Synthesis of γ-Sulfur-Substituted Ketones via Rh(II)/Sc(III) a Cocatalyzed Three-Component Reaction of Diazo Compounds with Thiophenols and Enones

Article abstract of DOI:10.1021/acs.joc.7b03074

A facile method for the synthesis of γ-sulfur-substituted ketones is developed via a Rh(II)/Sc(III) cocatalyzed three-component reaction of diazo compounds with thiophenols and enones. With this method, different γ-sulfur-substituted ketones were obtained

Full text of DOI:10.1021/acs.joc.7b03074

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Synthesis of #-Sulfur-Substituted Ketones via Rh(II)/Sc(III) Cocatalyzed Three-
Component Reaction of Diazo Compounds with Thiophenols and Enones
Guolan Xiao, Chaoqun Ma, Xiang Wu, Dong Xing, and Wenhao Hu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03074 • Publication Date (Web): 22 Mar 2018
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Synthesis of γ-Sulfur-Substituted Ketones via Rh(II)/Sc(III)
Cocatalyzed Three-Component Reaction of Diazo Compounds
with Thiophenols and Enones
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†
†
†
*,†
*,†,‡
Guolan Xiao, Chaoqun Ma, Xiang Wu, Dong Xing, and Wenhao Hu
†
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering,
East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
‡
School of Pharmaceutical Sciences, Sun Yatꢀsen University, Guangzhou, China
Abstract: A facile method for the synthesis of γꢀsulfurꢀsubstituted ketones is developed via a Rh(II)/Sc(III)
cocatalyzed threeꢀcomponent reaction of diazo compounds with thiophenols and enones. With this method,
different γꢀsulfurꢀsubstituted ketones were obtained in moderate to high yields with good diastereoselectivities.
Sulfurꢀcontaining compounds are widely existed in a large number of synthetic drugs, bioactive molecules and
1
2
natural products. For example, all of the top 10 bestꢀselling drugs in 2012 were sulfurꢀcontaining compounds.
Among different types of sulfurꢀcontaining molecules, γꢀsulfur substituted carbonyl compounds have drawn
considerable synthetic attention owing to their roles in various biological systems. For example, methionine, one
of the amino acids that contains γꢀsulfurꢀsubstituted carbonyl moiety, plays an important role both in protein
3
structure and in metabolism. The traditional ways for the synthesis of γꢀsulfur carbonyl compounds include the
conjugated addition of αꢀlithiosulphides or αꢀsulfur substituted alkylstannanes to α,βꢀunsaturated ketones
4
,5
(Scheme 1, part a), which require either the use of stoichiometric amount of organolithium reagents under harsh
reaction conditions or the use of highly toxic organotin reagents. As a result, it would be highly desirable to
develop more efficient and straightforward approaches to build γꢀsulfur carbonyl compounds under mild reaction
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conditions.
(a) Traditional methods for the synthesis of -sulfur substituted carbonyl compounds
R2
R2
1
R3
O
R S
1
R3
R S
O
+
R4
R5
0
1
2
3
4
5
6
7
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9
0
1
2
3
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0
1
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0
1
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8
9
0
1
2
3
4
5
6
7
8
9
0
R4
R5
M
M = Li, Sn
(
b) Our previously developed electrophilic trapping approach of active sulfonium ylide with imines
Ar1
Ar1
Rh(II)
chiral PPA
NH
N2
1
N
1
R SH
+
+
R S
R2 CO2R
2
R2
CO R3
2
Ar
Ar2
3
(
c) This work: construction of -sulfur substituted ketones by trapping of sulfonium ylide with enones
1
Ar1
R SH
+
1
1
Rh(II)
R HS
ORhLn
OR3
R S
CO Me
2
Sc(III)
O
R2
O
R2
R3
N2
R2
R3
Ar1
CO Me
2
Scheme 1 Synthesis of γꢀSulfurꢀSubstituted Ketones via the Trapping of Sulfonium Ylide with Enones.
Over the past ten years, our research group has been devoted to the development of multicomponent reactions
MCRs) via electrophilic trapping of in situ generated active intermediates from metal carbenes, therefore establish
(
6
ꢀ9
a powerful strategy for the rapid construction of complex molecules. Within this context, we have recently
developed the first example of MCR via electrophilic trapping of sulfonium ylide intermediates with imines by a
Rh(II)/chiral phosphoric acid (CPA) cocatalyzed reaction system, to generate a series of αꢀsulfurꢀβꢀamino esters in
8
good stereoselectivities (Scheme 1, part b). Based on this electrophilic trapping strategy, we envisioned whether
α,βꢀunsaturated ketones could also be used as electrophiles to undergo a Michaelꢀtype trapping of the in situ
generated sulfonium ylide intermediates, therefore established a rapid way for the synthesis of γꢀsulfur substituted
ketones. However, owing to the much lower electrophilic ability of α,βꢀunsaturated ketones as Michael acceptors,
the proposed electrophilic interception might be difficult to realize and appropriate activation of this kind of
electrophile is required. Herein, we reported our successful development of a Rh(II)/Sc(III) cocatalyzed system
that allows an efficient threeꢀcomponent reaction of diazo compounds, thiophenols and enones for the efficient
construction of γꢀsulfur substituted ketones.
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a
Table 1. Catalyst Screening and Optimization of Reaction Conditions
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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5
5
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0
1
2
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8
9
0
1
2
3
4
5
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8
9
0
1
2
3
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5
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2
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0
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0
b
c
entry
solvent
temp
rt
additive
ꢀꢀ
yield of 4a (%)
dr (syn : anti)
1
2
3
4
5
6
7
8
CH
2
Cl
2
2
2
2
2
< 5
< 5
20
ꢀꢀ
CH Cl
rt
Cu((OTf)2
ꢀꢀ
2
CH
CH
CH
2
2
2
Cl
Cl
Cl
rt
Zn(OTf)
2
87:13
73:27
87:13
84:16
86:14
66:34
ꢀꢀ
rt
Yb(OTf)
3
15
rt
Sc(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
3
25
DCE
rt
3
15
CHCl
3
rt
3
3
11
Toluene
THF
rt
11
9
rt
Sc(OTf)3
< 5
74
d
1
0
CH
CH
2
2
Cl
2
2
2
2
rt
Sc(OTf)
Sc(OTf)
ꢀꢀ
3
80:20
72:28
ꢀꢀ
d
o
11
Cl
40 C
3
77
o
12
CH Cl
40 C
< 5
< 5
2
e
o
1
3
CH
2
Cl
40 C
Sc(OTf)
3
ꢀꢀ
a
b
c
Reaction conditions: 1:2:3 = 1.5:1.5:1.0. Yield of isolated product after purification by column chromatography. syn/anti determined by
1
d
e
2 4
H NMR spectroscopy of the crude reaction mixture. Using 3 equiv. of 1a and 2a. Without the addition of Rh (OAc) .
We started our exploration by choosing 4ꢀmethylbenzenethiol (1a), methyl phenyl diazoacetate (2a) and chalcone
3a) as the model substrates. With Rh (OAc) alone as the catalyst, the S–H insertion product between 1a and 2a
(
2
4
was obtained as the major product and the desired threeꢀcomponent product was not observed (Table 1, entry 1).
This result indicates that chalcone 3a is not electrophilic enough to intercept the in situ formed sulfonium ylide
intermediate. We envisioned that an appropriate Lewis acid coꢀcatalyst might be able to activate 3a toward the
proposed electrophilic trapping process. With this thought in mind, we screened a number of Lewis acid
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coꢀcatalysts. When Cu(OTf)
2
was employed as the coꢀcatalyst, the desired threeꢀcomponent product 4a was not
observed (Table 1, entry 2), however, the use of Zn(OTf)
facilitate the desired threeꢀcomponent reaction and Sc(OTf) shows a superior efficiency, giving 4a in 25% yield
with 87:13 dr (Table 1, entries 3–5). Changing the solvent from CH Cl to other halogenated solvents such as
2 3 3
, Yb(OTf) or Sc(OTf) as the coꢀcatalyst indeed
3
2
2
0
1
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0
1
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3
4
5
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9
0
1
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0
1
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0
1
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3
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5
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0
1
3
,2ꢀdichloroethane (DCE) or CHCl also gave 4a but with even lower yields (Table 1, entries 6 and 7). The use of
toluene or THF as the solvent failed to improve the efficiency of this transformation (Table 1, entries 8 and 9).
When 3 equivalents of 1a and 2a was employed, the desired threeꢀcomponent product 4a was obtained in a 74%
o
isolated yield with 80:20 dr (Table 1, entry 10). Raising the reaction temperature to 40 C gave a slightly improved
yield of 4a but with a decreased dr ratio (Table 1, entry 11). Both catalysts are indispensable for the current
transformation as in the absence of Rh (OAc) and/or Sc(OTf) , the desired threeꢀcomponent product was not
2
4
3
observed (Table 1, entries 12 and 13). For all entries, the aldolꢀtype 1,2ꢀaddition products were not observed.
a
Table 2 ThreeꢀComponent Reaction of Thiophenols with Various Diazo Compounds and Enones
1
2
3
b
c
entry
1
Ar
R /R
Ph/Ph (3a)
pꢀNO /Ph (3b)
pꢀCH
pꢀBrC
4
yield (%)
74
dr (syn : anti)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
4a
4b
4c
4d
4e
4f
80:20
82:18
70:30
86:14
87:13
84:16
80:20
73:27
61:39
2
C
6
H
4
72
3
C
6
H
4
/Ph (3c)
73
6
H
4
/Ph (3d)
77
Me/Ph (3e)
65
COOMe/Ph (3f)
51
Ph/pꢀMeOC
6
H
4
(3g)
4g
4h
4i
79
Ph/pꢀClC H (3h)
79
6
4
Ph/pꢀNO
2
C
6
H
4
(3i)
77
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1
0
1a
1a
1b
1c
1d
1a
1a
1a
1a
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
mꢀClC H /Me (3j)
4j
68
45
62
61
77
81
75
69
79
93:7
6
4
11
12
Me/Me (3k)
Ph/Ph (3a)
Ph/Ph (3a)
Ph/Ph (3a)
Ph/Ph (3a)
Ph/Ph (3a)
Ph/Ph (3a)
Ph/Ph (3a)
4k
4l
>95:5
82:18
88:12
83:17
83:17
86:14
82:18
79:21
1
1
1
1
3
4
5
6
4m
4n
4o
4p
4q
4r
1
1
1
1
1
1
1
1
1
1
2
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2
2
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2
2
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2
2
3
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4
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5
5
5
6
0
1
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9
0
1
2
3
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0
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0
1
2
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9
0
1
2
3
4
5
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7
8
9
0
pꢀCF
3
C
6
H
4
(2b)
(2c)
mꢀBrC
6
H
4
17
18
pꢀMeOC H (2d)
6 4
3,4,5ꢀ(MeO)
3
C
6
H
2
(2e)
a
b
c
1
Reaction conditions: 1:2:3 = 3.0:3.0:1.0. Combined isolated yield of 4 (syn + anti). syn/anti determined by H NMR spectroscopy of
the crude reaction mixture.
With the optimal reaction conditions in hand, we then proceeded to investigate the substrate scope of this
threeꢀcomponent reaction. Different substituted enones were first tested. Both electronꢀdeficient and electronꢀrich
substituents on the aryl ring of the alkenyl terminal of the enones all gave the desired threeꢀcomponent products in
high yields with good diastereoselectivities (Table 2, entries 1–4). When methyl or ester group were present at
βꢀposition of the unsaturated ketone substrate, the reaction also proceeded albeit with slightly decreased yields
(
Table 2, entries 5–6). Different substituted aryl enones also gave the desired threeꢀcomponent products in high
efficiency (Table 2, entries 7–9). Methyl enone 3j was also a suitable substrate, yielding corresponding
threeꢀcomponent product 4j in 68% yield and with high diastereoselectivity (Table 2, entry 10). The alkyl
unsaturated ketone 3k gave the desired product in a relative low yield, however with an excellent
diastereoselectivity (Table 2, entry 11). Different paraꢀsubstituted thiophenols were then tested, and the desired
threeꢀcomponent products were obtained in good yields with high diastereoselectivities (Table 2, entries 12–14).
Finally, different substituted aryl diazoacetates were used as the carbene sources, and all of them could give the
desired threeꢀcomponent products in high efficiency regardless of the electronical characters (Table 2, entries 15–
1
8). The relative stereochemistry of products was assigned as syn by analogy with synꢀ4n as determined by
10
singleꢀcrystal Xꢀray diffraction (Figure 1).
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Figure 1 Xꢀray crystal structure of synꢀ4n, ellipsoids are drawn at the 50% probability level.
To gain some insights into the possible reaction pathway, the reaction between the S–H insertion product 5a and
chalcone 3a was conducted. However, under standard reaction conditions, the desired threeꢀcomponent product 4a
was not observed (eq 1). This result indicated that this threeꢀcomponent reaction most like proceed through an in
situ Michaelꢀtype sulfonium ylide trapping pathway instead of a stepwise S–H insertion/Michael addition pathway.
This transformation is proposed to proceed through a sulfonium ylide intermediate, which was in situ generated
from metal carbene and thiophenol. The in situ generated protic sulfonium ylide was then immediately trapped by
the tethered electrophilic enone unit that was activated by Sc(III), to give the desired threeꢀcomponent product via
a Michaelꢀtype addition (Scheme 2).
Scheme 2 Proposed Reaction Mechanism of the Title Reaction.
In summary, we have developed a Rh(II)/Sc(III) cocatalyzed threeꢀcomponent reaction of diazo compounds with
thiophenols and enones. With this strategy, different γꢀsulfur substituted ketones were synthesized in moderate to
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high yields with good diastereoselectivities. Control experiments indicate that this transformation may proceed
through an electrophilic trapping of the in situ generated sulfonium ylide with Sc(III)ꢀactivated enones.
EXPERIMENTAL SECTION
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
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5
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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0
1
2
3
4
5
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9
0
1
2
3
4
5
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9
0
1
13
General Information: All H NMR (400 MHz) and C NMR (100 MHz) spectra were recorded on Brucker
1
spectrometers in CDCl
3
. Tetramethylsilane (TMS) served as an internal standard (δ = 0) for H NMR, and CDCl
3
13
was used as internal standard (δ = 77.0) for C NMR. Chemical shifts are reported in parts per million as follows:
chemical shift, multiplicity (s =singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad). Infrared (IR)
ꢀ
1
spectra were recorded on a NICOLET NEXUS 670 FTꢀIR spectrometer, νmax in cm . Highꢀresolution mass
spectrometry (HRMS) was performed on IonSpec FTꢀICR or Waters Micromass QꢀTOF micro Synapt High
Definition Mass Spectrometer. Melting points were uncorrected. Single crystal Xꢀray diffraction data (synꢀ4n)
were recorded on BrukerꢀAXS SMART APEX II single crystal Xꢀray diffractometer.
2 2
Materials: CH Cl was distilled over calcium hydride. Chalcones 3aꢀ3d, 3g-3i were prepared according to the
11
12
literature procedure. 3j was synthesized following another literature procedure. Aryl diazoacetates 2aꢀ2e were
prepared by the treatment of corresponding arylacetate with pꢀacetamidobenzenesulfonyl azide (pꢀABSA) in the
13
presence of DBU following the general procedure. 4Å molecular sieve was dried in a Muffle furnace at 250℃
over 5 hours. All reactions were carried out under argon atmosphere in a wellꢀdried glassware.
General Experimental Procedure for the Synthesis of Product 4: A suspension of Rh
2 4
(OAc) (2 mol %),
Sc(OTf) (10 mol %), Chalcones 3 (0.20 mmol, 1.0 eq) and 4Å molecular sieve (0.1 g) was stirred in 2.0 mL of
3
CH
2
Cl
2
at room temperature, and then a mixture of the diazo compounds 2 (0.60 mmol, 3.0 eq) and thiols 1 (0.60
Cl was introduced to the suspension for 3 h via a syringe pump. After the addition
mmol, 3.0 eq) in 1.0 mL CH
2
2
completed, the reaction mixture was continued stirred at the same temperature until the diazo compound
decomposed completely. The reaction mixture was filtered and the filtrate was concentrated to give a residue
1
which was subjected to H NMR spectroscopy analysis for the determination of diastereoselectivity. Purification of
the crude products by flash chromatography on silica gel (eluent: EtOAc/light petroleum ether = 1/50~1/20)
afforded pure products 4.
methyl 5-oxo-2,3,5-triphenyl-2-(p-tolylthio)pentanoate (syn-4a). White solid (57 mg, 59% yield); mp 120−122 °C;
1
H NMR (400 MHz, CDCl ) δ 7.83 – 7.77 (m, 2H), 7.50 – 7.45 (m, 1H), 7.39 – 7.34 (m, 2H), 7.27 – 7.08 (m, 10H),
3
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3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
.02 – 6.97 (m, 4H), 4.62 (dd, J = 11.0, 2.2 Hz, 1H), 3.90 (dd, J = 17.6, 2.0 Hz, 1H), 3.71 – 3.59 (m, 4H), 2.29 (s,
1
3
3H); C NMR (100 MHz, CDCl
3
) δ 197.8, 171.4, 139.6, 139.0, 137.4, 137.2, 136.6, 132.9, 130.6, 129.5, 129.4,
−1
128.5, 128.0, 127.7, 127.6, 127.5, 127.1, 69.9, 52.1, 46.9, 41.5, 21.3; IR ν (cm ) 3064, 3032, 2949, 2918, 1711,
1
687, 1597, 1492, 1448, 1431, 1348, 1289, 1221, 1003, 807, 747, 703, 586, 502; HRMSꢀESI: calcd. for
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
C
31
H
28
O
3
NaS [M + Na] : 503.1657, found: 503.1667.
methyl 3-(4-nitrophenyl)-5-oxo-2,5-diphenyl-2-(p-tolylthio)pentanoate (syn-4b). White solid (62 mg, 59% yield);
1
mp 61−63 °C; H NMR (400 MHz, CDCl
3
) δ 7.93 – 7.88 (m, 2H), 7.84 – 7.78 (m, 2H), 7.54 – 7.48 (m, 1H), 7.43 –
7.36 (m, 2H), 7.35 – 7.28 (m, 3H), 7.26 – 7.17 (m, 4H), 7.11 – 7.03 (m, 4H), 4.61 (dd, J = 11.6, 2.0 Hz, 1H), 4.19
13
(
dd, J = 17.8, 1.8 Hz, 1H), 3.69 – 3.52 (m, 4H), 2.33 (s, 3H); C NMR (100 MHz, CDCl ) δ 197.2, 170.9, 147.2,
3
1
4
1
46.8, 140.4, 136.7, 136.6, 136.4, 133.3, 131.8, 129.8, 129.4, 128.7, 128.3, 127.9, 127.8, 126.8, 122.3, 69.0, 52.3,
−1
6.5, 41.3, 21.4; IR ν (cm ) 3060, 3025, 2949, 2921, 1728, 1685, 1597, 1519, 1491, 1447, 1346, 1282, 1228, 1181,
+
110, 1002, 857, 812, 779, 709, 700, 691, 507; HRMSꢀESI: calcd. for C31
H27NO
5
NaS [M + Na] : 548.1508, found:
548.1524.
methyl 5-oxo-2,5-diphenyl-3-(p-tolyl)-2-(p-tolylthio)pentanoate (syn-4c). White solid (51 mg, 51% yield); mp
1
1
7
46−148 °C; H NMR (400 MHz, CDCl ) δ 7.82 – 7.78 (m, 2H), 7.50 – 7.45 (m, 1H), 7.40 – 7.33 (m, 2H), 7.26 –
3
.16 (m, 5H), 7.15 – 7.08 (m, 2H), 7.01 – 6.96 (m, 2H), 6.95 – 6.87 (m, 4H), 4.60 (dd, J = 11.0, 2.2 Hz, 1H), 3.84
13
(
dd, J = 17.6, 2.0 Hz, 1H), 3.70 – 3.58 (m, 4H), 2.28 (s, 3H), 2.23 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 197.9,
171.5, 139.5, 137.5, 137.2, 136.6, 135.9, 132.9, 130.4, 129.5, 129.3, 128.5, 128.3, 128.0, 127.8, 127.6, 127.5, 70.1,
−
1
52.1, 46.5, 41.6, 21.3, 21.1; IR ν (cm ) 3051, 3023, 2949, 2920, 1729, 1676, 1597, 1492, 1448, 1361, 1298, 1231,
+
1
012, 814, 736, 693, 591; HRMSꢀESI: calcd. for C32
H
30
O
3
NaS [M + Na] : 517.1813, found: 517.1808.
methyl 3-(4-bromophenyl)-5-oxo-2,5-diphenyl-2-(p-tolylthio)pentanoate (syn-4d). White solid (74 mg, 66% yield);
1
mp 126−128 °C; H NMR (400 MHz, CDCl
3
) δ 7.84 – 7.76 (m, 2H), 7.54 – 7.46 (m, 1H), 7.43 – 7.35 (m, 2H),
7.31 – 7.26 (m, 3H), 7.23 – 7.13 (m, 6H), 7.08 – 7.00 (m, 2H), 6.84 – 6.76 (m, 2H), 4.52 (dd, J = 11.3, 2.2 Hz, 1H),
1
3
4.00 (dd, J = 17.8, 2.1 Hz, 1H), 3.63 (s, 3H), 3.55 (dd, J = 17.8, 11.4 Hz, 1H), 2.31 (s, 3H); C NMR (100 MHz,
CDCl ) δ 197.6, 171.1, 140.0, 138.1, 137.0, 136.8, 136.6, 133.1, 132.5, 130.5, 129.6, 128.6, 128.0, 127.6, 127.3,
3
−
1
1
1
21.2, 69.4, 52.2, 46.2, 41.2, 21.4; IR ν (cm ) 3058, 3030, 2948, 2921, 1728, 1686, 1596, 1580, 1489, 1447, 1432,
356, 1283, 1227, 1181, 1076, 1010, 812, 752, 722, 700, 691, 506; HRMSꢀESI: calcd. for C H BrO NaS [M +
31
27
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+
Na] : 581.0762, found: 581.0734.
1
methyl 3-methyl-5-oxo-2,5-diphenyl-2-(p-tolylthio)pentanoate (syn-4e). Colorless sticky oil (47 mg, 57% yield); H
NMR (400 MHz, CDCl ) δ 7.87 (d, J = 7.8 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.31 – 7.18
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
m, 5H), 7.10 (d, J = 7.9 Hz, 2H), 7.02 (d, J = 7.9 Hz, 2H), 3.74 (s, 3H), 3.53 (d, J = 17.2 Hz, 1H), 7.36 – 7.24 (m,
13
1
1
H), 2.73 (dd, J = 17.5, 10.5 Hz, 1H), 2.31 (s, 3H), 1.10 (d, J = 6.5 Hz, 3H). C NMR (100 MHz, CDCl
3
) δ 199.0,
71.8, 139.7, 137.5, 137.4, 136.9, 133.0, 129.4, 128.8, 128.5, 128.0, 127.7, 127.4, 127.2, 70.0, 52.2, 42.2, 34.5,
−
1
21.3, 17.3. IR ν (cm ) 2953, 2924, 2853, 1728, 1686, 1597, 1492, 1460, 1448, 1377, 1359, 1281, 1226, 1180,
+
1019, 1003, 810, 754, 691; HRMSꢀESI: calcd. for C26
H
26
O
3
NaS [M + Na] : 441.1500, found: 441.1494.
dimethyl 3-(2-oxo-2-phenylethyl)-2-phenyl-2-(p-tolylthio)succinate (syn-4f). Colorless sticky oil (40 mg, 43%
1
yield); H NMR (400 MHz, CDCl
3
) δ 7.87 (d, J = 7.6 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.42 (d, J = 7.7 Hz, 2H),
7
.24 – 7.17 (m, 3H), 77.14 – 7.05 (m, 4H), 7.00 (d, J = 7.8 Hz, 2H), 4.32 (d, J = 10.0 Hz, 1H), 3.84 (s, 3H), 3.71 –
1
3
3.54 (m, 4H), 3.40 (d, J = 18.1 Hz, 1H), 2.30 (s, 3H). C NMR (100 MHz, CDCl ) δ 197.5, 173.1, 171.4, 139.9,
3
137.4, 137.0, 136.5, 133.3, 129.4, 128.6, 128.2, 128.1, 128.0, 127.7, 126.6, 66.3, 52.7, 52.2, 46.6, 38.9, 21.3. IR ν
−
1
(
cm ) 3058, 3024, 2951, 2924, 2855, 1735, 1687, 1597, 1492, 1448, 1434, 1361, 1277, 1228, 1171, 1019, 1003,
+
8
12, 756, 692; HRMSꢀESI: calcd. for C H O SNa [M + Na] : 485.1399, found: 485.1371.
2
7
26
5
methyl 5-(4-methoxyphenyl)-5-oxo-2,3-diphenyl-2-(p-tolylthio)pentanoate (syn-4g). White solid (65 mg, 63%
1
yield); mp 50−52 °C; H NMR (400 MHz, CDCl ) δ 7.83 – 7.75 (m, 2H), 7.26 – 7.17 (m, 5H), 7.17 – 7.08 (m, 5H),
3
7.05 – 6.93 (m, 4H), 6.87 – 6.80 (m, 2H), 4.62 (dd, J = 11.1, 2.3 Hz, 1H), 3.87 – 3.76 (m, 4H), 3.68 – 3.55 (m, 4H),
1
3
2
1
2
3
.29 (s, 3H); C NMR (100 MHz, CDCl ) δ 196.3, 171.4, 163.3, 139.6, 139.1, 137.4, 136.6, 130.5, 130.3, 130.2,
−1
29.5, 129.3, 127.7, 127.6, 127.4, 127.1, 113.6, 70.0, 55.4, 52.1, 47.0, 41.0, 21.3; IR ν (cm ) 3058, 3031, 2948,
839, 1727, 1676, 1600, 1576, 1510, 1492, 1445, 1419, 1260, 1228, 1169, 1029, 993, 834, 811, 758, 702, 581, 506;
+
HRMSꢀESI: calcd. for C32
H
30
O
4
NaS [M + Na] : 533.1763, found: 533.1788.
methyl 5-(4-chlorophenyl)-5-oxo-2,3-diphenyl-2-(p-tolylthio)pentanoate (syn-4h). White solid (59 mg, 58% yield);
1
mp 130−132 °C; H NMR (400 MHz, CDCl
3
) δ 7.73 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 7.26 – 7.07 (m,
1
0H), 7.04 – 6.95 (m, 4H), 4.62 – 4.54 (m, 1H), 3.86 (dd, J = 17.5, 1.8 Hz, 1H), 3.68 – 3.53 (m, 4H), 2.30 (s, 3H);
13
C NMR (100 MHz, CDCl ) δ 196.8, 171.4, 139.7, 139.3, 138.8, 137.3, 136.6, 135.5, 130.5, 129.5, 129.4, 128.8,
3
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
−1
1
27.7, 127.6, 127.5, 127.2, 69.8, 52.1, 47.1, 41.5, 21.3; IR ν (cm ) 3030, 2921, 2852, 1732, 1684, 1588, 1492,
+
1399, 1285, 1228, 1091, 1011, 814, 702, 507; HRMSꢀESI: calcd. for C31
537.1285.
H27ClO
3
NaS [M + Na] : 537.1267, found:
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
methyl 5-(4-nitrophenyl)-5-oxo-2,3-diphenyl-2-(p-tolylthio)pentanoate (syn-4i). White solid (49 mg, 47% yield);
1
H NMR (400 MHz, CDCl
3
) δ 8.26 – 8.17 (m, 2H), 7.94 – 7.86 (m, 2H), 7.29 – 7.07 (m, 10H), 7.04 – 7.00 (m, 2H),
6
.99 – 6.94 (m, 2H), 4.56 (dd, J = 11.0, 2.5 Hz, 1H), 3.97 (dd, J = 17.6, 2.5 Hz, 1H), 3.70 – 3.60 (m, 4H), 2.31 (s,
1
3
3H); C NMR (100 MHz, CDCl
3
) δ 196.9, 171.3, 150.2, 141.6, 139.8, 138.5, 137.2, 136.5, 130.5, 129.5, 129.4,
−1
129.0, 127.8, 127.6, 127.6, 127.5, 127.4, 123.7, 69.7, 52.2, 47.3, 42.2, 21.3; IR ν (cm ) 3060, 3032, 2949, 2921,
1
728, 1694, 1602, 1526, 1453, 1446, 1433, 1345, 1318, 1284, 1227, 1031, 1005, 855, 812, 743, 702, 506;
+
HRMSꢀESI: calcd. for C31
H27NO
5
NaS [M + Na] : 548.1508, found: 548.1530.
methyl 5-(4-nitrophenyl)-5-oxo-2,3-diphenyl-2-(p-tolylthio)pentanoate (anti-4i). White solid; (32 mg, 30% yield);
1
mp 151−153 °C; H NMR (400 MHz, CDCl ) δ 8.25 (d, J = 8.6 Hz, 2H), 7.98 (d, J = 8.6 Hz, 2H), 7.41 – 7.28 (m,
3
5H), 7.23 – 7.05 (m, 5H), 6.99 (d, J = 7.7 Hz, 2H), 6.73 (d, J = 7.4 Hz, 2H), 4.49 (dd, J = 10.8, 2.2 Hz, 1H), 3.72
1
3
(
dd, J = 15.9, 2.4 Hz, 1H), 3.49 – 3.38 (m, 4H), 2.27 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 196.7, 171.6, 150.2,
1
4
1
41.4, 139.6, 137.0, 135.9, 135.8, 130.8, 130.7, 129.4, 129.2, 128.1, 127.9, 127.5, 127.4, 127.2, 123.7, 69.6, 52.0,
−1
9.5, 43.1, 21.2; IR ν (cm ) 3058, 3031, 2948, 2920, 2851, 1720, 1691, 1602, 1525, 1493, 1453, 1384, 1346, 1234,
+
004, 855, 811, 744, 702, 606, 506; HRMSꢀESI: calcd. for C31
H
27NO
5
NaS [M + Na] : 548.1508, found: 548.1501.
methyl 3-(3-chlorophenyl)-5-oxo-2-phenyl-2-(p-tolylthio)hexanoate (syn-4j). White solid (57 mg, 63% yield); mp
1
8
7
2
1
3−85 °C; H NMR (400 MHz, CDCl
3
) δ 7.36 – 7.25 (m, 3H), 7.22 – 7.18 (m, 2H), 7.16 – 7.11 (m, 3H), 7.10 –
.04 (m, 3H), 6.86 – 6.76 (m, 2H), 4.31 (dd, J = 11.5, 2.4 Hz, 1H), 3.63 (s, 3H), 3.56 (dd, J = 17.3, 2.3 Hz, 1H),
13
.91 (dd, J = 17.3, 11.5 Hz, 1H), 2.34 (s, 3H), 1.98 (s, 3H); C NMR (100 MHz, CDCl ) δ 206.3, 170.9, 140.9,
3
40.0, 136.5, 136.4, 133.2, 130.5, 129.6, 129.5, 129.2, 128.6, 127.9, 127.4, 127.3, 127.2, 69.2, 52.1, 46.3, 46.0,
−1
30.8, 21.3; IR ν (cm ) 3059, 3022, 2949, 2922, 1728, 1595, 1571, 1492, 1445, 1431, 1359, 1279, 1226, 1160,
+
1084, 1021, 902, 811, 791, 713, 699, 506; HRMSꢀESI: calcd. for C H ClO NaS [M + Na] : 475.1111, found:
26
25
3
4
75.1115.
1
methyl 3-methyl-5-oxo-2-phenyl-2-(p-tolylthio)hexanoate (syn-4k). Colorless sticky oil (32 mg, 45% yield); H
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NMR (400 MHz, CDCl
3
) δ7.29 – 7.21 (m, 3H), 7.20 – 7.13 (m, 2H), 7.09 (d, J = 7.9 Hz, 2H), 7.02 (d, J = 7.9 Hz,
1
3
2H), 3.70 (s, 3H), 3.14 – 3.00 (m, 2H), 2.30 (s, 3H), 2.16 – 2.00 (m, 4H), 1.01 (d, J = 6.7 Hz, 3H); C NMR (100
MHz, CDCl ) δ 207.5, 171.7, 139.7, 137.2, 136.8, 129.4, 128.8, 127.6, 127.4, 127.1, 69.6, 52.1, 47.2, 34.1, 30.6,
3
−
1
2
1.3, 17.2. IR ν (cm ) 3022, 2950, 2923, 1728, 1492, 1446, 1433, 1360, 1226, 1162, 1033, 1019, 812, 703, 509;
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
24 3
HRMSꢀESI: calcd. for C21H O NaS [M + Na] : 379.1344, found: 379.1367
methyl 2-((2-methoxyphenyl)thio)-5-oxo-2,3,5-triphenylpentanoate (syn-4l). White solid (50 mg, 51% yield); mp
1
1
7
1
1
5
31−133 °C; H NMR (400 MHz, CDCl
3
) δ 7.88 – 7.82 (m, 2H), 7.52 – 7.46 (m, 1H), 7.42 – 7.31 (m, 4H), 7.27 –
.24 (m, 5H), 7.09 – 7.00 (m, 3H), 6.91 – 6.79 (m, 4H), 4.54 (dd, J = 11.5, 2.0 Hz, 1H), 4.35 (dd, J = 17.9, 2.0 Hz,
1
3
H), 3.63 (s, 3H), 3.59 (s, 3H), 3.56 – 3.49 (m, 1H); C NMR (100 MHz, CDCl ) δ 197.8, 170.9, 161.1, 139.2,
3
39.1, 137.4, 136.7, 132.8, 131.7, 130.9, 129.8, 128.5, 127.9, 127.6, 127.1, 127.0, 126.7, 120.6, 119.0, 110.9, 69.7,
−1
5.6, 51.9, 46.1, 41.5; IR ν (cm ) 3061, 3032, 2950, 2920, 2837, 1727, 1686, 1582, 1475, 1448, 1432, 1276, 1229,
+
1180, 1023, 770, 753, 702, 603; HRMSꢀESI: calcd. for C31
H
28
O
4
NaS [M + Na] : 519.1606, found: 519.1630.
methyl 2-((4-methoxyphenyl)thio)-5-oxo-2,3,5-triphenylpentanoate (syn-4m). White solid (53 mg, 54% yield); mp
1
1
7
1
58−160 °C; H NMR (400 MHz, CDCl
3
) δ 7.84 – 7.77 (m, 2H), 7.50 – 7.45 (m, 1H), 7.39 – 7.33 (m, 2H), 7.28 –
.21 (m, 3H), 7.20 – 7.15 (m, 4H), 7.14 – 7.08 (m, 3H), 7.04 – 6.98 (m, 2H), 6.75 – 6.69 (m, 2H), 4.62 (dd, J =
13
1.0, 2.1 Hz, 1H), 3.89 (dd, J = 17.8, 2.1 Hz, 1H), 3.76 (s, 3H), 3.72 – 3.61 (m, 4H); C NMR (100 MHz, CDCl
3
)
δ 197.9, 171.4, 160.8, 139.0, 138.4, 137.5, 137.2, 132.9, 130.5, 129.4, 128.5, 128.0, 127.6, 127.5, 127.1, 121.8,
−
1
1
1
14.1, 70.1, 55.3, 52.1, 46.7, 41.6; IR ν (cm ) 3059, 3030, 2947, 2837, 1727, 1685, 1592, 1569, 1493, 1447, 1287,
+
249, 1225, 1173, 1029, 1003, 830, 750, 701, 527; HRMSꢀESI: calcd. for C31
H
28
O
4
NaS [M + Na] : 519.1606,
found: 519.1583.
methyl 2-((4-bromophenyl)thio)-5-oxo-2,3,5-triphenylpentanoate (syn-4n). White solid (70 mg, 64% yield); mp
1
122−124 °C; H NMR (400 MHz, CDCl
3
) δ 7.84 – 7.74 (m, 2H), 7.50 – 7.44 (m, 1H), 7.39 – 7.32 (m, 2H), 7.26 –
1
3
7
.20 (m, 5H), 7.20 – 7.08 (m, 7H), 7.06 – 6.96 (m, 2H), 4.69 (dd, J = 10.1, 2.8 Hz, 1H), 3.82 – 3.63 (m, 5H);
C
NMR (100 MHz, CDCl ) δ 197.7, 171.5, 138.8, 137.9, 137.6, 137.0, 133.0, 131.5, 130.8, 130.3, 129.0, 128.5,
3
−1
1
1
28.0, 127.8, 127.8, 127.8, 127.5, 123.9, 70.4, 52.3, 47.5, 41.7; IR ν (cm ) 3062, 3033, 2948, 2918, 1720, 1688,
597, 1494, 1472, 1448, 1432, 1384, 1287, 1229, 1180, 1069, 1010, 814, 748, 703, 591, 488; HRMSꢀESI: calcd.
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2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
3
for C30H25BrO NaS [M + Na] : 567.0605, found: 567.0630.
methyl 5-oxo-3,5-diphenyl-2-(p-tolylthio)-2-(4-(trifluoromethyl)phenyl)pentanoate (syn-4o). White solid (74 mg,
1
6
7% yield); mp 148−150 °C; H NMR (400 MHz, CDCl ) δ 7.86 – 7.75 (m, 2H), 7.52 – 7.44 (m, 3H), 7.40 – 7.30
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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6
7
8
9
0
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8
9
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9
0
(
m, 4H), 7.16 – 7.09 (m, 5H), 7.02 – 6.96 (m, 4H), 4.71 (dd, J = 10.8, 2.2 Hz, 1H), 3.85 (dd, J = 17.7, 2.2 Hz, 1H),
13
3
1
.69 – 3.56 (m, 4H), 2.28 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 197.4, 170.8, 141.6, 140.0, 138.5, 137.0, 136.5,
33.1, 130.3, 130.1, 129.8, 129.5, 129.5, 129.2, 128.5, 128.0, 127.7, 127.5, 127.2, 125.4, 124.3, 124.3, 122.7,
−
1
120.0, 69.8, 52.3, 47.0, 41.2, 21.3; IR ν (cm ) 3062, 3032, 2951, 2922, 1735, 1683, 1619, 1597, 1493, 1449, 1329,
+
1228, 1169, 1121, 1073, 1018, 817, 747, 706, 690, 509; HRMSꢀESI: calcd. for C32
71.1531, found: 571.1553.
H
27
F
3
O
3
NaS [M + Na] :
5
methyl 2-(3-bromophenyl)-5-oxo-3,5-diphenyl-2-(p-tolylthio)pentanoate (syn-4p). White solid (72 mg, 65% yield);
1
mp 63−65 °C; H NMR (400 MHz, CDCl
3
) δ 7.85 – 7.78 (m, 2H), 7.51 – 7.46 (m, 1H), 7.41 – 7.35 (m, 3H), 7.26 –
7.20 (m, 2H), 7.17 – 7.09 (m, 6H), 7.05 – 6.95 (m, 4H), 4.63 (dd, J = 11.0, 2.4 Hz, 1H), 3.85 (dd, J = 17.6, 2.4 Hz,
1
3
1H), 3.67 – 3.56 (m, 4H), 2.29 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 197.6, 170.8, 140.0, 139.6, 138.5, 137.1,
1
2
1
36.5, 133.0, 130.6, 130.4, 129.5, 128.9, 128.5, 128.1, 128.0, 127.6, 127.4, 127.3, 121.5, 69.7, 52.2, 47.1, 41.1,
−
1
1.3; IR ν (cm ) 3060, 3030, 2948, 2921, 1729, 1686, 1595, 1581, 1492, 1474, 1448, 1432, 1287, 1226, 1180,
+
080, 1019, 1002, 811, 762, 747, 701, 690, 505; HRMSꢀESI: calcd. for C31
H27BrO
3
NaS [M + Na] : 581.0762,
found: 581.0764.
methyl 2-(4-methoxyphenyl)-5-oxo-3,5-diphenyl-2-(p-tolylthio)pentanoate (syn-4q). White solid (58 mg, 57%
1
yield); mp 121−123 °C; H NMR (400 MHz, CDCl
3
) δ 7.88 – 7.80 (m, 2H), 7.54 – 7.48 (m, 1H), 7.43 – 7.37 (m,
2
H), 7.24 – 7.16 (m, 4H), 7.16 – 7.10 (m, 3H), 7.06 (m, 2H), 7.04 – 6.96 (m, 2H), 6.83 (d, J = 9.0 Hz, 2H), 4.61
13
(
dd, J = 11.1, 2.2 Hz, 1H), 3.95 (dd, J = 17.6, 2.2 Hz, 1H), 3.85 (s, 3H), 3.72 – 3.58 (m, 4H), 2.34 (s, 3H);
C
3
NMR (100 MHz, CDCl ) δ 197.9, 171.4, 158.9, 139.6, 139.0, 137.2, 136.5, 132.9, 130.9, 130.7, 129.4, 129.1,
−1
128.4, 127.9, 127.8, 127.4, 127.0, 112.7, 69.4, 55.3, 52.0, 46.9, 41.3, 21.3; IR ν (cm ) 3033, 2949, 2835, 1736,
1682, 1608, 1512, 1448, 1285, 1255, 1222, 1182, 1033, 813, 748, 703, 690, 569; HRMSꢀESI: calcd. for
+
C
32
H
30
O
4
NaS [M + Na] : 533.1763, found: 533.1772.
methyl 5-oxo-3,5-diphenyl-2-(p-tolylthio)-2-(3,4,5-trimethoxyphenyl)pentanoate (syn-4r). White solid (71 mg, 62%
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yield); mp 50−52 °C; H NMR (400 MHz, CDCl
3
) δ 7.84 – 7.78 (m, 2H), 7.53 – 7.46 (m, 1H), 7.40 – 7.35 (m, 2H),
7.19 – 7.13 (m, 5H), 7.11 – 7.07 (m, 2H), 7.05 – 7.00 (m, 2H), 6.35 (s, 2H), 4.65 (dd, J = 10.5, 2.3 Hz, 1H), 3.89
1
3
(dd, J = 17.8, 2.3 Hz, 1H), 3.83 (s, 3H), 3.76 – 3.69 (m, 4H), 3.66 (s, 6H), 2.30 (s, 3H); C NMR (100 MHz,
CDCl ) δ 198.0, 171.5, 152.0, 139.7, 139.1, 137.5, 137. 1, 136.6, 133.0, 132.9, 130.4, 129.4, 128.5, 127.9, 127.8,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
−
1
1
1
27.6, 127.3, 107.1, 70.4, 60.9, 56.0, 52.2, 47.0, 41.8, 21.3; IR ν (cm ) 2953, 2925, 2853, 1727, 1685, 1585, 1509,
34 6
492, 1449, 1413, 1324, 1278, 1227, 1181, 1127, 1004, 813, 748, 701, 691; HRMSꢀESI: calcd. for C34H O NaS
+
[
M + Na] : 593.1974, found: 593.1962.
Methyl 2-phenyl-2-(p-tolylthio)acetate (5a): The diazo compound 2a (70.4 mg, 0.40 mmol) and thiols 1a (49.6 mg,
.40 mmol) in 2.0 mL CH Cl were added to a suspension of Rh (OAc) (1.8 mg, 0.004 mmol) and 4 Å molecular
0
2
2
2
4
2 2
sieve (100 mg) in 2.0 mL of CH Cl dropwise for 1 h. After completion of the addition, stirring was continued
until the diazo compound decomposed completely. The reaction mixture was filtered and the filtrate was
concentrated to give a residue. The crude product was purified by chromatography on silica gel using petroleum
1
ether : ethyl acetate = 100:1. Colorless oil (89 mg, 82% yield). Data for 5a: H NMR (400 MHz, CDCl ) δ 7.42 (m,
3
1
3
2H), 7.36 – 7.22 (m, 5H), 7.07 (m, 2H), 4.84 (s, 1H), 3.66 (s, 3H), 2.31 (s, 3H); C NMR (100 MHz, CDCl
3
) δ
1
71.0, 138.4, 135.8, 133.4, 129.9, 129.8, 128.7, 128.5, 128.3, 56.8, 52.7, 21.2; HRMSꢀESI: calcd. for
+
C H O NaS [M + Na] : 295.0769, found: 295.0775.
1
6
16
2
ASSOCIATED CONTENT
Supporting Information
1
13
H NMR, C NMR and HRMS spectra of all compounds. Xꢀray data for compound synꢀ4n. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*
(D.X.) Eꢀmail: dxing@sat.ecnu.edu.cn.
*(W.H.) Eꢀmail: huwh9@mail.syu.edu.cn
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS
We are grateful for financial support from the National Natural Science Foundation of China (NSFC) (Grant No.
21332003, 21402051 and 21772043). We also acknowledge the financial support from the Program for
Guangdong Introducing Innovative and Entrepreneurial Teams (No. 2016ZT06Y337).
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X.ꢀF.; Zhou, J.; Liu, W.ꢀJ.; Huang, H.ꢀX.; Hu, J.; Yang, L.ꢀP.; Gong, L.ꢀZ. J. Am. Chem. Soc. 2008, 130
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(
7) For selected MCRs via the trapping of ammonium ylides developed by our group, see: (a) Jiang, J.; Xu,
H.ꢀD.; Xi, J.ꢀB.; Ren, B.ꢀY.; Lv, F.ꢀP.; Guo, X.; Jiang, L.ꢀQ.; Zhang; Z.ꢀY.; Hu, W.ꢀH. J. Am. Chem. Soc
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013, 52, 9289. (c) Ma, X.ꢀC.; Jiang, J.; Lv, S.ꢀY.; Yao, W.ꢀF.; Yang, Y.; Liu, S.ꢀY.; Xia, F.; Hu, W.ꢀH.
Angew. Chem. Int. Ed. 2014, 53, 13136.
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(
8) For MCR via the trapping of sulfonium ylides developed by our group, see: (a) Xiao, G.ꢀL; Ma, C.ꢀQ;
Xing, D.; Hu, W.ꢀH. Org. Lett. 2016, 18, 6086.
(9) For selected MCRs via the trapping of zwitterionic intermediate developed by our group, see: (a) Qiu,
H.; Li, M.; Jiang, L.ꢀQ.; Lv, F.ꢀP; Zan, L.; Zhai, C.ꢀW.; Doyle, M. P.; Hu, W.ꢀH. Nat. Chem. 2012,
b) Zhang, D.; Zhou, J.; Kang, Z.ꢀH; Hu, W.ꢀH. Nat. Commun. 2015, , 5801.
10) CCDC 1530984 (synꢀ4k) contains the supplementary crystallographic data for this paper. These data
4, 733;
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0
(
6
(
can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
(11) Luo, X.ꢀC.; Zhang, H.; Duan, H.; Liu, Q.; Zhu, L.ꢀZ.; Zhang, T.; Lei, A.ꢀW. Org. Lett. 2007, 9, 4571.
(
(
12) Mariella, R. P.; Raube, R. R. J. Am. Chem. Soc. 1952, 74, 521.
13) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds, Wiley, New York, 1998.
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