Enantioselective synthesis of pyrano[2,3-: C] pyrrole via an organocatalytic [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones

Article abstract of DOI:10.1039/c9ob00419j

An enantioselective [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones has been successfully developed through a squaramide catalysis strategy. This protocol provides an efficient and mild access to obtain pyrano[2,3-c]pyrrole scaffolds containing contiguous quaternary and tertiary stereogenic centers in excellent yields (up to 99%) with high levels of diastereo- and enantioselectivities (up to 99% ee). Two possible pathways were proposed to explain the observed stereoselectivity.

Full text of DOI:10.1039/c9ob00419j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Enantioselective Synthesis of Pyrano[2,3-c]pyrrole via
Organocatalytic [4+2] Cyclization Reaction of Dioxopyrrolidines
and Azlactones
Received 00th January 20xx,
Accepted 00th January 20xx
Yichen Wang a, Yuzhen Chen a, Xiaoping Li a, Yukang Mao a, Weiwen Chen a, Ruoting Zhan a and
Huicai Huang*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
An enantioselective [4+2] cyclization reaction of dioxopyrrolidines and azlactones has been successfully developed through
a squaramide catalysis strategy. This protocol provides an efficient and mild access to obtain pyrano[2,3-c]pyrrole scaffold
containing contiguous quaternary and tertiary stereogenic centers in excellent yields (up to 99%) with high levels of
diastereo- and enantioselectivity (up to 99% ee). Two possible pathways were proposed to explain the observed
stereoselectivity.
and synthetic products, displaying marvellous bioactivities (Fig.
1).8 Nevertheless, the strategy to synthesis pyrano-pyrrole via
[4+2] cycloaddition of azlactone has been not reported in the
literature. Herein, we disclose a mild and concise way to
synthesis enantiomerically enriched pyrano[2,3-c]pyrrole
derivatives via catalytic asymmetric [4+2] cyclizations of
azlactones (Scheme 1b).
Introduction
Azlactones are becoming to a class of important reactants in
organic synthesis because of their multiple reactive sites,1
endowing with both nucleophilic and electrophilic properties
due to their interconvertible keto and enol forms, which have
been widely investigated for the enantioselective synthesis of
amino acids containing a quaternary stereocenter.2 Briefly,
Oxazole-5-(4H)-ones represent a class of synthetically robust
and versatile building blocks enabling either [2+n] by utilizing
C4, C5 reactivity,3,5,6 [3+n] cycloadditions by activating as 1,3-
dipoles and other additive reactions.4 Among these reactions,
the catalytic asymmetric [2+4] cyclizations of azlactones using
its C4, C5-reactivity have provided an efficient strategy to access
cyclic carbonyl compound containing amino acid units.
Encouraged by the pioneering study of Gong,5a Feng5b and
Terada,5c lots of pyrane5 or dihydrocoemarins6 and their
derivatives were constructed through catalytic asymmetric
[2+4] cyclizations of azlactones (Scheme 1a).
OH
MeO
H
O
N
O
O
N
O
N
HO
OH
O
N
O
O
O
O
OH
Tazettine
anti-proliferative activity
Phaeosphaeride A
Figure 1 Natural and synthetic products containing the pyrane-
pyrrole moiety.
Despite these elegant works of azlactones, considerable
attention devoted to assemble pharmaceutically relevant
framework is still highly desirable. Pyrrole can be found as a
substructure in many natural and synthetic products, many of
which exhibit interesting biological activities.7 Fusion of
dihydropyranone with a privileged pharmacophore pyrrolidone
provides new synthetic possibilities for drug development.
Furthermore, such bicyclic backbones are also found in natural
a) Previous work
Construction of dihydrocoemarin or pyrane skeleton
O
Well-developed
R3
R1
NHCOR2
[2+4]

O
R1

+
X
R3
N
R2
X
O
b) This work
O
O
O
O
O
O
R1
O
Squaramide
a Research Center of Chinese Herbal Resource Science and Engineering, Guangzhou
University of Chinese Medicine; Key Laboratory of Chinese Medicinal Resource
from Lingnan (Guangzhou University of Chinese Medicine), Ministry of Education.
Guangzhou, 510006, P. R. China. E-mail: huanghc@gzucm.edu.cn
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
O
+
Bn
N
N
N
H
R2
N
Bn
R1
R3
R2
R3
Scheme 1 Synthesis of pyrane derivatives via [4+2] cyclizations
of azlactones.
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observed by crude 1H NMR. d Determined by chiral HPLVCieawnAarltyicsleisOonlninea
Results and discussion
DOI: 10.1039/C9OB00419J
chiral column
Base on the above considerations, our initial investigations
were carried out using a series of tertiary amine-thioureas
catalysts (3a-3d) for the model reaction of 1-benzyl-4-
benzylidenepyrrolidine-2,3-dione 1a and azlactone 2a in CHCl3
at room temperature. Generally, those catalysts effectively
promoted the model reaction to obtain the corresponding
product 4a as single diastereoisomer with moderate yield after
6 hours, but with low enantioselectivity (Table 1, entries 1-4).
Pleasingly, when squaramide scaffolds was introduced in these
catalysts for strengthening the hydrogen-bonding effect, they
led to an increase in the enantioselectivity of the process and
have a little effect on the yield of the reaction (entries 5-8). It
was found that catalyst 3e was the most potent in CHCl3 at room
temperature, and the cycloaddition product 4a was formed in
75% yield with >20:1 dr and 83% ee (entry 5).
Since the squaramide catalyst 3e provided the best initial
yield and enantioselectivity for the synthesis of 4a from 1a and
2a, further optimization was pursued with this scaffold. Among
the different kinds of solvents (Table 2, entries 1-6), CHCl3 was
proved to be the most effective in increasing both the yield and
enantioselectivity of 4a (entry 1). Lowering the reaction
temperature allowed further improvement in the selectivity of
reaction (entries 7-9), when the reaction was performed at -
20 °C, 4a was formed with 92% ee, albeit at a slight decrease of
the reaction yield. Subsequently, the optimization efforts were
directed towards the reaction concentration and time (entry 10).
To our delight, both yield and ee have been improved by
prolonged time and reduced concentration of reactant.
Furthermore, expanding the amount of reaction could increase
in yield to 91% was observed while maintaining the
enantioselectivity (entry 11).
Table 1 Evaluation of catalystsa
O
O
O
O
O
O
O
Bn
N
3
Cat.
O
N
H
PMP
Table 2 Optimization of the reaction conditionsa
+
Bn
N
CHCl3
Bn
Bn
N
PMP
O
O
O
O
O
O
O
1a
2a
4a
Bn
N
3e
Cat.
O
+
PMP=p-OMeC6H4
N
H
PMP
Bn
N
solvent
Bn
Bn
N
F3C
PMP
CF3
CF3
S
Ph
NH NH
3c
S
S
N
NH
Ph
H
F3C
CF3
1a
2a
4a
N
N
N
CF3
H
H
N
PMP=p-OMeC6H4
N
N
3b
3a
Entry
Solvent
Temp
time
Yieldb (%)
eec (%)
OMe
(°C)
F3C
O
O
O
OMe
O
CF3
CF3
N
1
2
3
4
5
6
7
CHCl3
CH2Cl2
DCE
rt
rt
rt
rt
rt
rt
0
6h
0.5h
2h
75
59
55
20
70
61
80
83
74
67
59
73
38
89
NH
N
H
N
F3C
N
HN
NH
S
H
N
NH
N
N
CF3
OMe
3d
3f
CCl4
48h
5.5h
1h
3e
F3C
OMe
Toluene
THF
CF3
O
O
N
Ph
Ph
NH
CF3
CF3
NH
NH
CHCl3
6h
N
H
N
CF3
O
N
8
9
CHCl3
CHCl3
-10
-20
6h
6h
87
83
90
92
O
3g
3h
10d
11e
CHCl3
CHCl3
-20
-20
48h
48h
85
91
94
94
Entry
Cat.
Solvent
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
84
63
66
88
75
50
70
72
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
46
34
a
The reaction was conducted with 0.05 mmol of 1a, 0.06 mmol of 2a
and 0.005 mmol of 3e in 1.0 mL solvent. b Isolated yields after column
chromatography on silica gel. c Determined by chiral HPLC analysis on
a chiral column. Only a single diastereoisomer was observed by crude 1H
NMR. d In 2.0 mL CHCl3. e The reaction was conducted with 0.10 mmol
of 1a, 0.12 mmol of 2a and 0.01 mmol of 3e in 4.0 mLCHCl3.
40
-26
83
70
Having established the optimum reaction conditions, we next
investigated the scope of dioxopyrrolidines 1 which were
employed to react with azlactone 2a. As shown in Table 3,
gratifyingly, excellent yields and enantioselectivities (all
cases >20:1dr) were obtained with substrates containing
various aryl and heteroaryl groups (4a-4w) at the terminal
3g
3h
75
-70
a
The reaction was conducted with 0.05 mmol of 1a, 0.06 mmol of 2a
b
and 0.005 mmol of 3 in 1.0 mL CHCl3. Isolated yields after column
c
chromatography on silica gel. Only a single diastereoisomer was
2 | J. Name., 2012, 00, 1-3
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Table 3 Substrate scope of dioxopyrrolidines 1a
position of the dioxopyrrolidines. With para-substitution
bearing either electron-donating or electron-withdrawing
groups, these substrates proceeded smoothly to desired
products 4b-4h in good yields as well as enantioselectivities. As
for the substrates with meta-position, the corresponding
products 4i-4m were afforded in good to excellent yields (82%-
99%), with excellent enantioselectivities (92-95% ee). For ortho-
substituent bearing electron-withdrawing, 4n and 4o were
delivered in good yields (83% and 70% respectively) and
enantioselectivities (95% and 90% ee respectively), especially,
product 4p with electron-donating substituent was delivered in
excellent yield and best enantioselectivity (90% yield and 99%
ee). Moreover, double substituents (3,5-Cl2, 2,4-Cl2, 2-Me-4-F)
could be introduced into aromatic ring of Ar group with a slight
effect on the yield and stereoselectivity, and no significant
electronic effect on the aromatic moiety was observed, except
that a slightly lower ee value (73%) was obtained for the 2,4-
Me2 substituent substrate 4s. The reaction of sterically more
congested dioxopyrrolidines 1u and 1v also acquired relevant
products 4u and 4v in 80% yield with 85% ee and 61% yield with
99% ee respectively. In addition, the scope of dioxopyrrplidine
could be extend to hetero substrate 1-benzyl-4-(thiophen-2-
View Article Online
DOI: 10.1039/C9OB00419J
O
O
O
O
R
O
3e
Cat. , 10 mol%
O
O
O
Bn
N
+
Bn
CHCl3, -20 o
C
N
N
H
PMP
N
R
PMP
Bn
Bn
4
1
2a
PMP = p-OMeC6H4
O
O
O
O
O
O
O
O
Bn
N
Bn
N
N
PMP
N
H
PMP
Bn
H
Bn
R
R
4i
4j
4k
4l
R = F, 99% yield, 94% ee, 48h
4a
4b
4c
4d
4e
4f
4g
4h
R = H, 91% yield, 94% ee, 48h
R = F, 99% yield, 91% ee, 48h
R = Cl, 74% yield, 95% ee, 24h
R = Br, 74% yield, 95% ee, 24h
R = CF3, 89% yield, 95% ee, 72h
R = NO2, 73% yield, 98% ee, 24h
R = CH3, 89% yield, 95% ee, 24h
R = OMe, 73% yield, 90% ee, 48h
O
R = Cl, 99% yield, 95% ee, 48h
R = Br, 82% yield, 95% ee, 72h
R = CH3, 99% yield, 95% ee, 48h
4m
R = OMe, 87% yield, 92% ee, 72h
O
O
O
O
O
O
Bn
N
O
Bn
N
N
H
PMP
Bn
N
H
PMP
Bn
R
ylmethylene)pyrrolidine-2,3-dione
1w,
furnished
the
Cl
Cl
cycloaddition product 4w. The absolute configuration of
product 4d was determined as 3R,4R by X-ray crystallography9
(Fig. 2), and the other products were assigned by analogy.
4n
4o
4p
R = Cl, 78% yield, 95% ee, 24h
R = Br, 71% yield, 90% ee, 48h
R = CH3, 90% yield, 99% ee, 48h
4q
68% yield, 93% ee, 48h
O
O
O
O
O
O
O
O
Bn
N
Bn
N
N
H
PMP
N
H
PMP
Bn
Bn
H3C
Cl
CH3
Cl
4r
79% yield, 99% ee, 48h
4s
68% yield, 73% ee, 36h
O
O
O
O
O
O
O
Bn
N
O
Bn
N
N
H
PMP
Bn
N
H
PMP
H3C
Bn
F
4u
4t
76% yield, 85% ee, 72h
81% yield, 98% ee, 48h
O
Figure 2 X-ray crystal structure of 4d
O
O
O
O
Bn
N
O
O
O
N
H
PMP
Bn N
Bn
N
H
PMP
Bn
S
Encouraged by the above mentioned results, the substrate
scope of azlactones 2 was investigated. Satisfyingly, substituent
R1 was examined to afford the corresponding adducts, both
benzyl and alkyl groups were well tolerated. Azlactones with
substituent on the phenyl ring in the R1 group could be smoothly
converted to corresponding products 5a-5c in moderate yields
and ee (70-83% yields and 77-92% ee). For alkyl substituted 5d
and 5e, excellent ee values (93% ee, 90% ee) and moderate
yields (71% and 63%) were obtained. Furthermore, azlactones
with various substitutions on the phenyl ring in the R2 group
were also evaluated and exhibited good tolerance for the
reaction, but product 5g obtained sharply decreased ee value
4w
75% yield, 71% ee, 72h
4v
61% yield, 99% ee, 48h
a The reaction was conducted with 0.10 mmol of 1, 0.12 mmol of 2a and 0.01
mmol of 3e in 4.0 mL CHCl3. Products 4 were obtained in isolated yields. ee
was determined by chiral HPLC analysis on a chiral column. Only a single
diastereoisomer
was
observed
by
crude
1H
NMR.
and yield. In addition, azlactone 2h with a benzyl group and a
benzene group was well tolerated in the reaction, giving 84%
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in excellent yield (91%) and (94% ee) stereoselectivity (Scheme
yield and 83% ee. In all cases, only a single diastereoisomer was
observed.
View Article Online
DOI: 10.1039/C9OB00419J
2).
Table 4 Substrate scope of azlactones 2a
O
O
O
O
OH
Bn
O
O
O
O
O
24h
rt
Bn
N
+
N
PMP
Ph
O
N
Bn
N
N
H
PMP
Bn
O
O
Bn
O
Ph
A
O
1a
O
R
O
Bn
N
3e
Cat. , 10 mol %
34%
4a
O
N
H
R2
O
+
R1
+
R1
-20 oC
single diastereoisomer
trace
N
CHCl ,
3
O
Bn
N
R2
Bn
24h
N
no reaction
PMP
- 20 o
C
2a
1a
2
5
Et3N
A
11%
+
4a 81%
O
O
O
O
rt, 10 min
single diastereoisomer single diastereoisomer
O
O
O
O
PMP
F
PMP
Bn
N
Bn N
NH
NH
3e
91%
4a
A
+
- 20 o
C
trace
single diastereoisomer
Cl
5a
5b
83% yield, 77% ee, 48h
75% yield, 92% ee, 48h
Scheme 3 Control experiments
O
O
O
O
O
O
PMP
O
O
PMP
Bn
N
Bn
N
NH
NH
O
O
F3C
OMe
N
H
N
H
O
O
Br
O
H
F3C
N
3e
O
+
5c
70% yield, 79% ee, 48h
H
5d
71% yield, 93% ee, 72h
O
Bn
N
O
R
O
Bn
N
O
PMP
Path B
O
O
O
N
Bn
endo
PMP
O
O
O
O
1a
2a
PMP
O
N
Bn
Bn
N
Bn N
R
NH
N
H
Bn
Path A
3e
Cl
5e
5f
99% yield, 89% ee, 48h
63% yield, 90% ee, 48h
O
O
O
OH
O
O
O
O
O
O
O
O
O
O
O
O
O
Bn
Bn
N
Bn
N
O
N
Bn

O
O

Bn
N
Bn N
N
PMP
N
H
PMP
N
Bn
Bn
PMP
N
H
N
H
R
R
R
Bn
Bn
high dr
Br
5g
5h
Scheme 4 Plausible reaction pathways
37% yield, 53% ee, 72h
84% yield, 83% ee, 48h
a The reaction was conducted with 0.10 mmol of 1a, 0.12 mmol of 2 and 0.01
mmol of 3e in 4.0 mL CHCl3. Products 5 were obtained in isolated yields. ee
was determined by chiral HPLC analysis on a chiral column. Only a single
diastereoisomer was observed by crude 1H NMR.
In order to investigate the reaction pathway, the control
experiment was carried out (Scheme 3). Actually, there have a
background reaction in this transformation, Michael adduct A
with complete diastereoselectivity can be isolated under
catalyst-free at room temperature. No reaction occurred when
the temperature dropped to -20 °C. The reaction can be
promoted by an organic base such as Et3N, afforded product 4a
and Michael adduct A, both of them were as a single
O
O
O
O
O
O
O
Bn
N
O
3e
, 10 mol%
Bn
+
N
N
H
PMP
Bn
CHCl3, -20 o
N
C
PMP
Bn
diastereoisomer, this catalytic process is similar to Terada's
1l
2a
4l
[5c]
(1.25 mmol)
(1.5 mmol)
observation
,
It can be considered that the
91% yield, 94% ee
423 mg
364 mg
652 mg
diastereoselectivity is an intrinsic feature of the reaction. Under
the catalysis of the bifunctional catalyst, Michael adduct
intermediates were trace (from TLC) in most cases.
Scheme 2 A larger-scale synthesis of 4l
Furthermore, considering Feng’s plausible transition state[5b]
,
we could not exclude the possibility that this reaction may
conduct via an inverse-electron-demand hetero-Diels–Alder
reaction process. Therefore, two plausible reaction pathways
are proposed to explain the reaction process as shown in
To show the synthetic potential of catalytic protocol, a large-
scale reaction of this transformation was performed by using
1.25 mmol of 1l and the corresponding adduct 4l was obtained
4 | J. Name., 2012, 00, 1-3
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Scheme 4. In path A, a catalysed Michael addition as the stereo- (s, 1H), 4.68 (d, J = 14.9 Hz, 1H), 4.50 (d, J = 14.9 Hz, 1VHie)w, 4A.r1tic3le(Od,nlJin=e
DOI: 10.1039/C9OB00419J
determining step, followed by intramolecular O-acylation of the 13.9 Hz, 1H), 3.83 (d, J = 18.9 Hz, 1H), 3.69 (s, 3H), 3.60 (d, J = 18.8
new born enolate and opening of the oxazolone ring. In path B, Hz, 1H), 3.19 (d, J = 13.8 Hz, 1H). 13C NMR (100 MHz, Chloroform-d) δ
under the catalysis of the bifunctional catalyst, the inverse- 167.6, 167.3, 163.5, 162.4, 162.0, 161.1, 141.5, 136.1, 135.5, 131.7,
electron-demand hetero-Diels-Alder (IEDDA) reaction may 129.8, 129.7, 129.1, 129.0, 128.5, 128.4, 128.3, 128.3, 128.1, 127.7,
proceed in an endo way affording intermediate, followed by 126.7, 115.5, 115.3, 113.8, 66.1, 55.4, 47.9, 47.6, 46.9, 38.8.HRMS
ring opening to furnish the target product.
(ESI) m/z calculated for C35H29FN2O5 [M+H]+:577.2133,
found:577.2122. HPLC analysis: (IB column, Hexane:2-propanol =
85:15, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 22.47
(minor), 25.06 (major).
Conclusions
In conclusion, we have developed a highly stereoselective [4+2]
cyclization reaction of dioxopyrrolidines and azlactones by a
Conflicts of interest
There are no conflicts to declare.
squaramide activation strategy.
A
wide range of
dioxopyrrolidines and azlactones were well tolerated to give the
corresponding multiply substituted pyrano[2,3-c]pyrrole
containing adjacent tertiary and quaternary stereogenic centers
in high yields (up to 99%) with excellent diastereo- and
enantioselectivity (up to 99% ee, all cases >20:1 dr). Two
possible pathways were proposed to explain the observed
stereoselectivity. Further studies on the synthetic application
and biological activity of cyclization products are currently
ongoing and will be reported in due course.
Acknowledgements
We are grateful for financial support of the start-up fund of
Guangzhou University of Chinese Medicine, Guangdong “Pearl
River Talents Plan” (2017GC010361), and Department of
Education of Guangdong Province (2014KTSPT016).
Notes and references
1 For reviews on azlactones, see: (a) J. S. Fisk, R. A. Mosey and J.
J. Tepe, Chem. Soc. Rev., 2007, 36, 1432; (b) R. A. Mosey, J. S.
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P. de Castro, A. G. Carpanez and G. W. Amarante, Chem. Eur.
J. 2016, 22, 10294.
Experimental
General Procedure for Asymmetric [4+2] Cyclization Reaction
Dioxopyrrolidines 1 (0.1 mmol, 1.0 equiv.) and 3e (0.01 mmol, 0.1
equiv.) in CHCl3 (3.0 mL) were cooled to -20 °C, then added
azlactones 2 (0.12 mmol, 1.2 equiv.) in CHCl3 (1.0 mL). The reaction
stirred at -20 °C for the time indicated at Table 3 or Table 4, and then
the solvent was removed under vacuum to give a residue, which was
purified by silica gel chromatography to yield the desired product 4
or 5. The enantiomeric ratio was determined by HPLC analysis on
chiral column.
2
For some early examples: (a) B. M. Trost and X. Ariza, Angew.
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N-((3R,4R)-3,6-dibenzyl-2,7-dioxo-4-phenyl-2,3,4,5,6,7-
hexahydropyrano[2,3-c]pyrrol-3-yl)-4-methoxybenzamide
(4a).
White solid, 50.7 mg, 91% yield, [α]20 D–43.3 (c 0.492, CH2Cl2), 94%
ee. 1H NMR (400 MHz, Chloroform-d) δ 7.38 – 7.28 (m, 6H), 7.21 (d, J
= 5.9 Hz, 6H), 7.14 (d, 4H), 6.79 (d, J = 8.3 Hz, 2H), 6.59 (s, 1H), 5.05
(s, 1H), 4.77 (d, J = 14.8 Hz, 1H), 4.61 (d, J = 14.8 Hz, 1H), 4.25 (d, J =
13.6 Hz, 1H), 3.94 (d, J = 18.8 Hz, 1H), 3.78 (s, 3H), 3.70 (d, J = 18.8
Hz, 1H), 3.34 (d, J = 13.6 Hz, 1H). 13C NMR (100 MHz, Chloroform-d) δ
167.7, 167.3, 162.3, 162.1, 141.5, 136.2, 135.7, 134.0, 130.1, 129.1,
129.0, 128.5, 128.5, 128.4, 128.3, 128.1, 127.8, 127.7, 126.9, 113.8,
66.2, 55.4, 48.0, 47.7, 46.9, 39.7. HRMS (ESI) m/z calculated for
+
C35H30N2O5 [M+H] : 559.2227, found 559.2222. HPLC analysis: (IB
column, Hexane:2-propanol = 80:20, flow rate = 1.0 mL/min,
wavelength = 254 nm): Rt = 15.65 (minor), 20.58 (major).
N-((3R,4R)-6-benzyl-3-(4-fluorobenzyl)-2,7-dioxo-4-phenyl-
2,3,4,5,6,7-hexahydropyrano[2,3-c]pyrrol-3-yl)-4-
methoxybenzamide (5a). White solid, 43.2 mg, 75% yield, [α]20 D-
32.7 (c 0.412, CH2Cl2), 92% ee. 1H NMR (400 MHz, Chloroform-d) δ
7.26 – 7.16 (m, 6H), 7.11 (d, J = 5.5 Hz, 3H), 7.00 (dt, J = 8.4, 4.5 Hz,
4H), 6.80 (t, J = 8.5 Hz, 2H), 6.70 (d, J = 8.7 Hz, 2H), 6.45 (s, 1H), 4.91
3
[2+n] Cyclizations by utilizing C4, C5 reactivity of azlactones.
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J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
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Asymmetric synthesis of pyrane derivatives through [2+4]
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6
Asymmetric synthesis of dihydrocoumarins through [2+4]
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Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C9OB00419J
The present work provides a simple and efficient access to chiral Pyrano[2,3-c]pyrrole via asymmetric [4 + 2] cyclization
reaction catalyzed by a cinchona-squaramide catalyst.