Domino reaction for the chemo- and stereoselective synthesis of trans-2,3-dihydrobenzofurans from N-thiophosphinyl imines and sulfur ylides

Article abstract of DOI:10.1021/jo2008737

A novel domino annulation between sulfur ylides and salicyl N-thiophosphinyl imines was developed. The method allows the synthesis of a highly substituted trans-2,3-dihydrobenzofuran skeleton with high yield and excellent chemo- and stereoselectivity.

Full text of DOI:10.1021/jo2008737

ARTICLE
pubs.acs.org/joc
Domino Reaction for the Chemo- and Stereoselective Synthesis of
trans-2,3-Dihydrobenzofurans from N-Thiophosphinyl Imines and
Sulfur Ylides
Peizhong Xie,† Liye Wang,† Lihua Yang, Erqing Li, Jianze, Ma, You Huang,* and Ruyu Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
S Supporting Information
b
ABSTRACT: A novel domino annulation between sulfur ylides and
salicyl N-thiophosphinyl imines was developed. The method allows
the synthesis of a highly substituted trans-2,3-dihydrobenzofuran
skeleton with high yield and excellent chemo- and stereoselectivity.
Scheme 1. Stereoselective Construction of trans- and cis-2,3-
Dihydrobenzofuran from Salicyl N-Thiophosphinyl Imines
and 1,1-Dipolar Synthona
’ INTRODUCTION
Domino reactions have garnered significant recent attention from
the synthetic community as a means to swiftly assemble complex
molecules from simple starting materials with minimal time and waste
as well as manipulation of reaction intermediates.1,2f In particular,
these strategies are powerful in the total synthesis of natural products
and bioactive molecules.2 The remarkable significance of the 2,3-
dihydrobenzofuran (DHB) ring system in biologically active com-
pounds, synthetic drugs, and natural products has motivated chemists
to develop various approaches for the construction of DHBs,3 such as
radical cyclizations, electrocyclizations,4 anionic cyclizations,5 biomi-
metic couplings and cycloadditions,6 Lewis acid promoted reactions,7
transition-metal-catalyzed processes,1a,8 and so on.9 However, several
drawbacks, including unsatisfactory yields, poor chemo- and/or
stereoselectivities, tedious processes for purification, and precious
reaction conditions, impede their wide application. Hence, simple,
convenient, and highly stereoselective methodologies to provide such
scaffolds represent an important and attractive objective at the
forefront of synthetic chemistry.2
Phosphine-catalyzed domino reactions have been extensively
employed for a wide range of useful synthetic organic transfor-
mation.10 Intrigued by those elegant studies, we have reported
phosphine-catalyzed domino reactions that can construct cis-11
and trans-dihydrobenzofuran skeletons with high stereoselec-
tivities.12 In those reactions allenoates and modified allyic
derivatives were first used as 1,1-dipolar synthons.13 Then, we
envisioned that the sulfur ylides, which have been gradually
developed as functional units in [2 + 1]14 and [4 + 1]
annulation,15 might also serve as a 1,1-dipolar synthon reacting
with salicyl N-thiophosphinyl imines11,12,17 to form trans-2,3-
dihydrobenzofurans (Scheme 1). However, according to the
literature, almost all previous endeavors with unstable or semi-
stabilized ylides have suffered from the kinetic preference to form
aziridines or cyclopropanes.15 Recently, electronic and steric
effects and high temperature/microwave have been used to alter
a LBBA: 20-(diethylphosphino)-[1,10-biphenyl]-2-ol.
the kinetic preference.15,16 On the basis of our previous study on
the chemistry of salicyl N-thiophosphinyl imines, we speculated
that the steric effects on the imine play an important role in the
reaction pathway and stereoselectivity.11,12,17 We envisioned that
the steric effects chould be a potential factor to overcome kinetic
preference and to form dihydrobenzofurans.
Herein, we report the domino annulation of salicyl N-thiopho-
sphinyl imines with sulfur ylides, which allows efficient construction of
trans-2,3-dihydrobenzofurans with high chemo- and stereoselectivity.
Received: April 29, 2011
Published: August 11, 2011
r
2011 American Chemical Society
7699
dx.doi.org/10.1021/jo2008737 J. Org. Chem. 2011, 76, 7699–7705
|

The Journal of Organic Chemistry
ARTICLE
Table 1. Studies on the Reaction of Salicyl N-Thiophosphinyl
Imines 1a with Sulfonium Salt 2a To Generate 2,3-Dihydro-
benzofurana
Table 2. Investgating the Scope of Salicyl N-Thiophosphinyl
Imines 1 and Sulfonium Salt 2 in the Domino Reactiona
entry
R1
R2
t
trans/cisb
yield (%)c
entry
solvent
base
DBU
t
yield (%)b
1
5-Br
5-NO2
H
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Me
CO2But
COPh
COPh
COPh
COPh
COR3
COR4
COR5
COR6
COR6
COMe
CO2Et
15 min
15 min
25 min
20 min
10 min
15 min
15 min
20 min
75 min
2.5 h
96/4
90 (3a)
96 (3b)
81 (3c)
88 (3d)
96 (3e)
92 (3f)
93 (3g)
95 (3h)
96 (3i)
95 (3j)
91 (3k)
87 (3l)
84 (3m)
86 (3n)
78 (3o)
95 (3p)
96 (3q)
86 (3r)
70 (3s)
1
toluene
toluene
toluene
toluene
CH3CN
THF
50 min
35 h
37
66
77
76
92
64
47
69
51
67
66
82
82
85
2
95/5
2
NEt3
3
91/9
3,5-But
3-Cl
3-Ph
3-Ph
3-Ph
5-OMe
5-CH3
5-But
5-Br
5-Br
5-Br
H
95/5
3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
45 h
4
4
6.5 h
5
94/6
5
15 min
90 min
30 min
30 min
3.5 h
6
95/5
6
7
95/5
7
DMF
8
94/6
9d
10
11
12
13e
14f
15g
16h
17h
18
19
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
94/6
8
CH3OH
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
10
11c
12d
13e
14f
15g
16h
15 min
15 min
30 min
15 min
25 min
8 h
2 h
60 min
70 min
75 min
2 h
H
90 min
40 min
15 min
50 min
96/4
K2CO3
8 h
3-Cl
3-Cl
4-OMe
>99/1
97/3
a The reaction was carried out in 0.2 mmol scale in solvent (2.0 mL) at rt.
The ratio of 1a/2a/base is 1/2.5/2.5. b Isolated yields. c 1.5 equiv of base
was used. d 1a/2a/base = 1/1.5/1.5. e 1a/2a/base = 1/5/5. f 1a/2a/base
= 1/1.5/2.5. g P-based ylide D was used instead of 2a. h N-based ylide E
was used instead of 2a.
95/5
a Unless otherwise noted, the reaction was carried out in 0.2 mmol scale
in solvent (2.0 mL), and 0.5 mmol of K2CO3 was used. The ratio of
1/2 = 1.0/2.5. b Determined by 31P NMR of the crude reaction mixture.
c Isolated yields. d Sulfur ylide was directly used without the addition
of K2CO3. R3 = p-Me(C6H4). R4 = p-Cl(C6H4). g R5 = furan-2-yl.
e
f
h R6 = thiophen-2-yl.
A variety of salicyl N-thiophosphinyl imines 1 and sulfonium
salts 2 were tolerated under the optimized reaction condi-
tions. As summarized in Table 2, the reaction displays a broad
scope for the salicyl N-thiophosphinyl imines. The electronic
property of the aromatic substitute has little effect on the yield
and stereoselectivity. Even with a sterically hindered substrate
(Table 2, entry 4), the reaction proceeded smoothly to give the
desired products in high yields. Additionally, a series of sulfur
ylides proved to be suitable for this reaction. Both ester (entries
1ꢀ8) and ketone carbonyl (entries 9ꢀ14) substituted sulfonium
salts 2 were favored to give trans-2,3-dihydrobenzofurans 3 in
high yields with excellent stereocontrol. Furthermore, the het-
eroaryl (entries 15ꢀ17) and alkenyl (entry 18) substituted
sulfonium salts could also be employed in this domino reaction.
Trisubstituted trans-2,3-dihydrofurans 3 could be achieved by
using a disubstituted sulfonium salt 2 as the starting material
(Figure 1, 3v). Preliminary studies about the asymmetric variant
of this reaction were conducted with (ꢀ)-menthyl ester 2 and 1
as the substrates, although 3w was obtained in 76% yield with
poor diastesoselectivity (Figure 1, 3w). Importantly, the reaction
can be carried out on gram scale without obvious loss in the
reaction efficiency (for the details see Experimental Section, 3d).
’ RESULTS AND DISCUSSION
We initiated our investigation by subjecting sulfur ylide 2a to
salicyl N-thiophosphinyl imine 1a in the presence of DBU (2.5
equiv) in toluene at room temperature. To our delight, 3a was
isolated in 37% yield (Table 1, entry 1). Optimization of the
reaction conditions revealed that bases and solvents strongly
influenced the yield. When K2CO3 (2.5 equiv) was used, 76%
yield of 3a could be obtained (entry 4), which is faster than
Na2CO3 under the same conditions (entry 3). Increasing or
decreasing the amount of base resulted in decrease of the
efficiency (entries 11 and 13). Of the solvent screened, CH3CN
was found to be the optimal one (entries 4ꢀ9). The ratio of 1a/
2a also affected the yield and the reaction time; 1/2.5 (1a/2a)
gave the best results (entries 5, 12ꢀ14). In addition, P- and
N-based ylides were also investigated under the reaction condi-
tions, although the reactions were disordered and no products 3a
were obtained.
The structure and stereochemistry of 3a were characterized by
combination of NMR and HRMS spectra and single-crystal X-ray
analysis (see the Supporting Information).
7700
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705

The Journal of Organic Chemistry
ARTICLE
Scheme 4. Newman Projections of Intermediate C
Figure 1. Generality for substituent at the 2,3-dihydrobenzofurans. The
reactions were carried out under the previous optimized reaction
conditions. The trans/cis and de value was measured by 31P NMR of
the crude reaction mixture.
could safely be made that CꢀC bond formation is prior to the
CꢀO bond formation.
According to our experimental results (Scheme 2) and other
related studies,15,16 we proposed a mechanism for this domino
reaction as follows (Scheme 3). The reaction might be initiated
by the formation of the sulfur ylide via the deprotonation of 2a.
Subsequent nucleophilic addition of the sulfur ylide to the
electron-dificient imine 1a yielded the intermediate A. The steric
hindrance between the COOEt and two phenyl groups on the
phosphorus atom alters the kinetic preference to form aziridines
B. Instead, A will transform into intermediate C under proton
transfer. As shown in Newman projections C-1 and C-2, inter-
mediate C-1 is the favored one, followed by SN2 substitution to
give the 2,3-disubstituted dihydrobenzofuran 3a with trans-
enriched configuration (Scheme 4). Moreover, the minor dia-
stereomer cis-3f was isolated, followed by being resubjected to
the reaction conditions. As expected, no trans-3f was obtained
under the conditions for 3 h. This, to some extent, could indicate
that the highly diastereoselectivity was determined by the kinetic
process not the equilibration. This is further supported by the 31P
NMR spectroscopy (Figure 2). For the keto-derived products,
which are formed with higher diastereoselectivity than the esters,
only one isomer was detected during the reaction process.
Scheme 2. Studies of the Mechanism
Scheme 3. Possible Mechanism for the Formation of 3a
’ CONCLUSION
In summary, we have developed a simple, convenient, and
highly chemo- and stereoselective domino reaction between
salicyl N-thiophosphinyl imines and sulfonium salts that provides
a new method for the construction of trans-2,3-dihydrobenzo-
furans in excellent yields. Significantly, we not only avert the
competitive reaction but also realize the reaction with excellent
stereoselectivity. This work could open up new opportunities for
selectively constructing other carbon- and heterocycles beyond
traditional small rings.
’ EXPERIMENTAL SECTION
In order to investigate the mechanism, control experiments
were carried out according to Scheme 2. Under the standard
reaction, N-thiophosphinyl imines of 2-methoxybenzaldehyde
4a, addition, phenol was used under the above reaction condi-
tion, and no CꢀO bond was formed (Reaction 2). This indicated
that the deprotonation of sulfonium salts is faster than CꢀO
bond formation. On the other hand, when the sulfur ylide,
instead of sulfonium salts, was directly used without base,
product 3 could also be obtained (Reaction 3). The conclusion
General Information. All the solvents were used without further
purification. The 1H NMR and spectra was recorded at 300 MHz or 400
MHz, 13C NMR was recorded at 75 MHz or 100 MHz. 31P NMR was
recorded at 162 MHz. 1H and 13C NMR Chemical shifts were calibrated
to tetramethylsilane as an external reference. Coupling constants are
given in Hz. The following abbreviations are used to indicate the
multiplicity: s, singlet; d, doublet: t, triplet; q, quartet; m, multiplet;
HRMS were obtained on an IonSpec FT-ICR mass spectrometer with
ESI resource. Melting points were measured on a RY-I apparatus and are
7701
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705

The Journal of Organic Chemistry
ARTICLE
Figure 2. 31P NMR experiments.
reported uncorrected. Salicyl N-thiophosphinyl imines11,12,17 and sulfo-
nium salt15 compound were prepared according to the known methods.
Method for the Synthesis of 4a. To a mixture 1a (414 mg, 1.0
mmol) and K2CO3 (280 mg, 2.0 mmol) in acetone (5 mL), was added
MeI (282 mg, 2.0 mmol), and the mixture was refluxed for 5 h, After
being cooled to room temperature, the mixture was filtered though Celite,
and concentrated in vacuo and the residue was purified via column
chromatography (Petroleum ether (60ꢀ90)/ethyl acetate =10:1) to
give 4a 426 mg (yield 99%). 1H NMR (400 MHz, CDCl3) δ = 9.78 (d,
J = 39.5, 1H), 8.30 (d, J = 2.6, 1H), 8.06ꢀ7.96 (m, 4H), 7.57 (dd, J = 8.9,
2.6, 1H), 7.51ꢀ7.39 (m, 6H), 6.85 (d, J = 8.9, 1H), 3.89 (s, 3H). 31P
NMR (162 MHz, CDCl3) δ = 61.74. 13C NMR (101 MHz, CDCl3)
δ = 170.3, 170.3, 160.8, 138.4, 136.1, 135.0, 132.3, 132.3, 132.1, 132.1,
132.1, 132.0, 132.0, 131.8, 129.2, 129.1, 126.4, 126.1, 114.2, 114.1, 56.7.
HRMS (ESI/[M + Na]+) calcd for C20H17BrNOPSNa 451.9844, found
451.9840.
Large Scale for the Construction of 3d. Imine 1d 2.24 g (5.0
mmol) and sulfonium salt 2a 2.85 g (12.5 mmol) were dissolved in dry
CH3CN (50 mL), and then, K2CO3 1.72 g (12.5 mmol) was added to
this solution. The reaction was stirred at room temperature overnight.
After completion of the reaction (The reaction was monitored by TLC),
all volatiles were removed in vacuo and the residue was dissolved in
CH2Cl2 and filtered through silica and solvent was evaporated to afford
the crude 3d 2.50 g (93%, trans/cis: 94/6). Further purification by
recrystallization afford pure 3d.
and the residue was purified via column chromatography (Petroleum
ether (60ꢀ90)/ethyl acetate =10:1).
Ethyl-5-bromo-3-(diphenylphosphorothioylamino)-trans-
2,3-dihydrobenzofuran-2-carboxylate (trans-3a). Mp: 142ꢀ
145 °C. 1H NMR (400 MHz, CDCl3) δ = 8.07ꢀ7.95 (m, 4H), 7.57 (d,
J = 1.5, 1H), 7.55ꢀ7.44 (m, 6H), 7.32 (dd, J = 8.6, 1.9, 1H), 6.78 (d, J =
8.6, 1H), 5.24 (dd, J = 10.6, 3.3, 1H), 5.19 (d, J = 3.3, 1H), 4.06 (q, J = 7.1,
2H), 3.14 (dd, J = 10.6, 5.8, 1H), 1.13 (t, J = 7.1, 3H). 31P NMR (162
MHz, CDCl3) δ = 59.35. 13C NMR (101 MHz, CDCl3) δ = 168.7,
158.3, 134.1, 133.9, 133.4, 133.1, 132.9, 132.2, 132.2, 132.1, 132.0, 132.0,
131.9, 131.7, 131.6, 129.2, 128.9, 128.9, 128.8, 128.7, 128.5, 113.7, 112.2,
87.0 (d, J = 5.0 Hz), 61.9, 57.4, 14.0. HRMS (ESI/[M + Na]+) calcd for
C23H21BrNO3PSNa 524.0047, found 524.0055.
Ethyl-3-(diphenylphosphorothioylamino)-5-nitro-trans-
2,3-dihydrobenzofuran-2-carboxylate (trans-3b). Mp: 142ꢀ143 °C.
1H NMR (400 MHz, CDCl3) δ = 8.34 (d, J = 2.0, 1H), 8.17 (dd, J = 8.9, 2.3,
1H), 8.09ꢀ7.96 (m, 4H), 7.60ꢀ7.44 (m, 6H), 6.97 (d, J = 8.9, 1H), 5.37 (d,
J= 3.8, 1H), 5.31 (td, J= 10.7, 3.7, 1H), 4.12 (q, J=7.1, 2H), 3.25(dd,J= 10.6,
5.7, 1H), 1.17 (t, J = 7.1, 3H). 31P NMR (162 MHz, CDCl3) δ = 59.67. 13
C
NMR (101 MHz, CDCl3) δ = 168.1, 164.0, 143.0, 133.9, 133.7, 132.9, 132.6,
132.4, 132.3, 132.2, 132.2, 131.9, 131.8, 131.7, 131.6, 128.9, 128.7, 128.6, 128.3,
128.2, 127.4, 122.9, 110.7, 88.1 (d, J = 5.0 Hz), 62.2, 56.8, 14.0. HRMS
(ESI/[M + Na]+) calcd for C23H21N2O5PSNa 491.0800, found 491.0801.
Ethyl-3-(diphenylphosphorothioylamino)-trans-2,3-dihy-
drobenzofuran-2-carboxylate (trans-3c). Mp: 131ꢀ133 °C. 1H
NMR (400 MHz, CDCl3) δ = 8.08ꢀ7.96 (m, 4H), 7.55ꢀ7.42 (m, 7H),
7.23 (t, J = 7.7, 1H), 6.95 (t, J = 7.4, 1H), 6.90 (d, J = 8.1, 1H), 5.25 (td,
J = 10.8, 3.4, 1H), 5.16 (d, J = 3.5, 1H), 4.06 (q, J = 7.1, 2H), 3.12 (dd, J =
10.1, 6.0, 1H), 1.12 (t, J = 7.1, 3H). 31P NMR (162 MHz, CDCl3) δ =
59.08. 13C NMR (101 MHz, CDCl3) δ = 169.2, 159.1, 134.3, 133.3,
132.1, 132.0, 131.9, 131.6, 131.5, 130.5, 128.7, 128.6, 128.5, 126.6, 126.6,
126.2, 122.0, 110.5, 86.6 (d, J = 5.0 Hz), 61.7, 57.7, 14.0. HRMS
General Procedure for the Synthesis of trans-2,3-Diyh-
drobenzofurans. Imine 1(1.00 equiv) and sulfonium salt 2 (2.5
equiv) were dissolved in dry CH3CN (2.0 mL), and then, K2CO3 (2.50
equiv) was added to this solution. The reaction was stirred at room
temperature. As indicated by TLC, after completion of the reaction (The
reaction was monitored by TLC), all volatiles were removed in vacuo
7702
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705

The Journal of Organic Chemistry
ARTICLE
(ESI/[M + Na]+) calcd for C23H22NO3PSNa 446.0950, found 446.-
0953.
134.4, 132.7, 132.6, 132.5, 132.3, 132.2, 130.9, 129.4, 129.4, 129.3, 129.2,
129.2, 129.1, 128.4, 128.3, 128.1, 125.9, 125.3, 123.2, 87.4 (d, J = 1.0 Hz),
83.3, 58.3, 28.7. HRMS (ESI/[M + Na]+) calcd for C31H30NO3PSNa
550.1576, found 550.1580.
Ethyl-5,7-di-tert-butyl-3-(diphenylphosphorothioylam-
ino)-trans-2,3-dihydrobenzofuran-2-carboxylate (trans-3d).
1
Mp: 141ꢀ142 °C. H NMR (400 MHz, CDCl3) δ = 8.08ꢀ7.97 (m,
N-(2-Benzoyl-5-methoxy-trans-2,3-dihydrobenzofuran-
3-yl)-P,P-diphenylphosphinothioic Amide (trans-3i). Mp:
4H), 7.54ꢀ7.42 (m, 6H), 7.36 (d, J = 1.6, 1H), 7.20 (d, J = 1.8, 1H),
5.27ꢀ5.09 (m, 2H), 4.11ꢀ3.96 (m, 2H), 3.11 (dd, J = 9.9, 6.0, 1H), 1.38
(s, 9H), 1.28 (s, 9H), 1.12 (t, J = 7.1, 3H). 31P NMR (162 MHz, CDCl3)
δ = 58.80. 13C NMR (101 MHz, CDCl3) δ = 169.7, 155.1, 144.7, 134.6,
134.6, 133.6, 133.5, 133.0, 132.1, 131.9, 131.9, 131.9, 131.9, 131.7, 131.6,
128.6, 128.6, 128.5, 128.5, 126.3, 126.3, 124.2, 120.4, 86.3 (d, J = 5.0 Hz),
61.4, 57.8, 34.7, 34.4, 31.8, 29.4, 14.0. HRMS (ESI/[M + Na]+) calcd for
C31H38NO3PSNa 558.2202, found 558.2203.
1
137ꢀ138 °C. H NMR (400 MHz, CDCl3) δ = 8.02 (dd, J = 23.8,
8.6, 6H), 7.59 (t, J = 7.3, 1H), 7.54ꢀ7.35 (m, 8H), 7.06 (s, 1H), 6.77 (s,
2H), 5.99 (d, J = 2.5, 1H), 5.51 (t, J = 10.2, 1H), 3.74 (s, 3H), 3.36 (s,
1H). 31P NMR (162 MHz, CDCl3) δ = 58.20. 13C NMR (101 MHz,
CDCl3) δ = 192.5, 153.9, 151.8, 133.5, 133.3, 132.6, 132.3, 130.9,
130.8, 130.7, 130.6, 130.5, 128.3, 127.6, 127.6, 127.5, 127.4, 126.8,
126.7, 115.3, 110.1, 109.6, 88.0 (d, J = 2.0 Hz), 55.1, 55.0. HRMS
(ESI/[M + Na]+) calcd for C28H24NO3PSNa 508.1103, found
508.1098.
Ethyl-7-chloro-3-(diphenylphosphorothioylamino)-trans-
2,3-dihydrobenzofuran-2-carboxylate (trans-3e). Mp: 177ꢀ
178 °C. 1H NMR (400 MHz, CDCl3) δ = 8.09ꢀ7.93 (m, 4H),
7.57ꢀ7.41 (m, 7H), 7.28ꢀ7.19 (m, 1H), 6.89 (t, J = 7.8, 1H), 5.30
(td, J = 11.0, 3.6, 1H), 5.19 (d, J = 3.7, 1H), 4.07 (q, J = 7.1, 2H), 3.17 (dd,
J = 10.5, 5.9, 1H), 1.13 (t, J = 7.1, 3H). 31P NMR (162 MHz, CDCl3) δ =
59.48. 13C NMR (101 MHz, CDCl3) δ = 168.4, 155.1, 134.2, 134.1,
133.2, 133.0, 132.1, 132.1, 132.1, 132.0, 131.9, 131.6, 131.5, 130.6, 128.7,
128.7, 128.6, 128.5, 124.7, 123.0, 115.9, 87.0 (d, J = 5.0 Hz), 61.8, 58.2,
14.0. HRMS (ESI/[M + Na]+) calcd for C23H21ClNO3PSNa 480.0561,
found 480.0567.
N-(2-Benzoyl-5-methyl-trans-2,3-dihydrobenzofuran-3-
yl)-P,P-diphenylphosphinothioic Amide (trans-3j). Mp: 152ꢀ
154 °C. 1H NMR (400 MHz, CDCl3) δ =8.08ꢀ7.96 (m, 4H), 7.91 (d, J =
7.9, 2H), 7.59ꢀ7.42 (m, 7H), 7.35ꢀ7.23 (m, 3H), 6.75 (d, J =
8.5, 1H), 6.10 (d, J = 3.0, 1H), 5.48 (t, J = 9.1, 1H), 3.22 (dd, J = 10.9,
5.5, 1H), 2.45 (s, 3H). 31P NMR (162 MHz, CDCl3) δ = 58.29. 13C NMR
(101 MHz, CDCl3) δ = 192.4, 158.1, 144.9, 134.3, 133.6, 133.2, 132.6,
132.2, 132.2, 132.1, 132.0, 131.9, 131.8, 131.6, 131.5, 129.5, 129.4, 129.0,
128.8, 128.7, 128.7, 128.6, 113.5, 112.1, 88.9 (d, J = 4.0 Hz), 55.5, 21.8.
HRMS (ESI/[M + Na]+) calcd for C28H24NO2PSNa 492.1157, found
492.1155.
Ethyl-3-(diphenylphosphorothioylamino)-7-phenyl-trans-
2,3-dihydrobenzofuran-2-carboxylate (trans-3f). Mp: 140ꢀ
1
141 °C. H NMR (400 MHz, CDCl3) δ = 8.10ꢀ7.95 (m, 4H), 7.72
N-(2-Benzoyl-5-tert-butyl-trans-2,3-dihydrobenzofuran-
3-yl)-P,P-diphenylphosphinothioic Amide (trans-3k). Mp:
153ꢀ155 °C. 1H NMR (400 MHz, CDCl3) δ = 8.04ꢀ7.92 (m, 6H),
7.55 (t, J = 7.4, 1H), 7.49ꢀ7.36 (m, 9H), 7.26ꢀ7.20 (m, 1H), 6.76 (d,
J = 8.5, 1H), 5.95 (d, J = 3.3, 1H), 5.52 (td, J = 10.5, 2.8, 1H), 3.27 (dd,
J = 10.3, 6.3, 1H), 1.27 (s, 9H). 31P NMR (162 MHz, CDCl3) δ =
58.21. 13C NMR (101 MHz, CDCl3) δ = 193.6, 156.7, 145.1, 134.6,
134.4, 133.7, 133.6, 133.4, 132.0, 131.9, 131.8, 131.7, 131.6, 129.4,
128.7, 128.7, 128.6, 127.5, 126.7, 126.6, 122.9, 109.7, 89.3 (d, J = 4.0
(d, J = 7.6, 2H), 7.57ꢀ7.35 (m, 10H), 7.31 (t, J = 7.3, 1H), 7.04 (t,
J = 7.6, 1H), 5.27 (td, J = 10.7, 2.9, 1H), 5.19 (d, J = 3.0, 1H), 4.06 (q, J =
7.1, 2H), 3.12 (dd, J = 10.2, 5.9, 1H), 1.13 (t, J = 7.1, 3H). 31P NMR (162
MHz, CDCl3) δ = 59.04. 13C NMR (101 MHz, CDCl3) δ = 169.2, 156.4,
136.4, 134.3, 133.3, 132.1, 132.0, 132.0, 131.7, 131.5, 130.3, 128.7, 128.6,
128.6, 128.5, 127.5, 127.4, 125.3, 124.7, 122.6, 86.4, 61.6, 57.7, 14.0.
HRMS (ESI/[M + Na]+) calcd for C29H26NO3PSNa 522.1263, found
522.1269.
Hz), 56.1, 34.5, 31.7. HRMS (ESI/[M
C31H30NO2PSNa 534.1627, found 534.1625.
+
Na]+) calcd for
Ethyl-3-(diphenylphosphorothioylamino)-7-phenyl-trans-
2,3-dihydrobenzofuran-2-carboxylate (cis-3f). H NMR (400
1
MHz, CDCl3) δ 8.04ꢀ7.90 (m, 4H), 7.70 (d, J = 7.2 Hz, 2H), 7.60ꢀ7.31
(m, 11H), 7.01 (t, J = 7.6 Hz, 1H), 5.59 (td, J = 11.8, 8.8 Hz, 1H), 5.20 (d,
J = 8.5 Hz, 1H), 4.63ꢀ4.61 (m, 1H), 4.22 (ddq, J = 76.2 (PꢀH), 10.8, 7.2
Hz, 2H), 3.40 (dd, J = 11.0, 6.6 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H). 31P
NMR (162 MHz, CDCl3) δ 59.63. 13C NMR (101 MHz, CDCl3) δ
168.53, 155.96, 136.40, 135.24, 134.64, 134.24, 133.60, 131.94, 131.68,
131.64, 131.57, 131.53, 130.01, 128.64, 128.62, 128.51, 128.49, 128.43,
127.83, 127.41, 125.29, 124.44, 83.28, 83.22, 61.65, 55.42, 14.13. HRMS
(ESI/[M + Na]+) calcd for C29H26NO3PSNa 522.1263, found 522.1269.
Methyl-3-(diphenylphosphorothioylamino)-7-phenyl-trans-
2,3-dihydrobenzofuran-2-carboxylate (trans-3g). Mp: 138ꢀ
140 °C. 1H NMR (400 MHz, CDCl3) δ = 8.12ꢀ8.01 (m, 4H), 7.76 (d,
J = 7.3, 2H), 7.60ꢀ7.40 (m, 10H), 7.35 (t, J = 7.4, 1H), 7.08 (t, J = 7.6,
1H), 5.30 (td, J = 10.4, 3.2, 1H), 5.25 (d, J = 3.3, 1H), 3.63 (s, 3H),
3.24ꢀ3.12 (m, 1H). 31P NMR (162 MHz, CDCl3) δ = 59.11. 13C NMR
(101 MHz, CDCl3) δ = 169.7, 156.4, 136.4, 134.2, 133.2, 132.1, 132.0,
131.9, 131.7, 131.6, 130.3, 128.7, 128.6, 128.6, 128.6, 128.6, 128.5, 128.5,
127.5, 127.4, 127.4, 125.3, 124.7, 122.7, 86.3 (d, J = 5.0 Hz), 57.8, 52.5.
HRMS (ESI/[M + Na]+) calcd for C28H24NO3PSNa 508.1103, found
508.1095.
N-(2-Benzoyl-5-bromo-trans-2,3-dihydrobenzofuran-3-
yl)-P,P-diphenylphosphinothioic Amide (trans-3l). Mp: 80ꢀ
81 °C. 1H NMR (400 MHz, CDCl3) δ = 8.06ꢀ7.91 (m, 6H), 7.58 (t,
J = 7.3, 1H), 7.54ꢀ7.37 (m, 10H), 7.29 (d, J = 8.0, 1H), 6.71 (d, J = 8.5,
1H), 6.10 (d, J = 3.0, 1H), 5.46 (t, J = 8.9, 1H), 3.26 (dd, J = 10.5, 5.2,
1H). 31P NMR (162 MHz, CDCl3) δ = 58.33. 13C NMR (101 MHz,
CDCl3) δ = 192.8, 158.0, 134.4, 134.2, 133.9, 133.5, 133.2, 132.5, 132.2,
132.2, 132.0, 131.9, 131.6, 131.5, 129.5, 129.4, 129.0, 128.8, 128.7, 128.7,
128.6, 113.5, 112.1, 88.9 (d, J = 3.0 Hz), 55.5. HRMS (ESI/[M + Na]+)
calcd for C27H21BrNO2PSNa 556.0106, found 556.0100.
N-(5-Bromo-2-(4-methylbenzoyl)-trans-2,3-dihydroben-
zofuran-3-yl)-P,P-diphenylphosphinothioic Amide (trans-
3m). Mp: 152ꢀ154 °C. 1H NMR (400 MHz, CDCl3) δ = 8.08ꢀ7.97
(m, 4H), 7.91 (d, J = 7.9, 2H), 7.59ꢀ7.43 (m, 7H), 7.32 (d, J = 8.6, 1H),
7.26 (d, J = 7.9, 2H), 6.75 (d, J = 8.5, 1H), 6.10 (d, J = 3.0, 1H), 5.48 (t,
J = 9.1, 1H), 3.22 (dd, J = 10.9, 5.5, 1H), 2.45 (s, 3H). 31P NMR (162
MHz, CDCl3) δ = 58.29. 13C NMR (101 MHz, CDCl3) δ = 192.4,
158.1, 144.9, 134.3, 133.6, 133.2, 132.6, 132.2, 132.2, 132.1, 132.0,
131.9, 131.8, 131.6, 131.5, 129.5, 129.4, 129.0, 128.8, 128.7, 128.7,
128.6, 113.5, 112.1, 89.0 (d, J = 3.0 Hz), 55.5, 21.8. HRMS (ESI/[M +
Na]+) calcd for C28H23BrNO2PSNa 570.0263, found 570.0265.
N-(5-Bromo-2-(4-chlorobenzoyl)-trans-2,3-dihydroben-
zofuran-3-yl)-P,P-diphenylphosphinothioic Amide (trans-
3n). Mp: 138ꢀ141 °C. 1H NMR (400 MHz, CDCl3) δ = 8.10ꢀ7.92
(m, 6H), 7.60ꢀ7.40 (m, 9H), 7.33 (d, J = 8.6, 1H), 6.75 (d, J = 8.6, 1H),
6.11 (d, J = 3.1, 1H), 5.47 (t, J = 9.0, 1H), 3.23 (dd, J = 11.0, 5.5, 1H). 31P
NMR (162 MHz, CDCl3) δ = 58.32. 13C NMR (101 MHz, CDCl3) δ =
tert-Butyl-3-(diphenylphosphorothioylamino)-7-phenyl-
trans-2,3-dihydrobenzofuran-2-carboxylate (trans-3h). Mp:
1
145ꢀ147 °C. H NMR (400 MHz, CDCl3) δ = 8.11ꢀ7.97 (m, 4H),
7.80 (d, J = 7.4, 2H), 7.58ꢀ7.40 (m, 10H), 7.35 (t, J = 7.4, 1H), 7.07 (t,
J = 7.6, 1H), 5.37 (td, J = 10.7, 2.4, 1H), 5.13 (d, J = 2.6, 1H), 3.15 (dd,
J = 10.1, 6.5, 1H), 1.39 (s, 9H). 31P NMR (162 MHz, CDCl3) δ = 58.68.
13C NMR (101 MHz, CDCl3) δ = 169.0, 157.4, 137.2, 135.4, 135.4,
7703
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705

The Journal of Organic Chemistry
ARTICLE
191.8, 157.9, 140.4, 134.2, 133.3, 133.1, 132.8, 132.3, 132.3, 132.2, 132.2,
132.0, 131.9, 131.5, 131.4, 130.8, 129.3, 129.2, 129.1, 128.9, 128.8, 128.7,
128.6, 113.6, 112.2, 88.8, 55.4. HRMS (ESI/[M + Na]+) calcd for
C27H20BrClNO2PSNa 589.9716, found 589.9710.
(162 MHz, CDCl3) δ = 58.95. 13C NMR (101 MHz, CDCl3) δ = 166.1,
155.1, 142.7, 133.2, 132.2, 131.8, 131.7, 131.6, 130.6, 128.8, 128.7, 128.6,
128.3, 124.7, 122.8, 121.8, 116.0, 89.0 (d, J = 3.0 Hz), 59.4, 51.7. HRMS
(ESI/[M + Na]+) calcd for C24H21ClNO3PSNa 492.0560, found
492.0568.
N-(2-(Furan-2-carbonyl)-trans-2,3-dihydrobenzofuran-3-
yl)-P,P-diphenylphosphinothioic Amide (trans-3o). Mp: 110ꢀ
112 °C. 1H NMR (400 MHz, CDCl3) δ = 8.10ꢀ7.98 (m, 4H),
7.58ꢀ7.40 (m, 8H), 7.37 (s, 1H), 7.24 (t, J = 7.7, 1H), 6.98 (t, J =
7.4, 1H), 6.89 (d, J = 8.1, 1H), 6.53 (s, 1H), 5.80 (d, J = 2.5, 1H), 5.44 (t,
J = 9.1, 1H), 3.27 (d, J = 5.0, 1H). 31P NMR (162 MHz, CDCl3) δ =
58.50. 13C NMR (101 MHz, CDCl3) δ = 181.7, 157.9, 149.5, 146.5,
133.3, 133.1, 132.3, 132.1, 130.9, 130.9, 130.9, 130.9, 130.7, 130.7, 130.6,
130.6, 129.3, 127.7, 127.6, 127.5, 127.4, 126.0, 125.9, 125.2, 120.9, 119.2,
111.5, 109.3, 88.0 (d, J = 3.0 Hz), 55.3. HRMS (ESI/[M + Na]+) calcd
for C25H20NO3PSNa 468.0794, found 468.0790.
(E)-Methyl-3-(3-(diphenylphosphorothioylamino)-7-phenyl-
trans-2,3-dihydrobenzofuran-2-yl)acrylate (trans-3u). Mp: 69ꢀ
70 °C. 1H NMR (400 MHz, CDCl3) δ = 8.13ꢀ7.92 (m, 4H), 7.68 (d, J =
7.4, 2H), 7.57ꢀ7.36 (m, 11H), 7.32 (t, J= 7.3, 1H), 7.04 (t, J=7.6, 1H), 6.85
(dd, J = 15.7, 5.0, 1H), 5.95 (dd, J = 15.7, 1.4, 1H), 5.50ꢀ5.40 (m, 1H), 4.85
(td, J = 10.3, 3.3, 1H), 3.66 (s, 3H), 3.17 (dd, J = 10.0, 6.3, 1H). 31P NMR
(162 MHz, CDCl3) δ = 58.62. 13C NMR (101 MHz, CDCl3) δ = 166.2,
156.3, 143.7, 136.3, 134.4, 134.2, 133.4, 133.1, 132.2, 132.1, 131.9, 131.8,
131.7, 131.6, 130.2, 128.8, 128.7, 128.7, 128.6, 128.5, 128.4, 127.5, 127.4,
125.3, 124.6, 122.4, 121.6, 88.4 (d, J = 3.0 Hz), 58.96, 51.7. HRMS (ESI/[M
+ Na]+) calcd for C30H26NO3PSNa 534.1263, found 534.1260.
N-(2-Benzoyl-2-methyl-trans-2,3-dihydrobenzofuran-3-
yl)-P,P-diphenylphosphinothioic Amide (trans-3v). Mp: 121ꢀ
123 °C. 1H NMR(400 MHz, CDCl3) δ= 7.93 (dd, J =13.8, 7.9, 2H), 7.81
(dd, J = 13.7, 8.1, 2H), 7.57ꢀ7.38 (m, 12H), 7.18 (t, J = 7.7, 1H),
7.00ꢀ6.85 (m, 2H), 5.50ꢀ5.35 (m, 1H), 3.61 (td, J = 10.7, 2.9, 1H), 1.06
(s, 3H). 31P NMR (162 MHz, CDCl3) δ = 59.47. 13C NMR (101 MHz,
CDCl3) δ = 150.2, 136.6, 136.5, 135.6, 135.5, 134.0, 131.7, 131.6, 131.5,
131.4, 131.2, 131.1, 130.3, 129.3, 129.0, 128.7, 128.6, 128.6, 128.5, 128.3,
127.4, 122.7, 121.8, 121.8, 117.0, 90.0, 67.7 (d, J = 3.0 Hz), 50.3, 17.0.
HRMS ESI/[M + Na]+) calcd for C28H24NO2PSNa 492.1157, found
492.1150.
2-Isopropyl-4-methylcyclohexyl-3-((diphenylphosphoro-
thioyl)amino)-7-phenyl-2,3-dihydrobenzofuran-2-carboxy-
late (trans-3w). Value of dr for the two stereomers was determined by
31P NMR of the crude product. The absolute configuration was not
determined. Mp: 69ꢀ71 °C. 1H NMR (400 MHz, CDCl3) δ =
8.10ꢀ7.94 (m, 4H), 7.73 (d, J = 7.7, 2H), 7.55ꢀ7.35 (m, 10H),
7.35ꢀ7.27 (m, 1H), 7.04 (t, J = 7.6, 1H), 5.35ꢀ5.13 (m, 2H),
4.68ꢀ4.54 (m, 1H), 3.09 (s, 1H), 1.68ꢀ1.55 (m, 3H), 1.44ꢀ1.33 (m,
1H), 1.30ꢀ1.24 (m, 1H), 0.89ꢀ0.76 (m, 10H), 0.61 (dd, J = 15.4, 6.8,
3H). 31P NMR (162 MHz, CDCl3) δ = 59.08, 58.62. 13C NMR (101
MHz, CDCl3) δ = 168.9 168.8, 156.5, 156.4, 136.5 136.4, 134.4, 134.3
133.4, 133.3 132.1, 132.0, 132.0, 131.9, 131.7, 131.6, 131.5, 130.3, 130.2,
128.7, 128.6, 128.5, 127.6, 127.4, 125.3, 124.7, 122.57, 86.5 (d, J = 4.0
Hz),, 75.8, 57.6, 46.6, 40.3, 34.1, 31.4, 25.90, 22.9, 22.0, 20.9, 15.9.
HRMS ESI/[M + Na]+) calcd for C37H40NO3PSNa 632.2359, found
632.2356.
P,P-Diphenyl-N-(2-(thiophene-2-carbonyl)-trans-2,3-di-
hydrobenzofuran-3-yl)phosphinothioic Amide (trans-3p).
1
Mp: 121ꢀ122 °C. H NMR (400 MHz, CDCl3) δ = 8.13ꢀ7.99 (m,
4H), 7.93 (d, J = 2.9, 1H), 7.69 (d, J = 4.3, 1H), 7.58ꢀ7.42 (m, 7H),
7.30ꢀ7.22 (m, 1H), 7.12 (s, 1H), 6.99 (t, J = 7.4, 1H), 6.91 (d, J = 8.0,
1H), 5.85 (d, J = 2.5, 1H), 5.45 (t, J = 8.9, 1H), 3.23 (s, 1H). 31P NMR
(162 MHz, CDCl3) δ = 58.24. 13C NMR (101 MHz, CDCl3) δ = 186.2,
157.8, 140.0, 134.1, 133.4, 133.1, 132.8, 132.1, 131.8, 131.0, 130.9, 130.8,
130.7, 130.6, 129.3, 127.7, 127.6, 127.6, 127.5, 127.3, 126.0, 125.9, 125.2,
121.0, 109.4, 88.9 (d, J = 4.0 Hz), 55.6. HRMS (ESI/[M + Na]+) calcd
for C25H20NO2PS2Na 484.0565, found 484.0560.
N-(7-Chloro-2-(thiophene-2-carbonyl)-trans-2,3-dihydroben-
zofuran-3-yl)-P,P-diphenylphosphinothioic Amide (trans-3q).
1
Mp: 163ꢀ165 °C. H NMR (400 MHz, CDCl3) δ = 8.14ꢀ7.93 (m,
6H), 7.71 (d, J = 4.8, 1H), 7.62ꢀ7.41 (m, 8H), 7.33ꢀ7.20 (m, 1H), 7.14
(t, J = 4.1, 1H), 6.93 (t, J = 7.7, 1H), 5.90 (d, J = 3.0, 1H), 5.51 (t, J = 8.9,
1H), 3.26 (dd, J = 9.6, 5.3, 1H). 31P NMR (162 MHz, CDCl3) δ = 58.59.
13C NMR (101 MHz, CDCl3) δ = 185.7, 153.8, 139.9, 134.5, 133.7,
132.9, 132.7, 131.9, 131.7, 131.1, 131.0, 130.8, 130.7, 130.64, 129.5,
127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 123.6, 122.0, 114.8, 89. Four (d,
J = 5.0 Hz), 56.3. HRMS (ESI/[M + Na]+) calcd for C25H19ClNO2PS2-
Na 518.0175, found 518.0170.
N-(2-Acetyl-7-chloro-trans-2,3-dihydrobenzofuran-3-yl)-
P,P-diphenylphosphinothioic Amide (trans-3r). Mp: 168ꢀ
169 °C. 1H NMR (400 MHz, CDCl3) δ = 8.09ꢀ7.95 (m, 4H),
7.58ꢀ7.44 (m, 6H), 7.40 (d, J = 7.3, 1H), 7.24 (d, J = 8.2, 1H), 6.90
(t, J = 7.6, 1H), 5.26 (d, J = 2.3, 1H), 5.17 (t, J = 10.3, 1H), 3.13 (dd, J =
10.0, 5.5, 1H), 2.18 (s, 3H). 31P NMR (162 MHz, CDCl3) δ = 58.77. 13
C
NMR (101 MHz, CDCl3) δ = 203.7, 155.0, 133.9, 133.8, 132.9, 132.8,
132.2, 131.9, 131.8, 131.7, 130.6, 128.8, 128.7, 128.6, 128.5, 124.8, 123.1,
115.9, 92.6 (d, J = 5.0 Hz), 56.7, 26.6. HRMS (ESI/[M + Na]+) calcd for
C22H19ClNO2PSNa 450.0455, found 450.0450.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of 3
S
b
Ethyl-3-((diphenylphosphorothioyl)amino)-6-methoxy-
2,3-dihydrobenzofuran-2-carboxylate (trans-3s). 1H NMR
(400 MHz, CDCl3) δ 8.10ꢀ7.94 (m, 4H), 7.55ꢀ7.38 (m, 7H),
6.54ꢀ6.45 (m, 2H), 5.20 (d, J = 3.0 Hz, 1H), 5.18ꢀ5.10 (m, 1H),
4.06 (q, J = 7.1 Hz, 2H), 3.76 (s, 1H), 3.05 (dd, J = 10.1, 5.7 Hz, 1H),
and 4 and CIF files for 3a. This material is available free of charge
via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
1.11 (t, J = 7.1 Hz, 3H). 31P NMR (162 MHz, CDCl3) δ 58.72. 13
C
Corresponding Author
*E-mail: hyou@nankai.edu.cn.
NMR (101 MHz, CDCl3) δ 169.20, 162.11, 160.68, 134.32, 133.30,
132.06, 131.95, 131.89, 131.63, 131.52, 131.23, 131.12, 128.69,
128.58, 128.56, 128.45, 128.40, 126.52, 118.51, 108.55, 96.26,
87.43, 87.38, 61.65, 57.38, 55.57, 13.99. HRMS (ESI/[M + Na]+)
calcd for C24H24NO3PSNa 476.1056, found 476.1062.
Author Contributions
†These authors contributed equally to this work.
(E)-Methyl-3-(7-chloro-3-(diphenylphosphorothioylam-
ino)-trans-2,3-dihydrobenzofuran-2-yl)acrylate (trans-3t).
’ ACKNOWLEDGMENT
1
Mp: 104ꢀ105 °C. H NMR (400 MHz, CDCl3) δ = 8.11ꢀ7.95 (m,
This work was financially supported by the National Natural
Science Foundation of China (20972076, 21172115) and the
Natural Science Foundation of Tianjin (10JCYBJC04000).
4H), 7.59ꢀ7.44 (m, 6H), 7.37 (d, J = 7.5, 1H), 7.26 (d, J = 8.0, 1H), 6.91
(t, J = 7.7, 1H), 6.83 (dd, J = 15.6, 4.8, 1H), 6.01 (d, J = 15.6, 1H), 5.49 (s,
1H), 4.88 (td, J = 10.5, 3.3, 1H), 3.70 (s, 3H), 3.24 (s, 1H). 31P NMR
7704
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705

The Journal of Organic Chemistry
ARTICLE
’ REFERENCES
(9) Such as synthesis via benzyne, intramolecular substitutions
without metal catalysts, and miscellaneous methods; see selected
examples: (a) Shen, Z.; Dong, V. M. Angew. Chem., Int. Ed. 2009,
48, 784. (b) Beltrꢁan-Rodil, S.; Pen~a, D.; Guitꢁan, E. Synlett 2007, 1308.
(c) Liu, G.; Lu, X. J. Am. Chem. Soc. 2006, 128, 16504.
(10) For reviews, see: (a) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res.
2001, 34, 535. (b) Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004,
346, 1035. (c) Lu, X.; Du, Y.; Lu, C. Pure. Appl. Chem. 2005, 77, 1985.
(d) Nair, V.; Menon, R. S.; Sreekanth, A. R.; Abhilash, N.; Biji, A. T. Acc.
Chem. Res. 2006, 39, 520. (e) Ye, L.-W.; Zhou, J.; Tang, Y. Chem. Soc. Rev.
2008, 37, 1140. (f) Marinetti, A.; Voituriez, A. Synlett 2010, 174. (g)
Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38, 3102.
(11) Meng, X.; Huang, Y.; Chen, R. Org. Lett. 2009, 11, 137.
(12) Xie, P.; Huang, Y.; Chen, R. Org. Lett. 2010, 12, 3768.
(13) 1,1-Dipolar synthon: A functional molecule possessing both
nucleophiles and leaving groups (Nu-LG). When the molecule used was
a C1 synthon, the molecule was named a 1,1-dipolar synthon.
(14) For recent reviews, see: (a) Aggarwal, V. K.; Winn, C. L. Acc.
Chem. Res. 2004, 37, 611. (b) McGarrigle, E. V.; Myers, E. L.; Illa, O.;
Shaw, M. A.; Riches, S. L.; Aggarwal, V. K. Chem. Rev. 2007, 107, 5841.
(c) Sun, X.-L.; Tang, Y. Acc. Chem. Res. 2008, 41, 937.
(15) (a) Lu, L.-Q.; Zhang, J.; Li, F.; Cheng, Y.; An, J.; Chen, J.-R.;
Xiao, W.-J. Angew. Chem., Int. Ed. 2010, 49, 4495. (b) Lu, L.-Q.; Cao, Y.-
J.; Liu, X.-P.; Ming, Z.-H.; Xiao, W.-J. J. Am. Chem. Soc. 2008, 130, 6946.
(c) Lu, L.-Q.; Li, F.; An, J.; Zhang, J.-J.; An, X.-L.; Hua, Q.-L.; Xiao, W.-J.
Angew. Chem., Int. Ed. 2009, 48, 9542. For reviews, see:(d) Aggarwal,
V. K.; Winn, C. L. Acc. Chem. Res. 2004, 37, 611. (e) McGarrigle, E. M.;
Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.; Aggarwal, V. K. Chem.
Rev. 2007, 107, 5841. (f) Sun, X.-L.; Tang, Y. Acc. Chem. Res. 2008,
41, 937.
(16) (a) Malik, S.; Nadir, U. P.; Pandey, P. S. Tetrahedron 2009,
65, 3918. (b) Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Am.
Chem. Soc. 1998, 120, 9690. (c) Zheng, J.-C.; Zhu, C.-Y.; Sun, X.-L.;
Tang, Y.; Dai, L.-X. J. Org. Chem. 2008, 73, 6909. (d) Zhu, C.-Y.; Deng,
X.-M.; Sun, X.-L.; Zheng, J.-C.; Tang, Y. Chem. Commun. 2008, 738. (e)
Zhu, C.-Y.; Sun, X.-L.; Deng, X.-M.; Zheng, J.-C.; Tang, Y. Tetrahedron
2004, 64, 5583. (f) Nadir, U. K.; Chaurasia, B. P.; Sharma, R. L. Chem.
Lett. 1989, 2023.
(17) (a) Meng, X.; Huang, Y.; Chen, R. Chem.—Eur. J. 2008,
14, 6852. (b) Meng, X.; Huang, Y.; Zhao, H.; Xie, P.; Ma, J.; Chen, R.
Org. Lett. 2009, 11, 991. (c) Ma, J.; Huang, Y.; Chen, R. Org. Biomol.
Chem. 2011, 9, 1791. (d) Ma, J.; Xie, P.; Hu, C.; Huang, Y.; Chen, R.
Chem.—Eur. J. 2011, 17, 7418.
(1) For general review on domino reaction, see, for example: (a)
Enders, D.; Grondal, C.; H€uttl, M. R. Angew. Chem., Int. Ed. 2007,
46, 1570.(b) Tietze, L. F.; Brasche, G.; Gericke, K. Domino Reactions in
Organic Synthesis; Wiley-VCH: Weinheim, 2006. (c) Guo, H.-C.; Ma, J.-
A. Angew. Chem., Int. Ed. 2006, 45, 354. (d) Tietze, L. F. Chem. Rev. 1996,
96, 115. (e) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. 1993, 32, 131.
(2) For selected examples, see: (a) Zu, L.; Wang, J.; Li, H.; Xie, H.;
Jiang, W.; Wang, W. J. Am. Chem. Soc. 2007, 129, 1036. (b) Baran, P. S.;
Maimone, T. J.; Richter, J. M. Nature 2007, 446, 404. (c) McDougal,
N. T.; Schaus, S. E. Angew. Chem., Int. Ed. 2006, 45, 3117. (d) Wang, J.;
Xie, H.; Li, H.; Zu, L.; Wang, W. Angew. Chem., Int. Ed. 2008, 47, 4177.
(e) Yao, W.; Wu, Y.; Wang, G.; Zhang, Y.; Ma, C. Angew. Chem., Int. Ed.
2009, 48, 9713. (f) Filloux, C. M.; Lathrop, S. P.; Rovis, T. Proc. Natl.
Acad. Sci. U.S.A. 2010, 107, 20666.
(3) (a) Coy, E. D.; Jovanovic, L.; Sefkow, M. Org. Lett. 2010,
12, 1976. (b) Bertolini, F.; Pineschi, M. Org. Prep. Proced. Int. 2009,
41, 385. (c) Sefkow, M. Synthesis 2003, 2595.
(4) (a) Meijs, G. F.; Beckwith, A. L. J. J. Am. Chem. Soc. 1986,
108, 5890. (b) Boisvert, G.; Giasson, R. Tetrahedron Lett. 1992, 33, 6587.
(c) Clive, D. L. J.; Joseph, E.; T., N.; Lown, J. M. J. Org. Chem. 1993,
58, 2442. (d) Rai, R.; Collum, D. B. Tetrahedron Lett. 1994, 35, 6221. (e)
Itoh, T.; Ohara, H.; Emoto, S. Tetrahedron Lett. 1995, 36, 3531. (f)
Snider, B. B.; Han, L.; Xie, C. J. Org. Chem. 1997, 62, 6978. (g) Terstiege,
I.; Maleczka, R. E. J. Org. Chem. 1999, 64, 342. (h) Vailard, S. E.; Postigo,
A.; Rossi, R. A. J. Org. Chem. 2002, 67, 8500. (i) Kurono, N.; Honda, E.;
Komatsu, F.; Orito, K.; Tokuda, M. Tetrahedron 2004, 60, 1791. (j) Lin,
H.; Schall, A.; Reiser, O. Synlett 2005, 2603. (k) Park, D. Y.;
Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc. 2005, 26, 1440.
(5) (a) Barlugenga, J.; Fananas, F. J.; Sanz, R.; Marcis, C. Chem.—
Eur. J. 2005, 11, 5397. (b) Kneisel, F. F.; Monguchi, Y.; Knapp, K. M.;
Zipse, H.; Knochel, P. Tetrahedron Lett. 2002, 43, 4875. (c) Plotkin, M.;
Chen, S.; Spoors, P. G. Tetrahedron Lett. 2000, 41, 2269. (d) Nakao, J.;
Inoue, R.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1997, 62, 1910.
(6) (a) Lomberget, T.; Baragona, F.; Fenet, B.; Barret, R. Org. Lett.
2006, 8, 3919. (b) Kuethe, J. T.; Wong, A.; Journet, M.; Davies, I. W.
J. Org. Chem. 2005, 70, 3727. (c) Nair, V.; Rajesh, C.; Dhanya, R.; Rath,
N. P. Org. Lett. 2002, 4, 953. (d) Apers, S.; Paper, D.; B€urgermeister, J.;
Baranikova, S.; Dick, S. V.; Lemiꢀere, G.; Vlietinck, A.; Pieters, L. J. Nat.
Prod. 2002, 65, 718. (e) Benbow, J. W.; Katoch-Rouse, R. J. Org. Chem.
2001, 66, 4965. (f) Engler, T. A.; Letavic, M. A.; Iyengar, R.; LaTessa,
K. O.; Reddy, J. P. J. Org. Chem. 1999, 64, 2391. (g) Engler, T. A.; Chai,
W.; LaTessa, K. O. J. Org. Chem. 1996, 61, 9297. (h) Engler, T. A.;
Combrink, K. D.; Ray, G. E. J. Am. Chem. Soc. 1988, 110, 7931.
(7) (a) Kokubo, K.; Harada, K.; Mochizuki, E.; Oshima, T. Tetra-
hedron Lett. 2010, 51, 955. (b) Engler, T. A.; Iyengar, R. J. Org. Chem.
1998, 63, 1929. (c) Rupprecht, K. M.; Boger, J.; Koogsteen, K.; Nachbar,
R. B.; Springer, J. P. J. Org. Chem. 1991, 56, 6180.
(8) For recent transation-metal-catalyzed processes, see: (a) Renꢁe,
O.; Lapointe, D.; Fagnou, K. Org. Lett. 2009, 11, 4560. (b) Natori, Y.;
Tsutsui, H.; Sato, N.; Nakamura, S.; Nambu, H.; Shiro, M.; Hsshimoto,
S. J. Org. Chem. 2009, 74, 4418. (c) Szlosek-Pinaud, M.; Diza, P.;
Martinez, J.; Lamaty, F. Tetrahedron 2007, 63, 3340. (d) Pelly, S. C.;
Govender, S.; Fernandes, M. A.; Schmalz, H.-G.; Koning, C. B. J. Org.
Chem. 2007, 72, 2857. (e) Grant, V. H.; Liu, B. Tetrahedron Lett. 2005,
46, 1237. (f) Pan, C.; Ma, Z.; Yu, J.; Zhang, Z.; Hui, A.; Wang, Z. Synlett
2005, 1922. (g) Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2004, 43, 6144. (h) Kurosawa, W.; Kobayashi, H.; Kan, T.;
Fukuyama, T. Tetrahedron 2004, 60, 9615. (i) Trost, B. M.; Thiel, O. R.;
Tsui, H.-C. J. Am. Chem. Soc. 2003, 125, 13155. (j) Cheung, W.-H.;
Zheng, S.-L.; Yu, W. Y.; Zhou, G.-C.; Che, C.-M. Org. Lett. 2003, 5, 2535.
(k) Zheng, S. L.; Yu, W. Y.; Xu, M. X.; Che, C.-M. Tetrahedron Lett.
2003, 44, 1445. (l) Kurosawa, W.; Kan, T.; Fukuyama, T. Synlett
2003, 1028. (m) Saito, H.; Oishi, H.; Kitagaki, S.; Nakamura, S.; Anada,
M.; Hashimoto, S. Org. Lett. 2002, 4, 3887. (n) Kuwabe, S.-I.; Torraca,
K. E.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 12202. (o) Davies,
H. M. L.; Grazini, M. V. A.; Aouad, E. Org. Lett. 2001, 3, 1475.
7705
dx.doi.org/10.1021/jo2008737 |J. Org. Chem. 2011, 76, 7699–7705