Catalytic diastereoselective tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts by C-C bond cleavage

Article abstract of DOI:10.1002/asia.201100863

Through the cleavage of the C-C bond, the first catalytic tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts has been presented. Various S_N2′-like C-, S-, and P-allylic compounds could be obtained with exclusive E

Full text of DOI:10.1002/asia.201100863

DOI: 10.1002/asia.201100863
Catalytic Diastereoselective Tandem Conjugate Addition–Elimination
À
Reaction of Morita–Baylis–Hillman C Adducts by C C Bond Cleavage
Wenguo Yang,[a] Davin Tan,[b] Richmond Lee,[b] Lixin Li,[a] Yuanhang Pan,[c]
Kuo-Wei Huang,*[b] Choon-Hong Tan,*[a, c] and Zhiyong Jiang*[a]
À
Abstract: Through the cleavage of the C C bond, the first catalytic tandem conju-
gate addition–elimination reaction of Morita–Baylis–Hillman C adducts has been
À
presented. Various SN2’-like C-, S-, and P-allylic compounds could be obtained
with exclusive E configuration in good to excellent yields. The Michael product
could also be easily prepared by tuning the b-C-substituent group of the a-methyl-
ene ester under the same reaction conditions. Calculated relative energies of vari-
ous transition states by DFT methods strongly support the observed chemoselec-
tivity and diastereoselectivity.
Keywords: catalysis
cleavage
·
C C bond
·
diastereoselectivity
·
·
density functional calculations
Morita–Baylis–Hillman adducts
Introduction
Morita–Baylis–Hillman[1] (MBH) adducts, such as acetates
and carbonates are attractive and synthetically interesting
compounds owing to their convenient synthesis and modifi-
cation. For example, the allylic alkylation (AA) reaction of
MBH adducts by the catalysis of Lewis bases has been dem-
onstrated to achieve various O-,[2] N-,[3] P-,[4] and C-allylic[5]
compounds. As postulated by established mechanisms, the
AA reaction could be considered as a double tandem conju-
gate addition–elimination (CA–E) reaction[6] [Scheme 1,
Scheme 1. Proposed mechanism of allylic alkylation (double CA–E) and
Eq. (1)]. On the other hand, in the presence of Brønsted
bases, the CA–E reactions of MBH acetates often afford
SN2’-like allylic alkylation adducts, which contain internal al-
kenes instead [Scheme 1, Eq. (2)].[7] This class of compound
CA–E of MBH acetates and carbonates. PG=protecting group.
has great commercial potential, especially in the synthesis of
N-heterocyclic compounds. To remove acetic acid generated
in situ from MBH acetates, the use of stoichiometric or
excess base is unavoidable. To the best of our knowledge,
the CA–E reaction of MBH carbonates is rare.[8] The main
driving force for the CA–E reaction as mentioned in these
[a] W. Yang,+ L. Li, Prof. C.-H. Tan, Prof. Z. Jiang
Key Laboratory of Natural Medicine and Immuno-Engineering of
Henan Province
À
reports is facile cleavage of the C O bond. Herein, we wish
Henan University
Kaifeng, Henan, 475004 (P. R. China)
Fax : (+86)378-2864-665
to report the first catalytic CA–E reaction of MBH C ad-
À
ducts through an intriguing cleavage of the C C bond to
E-mail: chmjzy@henu.edu.cn
afford various CA–E adducts with excellent yields and dia-
stereoselectivies.
[b] D. Tan,+ R. Lee, Prof. K.-W. Huang
KAUST Catalysis Center and Division of Chemical and Life Sciences
and Engineering
Recently, our research group have developed an enantio-
selective allylic alkylation of MBH carbonates with bis(phe-
nylsulfonyl)methane (BSM) and fluoro-bis(phenylsulfonyl)-
King Abdullah University of Science and Technology
Thuwal, 23955-6900 (Kingdom of Saudi Arabia)
E-mail: hkw@kaust.edu.sa
methane (FBSM).[5p] With the removal of sulfonyl groups of
[9]
[c] Dr. Y. Pan, Prof. C.-H. Tan
Department of Chemistry
À
AA adducts from the breakage of the C S bond, various
enantiopure b-methyl-g-monofluoromethyl-substituted alco-
hols were attained. As the allylic alkylation adducts could
also serve as Michael acceptors, we attempted to synthesize
chiral g-amino acids bearing the BSM group. However,
when the AA adduct 1a was treated with 10 mol% 1,1,3,3-
tetramethylguanidine[10] (TMG) with CH3NO2 as solvent at
National University of Singapore
3 Science Drive 3, 117543, Singapore (Singapore)
E-mail: chmtanch@nus.edu.sg
[+] W. Yang and D. Tan made equal contributions to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100863.
Chem. Asian J. 2012, 7, 771 – 777
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771

FULL PAPERS
room temperature, the CA–E product 2a was obtained
rather than the desired Michael adduct 2a-M. This indicates
that the BSM group is cleaved in the elimination step
1a also formed 2a when CH3NO2 was utilized as a reagent
in different solvents (Table 1, entries 7–10). Under these
conditions, no Michael adduct 2a-M was detected. The best-
performing solvent with regard to reactivity and yield was
1,4-dioxane (Table 1, entry 8). Under all of the above-men-
tioned conditions, only the E isomer of 2a was observed.
A wide range of MBH adducts (1a–i) and nitroalkanes as
C nucleophiles were explored under the optimized neat re-
action conditions (Table 2). All reactions completed in
À
through the cleavage of the C C bond (Scheme 2). Notably,
Table 2. Reactions between MBH adducts (1a–i) and nitroalkanes.[a]
Scheme 2. Initial result of the reaction between 1a with CH3NO2.
in 2010, Mayr and co-workers presented the first example of
À
the C C bond cleavage of MBH C adducts in a tandem
Entry R1
R2
R3
COOCH3 1b 2b
COOCH3 1c 2c 12
COOCH3 1d 2d
COOCH3 1e 2e 12
1
2
t [h] Yield [%][b]
CA–E reaction of allylammonium halides and potassium
malonates.[11] On the basis of these results, we were interest-
ed in the possibility of developing a catalytic tandem CA–E
reaction between the MBH C adducts with different nucleo-
philes.
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
4-CF3C6H4
2-FC6H4
2-ClC6H4
4-MeC6H4
4-MeOC6H4 COOCH3 1 f 2 f
2-naphthyl
C6H5
9
96
85
89
81
89
89
92
91
89
9
9
9
COOCH3 1g 2g
COOtBu
1h 2h 12
C6H5
CN
1i
2i
12
12
CH3 C6H5
COOCH3 1a 2j
Results and Discussion
[a] Unless otherwise noted, the reaction was carried out with 0.1 mmol of
1 in 1.0 mL R1NO2. [b] Yield of isolated product.
Preliminary studies with the model substrate 1a were car-
ried out in neat CH3NO2. Initially, we found that the reac-
tion proceeded slowly at room temperature in the presence
of 10 mol% TMG. We then examined the catalytic ability of
organic Brønsted bases at 508C (Table 1, entries 1–5), and
all reactions were completed in 24 hours with moderate
yields except when Et3N was used (Table 1, entry 4). The
best yield was achieved when inorganic base Cs2CO3 was
used (Table 1, entry 6). Furthermore, the CA–E reaction of
12 hours and the CA–E products (2b–j) with E configura-
tions were efficiently synthesized in good to excellent yields
(81–96%). The trend in the electronic and steric effects of
the substituents on the aromatic ring of the allylic alkylation
adducts was not obvious.
To further expand the scope of this protocol, various C-,
S-, and P-nucleophiles were investigated (Table 3). The reac-
tions with these nucleophiles were conducted in 1,4-dioxane.
Dimethyl malonate (3a) as the C nucleophile gave product
3a in 99% yield after 12 hours (Table 3, entry 1). S nucleo-
Table 1. Screening studies of the CA–E of 1a with CH3NO2.[a]
Table 3. Reactions between S- and P-nucleophiles (3a–h) with 1a.[a]
Entry
Catalyst
Solvent
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
TMG
DBU
Et3N
Imidazole
DABCO
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Neat
Neat
Neat
Neat
Neat
Neat
DCE
1,4-dioxane
THF
24
24
24
14
16
24
12
12
12
14
70
54
N.R.[c]
72
Entry
NuH
CH2A(COOMe)2
PhSH
BnSH
EtSH
nPrSH
tBuSH
E
3
4
t [h]
Yield [%][b]
99[c]
92
97
97
65
96
trace
82
trace
40%
1
2
3
4
5
6
7
8
G
3a
3b
3c
3d
3e
3 f
3g
3h
4a
4b
4c
4d
4e
4 f
4g
4h
12
13
13
13
12
13
75
48
9
10
DMF
91
90
[a] Unless otherwise noted, the reaction was carried out with 0.1 mmol of
1a in 1.0 mL CH3NO2 (neat) or 1.0 mmol of 1a and 10 mmol CH3NO2 in
1.0 mL solvent. [b] Yield of isolated product. [c] N.R.=No reaction.
81
N.R.[d]
DBU=1,8-diazabicyclo
[2,2,2]octane, DCE=dichloroethane, THF=tetrahydrofuran, DMF=
N,N-dimethylformamide.
[5,4,0]undec-7-ene,
DABCO=1,4-diazabicyclo-
[a] Reactions were carried out with 1.0 mmol of 1a and 10 mmol 3a–h in
1.0 mL 1,4-dioxane. [b] Yield of isolated product. [c] d.r.=20:1.
[d] N.R.=No reaction.
ACHTUNGTRENNUNG
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Chem. Asian J. 2012, 7, 771 – 777

Catalytic Diastereoselective Tandem Conjugate Addition–Elimination Reactions
Table 4. The reaction between allylic alkylation adducts (5a–g) and ni-
tromethane.[a]
philes, such as aromatic (3b), benzyl (3c), and aliphatic
thiols (3d–f), showed relatively higher reactivities and af-
forded CA–E products (4b–f) in excellent yields (90–97%;
Table 3, entries 2–6). P nucleophiles, on the other hand,
were less reactive. For diphenylphosphite (3g), the reaction
required 75 hours to afford 4g in 81% yield (Table 3,
entry 7). No reaction occurred for diphenylphosphine oxide
(3h) (Table 3, entry 8). In all reactions, only the E-isomeric
Entry
1
R
5
t [h]
Product
Yield [%][b]
92
1
products were detected by H NMR spectroscopy. It is note-
worthy that this is the first integrated report of the CA–E
reaction of MBH adducts with various C-, S-, and P-nucleo-
philes.[7]
As the MBH adducts (1a–i) were prepared from the allyl-
ic alkylation of MBH carbonates and BSM, it is necessary to
investigate the reaction between MBH carbonates and
CH3NO2. As shown in Scheme 3, the reaction between
5a
17
2a
2
3
5b
5c
39
39
2a
2a
84
99
4
5
5d
5e
24
24
2a
2a
93
89
6
7
5 f
5g
24
6
6 f
6g
83[c]
79[d]
CH2NO2
Scheme 3. The CA–E reaction between MBH carbonate 3 with CH3NO2.
[a] Unless otherwise noted, the reaction was carried out with 0.1 mmol of
2 in 1.0 mL nitromethane 1. [b] Yield of isolated product. [c] d.r.>99:1.
[d] d.r.=1:1.
MBH carbonate 3 and CH3NO2 could afford CA–E product
2a in 4 hours with 94% yield, however, the diastereoselec-
tivty was unsatisfactory even at ambient temperature.
In addition, gram-scale synthesis of 2a was carried out
smoothly under the established reaction conditions in 91%
yield (Scheme 4). In this case, BSM was isolated as the only
by-product in 97% yield, which could then be recycled to
prepare 1a. Thus, this process is atom-economic.
these results, we rationalized that the formation of different
product was determined by the anionic stability of the leav-
ing group. This allows for greater tunability and control over
the type of product formation by simple alteration of the R
group substituent.
A summary of the results from the examination of various
Density functional theory (DFT)[12] calculations were per-
formed to provide an explanation for the formation of the
observed products. Preliminary calculations in the gas phase
revealed that the product 2a was more stable than the prod-
uct 2a-M by a significant energy difference of 10.6 kcal
molÀ1 (Scheme 5). In addition, by comparison of the ener-
gies of the cis and trans conformers of 2a, it was found that
the trans isomer was 2.6 kcalmolÀ1 more stable than the ci-
s isomer. Cs2CO3 and substrate 2a were then selected for
the modeling of the reaction profile using nitromethane as
the solvent (neat conditions) as Cs2CO3 gave the best yield
among all catalysts screened (Figure 1). It is conceivable
Scheme 4. Gram-scale synthesis of 2a.
C-allylic alkylation compounds with CH3NO2 under the op-
timized neat reaction conditions is described in Table 4.
When the R groups were FBSM (5a), ethyl benzylacetate
(5b), 2-fluoroethyl benzylacetate (5c), malonitrile (5d), and
a,b-butenolide (5e)[5g] good to excellent yields of 2a could
be achieved (Table 4, entries 1–5), with no detection of the
corresponding Michael adducts (6a–e). Interestingly, Chen
and co-workers previously reported that the reaction of 5e
and nitromethane catalyzed with TMG in refluxing tetrahy-
dofuran (THF) led to the bis-Michael adduct.[5g] In our reac-
tion system, the Michael adducts 6 f/g could be obtained
from 5 f/g, in which the R group substituents were thioalkyl
acetate and nitromethane (Table 4, entries 6 and 7). From
Scheme 5. DFT calculation of the free energies of the CA–E reaction
and Michael addition between 1a and nitromethane.
Chem. Asian J. 2012, 7, 771 – 777
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773

K.-W. Huang, C.-H. Tan, Z. Jiang et al.
FULL PAPERS
high yields and diastereoselec-
tivities. From a green chemis-
try standpoint, this is an atom-
economic methodology. Based
on our established protocol, we
can synthesize SN2’-like allylic
alkylation or Michael products
by simply tuning the b-C-sub-
stituent groups of a-methylene
esters under the same reaction
conditions. Quantum modeling
revealed that the CA–E reac-
tion from the cleavage of the
À
C C bond with BSM as a leav-
ing group is both the thermo-
dynamically and kinetically fa-
vored pathway. Further devel-
opment on this system is cur-
rently ongoing in our laborato-
ries.
Experimental Section
Typical Experimental Procedure for
the Reaction between MBH Adduct
1a in CH3NO2 Catalyzed by Cs2CO3
1a (47 mg, 0.1 mmol, 1.0 equiv) and
Cs2CO3 (3.3 mg, 0.01 mmol, 0.1 equiv)
were dissolved in nitromethane
(1.0 mL). The reaction mixtures were
stirred at 508C and monitored by
Figure 1. Reaction profile for the CA–E reaction catalyzed by Cs2CO3. Relative free energies of possible inter-
mediates and transition states are shown.
TLC. Upon complete consumption of
1a, the reaction mixtures were direct-
that Cs2CO3 initially abstracted a proton from nitromethane
to form a Cs+-stabilized nitronate anion IntA. Subsequent
nucleophilic Michael addition of the nitronate to the a,b-un-
saturated ketone substrate generated intermediate IntB via
transition state TS1, thereby overcoming an activation barri-
er of 15.4 kcalmolÀ1. The reaction might proceed through
two pathways: 1) protonation and tautomerization to form
the ketone product 2a-M through TS2b, and 2) elimination
of a BSM molecule to form 2a through TS2a. Based on the
calculated result, the former pathway will need to overcome
a higher overall activation barrier of 19.3 kcalmolÀ1 while
the latter one requires a lower barrier of 10.6 kcalmolÀ1.
The second pathway will be both the kinetically and thermo-
dynamically preferred course owing to the lower activation
barrier and the formation of the more stable product.[13]
ly loaded onto a short silica-gel column, followed by gradient elution
with a PE/EtOAc mixture (15:1–10:1). Removing the solvent in vacuo af-
forded products 2a (22.6 mg, 96% yield).
Typical Experimental Procedure for the Reaction between MBH
Carbonate 1a and CH3NO2 in 1,4-Dioxane Catalyzed by Cs2CO3
1a (47 mg, 0.1 mmol, 1.0 equiv), nitromethane (61 mg, 1.0 mmol,
10.0 equiv), and Cs2CO3 (3.3 mg, 0.01 mmol, 0.1 equiv) were dissolved in
1,4-dioxane (1.0 mL). The reaction mixtures were stirred at 508C and
monitored by TLC. Upon complete consumption of 1a, the reaction mix-
tures were directly loaded onto a short silica-gel column, followed by gra-
dient elution with a PE/EtOAc mixture (15:1–10:1). Removing the sol-
vent in vacuo afforded products 2a (19.2 mg, 82% yield).
Compound 2a[7o]
Colorless oil, 96% yield; 1H NMR (400 MHz, CDCl3): d=7.90 (s, 1H),
7.45–7.36 (m, 3H), 7.32 (d, J=7.2 Hz, 2H), 4.58 (t, J=7.7 Hz, 2H), 3.85
(s, 3H), 3.26 ppm (t, J=7.7 Hz, 2H).
2À
In addition, modeling was also performed using CO3
Compound 2b
2À
(Figure 2). The CO3 modeling profile showed an even
Colorless oil, 96% yield; 1H NMR (400 MHz, CDCl3): d=7.90 (s, 1H),
7.69 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 4.60 (t, J=7.3 Hz, 2H),
3.87 (s, 3H), 3.19 ppm (t, J=7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=166.9, 141.8, 138.1, 131.0, 130.7, 128.9, 128.8, 125.8 (three peaks),
125.7, 125.1, 122.4, 73.5, 52.5, 25.8 ppm; LRMS (ESI): m/z: 326.3
[M+Na+]; HRMS (ESI): m/z: 326.0611 [M+Na+], calcd for
C13H12F3O4NNa 326.0622.
more pronounced energy difference and preference for the
formation of 2a over 2a-M. The activation barrier for the
TS2a was only 7.1 kcalmolÀ1, compared to that of TS2b,
which was a staggering 25.0 kcalmolÀ1.[13]
In summary, we have reported an unusual catalytic diaste-
reoselective CA–E reaction of MBH C adducts through the
À
cleavage of a C C bond. A series of C-, S-, and P-allylic
compounds with inner alkenes have been synthesized in
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Catalytic Diastereoselective Tandem Conjugate Addition–Elimination Reactions
Compound 2h[7o]
Colorless oil, 92% yield; 1H NMR
(400 MHz, CDCl3): d=7.79 (s, 1H),
7.44–7.29 (m, 5H), 4.57 (t, J=7.6 Hz,
2H), 3.20 (t, J=7.6 Hz, 2H),
1.56 ppm (s, 9H).
Compound 2i
Colorless oil, 91% yield; 1H NMR
(400 MHz, CDCl3): d=7.74–7.72 (m,
2H), 7.44–7.43 (m, 3H), 7.09 (s, 1H),
4.69 (t, J=6.7 Hz, 2H), 3.11 ppm (t,
J=6.7 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d=147.2, 132.7, 130.9, 129.0,
128.9, 117.4, 104.6, 72.8, 33.6 ppm;
LRMS (EI): m/z: 202.1 [M+]; HRMS
(EI): m/z: 202.0742 [M+], calcd for
C11H10O2N2 202.0748.
Compound 2j[7i]
Colorless oil, 89% yield; 1H NMR
(400 MHz, CDCl3): d=7.89 (s, 1H),
7.43 À7.34 (m, 3H), 7.29 (d, J=
7.0 Hz, 2H), 4.93–4.88 (m, 1H), 3.85
(s, 3H), 3.26 (dd, J=8.0, 14.2 Hz,
1H), 2.96 (dd, J=6.4, 14.2 Hz, 1H),
1.47 ppm (d, J=6.4 Hz, 3H).
Compound 4a
Colorless oil, 99% yield; 1H NMR
(400 MHz, CDCl3): d=7.80 (s, 1H),
7.41–7.30 (m, 5H), 3.82 (s, 3H), 3.76
(t, J=7.9, 1H), 3.60 (s, 6H), 3.21 ppm
(d, J=7.8, 2H); 13C NMR (100 MHz,
CDCl3): d=169.2, 167.9, 142.2, 134.9,
129.0, 128.7, 128.6, 128.5, 52.4, 52.2,
50.3, 26.2 ppm; LRMS (EI): m/z:
Figure 2. Reaction profile for the CA–E reaction catalyzed by CO32À. Relative free energies of possible inter-
mediates and transition states are shown.
306.1 [M+]; HRMS (EI): m/z: 306.1101 [M+], calcd for C16H18O6
306.1103.
Compound 2c[7o]
Colorless oil, 85% yield; 1H NMR (400 MHz, CDCl3): d=7.84 (s, 1H),
7.31 (t, J=7.8 Hz, 2H), 7.12 (t, J=8.2 Hz, 2H), 4.58 (t, J=7.2 Hz, 2H),
3.84 (s, 3H), 3.23 ppm (t, J=7.5 Hz, 2H).
Compound 4b[7p]
Colorless oil, 92% yield; 1H NMR (400 MHz, CDCl3): d=7.78 (s, 1H),
7.42–7.33 (m, 7H), 7.25–7.20 (m, 2H), 4.05 (s, 2H), 3.82 ppm (s, 3H).
Compound 2d[7o]
Colorless oil, 89% yield; 1H NMR (400 MHz, CDCl3): d=7.91 (s, 1H),
7.46–7.44 (m, 1H), 7.34–7.31 (m, 2H), 7.20–7.18 (m, 1H), 4.55 (t, J=
7.4 Hz, 2H), 3.87 (s, 3H), 3.08 ppm (t, J=7.4 Hz, 2H).
Compound 4c
Colorless oil, 97% yield; 1H NMR (400 MHz, CDCl3): d=7.78 (s, 1H),
7.46–7.44 (m, 2H), 7.37–7.26 (m, 8H), 3.87 (s, 3H), 3.79 (s, 2H),
3.62 ppm (s, 2H), 13C NMR (100 MHz, CDCl3): d=167.8, 140.6, 138.1,
134.7, 129.6, 129.0, 128.8, 128.5, 128.3, 126.8, 52.1, 37.2, 28.4 ppm; LRMS
(EI): m/z: 298.1 [M+]; HRMS (EI): m/z: 298.1025 [M+], calcd for
C18H18O2S 298.1028.
Compound 2e[7o]
Colorless oil, 81% yield; 1H NMR (400 MHz, CDCl3): d=7.86 (s, 1H),
7.24 (s, 4H), 4.58 (t, J=7.8 Hz, 2H), 3.84 (s, 3H), 3.27 (t, J=7.8 Hz, 2H),
2.38 ppm (s, 3H).
Compound 4d
Compound 2 f[7o]
Colorless oil, 97% yield; 1H NMR (400 MHz, CDCl3): d=7.43 (s, 1H),
7.50 (d, J=7.4 Hz, 2H), 7.41 (t, J=7.0 Hz, 2H), 7.35 (d, J=7.2 Hz, 1H),
3.85 (s, 3H), 3.66 (s, 2H), 2.56 (q, J=11.1 Hz, 2H), 1.19 ppm (t, J=
7.4 Hz, 3H), 13C NMR (100 MHz, CDCl3): d=167.9, 140.3, 129.6, 129.5,
128.8, 128.5, 52.2, 28.2, 26.8, 14.6 ppm; LRMS (ESI): m/z: 236.8; HRMS
(ESI): m/z: 237.0944 [M+H]+, calcd for C13H17O2S 237.0942.
Colorless oil, 89% yield; 1H NMR (400 MHz, CDCl3): d=7.82 (s, 1H),
7.33 (d, J=8.8 Hz, 2H), 6.95 (d, J=8.8 Hz, 2H), 4.59 (t, J=7.8 Hz, 2H),
3.84 (s, 3H), 3.83 (s, 3H), 3.20 ppm (t, J=7.8 Hz, 2H).
Compound 2g
White solid, M.p. 79.4–81.28C; 89% yield; 1H NMR (400 MHz, CDCl3):
d=8.05 (s, 1H), 7.90–7.83 (m, 4H), 7.56–7.51 (m, 2H), 7.43 (dd, J=1.6,
10.1 Hz, 1H), 4.64 (t, J=7.7 Hz, 2H), 3.88 (s, 3H), 3.35 ppm (t, J=
7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=167.5, 143.4, 133.3, 133.1,
131.8, 128.9, 128.6, 128.4, 127.7, 127.2, 126.8, 126.6, 125.9, 73.7, 52.4,
26.0 ppm; LRMS (ESI): m/z: 308.0 [M+Na+]; HRMS (ESI): m/z:
308.0893 [M+Na+], calcd for C16H15O4NNa 308.0904.
Compound 4e
Colorless oil, 91% yield; 1H NMR (400 MHz, CDCl3): d=7.74 (s, 1H),
7.50 (d, J=7.3 Hz, 2H), 7.41 (t, J=7.0 Hz, 2H), 7.36 (d, J=7.1, 1H), 3.85
(s, 3H), 3.64 (s, 2H), 2.51 (t, J=7.2 Hz, 2H), 1.58–1.49 (m, 2H),
0.92 ppm (t, J=7.3 Hz, 3H), 13C NMR (100 MHz, CDCl3): d=167.9,
140.3, 135.0, 129.7, 129.5, 128.8, 128.6, 52.2, 34.9, 28.5, 22.8, 13.4; LRMS
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K.-W. Huang, C.-H. Tan, Z. Jiang et al.
FULL PAPERS
(ESI) m/z 250.9 ppm; LRMS (ESI): m/z: 250.1 [M+]; HRMS (EI): m/z:
250.1030 [M+], calcd for C14H18O2S 250.1028.
[2] For selected examples, see: a) B. M. Trost, H.-C. Tsui, F. D. Toste, J.
Am. Chem. Soc. 2000, 122, 3534; b) J. N. Kim, H. J. Lee, J. H. Gong,
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Sun, Y.-C. Chen, Chem. Commun. 2011, 47, 4784; e) H.-P. Deng, Y.
Wei, M. Shi, Eur. J. Org. Chem. 2011, 1956.
Compound 4 f
Colorless oil, 90% yield; 1H NMR (400 MHz, CDCl3): d=7.72 (s, 1H),
7.61 (d, J=7.3 Hz, 2H), 7.43–7.35 (m, 3H), 3.84 (s, 3H), 3.66 (s, 2H),
1.37 ppm (s, 9H), 13C NMR (100 MHz, CDCl3): d=167.8, 141.0, 135.0,
129.6, 128.9, 128.5, 128.1, 52.2, 43.2, 30.6, 25.9 ppm; LRMS (EI): m/z:
264.1 [M+]; HRMS (EI): m/z: 264.1188 [M+], calcd for C15H20O2S
264.1184.
Compound 4g
Colorless oil, 81% yield; 1H NMR (400 MHz, CDCl3): d=7.94 (d, J=
5.7 Hz, 1H), 7.59 (d, J=6.8 Hz, 2H), 7.41–7.35 (m, 3H), 7.30–7.26 (m,
4H), 7.16–7.11 (m, 6H), 3.79 (s, 3H), 3.59 ppm (d, J=22.6 Hz, 2H),
13C NMR (100 MHz, CDCl3): d=167.6, 150.4, 150.3, 142.8, 142.7, 134.5
(two peaks), 129.6, 129.3 (two peaks), 129.1, 128.7, 125.0, 122.8, 122.7,
120.4, 120.3, 52.4, 27.5, 26.0 ppm, 15P NMR (162 MHz, CDCl3): d=
18.7 ppm; LRMS (EI): m/z: 408.1 [M+]; HRMS (ESI): m/z: 408.1133
[M+], calcd for C23H21O5P 408.1127.
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Lu, Angew. Chem. 2011, 123, 7983; Angew. Chem. Int. Ed. 2011, 50,
7837; n) L. Jiang, Q. Lei, X. Huang, H.-L. Cui, X. Zhou, Y.-C. Chen,
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50, 9684; r) X. Companyꢁ, G. Valero, V. Ceban, T. Calvet, M. Font-
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Compound 6 f
Colorless oil, 83% yield; 1H NMR (400 MHz, CDCl3): d=7.31 (t, J=
7.0 Hz, 2H), 7.25–7.23 (m, 1H), 7.13 (d, J=7.1 Hz, 2H), 4.32–4.18 (m,
2H), 3.75 (s, 3H), 3.50–3.44 (m, 1H), 2.81–2.75 (m, 3H), 2.05–1.96 (m,
2H), 1.30 ppm (s, 9H), 13C NMR (100 MHz, CDCl3): d=197.6, 173.6,
139.2, 128.8, 128.0, 127.5, 73.1, 52.2, 48.5, 48.2, 47.6, 44.4, 29.6, 27.3 ppm;
LRMS (EI): m/z: 367.1; HRMS (EI): m/z: 367.1458, calcd for
C18H25NO5S 367.1453.
Compound 6g
Colorless oil, 79% yield; 1H NMR (400 MHz, CDCl3): d=7.39–7.31 (m,
3H), 7.20–7.09 (m, 2H), 4.94–4.80 (m, 1H), 4.67 (dd, J=7.3, 2.8 Hz, 1H),
4.47–4.25 (m, 2H), 3.84–3.78 (m, 1H), 3.69 (d, J=57.7, 3H), 2.94–2.84
(m, 1H), 2.27 À2.21 (m, 1H), 2.11–2.03 ppm (m, 1H), 13C NMR
(100 MHz, CDCl3): d=172.8, 171.7, 135.9, 135.4, 129.4, 129.1, 128.7,
128.6, 127.9, 127.8, 78.3, 77.2, 73.0, 72.6, 52.5, 52.2, 45.7 (two peaks), 45.4,
45.2, 27.4, 27.1 ppm; LRMS (EI): m/z: 296.6; HRMS (EI): m/z: 296.1012,
calcd for C13H16N2O6 296.1008.
Density Functional Theory Calculation Perimeters
All intermediates and transition state geometries were optimized at the
B3LYP level of theory[14] using 6–31G(d) and 6–31+G(d) Pople basis
2À
sets[15] for the Cs2CO3 and CO3 models, respectively, with Polarizable
Continuum Model (PCM) utilizing the integral equation formalism var-
iant (IEF) as the Self-Consistent Reaction Field (SCRF)[16] with nitrome-
thane as the solvent. This was achieved by employing the Gaussian 09
program. In addition, the LANL2DZ effective core potential (ECP) of
Hay and Wadt was applied for Cs.[17]
Acknowledgements
Financial support from the National Natural Science Foundation of
China (21072044), Excellent Youth Foundation of Henan Scientific Com-
mittee (114100510003), Specialized Research Fund for the Doctoral Pro-
gram of Higher Education (20104103120002) to Z.J., International Coop-
eration Foundation of Henan Province (104300510062) to Z.J. and C.H.T.
and KAUST (4000000076) to K.-W. H. are greatly appreciated.
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Received: October 17, 2011
Published online: February 8, 2012
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