Access to N-Substituted 2-Pyridones by Catalytic Intermolecular Dearomatization and 1,4-Acyl Transfer

Article abstract of DOI:10.1002/anie.201812937

A novel rhodium-catalyzed dearomatization of O-substituted pyridines to access N-substituted 2-pyridones has been developed. A computational study suggests a mechanism involving the formation of a pyridinium ylide followed by an unprecedented 1,4-acyl migratory rearrangement from O to C. Furthermore, the chiral dirhodium complexes serve as the catalyst for the asymmetric transformation with excellent enantioselective control. DFT calculations indicate the chirality is transferred from axial chirality to the central stereogenic centre. The stronger π–π interaction and CH–π interaction account for the high enantioselectivity.

Full text of DOI:10.1002/anie.201812937

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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International Edition
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Accepted Article
Title: Access to N-Substituted 2-Pyridones by Catalytic Intermolecular
Dearomatization and 1,4-Acyl Transfer
Authors: Jiangtao Sun, Guangyang Xu, Ping Chen, Pei Liu, Shengbiao
Tang, and Xinhao Zhang
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201812937
Angew. Chem. 10.1002/ange.201812937
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http://dx.doi.org/10.1002/ange.201812937

10.1002/anie.201812937
Angewandte Chemie International Edition
COMMUNICATION
Access to N-Substituted 2-Pyridones by Catalytic Intermolecular
Dearomatization and 1,4-Acyl Transfer
Guangyang Xu,† Ping Chen,† Pei Liu, Shengbiao Tang, Xinhao Zhang* and Jiangtao Sun*
Abstract:
A
novel rhodium-catalyzed dearomatization of O-
ylide,11 followed by 1,4-acyl rearrangement, the desired N-
substituted 2-pyridones would be achieved (Scheme 1d).
Moreover, upon the choice of chiral rhodium catalysts, a novel
catalytic asymmetric dearomatization (CADA)12 would be
established.
substituted pyridines to access N-substituted 2-pyridones has been
developed. Computational study suggested a mechanism involving
the formation of a pyridinium ylide followed by an unprecedented 1,4-
acyl migratory rearrangement from O-to-C. Furthermore, using chiral
dirhodium complexes as the catalyst, the asymmetric transformation
has been achieved with excellent enantioselective control. DFT
calculations indicate the chirality has been established from axial
chirality to central stereogenic centre. The stronger π-π interaction
and CH-π interaction accounts for the high enantioselectivity.
a) Background
alkylation
+
N
R
O
R
N
O
N
OH
N
O
H
mixed products
strong base
b) Intramolecular O-to-N rearrangement
N-Substituted 2-pyridones are key motifs found in many naturally
occurring products and biologically active pharmaceuticals.1
However, the ambident nucleophilic nature of 2-pyridones makes
the direct N-alkylation a significant challenge that has intrigued
organic chemists for decades (Scheme 1a).2 Traditional methods
for N-substituted 2-pyridone formation often rely on a variety of
reaction parameters including solvents, bases, temperature, and
the nature of electrophiles.3 Recently, several elegant approaches
[M]
R
N
R
O
M = Ru, Ir, Pd, Cu
N
O
R
c) Enantioselective N-alkylation
Rh (Breit)
Ir (You)
+
N
O
or

N
O
H
R
OCO2Me
R
this work
d) Catalytic dearomatization and 1,4-Acyl rearrangement (
)
O
O
[Rh]/L
have
been
developed,
including
intramolecular
N
+
N2
N
O
benzylic/propargylic [1,3]- and allylic [3,3]-rearrangement of O-
alkylated pyridines (Scheme 1b).4 Recently, the Breit group5 and
You group6 independently developed rhodium/iridium-catalyzed
intermolecular asymmetric allylic amination reactions to achieve
this goal (Scheme 1c). Despite the considerable progress, there
are still limitations, including narrow substrate scope, the need of
stoichiometric amounts of strong bases and unavoidable O-
substituted side products. For these reasons, the development of
predictable and reliable protocols for the synthesis of N-
substituted 2-pyridones is highly desirable.
In our continuing research interests in developing novel metal-
carbene transformations,7 we sought to develop an efficient
protocol to achieve N-alkylated 2-pyridones using diazo
compounds as the alkylation reagents. However, a published
report8 and our own investigation9 disclosed that reaction of 2-
pyridones with diazo compounds, catalyzed by rhodium or gold
complexes, exclusively led to O-alkylated pyridines rather than N-
alkylated pyridones. Clearly, the preferred O- over N-reactivity of
2-pyridones makes this an insuperable problem. Inspired by
recent advances in metal-carbene and ylide chemistry,10 we
envisaged that the reaction of 2-O-substituted pyridines with
diazo compounds might allow the in situ formation of pyridinium
O
C-N bonding
C-O cleavage
O
N
O
C-C bonding
N
O
O
[Rh]
Scheme 1. Previous reports and our new strategy
We commenced our studies using O-Boc-pyridine (1) and
vinyldiazoacetate (2) as model substrates to establish the optimal
reaction conditions (Table 1). Initially, performing the reaction in
dichloromethane at room temperature with 1 mol% of dirhodium
catalyst, such as Rh2(OAc)4, Rh2(TFA)4, Rh2(Oct)4 and
Rh2(OPiv)4, delivered 3 in moderate yields (entries 1-4). To our
delight, the use of bulky Rh2(esp)2 (Du Boisʹ catalyst) formed 3 in
67% yield and the reaction was completed in five minutes (entry
5). Next, solvent screening showed that the use of 1,2-
dichloroethane (DCE), acetonitrile, and hexane failed to give
better results (entries 6-8). To improve the reaction further, mixed
solvents were tested (entries 9-11). Gratifyingly, after intensively
examination, we found that the use of dichloromethane/hexane in
a 4:1 ratio afforded 3 in 82% yield (entry 11).
Table 1. Selected optimization[a]
O
[a] G. Xu, P. Liu, S. Tang, Prof. Dr. J. Sun
CO2Me
[Rh]
N2
Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology,
School of Petrochemical Engineering, Changzhou University, 1 Gehu
Road, 213164 Changzhou, China
E-mail: jtsun08@gmail.com or jtsun@cczu.edu.cn
P. Chen, Prof. Dr. X. Zhang
Lab of Computational Chemistry and Drug Design, State Key
Laboratory of Chemical Oncogeomics, Peking University Shenzhen
Graduate School, Shenzhen 518055, China.
Ph
N
+
Boc
solvent
N
O
Ph
Boc CO2Me
2
1
3
Me
Me
Me
Me
O
O
O
O
O
Rh
Rh
O
O
Rh
Rh
Rh
Rh
O
O
O
O
Rh2(esp)2
(Du Bois' catalyst)
O
4
Rh2(OPiv)44
Me
Me
Me
Me
Rh2(Oct)4
Email：zhangxh@pkusz.edu.cn
Entry
Catalyst
Solvent
Time (min)
Yield (%)[b]
[†] G. Xu and P. Chen contributed equally to this work.
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
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10.1002/anie.201812937
Angewandte Chemie International Edition
COMMUNICATION
1
2
3
4
5
6
7
8
9
Rh2(OAc)4
Rh2(TFA)4
Rh2(Oct)4
Rh2(OPiv)4
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
MeCN
hexane
60
60
60
60
5
31
20
47
53
67
56
66
55
74
69
82
in good yields. The reaction of O-Ac pyridine with phenyl
diazoacetate provided 36 in 73% yield, whereas alkyl and cyclic
diazo substrates all gave the desired products (37-38) in higher
yields than the products derived from the O-Boc pyridine. The use
of malonate diazoacetate afforded 39 with removal of the Ac
group in 57% yield after flash chromatography. Notably, the diazo
compounds generated in situ from the corresponding hydrazones,
were also tolerated, although moderate yields were observed (40
and 42). Additionally, pyridines bearing different O-carbonyl
groups, such as propyl, butyl, phenyl and cyclopropanyl were also
amenable to this reaction, providing the corresponding products
(43-46) in good yields. Finally, O-amide pyridines bearing NMe2,
NPh2, piperidine, and Weinreb amide groups were all suitable
substrates, delivering the products (47-52) in good yields (67%-
87%). The structures of 6 and 36 were determined by single
crystal X-ray diffraction.13
A density functional theory (DFT) study was conducted to
understand the reaction mechanism (Figure 1). The process was
found to be rather facile with an overall barrier of only 12.7
kcal/mol. The formation of ylide Int3 is almost energetically
neutral referred to Int1, indicating the feasibility of pyridine ylide
formation. The transition states provide geometrical insights on
the large substrate scope. As illustrated in TS1, the substituents
of rhodium carbene can be easily changed by varying the diazo
compounds. The perpendicular orientation of the pyridine allows
installation of substituents at 3, 4, or 5-position of pyridine. Due to
a significant steric repulsion from the center of the catalyst, the
substitution at 6-position of pyridine leads to a much higher barrier
for TS1ʹ, which is consistent with the experimental observation
(Figure S1). Because of the substituents restrict the rotation of C-
N bond in the ylide Int3, an axial chirality can be constructed.
Such an axial chirality may be transformed to a stereogenic center
via TS2, suggesting the possibility for achieving an asymmetric
transformation.
5
20
20
20
20
20
CH2Cl2/hexane (1:1)
CH2Cl2/hexane (1:4)
CH2Cl2/hexane (4:1)
10
11
[a] Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), catalyst (1 mol%), solvent
(5.0 mL) at rt. [b] Isolated yields.
With the optimal reaction conditions in hand, we next explored
the substrate scope (Scheme 2). Initially, an array of aryl
vinyldiazoacetates bearing various substituents, such as methyl,
methoxy, chloro, fluoro and nitrile groups, at the para position of
phenyl ring, were tested and the products were obtained in
moderate to good yields (4-11). The use of 2-thienyl
vinyldiazoacetate delivered 12 in 74% yield. For benzyl
vinyldiazoacetate, 13 was isolated in 67% yield, whereas styryl
vinyldiazoacetate gave 14 in 61% yield. The reaction is also
amenable to other types of diazo compounds. For instance, use
of alkyl and aryl diazo compounds produced 15 and 16 in 55%
and 72% yield, respectively. Notably, acceptor/acceptor
(malonate diazoacetate) and acceptor/H diazo substrates (α-
benzoyl diazo, ethyl diazoacetate and diazo arylacetamide) were
all tolerated in this reaction, providing 17-20 in moderate yields.
Next, the scope of pyridines was explored. Substitution on the
pyridine ring with electron-donating and electron-withdrawing
groups had a slight effect on the reaction efficiency (21-27).
Additionally, other O-carboxyl groups, such as methyl ester (28)
and 9-fluorenylmethyl ester (Fmoc) (29) were all tolerated, and
the Fmoc group was readily removed upon silica gel
chromatography.
Compared with O-Boc pyridines, O-Ac pyridines exhibited
better reactivity, and the desired products (30-35) were obtained
O
O
O
O
Cl
Cl
O
R
O
4 (R = Me), 65%
S
5 (R = MeO), 61%
6 (R = Cl), 83% (X-ray)
N
N
N
N
N
N
Ph
Me
7
8
(R = F), 85%
(R = CN), 81%
Boc CO2Me
Boc CO2Me
Boc CO2Me
Boc CO2Me
Boc CO2Me
MeO2C Boc
9, 73%
10, 72%
11, 78%
12, 74%
13, 67%
O
O
O
O
O
O
O
O
O
Boc
N
N
H
N
ArHN
Boc
Ph
N
Me
N
MeO2C
N
N
Ph
O
H
Boc CO2Et
Boc CO2Me
Boc CO2Me
15
Boc CO2Me
N
Boc
H
20
, 66%
d
c
19
, 53%
(Ar = 4-ClC6H4)
14
16
18
, 61%
, 55%
, 72%
R
, 60%
Me
17
, 66%
O
R
O
O
O
O
R
O
O
R
Ph
31
N
Ph
N
Ph
N
Ph
N
Ph
(Fmoc)
N
Ph
N
Ph
N
Ac CO2Me
(R= 3-Me), 79%
32 (R = 4-Br), 84%
(R = 5-Me), 73%
Boc CO2Me
(R = Br), 80%
26 (R = CF3), 75%
(R = Me), 69%
Ac CO2Me
, 90%
MeO2C CO2Me
H
CO2Me
Boc CO2Me
(R = Cl), 78%
22 (R = Me), 64%
Boc CO2Me
23
25
30
29
28
, 62%
, 75%
O
21
(R = Me), 70%
33
24 (R = Br), 77%
34 (R = 5-Br), 82%
27
O
O
O
O
O
O
Ph
Ac
N
Ph
N
Ac
MeO2C
N
N
Me
N
R
N
Ph
N
Ph
CO2Me
R
e
(Ac) H CO2Me
40
(R = Me), 51%
41 (R = CF3), 63%
O
Ac CO2Me
Ac CO2Me
, 75%
Ac CO2Me
O
c
N
43 (R = n-Pr), 86%
44 (R = n-Bu), 83%
39
35
, 57%
X-ray
)
36
(
, 73%
38
, 75%
37
, 61%
e
42
Me
(R = H), 55%
O
O
N
O
O
N
O
O
N
O
O
Ph
Ph
N
Ph
Ph
R2N
N
Ph
N
Ph
H
N
CO2Me
CO2Me
OMe
CO2Me
CO2Me
O
CO2Me
O
O
CO2Me
CO2Et
Me2N
Ph
N
N
O
O
N
OMe
O
47
(R = Me), 82%
48 (R = Ph), 87%
Me
Me
d
46
, 85%
49
, 71%
50
, 78%
51
, 78%
52
, 67%
45, 86%
Scheme 2. Substrate scope. [a] Reaction conditions: pyridines (0.2 mmol), diazo compounds (0.3 mmol), Rh2(esp)2 (1 mol%), CH2Cl2/hexane (4:1, 5.0 mL), rt, 20
min. [b] Isolated yields. [c] 60 oC for 2 h. [d] 2 equiv of diazo compound was used. [e] Hydrazone was used as the substrate.
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10.1002/anie.201812937
Angewandte Chemie International Edition
COMMUNICATION
G (E)
We next extended this enantioselective protocol to a range of
substrates using Rh2(S-TCPTTL)4 as the catalyst. The reaction of
pyridine 1 with aryl vinyldiazoacetates bearing either electron-
donating or electron-withdrawing groups on the phenyl ring
proceeded smoothly to afford the desired products (54-60) in
good to excellent yields with excellent enantioselectivities (up to
97% ee), whereas thienyl vinyldiazoacetate provided 61 in 71%
yield and 96% ee. Also, the use of styryl vinyldiazoacetate
delivered 62 in 98% ee albeit with moderate yield. For the scope
of pyridines, the pyridine ring bearing a chloro group at the C3
position afforded the desired product 63 in 84% yield and 86% ee.
Compound 64 bearing a bromo group at the C4 position was
obtained in 60% yield and 99% ee. The absolute configuration of
(S)-64 was determined by single crystal X-ray diffraction.13
However, the 5-CF3 substituted pyridine provided 65 in moderate
enantioselectivity. Next, replacing Boc with Ac group, compound
66 was obtained in 83% yield and 95% ee. It should be noted that
the reaction of O-Ac-pyridine with α-phenyl diazoacetate provided
67 in 56% yield and 84% ee catalyzed by 1 mol% of Rh2(S-
DOSP)415 at 0 oC for 5 h. Other acyl groups were also examined,
and the desired products (68-70) were obtained in good yields
and with high ee values. The amide group was also applicable to
this reaction, and 71 was obtained in 63% yield and 92% ee.
kcal mol-1
tBu
O
MeO
L4Rh2
O
O
O
O
tBu
O
N
O
N
O
Ph
MeO
TS1
12.7(-4.7)
TS1
Ph
TS2
5.1(-13.5)
OtBu
TS2
O
O
Int1
0.0(0.0)
N
Rh2L4
tBu
MeO
Int3
O
0.1(-0.7)
O
N
O
L4Rh2
Int2
-6.9(-24.1)
O
MeO2C
Boc
O
O
N
O
tBu
O
MeO
O
O
Ph
L=OPiv
MeO
L4Rh2
Ph
-20.8(-21.2)
Pro
N
Ph
Ph
Figure 1. Computational exploration
Based on the aforementioned results, we next surveyed the
asymmetric version of this reaction (Scheme 3). The reaction of 1
and diazo 2 in the presence of a variety of chiral dirhodium
o
tetracarboxylate catalysts was explored at 0 C (See Supporting
Information for details). After intensively screening, we found the
use of toluene/hexane (1:1) in the presence of 1 mol% of Rh2(S-
TCPTTL)414 furnished 53 in 79% yield and with 94% ee.
O
Scheme 3. Enantioselective transformation[a,b]
Ph
N
Ph
72
R1
Boc CO2Me
O
R3
R1
Rh2(S-TCPTTL)4 (1 mol %)
PhB(OH)2 (1.1 equiv)
Pd(dppf)Cl2 (5 mol%)
Et3N (3 eq)
dioxane/H2O (10:1)
80 C, 24 h
R3
N
R2
+
N2
toluene/hexane (1:1)
0 oC, 1 h
R4
N
O
R2 R4
76%
O
R
O
54 (R = Me), 90%, 95% ee
55
(R = MeO), 81%, 96% ee
(R = Br)
Ph
N
N
57
(R = Cl), 92%, 97% ee
58 (R = CN), 73%, 92% eec
O
O
Boc CO2Me
Boc CO2Me
O
Pd/C (5 mol%), H2
53, 79%, 94% ee
HCl/dioxane
Ph
N
Ph
N
Ph
N
MeOH, 50 C, 10 h
87%
R
86%
(R = H)
O
Cl
Cl
O
O
Boc CO2Me
Boc CO2Me
H
CO2Me
(R = H)
29
73
N
N
N
Me
Pt/C (5 mol%), H2
84%
O
Boc CO2Me
56, 89%, 95% ee
Boc CO2Me
, 72%, 87% ee
MeOH, 50 C, 20 h
Boc CO2Me
, 81%, 93% ee
Cl
(R = H)
60
59
62
O
N
O
O
S
N
74
Ph
N
Ph
N
Boc CO2Me
Boc CO2Me
, 68%, 98% ee
Boc CO2Me
Boc CO2Me
63, 84%, 86% ee
c
Scheme 4. Further transformations
61
, 71%, 96% ee
O
N
O
Br
Next, further transformations have been conducted to extend
the utility of this methodology (Scheme 4). Treatment of
compound 3 with HCl in dioxane provided 29 in 86% yield. The
reaction of 25 with phenylboronic acid under Suzuki-coupling
reaction conditions generated compound 72 in 76% yield.
Hydrogenation of 3 with Pd/C gave 73 in 87% yield. However,
when Pt/C was used as catalyst for the hydrogenation, the double
bond, the pyridone ring and the phenyl moiety were all
hydrogenated, delivering 74 in 84% yield.
To gain insights into the origin of the enantioselectivity, a
mechanistic study was performed. Rh2(S-TCPTTL)4 carbene was
reported to adopt an α,α,α,α-chiral crown conformation in which
the carbene binds to the top face.16 Three optimized carbene
isomers were shown in Figure 2a and Figure S2. The staggered
conformation Int1L2 was found to be more stable than the eclipsed
Int1L2-a. The bottom face Int1L2-b was considered and found to be
much less stable than Int1L2 by 6.1 kcal/mol.17 Such an energy
difference reveals a significant stabilization from the π-π stacking
in the TCPT pocket. In both Int1L2 and Int1L2-a conformations, two
Ph
Ph
N
CF3
Boc CO2Me
Boc CO2Me
65, 67%, 66% ee
64, 60%, 99% ee
O
O
O
Ph
N
Ph
N
Ph
N
Ac CO2Me
Ac CO2Me
, 56%, 84% ee
O
CO2Me
O
66, 83%, 95% ee
67
68
, 83%, 96% ee
O
O
Ph
N
Ph
N
Ph
Ph2N
N
CO2Me
CO2Me
O
70, 66%, 92% eed
CO2Me
O
O
69, 71%, 93% eed
71, 63%, 92% ee
Cl
Cl
Cl
Cl
O
O
Rh
Rh
4
O
N
S
R
N
O
Rh
Rh
O
O
O
O
Rh ( -DOSP)
2 S
(R = 4-(C12H25)C6H4,)
4
4
Rh2(S-TCPTTL)4
[a] Reaction conditions: pyridine (0.2 mmol), diazo (0.3 mmol), catalyst (1 mol%),
toluene/hexane (1:1, 5 mL), 0 oC, 1 h. [b] Isolated yields. Ee was determined by
HPLC with a chiral stationary phase. [c] 0 oC for 12 h. [d] 0 oC for 2 h
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10.1002/anie.201812937
Angewandte Chemie International Edition
COMMUNICATION
[1] For selected examples, see: a) J. A. Pfefferkorn, J. Lou, M. L. Minich, K. J.
Filipski, M. He, R. Zhou, S. Ahmed, J. Benbow, A.-G. Perez, M. Tu, J.
Litchfield, R. Sharma, K. Metzler, F. Bourbonais, C. Huang, D. A. Beebe,
P. J. Oates, Bioorg. Med. Chem. Lett. 2009, 19, 3247; b) J. A. D. Good, J.
Silver, C. Núñez-Otero, W. Bahnan, K. S. Krishnan, O. Salin, P. Engström,
R. Svensson, P. Artursson, Å. Gylfe, S. Bergström, F. Almqvist, J. Med.
Chem. 2016, 59, 2094; c) S. H. Reich, P. A. Sprengeler, G. G. Chiang, J.
R. Appleman, J. Chen, J. Clarine, B. Eam, J. T. Ernst, Q. Han, V. K. Goel,
E. Z. R. Han, V. Huang, I. N. J. Hung, A. Jemison, K. A. Jessen, J. Molter,
D. Murphy, M. Neal, G. S. Parker, M. Shaghafi, S. Sperry, J. Staunton, C.
R. Stumpf, P. A. Thompson, C. Tran, S. E. Webber, C. J. Wegerski, H.
Zheng, K. R. Webster, J. Med. Chem. 2018, 61, 3516.
tetrachlorophthalimido (TCPT) groups were twisted to parallel
with the carbene, blocking both the Re and Si faces. Therefore,
the origin of enantioselectivity cannot be revealed from the face
preference of Rh-carbene.18 We then calculated full potential
energy surface (Figure S3). The nucleophilic attack of pyridine to
carbene (TS1) is irreversible and supposed to be the
enantioselectivity determining step. A systematic conformation
search (Figure S4) was conducted to obtain possible
conformations. Rotation of three dihedral angles, Ψ1, Ψ2 and Ψ3
leads to 8 conformations (Figure S4 and S5). According to the
Boltzmann distribution and Eyring equation, the theoretical ee
was calculated to be 99% favoring the S-isomer, which is in good
agreement with our observations. The most stable structures
TS1L2-S-cf1 and TS1L2-R-cf5 were depicted in Figure 2b. The π-
π interaction between pyridine and TCPT in TS1L2-S-cf1 (~3.78
Å) is stronger than that in TS1L2-R-cf5 (~4.09 Å). Moreover,
TS1L2-S-cf1 also possesses a relatively stronger CH-π interaction.
To sum up, the stronger π-π interaction and CH-π interaction are
responsible for the enantioselectivity.
[2] a) H. Mayr, M. Breugst, A. R. Ofial, Angew. Chem. Int. Ed. 2011, 50, 6470;
b) M. Breugst, H. Mayr, J. Am. Chem. Soc. 2010, 132, 15380.
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a) Y.-Q. Fang, M. M. Bio, K. B. Hansen, M. S. Potter, A. Clausen, J. Am.
Chem. Soc. 2010, 132, 15525; b) X. Hao, Z. Xu, H. Lu, X. Dai, T. Yang,
X. Lin, F. Ren, Org. Lett. 2015, 17, 3382.
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Figue 2. DFT calculation on the origin of enantioselectivity
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We thank the NNSFC (21572024, 21572192), Shenzhen STIC
(JCYJ20170412150343516), and the Jiangsu Key Laboratory of
Advanced Catalytic Materials and Technology (BM2012110) for
their financial support.
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Keywords: dearomatization • carbene • rearrangement• diazo
compounds• asymmetric catalysis
This article is protected by copyright. All rights reserved.

10.1002/anie.201812937
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Guangyang Xu, Ping Chen, Pei Liu,
Shengbiao Tang, Xinhao Zhang* and
Jiangtao Sun*
Page No. – Page No.
Access to N-Substituted 2-Pyridones
by Catalytic Intermolecular
Dearomatization and 1,4-Acyl
Transfer
A novel rhodium-catalyzed dearomatization of O-substituted pyridines to access N-
substituted 2-pyridones has been developed. Computational study suggested a
mechanism involving the formation of a pyridinium ylide followed by 1,4-acyl
migratory rearrangement from O-to-C. Furthermore, using chiral dirhodium
complexes as the catalyst, the asymmetric transformation has been achieved with
excellent enantioselective control.
This article is protected by copyright. All rights reserved.