H), 0.94 (t, J = 6.5 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 157.7, 139.7, 138.4, 136.3, 136.1, 129.3, 129.1, 126.2,
125.7, 123.3, 117.0, 113.2, 30.3, 26.8, 22.5, 21.4, 21.1, 13.9; MS (EI,
m/z) 280 (M+, 100), 237 (23), 223 (22), 209 (68), 179 (48); HRMS
(EI, m/z) calcd for C20H24O (M+) 280.1827, found 280.1826.
NMR (600 MHz, CDCl3) δ 8.08−8.04 (m, 2 H), 7.48 (d, J = 8.3 Hz, 2
H), 7.26 (t, J = 7.8 Hz, 1 H), 6.98−6.86 (m, 4 H), 4.43 (q, J = 7.1 Hz,
2 H), 2.73 (t, J = 7.5 Hz, 2 H), 2.40 (s, 3 H), 1.51−1.37 (m, 7 H), 0.95
(t, J = 7.3 Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ 166.4, 157.4,
143.9, 140.6, 139.8, 129.7, 129.4, 128.5, 125.7, 124.4, 123.8, 117.2,
113.5, 60.8, 30.3, 26.4, 22.4, 21.4, 14.3, 13.8; MS (EI, m/z) 338 (M+,
27), 221 (21), 195 (39), 178 (50), 163 (100); HRMS (EI, m/z) calcd
for C22H26O3 (M+) 338.1882, found 338.1886.
1
Data for compound 3ac: 115 mg, 82% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.33−7.21 (m, 4 H), 7.18−7.10 (m, 1 H),
6.96−6.89 (m, 3 H), 6.77 (s, 1 H), 2.71 (t, J = 7.4 Hz, 2 H), 2.43 (s, 3
H), 2.41 (s, 3 H), 1.54−1.37 (m, 4 H), 0.96 (t, J = 7.2 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 157.7, 139.7, 139.1, 138.9, 137.9, 129.3,
128.3, 127.4, 127.0, 125.8, 123.4, 123.3, 117.0, 113.3, 30.3, 26.9, 22.5,
21.5, 21.4, 13.9; MS (EI, m/z) 280 (M+, 100), 237 (20), 209 (51), 194
(20), 179 (27); HRMS (EI, m/z) calcd for C20H24O (M+) 280.1827,
found 280.1832.
1
Data for compound 3ao: 118 mg, 81% yield, colorless oil; H
NMR (600 MHz, CDCl3) δ 7.67 (t, J = 1.5 Hz, 1 H), 7.63−7.60 (m, 1
H), 7.57−7.54 (m, 1 H), 7.46 (t, J = 7.8 Hz, 1 H), 7.25 (t, J = 7.8 Hz, 1
H), 6.95 (d, J = 7.5 Hz, 1 H), 6.91−6.86 (m, 2 H), 6.80 (s, 1 H), 2.78
(t, J = 7.2 Hz, 2 H), 2.39 (s, 3 H), 1.47−1.34 (m, 4 H), 0.93 (t, J = 7.2
Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ 157.3, 140.7, 140.6, 139.9,
130.4, 129.9, 129.6, 129.4, 129.3, 124.0, 123.3, 119.0, 117.2, 113.5,
112.6, 30.1, 26.5, 22.4, 21.4, 13.8; MS (EI, m/z) 291 (M+, 24), 270
(10), 195 (56), 180 (45), 174 (100); HRMS (EI, m/z) calcd for
C20H21NO (M+) 291.1623, found 291.1615.
1
Data for compound 3ad: 109 mg, 78% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.32−7.19 (m, 5 H), 6.95−6.85 (m, 3 H),
6.41 (s, 1 H), 2.58 (t, J = 6.6 Hz, 2 H), 2.44 (s, 3 H), 2.41 (s, 3 H),
1.44−1.36 (m, 4 H), 0.97−0.90 (m, 3 H); 13C NMR (100 MHz,
CDCl3) δ 157.6, 139.7, 139.1, 139.0, 136.6, 130.1, 130.1, 129.3, 127.0,
126.1, 125.4, 123.1, 116.8, 113.0, 29.8, 28.9, 22.7, 21.4, 20.2, 13.9; MS
(EI, m/z) 280 (M+, 100), 237 (29), 209 (48), 194 (17), 179 (38);
HRMS (EI, m/z) calcd for C20H24O (M+) 280.1827, found 280.1830.
Data for compound 3ae: 128 mg, 90% yield from 2e, colorless oil;
Data for compound 3ap: 82 mg, 60% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.23−7.16 (m, 1 H), 7.11−7.06 (m, 1 H), 6.99−
6.95 (m, 2 H), 6.91 (s, 1 H), 6.90−6.82 (m, 3 H), 2.61 (t, J = 7.6 Hz, 2
H), 2.34 (s, 3 H), 1.59−1.49 (m, 2 H), 1.45−1.33 (m, 2 H), 0.92 (t, J
= 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 157.4, 142.8, 139.8,
138.4, 129.4, 127.2, 123.6, 122.4, 122.3, 120.1, 117.2, 113.4, 30.6, 27.9,
22.5, 21.4, 13.9; MS (EI, m/z) 273 (17), 272 (M+, 100), 243 (12), 215
(50), 167 (71); HRMS (EI, m/z) calcd for C17H20OS (M+) 272.1235,
found 272.1232.
1
it was also prepared from 2l in 88% yield (125 mg); H NMR (600
MHz, CDCl3) δ 7.40 (dd, J = 8.2, 5.6 Hz, 2 H), 7.28 (t, J = 7.9 Hz, 1
H), 7.10 (t, J = 8.6 Hz, 2 H), 7.00−6.90 (m, 3 H), 6.74 (s, 1 H), 2.72
D
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1
Data for compound 3aq: 104 mg, 71% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.6 Hz, 2 H), 7.34 (t, J = 7.6
Hz, 2 H), 7.28−7.18 (m, 2 H), 6.96−6.85 (m, 3 H), 6.79−6.71 (m, 2
H), 6.56 (d, J = 16.1 Hz, 1 H), 2.53 (t, J = 7.5 Hz, 2 H), 2.39 (s, 3 H),
1.61−1.40 (m, 4 H), 1.02−0.94 (m, 3 H); 13C NMR (100 MHz,
CDCl3) δ 157.4, 143.4, 139.8, 138.0, 129.4, 128.6, 127.4, 126.7, 125.9,
125.2, 124.2, 123.7, 117.2, 113.5, 30.6, 23.9, 22.7, 21.4, 14.0; MS (EI,
m/z) 292 (M+, 71), 235 (6), 184 (42), 141 (93), 129 (100); HRMS
(EI, m/z) calcd for C21H24O (M+) 292.1827, found 292.1828.
Data for compound 3ar: 114 mg, 70% yield, white solid, mp 77−
79 °C; 1H NMR (400 MHz, CDCl3) δ 7.35−7.17 (m, 5 H), 6.92−6.80
(m, 3 H), 6.74−6.63 (m, 2 H), 6.45 (d, J = 16.0 Hz, 1 H), 2.48 (t, J =
7.5 Hz, 2 H), 2.35 (s, 3 H), 1.58−1.35 (m, 4 H), 0.94 (t, J = 7.2 Hz, 3
H); 13C NMR (100 MHz, CDCl3) δ 157.2, 143.8, 139.8, 136.5, 132.0,
129.4, 128.7, 128.1, 127.0, 123.9, 123.8, 123.7, 117.2, 113.5, 30.5, 23.9,
22.7, 21.4, 14.0; MS (EI, m/z) 328 (17), 326 (M+, 56), 283 (100), 235
(34), 172 (17); HRMS (EI, m/z) calcd for C21H23ClO (M+)
326.1437, found 326.1435.
(100), 156 (25); HRMS (EI, m/z) calcd for C18H18O (M+) 250.1358,
found 250.1356.
Data for compound 3ga: 126 mg, 86% yield, colorless oil, rr = 5:1;
1H NMR (600 MHz, CDCl3) (β-regioisomer) δ 7.44−7.34 (m, 5 H),
7.33−7.27 (m, 1 H), 7.00−6.95 (m, 3 H), 6.49 (s, 1 H), 2.92 (ddt, J =
15.3, 12.3, 3.1 Hz, 1 H), 2.44 (s, 3 H), 1.94−1.61 (m, 6 H), 1.49−1.19
(m, 4 H); 13C NMR (150 MHz, CDCl3) (β-regioisomer) δ 157.6,
139.7, 139.6, 138.8, 131.4, 129.3, 128.7, 127.9, 126.6, 123.3, 117.0,
113.2, 39.7, 31.4, 26.9, 26.1, 21.4; MS (EI, m/z) 291 (M+, 100), 249
(2), 185 (28), 155 (11), 141 (47); HRMS (EI, m/z) calcd for
C21H24O (M+) 292.1827, found 292.1826.
Data for compound 3ha: 91 mg, 81% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.52−7.47 (m, 2 H), 7.42−7.26 (m, 8 H), 6.57
(s, 1 H), 4.05 (q, J = 7.1 Hz, 2 H), 1.41 (t, J = 7.1 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 145.1, 140.7, 137.8, 129.8, 128.3, 128.2, 127.8,
126.3, 126.3, 120.2, 68.9, 15.4; MS (EI, m/z) 225 (14), 224 (M+, 87),
196 (42), 195 (25), 167 (100); HRMS (EI, m/z) calcd for C16H16O
(M+) 224.1201, found 224.1203.
Data for compound 3hb: 95 mg, 80% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.44−7.38 (m, 2 H), 7.34−7.27 (m, 2 H), 7.26−
7.21 (m, 1 H), 7.20−7.02 (m, 4 H), 6.47 (s, 1 H), 3.97 (q, J = 7.1 Hz,
2 H), 2.34 (s, 3 H), 1.33 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz,
CDCl3) δ 144.7, 137.9, 137.8, 136.0, 129.8, 128.9, 128.3, 127.8, 126.3,
120.0, 68.8, 21.1, 15.4; MS (EI, m/z) 238 (M+, 74), 209 (29), 181
(93), 165 (100); HRMS (EI, m/z) calcd for C17H18O (M+) 238.1358,
found 238.1356.
1
Data for compound 3as: 100 mg, 62% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.7 Hz, 2 H), 7.25 (t, J = 7.9
Hz, 1 H), 7.00−6.80 (m, 5 H), 6.72 (s, 1 H), 6.64 (d, J = 16.1 Hz, 1
H), 6.52 (d, J = 16.1 Hz, 1 H), 3.84 (s, 3 H), 2.52 (t, J = 7.5 Hz, 2 H),
2.39 (s, 3 H), 1.62−1.40 (m, 4 H), 0.98 (t, J = 7.2 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 158.5, 157.4, 142.5, 139.8, 130.8, 129.3, 126.9,
125.3, 124.7, 124.4, 123.5, 117.1, 114.0, 113.4, 55.2, 30.6, 23.9, 22.7,
21.4, 14.0; MS (EI, m/z) 322 (M+, 12), 307 (80), 234 (45), 214 (100),
198 (87); HRMS (EI, m/z) calcd for C22H26O2 (M+) 322.1933, found
322.1923.
1
Data for compound 3hf: 108 mg, 84% yield, colorless oil; H
NMR (400 MHz, CDCl3) δ 7.40−7.28 (m, 4 H), 7.27−7.19 (m, 3 H),
7.17−7.12 (m, 2 H), 6.48 (s, 1 H), 3.99 (q, J = 7.1 Hz, 2 H), 1.34 (t, J
= 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 145.3, 139.2, 137.3,
132.0, 129.7, 129.5, 128.3, 128.0, 126.6, 119.2, 69.1, 15.4; MS (EI, m/
z) 260 (18), 258 (M+, 57), 230 (25), 203 (16), 165 (100); HRMS (EI,
m/z) calcd for C16H15ClO (M+) 258.0811, found 258.0814.
Data for compound 3ia: 110 mg, 87% yield, colorless oil; 1H
NMR (600 MHz, CDCl3) δ 7.37−7.32 (m, 2 H), 7.28−7.24 (m, 2 H),
7.23−7.19 (m, 3 H), 6.87−6.83 (m, 2 H), 6.43 (s, 1 H), 3.95 (q, J =
7.1 Hz, 2 H), 3.78 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3 H); 13C NMR (150
MHz, CDCl3) δ 158.0, 144.3, 140.9, 130.9, 130.2, 128.3, 128.1, 126.2,
119.8, 113.3, 68.7, 55.1, 15.4; MS (EI, m/z) 254 (M+, 21), 239 (12),
210 (15), 194 (100), 178 (41); HRMS (EI, m/z) calcd for C17H18O2
(M+) 254.1307, found 254.1306.
1
Data for compound 3ba: 108 mg, 86% yield, colorless oil; H
NMR (600 MHz, CDCl3) δ 7.44 (d, J = 7.8 Hz, 2 H), 7.42−7.37 (m, 4
H), 7.35−7.31 (m, 1 H), 7.15−7.10 (m, 3 H), 6.79 (s, 1 H), 2.73 (t, J
= 7.5 Hz, 2 H), 1.54−1.39 (m, 4 H), 0.96 (t, J = 7.2 Hz, 3 H); 13C
NMR (150 MHz, CDCl3) δ 157.7, 139.1, 138.9, 129.6, 128.4, 126.7,
126.3, 126.0, 122.6, 116.3, 30.3, 26.9, 22.5, 13.9; MS (EI, m/z) 252
(M+, 100), 209 (19), 181 (63), 166 (27), 131 (12); HRMS (EI, m/z)
calcd for C18H20O (M+) 252.1514, found 252.1512.
1
Data for compound 3ca: 125 mg, 88% yield, colorless oil; H
NMR (600 MHz, CDCl3) δ 7.45−7.38 (m, 4 H), 7.34−7.32 (m, 3 H),
7.07−7.02 (m, 2 H), 6.70 (s, 1 H), 2.71 (t, J = 7.6 Hz, 2 H), 1.50−1.37
(m, 4 H), 0.94 (t, J = 7.2 Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ
156.2, 138.4, 129.5, 129.4, 128.5, 126.9, 126.3, 125.1, 117.5, 116.7,
30.2, 26.9, 22.5, 13.9; MS (EI, m/z) 288 (31), 286 (M+, 100), 215
(30), 179 (42), 165 (17); HRMS (EI, m/z) calcd for C18H19ClO (M+)
286.1124, found 286.1125.
Data for compound 3ja: 101 mg, 78% yield, colorless oil, rr = 9:1;
1H NMR (400 MHz, CDCl3) (β-regioisomer) δ 7.42−7.36 (m, 2 H),
7.36−7.27 (m, 5 H), 7.26−7.20 (m, 2 H), 6.53 (s, 1 H), 4.03 (q, J =
7.1 Hz, 2 H), 1.38 (t, J = 7.1 Hz, 3 H); 13C NMR (150 MHz, CDCl3)
(β-regioisomer) δ 145.5, 140.2, 136.2, 131.9, 131.1, 128.4, 128.3,
128.0, 126.5, 119.1, 69.1, 15.4; MS (EI, m/z) 260 (19), 258 (M+, 56),
230 (34), 203 (32), 165 (100); HRMS (EI, m/z) calcd for C16H15ClO
(M+) 258.0811, found 258.0814.
1
Data for compound 3da: 144 mg, 92% yield, colorless oil; H
NMR (600 MHz, CDCl3) δ 7.39−7.32 (m, 4 H), 7.28−7.22 (m, 3 H),
7.21−7.13 (m, 4 H), 6.86 (d, J = 7.5 Hz, 1 H), 6.80−6.76 (m, 2 H),
6.71 (s, 1 H), 2.96 (dd, J = 9.4, 6.8 Hz, 2 H), 2.76 (dd, J = 9.4, 6.8 Hz,
2 H), 2.32 (s, 3 H); 13C NMR (150 MHz, CDCl3) δ 157.5, 142.0,
139.7, 139.6, 138.7, 129.3, 128.5, 128.5, 128.2, 126.8, 126.2, 125.7,
124.5, 123.5, 117.1, 113.4, 34.4, 29.2, 21.4; MS (EI, m/z) 314 (M+,
63), 223 (69), 195 (100), 180 (30), 165 (44); HRMS (EI, m/z) calcd
for C23H22O (M+) 314.1671, found 314.1662.
1
Data for compound 3ka: 126 mg, 88% yield, colorless oil; H
NMR (600 MHz, CDCl3) δ 7.42−7.22 (m, 9 H), 6.73 (s, 1 H), 1.41
(s, 9 H); 13C NMR (150 MHz, CDCl3) δ 141.0, 140.2, 136.6, 133.8,
133.7, 131.1, 128.6, 128.3, 127.9, 126.4, 77.7, 28.2; MS (EI, m/z) 288
(4), 286 (M+, 13), 229 (100), 195 (20), 165 (69); HRMS (EI, m/z)
calcd for C18H19ClO (M+) 286.1124, found 286.1131.
Data for compound 3ea: 77 mg, 65% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.47 (d, J = 8.0 Hz, 2 H), 7.43−7.35 (m, 4 H),
7.34−7.30 (m, 1 H), 7.17−7.10 (m, 3 H), 6.92 (s, 1 H), 6.04−5.90
(m, 1 H), 5.21 (dd, J = 17.1, 1.5 Hz, 1 H), 5.08 (dd, J = 10.1, 1.3 Hz, 1
H), 3.49 (d, J = 6.0 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 157.5,
139.7, 138.7, 135.8, 129.6, 128.4, 126.8, 126.0, 122.8, 122.7, 116.5,
115.5, 31.9; MS (EI, m/z) 236 (M+, 13), 212 (43), 159 (100), 142
(32); HRMS (EI, m/z) calcd for C17H16O (M+) 236.1201, found
236.1201.
Data for compound 3la: 57 mg, 55% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.41−7.31 (m, 5 H), 6.74 (s, 1 H), 4.64 (d, J =
6.1 Hz, 2 H), 2.04 (t, J = 6.2 Hz, 1 H), 1.39 (s, 9 H); 13C NMR (100
MHz, CDCl3) δ 140.7, 138.6, 128.5, 126.2, 125.7, 119.9, 77.6, 59.3,
28.1; MS (EI, m/z) 206 (M+, 9), 182 (20), 150 (31), 132 (100), 119
(58); HRMS (EI, m/z) calcd for C13H18O2 (M+) 206.1307, found
206.1308.
1
Data for compound 3ma: 61 mg, 62% yield, colorless oil; H
Data for compound 3fa: 80 mg, 64% yield, colorless oil; 1H NMR
(400 MHz, CDCl3) δ 7.46−7.41 (m, 2 H), 7.39−7.33 (m, 2 H), 7.31−
7.22 (m, 2 H), 6.96−6.86 (m, 4 H), 5.99−5.87 (m, 1 H), 5.17 (dd, J =
17.1, 1.7 Hz, 1 H), 5.04 (dd, J = 10.1, 1.6 Hz, 1 H), 3.44 (d, J = 6.1 Hz,
2 H), 2.38 (s, 3 H); 13C NMR (150 MHz, CDCl3) δ 157.5, 139.8,
138.8, 135.9, 129.4, 128.4, 126.7, 126.0, 125.4, 123.6, 122.5, 117.2,
115.4, 113.4, 31.9, 21.4; MS (EI, m/z) 250 (M+, 32), 226 (64), 172
NMR (600 MHz, CDCl3) δ 7.44−7.34 (m, 6 H), 7.29−7.22 (m, 2 H),
7.19−7.11 (m, 3 H), 6.42 (d, J = 12.4 Hz, 1 H); 13C NMR (150 MHz,
CDCl3) δ 157.1, 143.4, 135.1, 129.7, 128.7, 126.6, 125.6, 123.2, 116.9,
113.6; MS (EI, m/z) 196 (M+, 100), 119 (87), 103 (36), 101 (31);
HRMS (EI, m/z) calcd for C14H12O (M+) 196.0888, found 196.0888.
General Procedure for the Synthesis of Diarylacetaldehydes
via TFA-Promoted Hydrolysis of β,β-Disubstituted Vinyl
E
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Ethers. To a solution of 3ha (112 mg, 0.5 mmol) in 2 mL of CH2Cl2
was added CF3CO2H (285 mg, 2.5 mmol). After being stirred at room
temperature for 1 h, the reaction mixture was quenched with saturated
NaHCO3 solution, extracted with CH2Cl2, washed with brine, and
dried. Concentration gave 83 mg (85% yield) of compound 4a59 as a
pale yellow oil: 1H NMR (400 MHz, CDCl3) δ 9.99 (d, J = 2.4 Hz, 1
H), 7.41 (t, J = 7.4 Hz, 4 H), 7.35 (d, J = 7.2 Hz, 2 H), 7.26 (d, J = 7.2
Hz, 4 H), 4.93 (d, J = 2.1 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ
198.6, 136.3, 129.1, 129.0, 127.6, 64.1; MS (EI, m/z) 196 (M+, 11),
167 (100), 152 (63), 139 (12), 115 (13).
(14) Davies, P. W.; Cremonesi, A.; Dumitrescu, L. Angew. Chem., Int.
Ed. 2011, 50, 8931.
(15) Komine, Y.; Tanaka, K. Org. Lett. 2010, 12, 1312.
(16) Mejuch, T.; Botoshansky, M.; Marek, I. Org. Lett. 2011, 13,
3604.
(17) Tran, V.; Minehan, T. G. Org. Lett. 2011, 13, 6588.
(18) Tran, V.; Minehan, T. G. Org. Lett. 2012, 14, 6100.
(19) Verrier, C.; Carret, S.; Poisson, J.-F. Org. Lett. 2012, 14, 5122.
(20) Moyano, A.; Charbonnier, F.; Greene, A. E. J. Org. Chem. 1987,
52, 2919.
(21) Levin, A.; Basheer, A.; Marek, I. Synlett 2010, 329.
(22) Qi, X.; Ready, J. M. Angew. Chem., Int. Ed. 2008, 47, 7068.
(23) Hashmi, A. S. K.; Rudolph, M.; Huck, J.; Frey, W.; Bats, J. W.;
Hamzic, M. Angew. Chem., Int. Ed. 2009, 48, 5848.
́
(24) Yamasaki, R.; Terashima, N.; Sotome, I.; Komagawa, S.; Saito, S.
J. Org. Chem. 2010, 75, 480.
(25) Miyauchi, Y.; Noguchi, K.; Tanaka, K. Org. Lett. 2012, 14, 5856.
(26) Miyauchi, Y.; Kobayashi, M.; Tanaka, K. Angew. Chem., Int. Ed.
2011, 50, 10922.
(27) Lemoine, P.; Daoust, B. Tetrahedron Lett. 2008, 49, 6175.
(28) Hanna, R.; Daoust, B. Tetrahedron 2011, 67, 92.
(29) Chen, X.; Kong, W.; Cai, H.; Kong, L.; Zhu, G. Chem. Commun.
2011, 47, 2164.
Data for compound 4b:60 94 mg, 89% yield, pale yellow oil; H
1
NMR (400 MHz, CDCl3) δ 9.96 (d, J = 2.5 Hz, 1 H), 7.42−7.36 (m, 2
H), 7.35−7.32 (m, 1 H), 7.27−7.19 (m, 4 H), 7.13 (d, J = 8.1 Hz, 2
H), 4.88 (d, J = 2.2 Hz, 1 H), 2.37 (s, 3 H); 13C NMR (100 MHz,
CDCl3) δ 198.8, 137.4, 136.5, 133.2, 129.7, 129.1, 129.0, 128.9, 127.5,
63.7, 21.1; MS (EI, m/z) 210 (M+, 3), 181 (100), 165 (43), 152 (6).
1
Data for compound 4c: 112 mg, 97% yield, pale yellow oil; H
NMR (400 MHz, CDCl3) δ 9.95 (d, J = 2.2 Hz, 1 H), 7.46−7.33 (m, 5
H), 7.26−7.21 (m, 2 H), 7.21−7.15 (d, J = 8.4 Hz, 2 H), 4.91 (d, J =
1.9 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 198.0, 135.7, 134.8,
133.6, 130.4, 129.2, 129.1, 129.0, 127.8, 63.3; MS (EI, m/z) 232 (2),
230 (M+, 6), 201 (100), 165 (78), 139 (10); HRMS (EI, m/z) calcd
for C14H11ClO (M+) 230.0498, found 230.0493.
(30) Chen, D.; Cao, Y.; Yuan, Z.; Cai, H.; Zheng, R.; Kong, L.; Zhu,
G. J. Org. Chem. 2011, 76, 4071.
(31) Chen, X.; Chen, D.; Lu, Z.; Kong, L.; Zhu, G. J. Org. Chem.
2011, 76, 6338.
(32) Lu, Z.; Kong, W.; Yuan, Z.; Zhao, X.; Zhu, G. J. Org. Chem.
ASSOCIATED CONTENT
* Supporting Information
Spectroscopic data of products 3 and 4. This material is
■
S
available free of charge via the Internet at http://pubs.acs.org.
2011, 76, 8524.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gangguo@zjnu.cn.
Notes
(33) Lu, Z.; Xu, X.; Yang, Z.; Kong, L.; Zhu, G. Tetrahedron Lett.
2012, 53, 3433.
(34) Lu, Z.; Cui, W.; Xia, S.; Bai, Y.; Luo, F.; Zhu, G. J. Org. Chem.
■
2012, 77, 9871.
(35) Zhu, G.; Chen, D.; Wang, Y.; Zheng, R. Chem. Commun. 2012,
48, 5796.
The authors declare no competing financial interest.
(36) Cai, H.; Yuan, Z.; Zhu, W.; Zhu, G. Chem. Commun. 2011, 47,
8682.
ACKNOWLEDGMENTS
■
This work was supported by the Natural Science Foundation of
Zhejiang Province (Grant LR12B02001), National Natural
Science Foundation of China (Grants 20902084 and
21172199), and Open Research Fund of the Key Laboratory
of the Ministry of Education for Advanced Catalysis Materials
(Grant ZJHX201310).
(37) Bai, Y.; Yin, J.; Kong, W.; Mao, M.; Zhu, G. Chem. Commun.
2013, 49, 7650.
(38) Satoh, M.; Miyaura, N.; Suzuki, A. Synthesis 1987, 373.
(39) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(40) Gridnev, I. D.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58,
5351.
(41) Miyaura, N.; Maeda, K.; Suginome, H.; Suzuki, A. J. Org. Chem.
1982, 47, 2117.
REFERENCES
■
(42) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992, 57,
3482.
(43) Brown, H. C.; Campbell, J. B., Jr. Aldrichimica Acta 1981, 14, 3.
(44) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957.
(45) Trost, B. M.; Ball, Z. T. Synthesis 2005, 853 and references
therein.
(46) Gridnev, I. D.; Miyaura, N.; Suzuki, A. Organometallics 1993, 12,
589.
(47) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000,
122, 4990.
(48) Hoffmann, R. W.; Kruger, J.; Bruckner, D. New J. Chem. 2001,
(1) Dehi, J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005, 973.
(2) Nordmann, G.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125,
4978.
(3) Willis, M. C.; Taylor, D.; Gillmore, A. T. Chem. Commun. 2003,
2222.
(4) Alcazar, E.; Pletcher, J. M.; McDonald, F. E. Org. Lett. 2004, 6,
3877.
(5) Shade, R. E.; Hyde, A. M.; Olsen, J.-C.; Merlic, C. A. J. Am. Chem.
Soc. 2010, 132, 1202.
(6) Winternheimer, D. J.; Merlic, C. A. Org. Lett. 2010, 12, 2508.
(7) DeBergh, J. R.; Spivey, K. M.; Ready, J. M. J. Am. Chem. Soc.
2008, 130, 7828.
(8) Song, Z.; Kui, L.; Sun, X.; Li, L. Org. Lett. 2011, 13, 1440.
(9) Winternheimer, D. J.; Shade, R. E.; Merlic, C. A. Synthesis 2010,
2497 and references therein.
̈
̈
25, 102.
(49) Lipshutz, B. H.; Bosk
Ed. 2008, 47, 10183.
̌
ovic,
́
Z. V.; Aue, D. H. Angew. Chem., Int.
(50) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Chem.Eur. J. 2012,
18, 4179.
(10) Whelligan, D. K.; Thomson, D. W.; Taylor, D.; Hoelder, S. J.
Org. Chem. 2010, 75, 11.
(11) Shindo, M.; Kita, T.; Kumagai, T.; Matsumoto, K.; Shishido, K.
J. Am. Chem. Soc. 2006, 128, 1062.
(12) Sosa, J. R.; Tudjarian, A. A.; Minehan, T. G. Org. Lett. 2008, 10,
5091.
(51) Gunanathan, C.; Holscher, M.; Pan, F.; Leitner, W. J. Am. Chem.
Soc. 2012, 134, 14349.
(52) Haberberger, M.; Enthaler, S. Chem.Asian J. 2013, 8, 50.
(53) Pereira, S.; Srebnik, M. Organometallics 1995, 14, 3127.
(54) Shirakawa, K.; Arase, A.; Hoshi, M. Synthesis 2004, 1814.
(55) Jouvin, K.; Bayle, A.; Legrand, F.; Evano, G. Org. Lett. 2012, 14,
1652.
̈
(13) Mak, X. Y.; Ciccolini, R. P.; Robinson, J. M.; Tester, J. W.;
Danheiser, R. L. J. Org. Chem. 2009, 74, 9381.
F
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The Journal of Organic Chemistry
Article
(56) The following control experiments indicated that the hydro-
boration of ynol ethers in this paper should be an uncatalyzed reaction.
For details on the hydroboration product IIA, see the Supporting
Information.
(57) Selected NOE data are provided in the Supporting Information.
Although we cannot obtain all NOE data of the products due to the
peak overlap in the NMR spectra in some cases, the stereochemistry of
other products should be reasonably deduced.
(58) Tanaka, R.; Miller, S. I. Tetrahedron Lett. 1971, 12, 1753.
(59) Lessi, M.; Masini, T.; Nucara, L.; Bellina, F.; Rossi, R. Adv.
Synth. Catal. 2011, 353, 501.
́
(60) Barluenga, J.; Escribano, M.; Moriel, P.; Aznar, F.; Valdes, C.
Chem.Eur. J. 2009, 15, 13291.
(61) Nilsson, P.; Larhed, M.; Hallberg, A. J. Am. Chem. Soc. 2001,
123, 8217.
G
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