A three-component reaction of phosphorus ylides with isocyanates: facile synthesis of 2-amino-3-carboxylate-4-quinolones

Article abstract of DOI:10.1039/d0cc01401j

A three-component reaction between one molecule of phosphorus ylides (P-ylides) and two molecules of isocyanates for the rapid assembly of 2-amino-3-carboxylate-4-quinolones is described. The mechanism may involve the addition of a P-ylide to an isocyanat

Full text of DOI:10.1039/d0cc01401j

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DOI: 10.1039/D0CC01401J
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Three-Component Reaction of Phosphorus Ylides with
Isocyanates: Facile Synthesis of 2-Amino-3-Carboxylate-4-
Quinolones
Received 00th January 20xx,
Accepted 00th January 20xx
Kaki Raveendra Babu,a Wendan Han,a Jian-Bo Chen,b Yang Li,a Yuhai Tang,a Wenquan Zhang,b
DOI: 10.1039/x0xx00000x
Wenbo Xu*c and Silong Xu*a
Three-component reaction between one molecule of phosphorus annulation for the assembly of 4-quinolones from N-
ylides (P-ylides) and two molecules of isocyanates for the rapid nitrosoanilines and cyclopropenones has been demonstrated
assembly of 2-amino-3-carboxylate-4-quinolones is described. The by Chen et al. (eq. c).10n Wu and Li10o also described a gold-
mechanism may involve the addition of P-ylide to an isocyanate catalyzed cyclization of 1-(2’-azidoaryl) propynols for the
followed by 1,3-H shift to form a carbamoyl stabilized P-ylide. The synthesis of 4-quinolones (eq. d). Despite the progress, the
intermediate then reacts with another aryl isocyanate via search of convenient synthesis of 4-quinolones, especially with
Wittig/ketenimine-ketene
rearrangement/6π- varied substitution patterns, is still an upsurge field.2
electrocyclization/1,3-H shift to finally afford the 4-quinolones.
a) Representative drugs of 4-quinolones
OH
F
O
N
O
O
O
Cl
CO2H
The 4-quinolones and their derivatives are extremely
important compounds that display highly broad
pharmacological activities.1 Since the discovery of 4-quinolone
N
H
O
N
H
N
H
HO
4-quinolone
O
lvacaftor
elvitegravir
F
as drugs in 1960s, they have been extensively used in clinics to
2
advance to their 4th generation.1b,
Prominent examples
O
N
O
N
O
N
F
CO2H
CO2
H
include elvitegravir (treatment of HIV),3 lvacaftor (treatment of
cystic fibrosis),4 nedocromil (treatment of asthma),5 and
marketed antibiotics such as ciprofloxacin and levofloxacin
which have persistently found among the top 200 most
frequently prescribed medications worldwide (Figure 1a).1a
Due to their vital importance, the synthesis of 4-quinolones
N
N
HO2
C
O
CO2H
HN
N
O
nedocromil
ciprofloxacin
levofloxacin
HO R1
b) Recent reports on the synthesis of 4-quinolones
O
JohnPhosAuNTf2
(5 mol %)
R2CHO, aq. NH3
R1
6
has captured long-term interest from synthetic chemists.2,
Ar
DCE, 65 o
C
CuCl2 (5 mol %), L-proline
K2CO3, H2O, reflux
Ar
R2
X
Traditional synthetic approaches include Conrad–Limpach,7
Gould–Jacobs,8 and Camps cyclizations.9 Various renewed
methods for the construction of 4-quinolones have also been
developed in recent years.10 In particular, very recently Wang
and co-workers10l has developed a copper-catalyzed synthesis
N3
R = H
X = Cl, Br, I
O
R = H
R1
R2
(a) ref. 10l
(d) ref. 10o
Ar
N
R
O
O
R
N
RNHSO2R1
O
R1
R2
N
Ar
R2
Ar
Cs2CO3 (3 equiv)
X
[Cp*RhCl2
Ag2SO4, NaF
TFE, air, 100 o
]2 (2 mol %)
of
4-quinolones from
3-(2-halophenyl)-3-oxopropane,
DMSO, air, 100 o
C
X = F, Cl, Br, OMe
C
aldehydes and aq. NH3 using water as reaction media (Figure
1b, eq. a). A base-promoted construction of 4-quinolones from
ynones and sulfonamides through a cascade reaction has been
achieved by Cheng group (eq.b).10m A Rh(III)-catalyzed [3 + 3]
(b) ref. 10m
(c) ref. 10n
Figure 1. Representative drugs of 4-quinolones and recent synthetic reports
Phosphorus ylides (P-ylides) are a versatile class of compounds
in organic chemistry. In addition to their Wittig reaction, P-
ylides are also reported to undergo Michael reaction,12
a. Department of Chemistry, School of Science, and Xi’an Key Laboratory of
Sustainable Energy Materials Chemistry, Xi’an Jiaotong University, Xi’an 710049,
P. R. China. E-mail: silongxu@mail.xjtu.edu.cn
b. Institute of Chemical Materials, China Academy of Engineering Physics (CAEP),
Mianyang 621900, P. R. China.
c. College of Chemistry, Chemical Engineering and Materials Science, Shandong
Normal University, Jinan 250014, P. R. China. E-mail: xuwenbo@sdnu.edu.cn
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See DOI:
10.1039/x0xx00000x
Mannich
reaction,13
Tsuji–Trost
allyation,14
allylic
substitution,15 SN2′ allylation,16 decarboxylative allylation,17
propargylic alkylation,18 and so on.19 As part of our interest in
organophosphorus chemistry,16,20 we herein report an
interesting reactivity of P-ylides toward isocyanates for the
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rapid assembly of 2-amino-3-carboxylate-4-quinolones under Investigation on conditions revealed that the reaction in 1,2-
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o
DOI: 10.1039/D0CC01401J
catalyst free conditions (vide infra).
DCE at 100 C remained optimal (For details, see Electronic
Supplementary Information). Under the conditions, the scope
of the reaction was then examined (Scheme 2). It was found
that isocyanates with either electron-donating or -withdrawing
groups on the benzene ring, such as CH3-, PhO-, CF3-, CF3O-,
were all competent in the reaction, providing 4-quinolones
4b–e in 48–67% yields. Isocyanates with disubstituted phenyl
rings also worked well, affording products 4f and 4g in 72%
and 60% yields, respectively. Naphthyl isocyanate was viable
to furnish 4h in 78% yield. Of note, substitution positions at
ortho, meta, or para of the phenyl isocyanates were all
compatible. Next, the scope of the reaction with respect to P-
ylides was examined. It was found that P-ylides bearing esters
of CO2Me and CO2Bn were well-matched giving products 4i
and 4j in good yields, while those bearing CHO or COMe failed
under standard conditions providing complex mixture.
O
p-tolyl
Me
CO2Et
p-tolyl
O
C
N
HN
O
1,2-DCE
condition
EtO2C
+
+
PPh3
N
H
N
Ph3P
CO2Et
H
p-tolyl
4a
1a
3a
2a
1a
2a
3a
4a
entry
condition
rt, 1 h
/yield
/yield
/
1
2
0.50 mmol
0.50 mmol
0.50 mmol
1.0 mmol
96%
100 °C, 36 h
trace
74%
Scheme 1. Initial investigation.
Trippett and Walker21 have reported that P-ylides bearing α
hydrogens can react with phenyl isocyanate to form carbamoyl
stabilized P-ylides. However, our reinvestigation on this
chemistry demonstrated that the reaction is dependent on the
equivalents of isocyanates as well as temperature. For
example, while the reaction of P-ylide 1a (0.50 mmol) and
isocyanate 2a (0.50 mmol) at rt in 1,2-DCE afforded a
carbamoyl stabilized P-ylide 3a in 96% yield (Scheme 1, entry
1), the reaction with two equivalents of isocyanate 2a at a
O
O
NCO
Ar
EtO2C
CO2Et
R
NCO
R
CO2Et
PPh3
N
Ar
H
PPh3
R
N
1,2-DCE
100 °C,36 h
1,2-DCE
rt, 1h
N
3
H
H
1a
5
o
higher temperature (100 C) produced 2-amino-3-carboxylate-
O
O
Me
CO2Et
4-quinolone 4a in 74% yield, with the concomitant formation
of Ph3P=O (entry 2).22 The structure of the products 3a and 4a
has been confirmed by X-ray crystallographic analysis.23 Of
note, Xu and co-workers10h have reported a single case of
similar reaction of a phosphonium salt and α-naphthyl
isocyanate under the catalysis of Ag2CO3/Li2CO3.24 However,
the current reaction of one molecule of P-ylides with two
molecules of isocyanates under catalyst-free conditions
provides a simpler and more convergent synthesis of 4-
quinolones from very simple substrates.
CO2Et
PPh3
N
H
N
H
NH
Ph
R
3b
3c
3d
3e
3f
(R = H), 96%
(R = Me), 91%
5a
, 64%
O
t
(R = Bu), 93%
(R = F), 90%
(R = CF3), 91%
Me
CO2Et
NH
5b
5c
5d
5e
(R = Me), 83%
t
(R = Bu), 84%
Me
O
N
H
(R = F), 56%
CO2Et
N
(R = CF3), 50%
H
PPh3
R
O
3g
, 96%
O
Me
CO2Et
Me
CO2Et
NH
O
R
O
R
R
1,2-DCE
N
NH
Ph
O
CO2Et
PPh3
H
Ar
N
H
Me
+
Ar
Ar
C
N
PPh3
N
H
100 °C, 36 h
R
N
N
H
H
g
h
5
5
(R = Me), 30%
(R = Ph), 70%
2
1
4
5f
, 71%
3h
(R = Me), 91%
3i
(R = Ph), 98%
O
O
O
R
CO2Et
NH
Me
CO2Et
NH
Me
CO2Et
R
R
5i
5j
(R = H), 55%
(R = Me), 62%
O
N
H
N
H
CO2Et
PPh3
N
H
N
H
N
H
4b
4c
4d
(R = OPh), 48%
(R = CF3), 65%
(R = OCF3), 52%
O
O
4a
, 74%
O
3j
(R = H), 94%
3k (R = Me), 92%
F3C
CO2Et
NH
CO2Et
R
Me
CF3
O
O
N
N
H
NH
H
CO2Et
O
CO2Et
CO2Et
O
O
S
CO2Et
PPh3
N
F3C
N
H
NH
Me
N
NH
H
N
H
NH
H
Me
Me
Me
Me
4e
Me
Me
Me
Me
, 67%
4g
, 60%
4f
, 72%
b
3l, 100%
5k
5l
, 67%
, 64% (56%)
F3C
CF3
Scheme 3. Temperature-controlled sequential reaction of p-ylides with two
different isocyanates a Reaction conditions: under N2, P-ylide 1a (1.0 mmol) and
isocyanates 2 (1.0 mmol) in 1,2-DCE (3 mL) at room temperature for 1 h; P-ylides
3 (0.50 mmol) and isocyanates 2 (0.50 mmol) in 1,2-DCE (3 mL) at 100 oC for 36
h; Yields of isolated products. b Yield from one-pot procedure.
O
O
CO2Et
NH
Me
R
Me
N
H
N
H
N
H
4i
(R = CO2Me), 60%
4j
(R = CO2Bn), 60%
Since the reaction sequence is highly dependent on
temperature, as shown in Scheme 1, a two-step manipulation
was employed to achieve a sequential reaction of P-ylides with
two different molecules of isocyanates. Thus, the reaction of
1a with a range of isocyanates 2 was performed in 1,2-DCE at
4h
, 78%
Scheme 2. Three-component reaction of p-ylides with isocyanates. Reaction
conditions: P-ylides 1 (0.50 mmol) and isocyanates 2 (1.0 mmol) in 1,2-DCE (3
mL) at 100 oC under N2 for 36 h; Yields of isolated products.
2 | J. Name., 2012, 00, 1-3
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rt to produce the carbamoyl stabilized P-ylides 3.21 The one pot under standard conditions produced proVdieuwcAtsrtic4leaOanlninde
DOI: 10.1039/D0CC01401J
resultant P-ylides 3 were then treated with a different aryl 5k in equal ratio (1:1) (Scheme 5). Since the electronic
isocyanate 2 at 100 oC for 36 h to provide the 4-quinolone properties of the aromatic ring hardly influence the reaction, it
products 5 (Scheme 3). Various primary alkyl isocyanates could excludes the Friedel–Crafts pathway for the C–H acylation.
be intercepted in the first step to form P-ylides 3 in excellent
yields, which then reacted with isocyanate 2a to afford the 4-
O
O
EtO2C
p-tolyl
2a
(R = Me)
N
R
CO2Et
NCO
H
3a
quinolones 5a–f in 50–84% yields. The structure of 5a has
been confirmed by X-ray crystallographic analysis.23 Secondary
alkyl isocyanates were also feasible, as exemplified by the
formation of products 5g and 5h in moderated yields. Using
two different aryl isocyanates, the corresponding products, i.e.
5k, 5l, could be generated in 64% and 67% yields, respectively.
However, a sulfonamide P-ylide 3l, though generated in
excellent yield, failed in the subsequent reaction. Finally, a
one-pot sequential reaction without the isolation of the
intermediate was demonstrated, which produced product 5k
in a slightly lowered 56% yield.
To further investigate the scope (Scheme 4), it was found that
P-ylide 6 bearing a N,N-disubstituted amide reacted well with
isocyanate 2a to produce the corresponding product 7 in 50%
yield, and P-ylide 8 possessing geminal two esters also worked
well to generate 2-phenoxyl-3-carboxylate-4-quinolone 9 in
51% yield (eq 1). However, employing P-ylide 10 bearing a
thioamide unit failed in the reaction, which, instead, produced
a thiazolidine 11 in 42% yield with solvent 1,2-DCE participated
in cyclization (eq 2). The structure of 11 was confirmed by X-
ray crystallographic analysis.23
(0.25 mmol)
+
2c
PPh3
)
(0.25 mmol
p-tolyl
N
H
N
H
(R = CF3)
1,2-DCE
4a
5k
(R = CF3)
(R = Me) +
(0.25 mmol)
100 °C, 36 h
R
a 4a 5k
= 1 : 1
ratio
/
a Identified by 1H NMR of the crude mixture
Scheme 5. Control experiment
Based on the above results and literature,10h,21,28 a plausible
mechanism is depicted in Scheme 6. Initially, the addition of P-
ylide 1a to isocyanate 2a followed by 1,3-H shift generates the
P-ylide 3a.21 The resultant 3a, at high temperature, undergoes
the Wittig reaction with another molecule of isocyanate 2a to
form α-amidoketenimine A.28e,28f Subsequent rearrangement
with 1,3-migration of the amino group via a four-membered
intermediate B leads to an α-imidoylketene C.28a,28b Next, 6π-
electrocyclization of C takes place to generate a fused
heterocycle D28c,28d that finally undergoes 1,3-H shift to restore
aromaticity and give 2-amino-3-carboxylate-4-quinolone 4a.
O
O
H
EtO2
C
Addition
1,3-H shift
p-tolyl
CO2Et
p-tolyl
CO2Et
N
N
H
1a
PPh3
3a
NCO
PPh3
PPh3
Wittig
2a
O
O
Me
Me
2a
p-tolyl NCO
Ph3P=O
CO2Et
Me
CO2Et
O
A
(0.5 mmol)
O
O
C
(1)
PPh3
(0.5 mmol)
p-tolyl
CO2Et
p-tolyl
N
CO2Et
1,2-DCE
N
H
A
N
H
H
100 °C, 36 h
Me
Me
p-tolyl
C
N
N
N
6
7
9
, A =
N
, 50%, A = N
CO2Et
p-tolyl
p-tolyl
ketenimine-ketene
rearrangement
C
B
A
HN
8
, A = OPh
S
, 51%, A = OPh
Me
Me
6-electrocyclization
Ph
N
Cl
Cl
as above
Ph
CO2Et
O
O
H
CO2Et
(2)
N
H
Me
CO2Et
p-tolyl
Me
CO2Et
S
1,3-H shift
PPh3
p-tolyl
11
, 42%
10
(0.5 mmol)
N
H
N
N
N
H
H
D
4a
Scheme 4. Further investigation of substrate scope
Scheme 6. Proposed mechanism
As shown above, the tandem reaction between P-ylides and
isocyanates enables an efficient synthesis of 2-amino-3-
carboxylate-4-quinolones. It should be mentioned that the
presence of 3-carboxylate on 4-quinolones is essential in many
drugs25 (Figure 1). In addition, the presence of 2-amino group
on 4-quinolones also delivers promising bioactivity (e.g.,
IMPDH inhibitor).26 Thus, the obtained 2-amino-3-carboxylate-
4-quinolones are expected to possess significant
pharmaceutical activities. However, the synthesis of this group
of 4-quinolones has been seldom documented.27
To gain insight into the mechanism, 31P NMR monitoring on
the reaction of 2a with 3a was conducted, which showed only
two peaks at δ 18.39 and δ 29.19 ppm corresponding to 3a
and O=PPh3, respectively (for details, see Electronic
Supplementary Information). These 31P NMR signals might
imply the Wittig process in the tandem sequence. In addition,
a control experiment by treating P-ylide 3a with both p-tolyl
isocyanate 2a and p-trifluoromethylphenyl isocyanate 2c in
In conclusion, a one-pot tandem reaction of P-ylides with two
equivalents of isocyanates for the rapid construction of 2-
amino-3-carboxylate-4-quinolones is described. By employing
the temperature-dependent two-step procedure, the
sequential reaction of P-ylides with two different isocyanates
can be realized. The proposed mechanism involves the
addition of P-ylide to an isocyanate followed by 1,3-H shift to
form a carbamoyl stabilized P-ylide, which is then intercepted
by a second aryl isocyanate via tandem Wittig/ketenimine-
ketene rearrangement/6π-electrocyclization/1,3-H shift to
finally afford 2-amino-3-carboxylate-4-quinolones. This
reaction demonstrates an interesting reactivity of P-ylides
toward isocyanates and provides an efficient synthesis of
biologically important 4-quinolones. Other merits of the
reaction include catalyst free conditions, simple and
commercially available starting materials, and flexible
substitution patterns. Future study will focus on the medicinal
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Lett., 2009, 11, 5246–5249; (c) J.-B. Zhu, P. Wang, S. Liao
utility of 2-amino-3-carboxylate-4-quinolones and exploiting
new reactivity of P-ylides.
View Article Online
and Y. Tang, Org. Lett., 2013, 15, 3054–3057.
13 Y. Zhang, Y.-K. Liu, T.-R. Kang, Z.-K. HuDaOnId: 1Y0..1-0C3.9C/Dh0eCnC, 0J.14A0m1J.
Chem. Soc., 2008, 130, 2456–2457.
14 (a) W.-B. Liu, H. He, L.-X. Dai and S.-L. You, Chem–Eur. J.,
2010, 16, 7376–7379; (b) X.-T. Ma, Y. Wang, R.-H. Dai, C.-R.
Liu and S.-K. Tian, J. Org. Chem., 2013, 78, 11071–11075.
15 A. Lin, J. Wang, H. Mao, Y. Shi, Z. Mao and C. Zhu, Eur. J. Org.
Chem., 2013, 2013, 6241–6245.
We are thankful for financial support from the National Natu-
ral Science Foundation of China (No. 21871218), Presidential
Foundation of CAEP (No. YZJJLX2017003), Fundamental Rese-
arch Funds for the Central Universities, and Key Laboratory
Construction Program of Xi'an Municipal Bureau of Science
and Technology (No. 201805056ZD7CG40). Prof. Jiangxi Yu
(HYNU) is thanked for X-ray crystallographic analysis.
16 S. Xu, S. Zhu, J. Shang, J. Zhang, Y. Tang and J. Dou, J. Org.
Chem., 2014, 79, 3696–3703.
17 W.-L. Leng, H. Liao, H. Yao, Z.-E. Ang, S. Xiang and X.-W. Liu,
Org. Lett., 2017, 19, 416–419.
18 K. Zhang, L.-Q. Lu, S. Yao, J.-R. Chen, D.-Q. Shi and W.-J. Xiao,
J. Am. Chem. Soc., 2017, 139, 12847–12854.
Conflicts of interest
There are no conflicts to declare.
19 (a) D. Pierrot, M. Presset, J. Rodriguez, D. Bonne and Y.
Coquerel, Chem–Eur. J., 2018, 24, 11110–11118; (b)H.-Y. Bi,
F.-P. Liu, C. Liang, G.-F. Su and D.-L. Mo, Adv. Synth. Catal.,
2018, 360, 1510–1516; (c) T. Miura, Y. Funakoshi, J.
Nakahashi, D. Moriyama and M. Murakami, Angew. Chem.,
Int. Ed., 2018, 57, 15455–15459; (d) D.-J. Dong, H.-H. Li and
S.-K. Tian, J. Am. Chem. Soc., 2010, 132, 5018–5020; (e) X.-L.
Sun and Y. Tang, Acc. Chem. Res., 2008, 41, 937–948.
20 (a) S. Xu and Z. He, RSC Adv., 2013, 3, 16885–16904; (b) S.
Xu and Z. He, Chin. J. Org. Chem., 2014, 34, 2438–2447; (c) S.
Xu, J. Shang, J. Zhang and Y. Tang, Beilstein J. Org. Chem.,
2014, 10, 990–995; (d) S. Xu and Y. Tang, Lett. Org. Chem.,
2014, 11, 524–533; (e) J. Wu, Y. Tang, W. Wei, Y. Wu, Y. Li, J.
Zhang, Y. Zheng and S. Xu, Angew. Chem., Int. Ed., 2018, 57,
6284–6288; (f)X. He, Y. Tang, Y. Wang, J.-B. Chen, S. Xu, J.
Dou and Y. Li, Angew. Chem., Int. Ed., 2019, 58, 10698–
10702.
Notes and references
1
(a) L. A. Mitscher, Chem. Rev., 2005, 105, 559–592; (b) H. H.
M. Hamada, A. A. A.-R. Gamal El-Din, H. A. Samar and M. N.
A. El-Shimaa, Curr. Med. Chem., 2019, 26, 3132–3149; (c)
H. Huse and M. Whiteley, Chem. Rev., 2011, 111, 152–159.
P. Ghosh and S. Das, Eur. J. Org. Chem., 2019, 2019, 4466–
4516.
K. Shimura, E. Kodama, Y. Sakagami, Y. Matsuzaki, W.
Watanabe, K. Yamataka, Y. Watanabe, Y. Ohata, S. Doi and
M. Sato, J. Virol., 2008, 82, 764–774.
2
3
4
5
6
M. E. Condren and M. D. Bradshaw, J. Pediatr. Pharmacol.
Ther., 2013, 18, 8–13.
H. Cairns, D. Cox, K. J. Gould, A. H. Ingall and J. L. Suschitzky,
J. Med. Chem., 1985, 28, 1832–1842.
C. Shen, A. Wang, J. Xu, Z. An, K. Y. Loh, P. Zhang and X. Liu,
Chem, 2019, 5, 1059–1107.
21 S. Trippett and D. M. Walker, J. Chem. Soc., 1959, 3874–
3876.
22 Treatment of P-ylide 3a (0.50 mmol) with 2a (0.50 mmol) at
o
7
8
R. H. Reitsema, Chem. Rev., 1948, 43, 43–68.
R. G. Gould and W. A. Jacobs, J. Am. Chem. Soc., 1939, 61,
2890–2895.
100 C in 1,2-DCE also afforded 4a in 76% yield, suggesting
that 3a is an intermediate for the reaction.
23 Crystallographic data are available as ESI† or as CCDC (3a:
9
R. Camps, Ber. Dtsch. Chem. Ges., 1899, 32, 3228–3234.
1964343; 4a: 1963704; 5a: 1963707; 11: 1969290).
O
10 (a) L. Aakerbladh, P. Nordeman, M. Wejdemar, L. R. Odell
and M. Larhed, J. Org. Chem., 2015, 80, 1464–1471; (b) X. Ji,
D. Li, Z. Wang, M. Tan, H. Huang and G.-J. Deng, Asian J. Org.
O
Ag2CO3 (30 mol %)
Li2CO3 (30 mol %)
NCO
Me
N
Me
N
+
24
CH3CN, 100 , 2 h
80% yield
N
PPh3
O
H
Chem., 2018, 7, 711–714; (c) R.
Santhosh
Reddy,
C.
Br
O
Lagishetti, I. N. C. Kiran, H. You and Y. He, Org. Lett., 2016,
18, 3818–3821; (d) F. Wang, L. Jin, L. Kong and X. Li, Org.
Lett., 2017, 19, 1812–1815; (e) C. Wu, P. Huang, Z. Sun, M.
Lin, Y. Jiang, J. Tong and C. Ge, Tetrahedron, 2016, 72, 1461–
1466; (f) T.-K. Zhao and B. Xu, Org. Lett., 2010, 12, 212–
215; (g) B. S. Gore, C. C. Lee, J. Lee and J.-J. Wang, Adv.
Synth. Catal., 2019, 361, 3373–3386; (h) Z. Hu, J. Dong, Y.
Men, Z. Lin, J. Cai and X. Xu, Angew. Chem., Int. Ed., 2017, 56,
1805–1809; (i) S.-F. Jiang, C. Xu, Z.-W. Zhou, Q. Zhang, X.-H.
Wen, F.-C. Jia and A.-X. Wu, Org. Lett., 2018, 20, 4231–4234;
(j) X. Xu, R. Sun, S. Zhang, X. Zhang and W. Yi, Org. Lett.,
2018, 20, 1893–1897; (k) X. Xu and X. Zhang, Org. Lett.,
2017, 19, 4984–4987; (l) B. S. Gore, C. C. Lee, J. Lee and J.-J.
Wang, Adv. Synth. Catal., 2019, 361, 3373–3386; (m) J. Liu,
D. Ba, W. Lv, Y. Chen, Z. Zhao and G. Cheng, Adv. Synth.
Catal., 2020, 362, 213–223; (n) Y. Liu, Y. Tian, K. Su, P.
Wang, X. Guo and B. Chen, Org. Chem. Front., 2019, 6, 3973–
3977; (o) X. Wu, L.-L. Zheng, L.-P. Zhao, C.-F. Zhu and Y.-G.
Li, Chem. Commun., 2019, 55, 14769–14772.
25 (a) Z. Hajimahdi, R. Zabihollahi, M. R. Aghasadeghi, S. H.
Ashtiani and A. Zarghi, Med. Chem. Res., 2016, 25, 1861–
1876; (b) Y. Zhi, L.-X. Gao, Y. Jin, C.-L. Tang, J.-Y. Li, J. Li and
Y.-Q. Long, Biorg. Med. Chem., 2014, 22, 3670–3683.
26 A. F. Haughan, H. J. Dyke, G. M. Buckley, N. Davies, D. R.
Hannah, M. D. Richard, A. Sharpe and S. C. Williams,
WO2003035066A1, 2003.
27 M. P. Wentland, R. B. Perni, P. H. Dorff, R. P. Brundage, M. J.
Castaldi, T. R. Bailey, P. M. Carabateas, E. R. Bacon, D. C.
Young and a. et, J. Med. Chem., 1993, 36, 1580–1596.
28 (a) J. J. Finnerty and C. Wentrup, J. Org. Chem., 2004, 69,
1909–1918; (b) C. Wentrup, V. V. R. Rao, W. Frank, B. E.
Fulloon, D. W. J. Moloney and T. Mosandl, J. Org. Chem.,
1999, 64, 3608–3619; (c) V. V. Ramana Rao and C. Wentrup,
J. Chem. Soc., Perkin Trans. 1, 1998, 2583–2586; (d) B.
E.
Fulloon and C. Wentrup, J. Org. Chem., 1996, 61, 1363–1368;
(e) P. Frøyen, Acta Chem. Scand. B, 1974, 28b, 586–588; (f)P.
Lu and Y. Wang, Chem. Soc. Rev., 2012, 41, 5687–5705; (g) X.
Yi and X. Hu, Angew. Chem., Int. Ed., 2019, 58, 4700–4704;
(h) J. Cai, H. Bai, Y. Wang, X. Xu, H. Xie and J. Liu, Chem.
Commun., 2019, 55, 3821–3824.
11 B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863–
927.
12 (a) A. Lin, J. Wang, H. Mao, H. Ge, R. Tan, C. Zhu and Y.
Cheng, Org. Lett., 2011, 13, 4176–4179; (b) B.-C. Hong, R.-H.
Jan, C.-W. Tsai, R. Y. Nimje, J.-H. Liao and G.-H. Lee, Org.
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