Diastereoselective Synthesis of Structurally and Stereochemically Diversified 2-Oxa-7-azabicyclo[4.1.0]hept-3-enyl Carboxylates and Their Potential Application toward the Synthesis of Functionalized Pyranooxazolone and Pyrrole Derivatives through Skeletal Transformations

Article abstract of DOI:10.1021/acs.joc.6b00849

An advanced protocol for the diastereoselective intramolecular aziridination reaction has been developed to synthesize 2-oxa-7-azabicyclo[4.1.0]hept-3-en-1-yl carboxylates from their corresponding 4-H-pyrans and spiropyrans analogues employing iodosylbenznene as the exclusive oxidant in the presence of carboxylic acid and triethylamine. High structural and stereochemical diversity of these pyran fused NH-azridine scaffolds makes them useful in evaluating their biological and pharmacological activities by SAR studies. Additionally, their potential synthetic application has been uncovered by efficient transformation into biologically relevant novel pyranooxazolone and pyrrole derivatives.

Full text of DOI:10.1021/acs.joc.6b00849

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN
Article
Diastereoselective synthesis of structurally and stereochemically
diversified 2-oxa-7-azabicyclo[4.1.0]hept-3-enyl carboxylates and
their potential application towards the synthesis of functionalized
pyranooxazolone and pyrrole derivatives through skeletal transformations
Prasun Mukherjee, and Asish R. Das
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00849 • Publication Date (Web): 26 May 2016
Downloaded from http://pubs.acs.org on May 27, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Diastereoselective synthesis of structurally and stereochemically diversified 2-oxa-7-
azabicyclo[4.1.0]hept-3-enyl carboxylates and their potential application towards the
synthesis of functionalized pyranooxazolone and pyrrole derivatives through skeletal
transformations
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Prasun Mukherjee, Asish R. Das*
Department of Chemistry, University of Calcutta, Kolkataꢀ700009, India
*Corresponding author: Tel.: +913323501014, +919433120265; fax: +913323519754;
Eꢀmail address: ardchem@caluniv.ac.in, ardas66@rediffmail.com (A R Das)
TABLE OF CONTENT:
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
ABSTRACT
An advanced protocol for the diastereoselective intramolecular aziridination reaction has been
developed to synthesize 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl carboxylate from their
corresponding 4ꢀHꢀpyrans and spiropyrans analogues employing iodosylbenznene as the
exclusive oxidant in presence of carboxylic acid and triethylamine. High structural and
stereochemical diversity of these pyran fused NHꢀazridine scaffolds make them useful in
evaluating their biological and pharmacological activities by SAR studies. Additionally their
potential synthetic application has been uncovered by efficient transformation into biologically
relevant novel pyranooxazolone and pyrrole derivatives.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
INTRODUCTION
Fused heterocyclic moiety is one of the fundamental structural requirements for numerous
natural products and synthetic compounds to exhibit their extensive variety of biological
1
activities. Fused heterocycles, being essentially the hybrid of two or more bioactive heterocyclic
fragments, possess versatile biological and pharmacological activities originated due to the
presence of multiple pharmacophores in a single molecular entity. Further, carefully designed
synthetic hybrid molecules, possessing high skeletal and stereochemical diversity, with
bioactivity can be used as protein function modulator and key leads in drug development of
2
medicinal field. Thus development of efficient and direct synthetic route to synthesize fused
heterocyclic compounds bearing multiple chiral centers has taken a great deal of attention over
3
the past decades.
Pyran framework is a privileged pharmacophore embedded as the structural core in numerous
4
biologically relevant natural products and synthetic compounds. On the other hand aziridine is
ACS Paragon Plus Environment

Page 3 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
5
the key constituent of several bioactive natural products regardless of its high affinity towards
6
countless ring opening reactions due to the ring strain. Although various literature reports
concerning bioactivities of pyran and aziridine derivatives intensely justify the construction of
hybrid molecular entities having aziridine fused pyran scaffold as the structural motif, but much
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7
less effort has been specified to develop the synthetic methodologies to achieve them.
Availability of a handful literature data regarding the synthesis of pyran fused aziridine
molecular entities may be due to their inherent instability which prevents their isolation as stable
molecular entity. In this context, it is noteworthy to mention some previous reports enlighten the
in situ synthesis of pyran fused aziridine molecular scaffolds which then induced immediate
8
chemical transformations without isolating them as stable compounds. Consequently, their
preparation and isolation are still remaining challenging as well as important synthetic targets to
the organic chemists.
Plentiful synthetic methods have been developed over the past decades to synthesize aziridine
9
derivatives in their protected and unprotected form. Most of them consist of intramolecular
substitution reaction within the amine derivatives, reaction of carbenes with imines and reaction
of nitrenes with olefins. Recently Zhao et al. have established a synthetic route to construct 2Hꢀ
1
0
azirines from several enamine derivatives using iodobenzene diacetate (scheme 1, entry 1). In
7d
our previous work, we have demonstrated an intramolecular aziridination reaction to construct
pyran fused 2ꢀacetoxyꢀNHꢀaziridine molecular scaffold by exploiting the enamine fragment of 2ꢀ
aminoꢀ4Hꢀpyrans and 2ꢀaminoꢀspiropyrans employing iodobenzene diacetate (scheme 1, entry
2
). It was indeed the first report of the synthesis and isolation of highly stable pyran fused 2ꢀ
acetoxyꢀNHꢀaziridines. The use of hypervalent iodine as the sole reagent for aziridination is
beneficial since it offers a metal free mild reaction condition. In addition, hypervalent iodine
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
reagents are easily available, less toxic and easy to handle. Despite of the success, our previous
protocol suffers from generalized functionalization of the target molecule, since only acetoxy
group can be introduced in the angular position of the 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀene
framework. Also the protocol has the limitation to be unproductive when ꢀCN group is replaced
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
by ꢀCO Et group in the starting pyran derivatives. Thus development of a comprehensive
2
methodology with broader substrate scope and higher functional group tolerance, and suitable
for introducing higher degree of diversity in the resulting pyran fused NHꢀaziridines is still
challenging and of course in demand.
Concentrating to the efforts in the development of innovative and efficient methodologies
11
towards the synthesis of biologically relevant compounds, herein we wish to reveal a simple
and robust diastereoselective protocol to construct a stable, highly functionalized and
stereochemically diversified pyran fused NHꢀaziridine scaffold by reacting 2ꢀaminoꢀ4Hꢀpyran
and 2ꢀaminospiropyran derivatives with iodosylbenzene as the exclusive oxidant in presence of
triethylamine and carboxylic acids (1:2) at room temperature avoiding metal catalysts (Scheme
1, entry 3).
ACS Paragon Plus Environment

Page 5 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Scheme 1. Synthesis of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl carboxylates by intramolecular
aziridination
Additionally, synthetic applications of these synthesized NHꢀ aziridine derivatives was also
explored by carrying out their ring opening transformations under different reaction conditions.
Interestingly, they have found to be the key precursor in synthesizing densely functionalized
novel pyranooxazolone molecular scaffolds when treated with tetrabutylammoniumfluoride. In
addition, acid catalyzed ring opening of these NHꢀ aziridines leads to the formation of
biologically privileged highly functionalized pyrrole derivatives (scheme 2). To the best of our
knowledge, this is the first report revealing the synthesis of these particular functionalized
pyranooxazolone and pyrrole molecular scaffolds originating from pyran fused aziridine
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
derivatives
upon
simple
and
efficient
ring
transformation
conditions.
Scheme 2. Acid and fluoride ion catalyzed ring opening of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl
carboxylates
RESULTS AND DISCUSSION
To investigate the feasibility of this strategic approach for intramolecular aziridination reaction,
2ꢀaminoꢀ5ꢀoxoꢀ4ꢀphenylꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀchromeneꢀ3ꢀcarbonitrile 1a was synthesized
12a
using a known method and employed as a model substrate in this reaction. When 1a was
treated with iodosylbenzene (1 mmol) in presence of 4ꢀnitrobenzoic acid (1 mmol) in DCM (5
mL) at room temperature, after 60 min 2a was obtained in very low yield (Table 1, entry 1).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Interestingly, use of triethylamine (1 mmol) as an additive increased the product yield to 40% in
comparatively shorter reaction time (Table 1, entry 2). Use of higher amount of oxidant found to
be effective for improving the product yield within shorter reaction time (Table 1, entry 3and 4).
However further enhancement of product yield was not observed when more than 1.5 mmol of
iodosylbenzene was used (Table 1, entry 5). When carboxylic acid loading was increased, the
yield of 2a was greatly elevated and isolated yield was 92% (applying 2mmol of carboxylic acid
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
)
(Table 1, entry 6ꢀ8). Further increase of carboxylic acid amount did not afford any better result
(Table 1, entry 9). Furthermore, to improve the reaction time and product yield, the reaction was
performed in presence of different additives and different
a
Table 1. Optimization of reaction conditions
b
Entry PhIO
Carboxylic
Additive
Solvent
Time Yield (%)
(mmol) acid (mmol) (1 mmol)
(min)
1
2
3
4
5
6
1.0
1.0
1.2
1.5
1.6
1.5
1
1
_
DCM
DCM
DCM
DCM
DCM
DCM
60
40
35
30
30
30
10
40
45
55
50
70
Et N
3
1
Et N
3
1
Et N
3
1
Et N
3
1.5
Et N
3
ACS Paragon Plus Environment

Page 7 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
7
8
9
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.8
2.0
2.1
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Et N
DCM
DCM
30
30
30
45
55
50
50
45
55
52
55
90
92
91
15
12
74
62
60
65
70
72
3
Et N
3
Et N
DCM
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
0
1
2
Cs CO
DCM
2
3
1
1
NaOAc
DCM
Et N
DCE
3
13
Et N
EtOAc
Toluene
Dioxane
THF
3
14
15
16
17
Et N
3
Et N
3
Et N
3
Et N
Acetonitrile
3
a
b
1 mmol of 1a was taken in 5mL of solvent in all the cases. Yield of the isolated product.
solvents. Bases like Cs CO and NaOAc were found to be inefficient compared to triethylamine
2
3
(
Table 1, entry 10 and 11) and 2a was isolated in low yield when solvents like dichloroethane,
ethylacetate, toluene, dioxane, tetrahydrofuran and acetonitrile were used replacing DCM (Table
, entry 12ꢀ17).
1
With this optimized reaction conditions (Table 1, entry 8), we then focused our attention to
explore the feasibility of this intramolecular aziridination reaction. Several known 2ꢀaminoꢀ
1
2aꢀj
3
cyanoꢀ4Hꢀpyran derivatives
with high functionalization were synthesized via the above
1
2a
mentioned three component reaction
in which a variety of aromatic and heteroaromatic
aldehydes along with phenylglyoxal were reacted with malononitrile and ethylcyanoacetate in
presence of various 1,3ꢀdicarbonyls such as dimedone, cyclohexaneꢀ1,3ꢀdione, 4ꢀ
hydroxycoumarin and 2ꢀhydroxyꢀ1,4ꢀnaphthoquinone. These pyran derivatives were then treated
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
with iodosylbenzene (1.5 mmol) in presence of carboxylic acid (2 mmol) and triethylamine
(1mmol) in 5 mL of DCM to synthesize 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenes. In this purpose a
large variety of aromatic as well as aliphatic carboxylic acids were employed to amplify this
developed protocol. Astonishingly, this protocol was found to be really efficient in affording
diversified 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenes in good to excellent yields (Table 2 and 3). A
wide range of aromatic carboxylic acids containing electron donating as well as electron
withdrawing groups at different positions of the ring along with aliphatic acids such as acetic
acid, phenylacetic acid and sterically bulky diphenyl acetic acid were successfully introduced at
the angular position of the 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀene framework. This protocol offers
absolutely clean reaction as no other side products were obtained after completion of the
reaction. It may be due to the high reactivity of the oxidant towards the enamine fragment of the
starting material while alternative double bond of pyran ring and other functional groups during
the reaction remained non reactive. Notably the reaction has found to proceed with the same
efficiency in case of ethyl 2ꢀaminoꢀ4Hꢀpyranꢀ3ꢀcarboxylate derivatives which broadens the
scope of this protocol further (Table 3, entry 4aꢀ4i). Compounds 4a-i were obtained at slightly
lower yield compared to 2a-s which seem to be probably due to the greater electron withdrawing
ability of nitrile than that of ethoxycarbonyl group. Apart from their role in protecting the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
enamine tautomeric form in starting materials, ꢀCN and ꢀCO Et groups also induce nucleophilic
2
property of the carbon center to which they are stitched, since the pyran oxygen atom and amine
group are in conjugation with them through the intervening double bond. To test the viability of
1
2k
the reaction in case of spiropyran system a known spiropyran derivative was synthesized using
1
2a
the same procedure which was used to synthesize 4Hꢀpyrans. The reaction also found to be
convenient in transforming the spiropyran into the corresponding pyran fused NHꢀaziridine with
ACS Paragon Plus Environment

Page 9 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
excellent product yield (Table 2, entry 2r). The starting materials which possess coumarin or
naphthoquinone fused pyran substructures were found to take longer reaction time for this
transformation, however not affecting the yield of their corresponding products (Table 2, entry
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
iꢀo and Table 3, entry 4dꢀi). The reaction proceeded with almost equal efficiency in presence of
several aromatic and aliphatic acids (Table 2, entry 2aꢀr and Table 3, entry 4aꢀi). All the
synthesized 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl carboxylates are significantly stable and
they remain unaffected during column chromatographic separation of the reaction mixture (silica
1
13
gel mesh size 100ꢀ200). All products are well characterized through H NMR, C NMR, IR,
HRMS and elemental analysis data and finally the structural motif of the synthesized compounds
were established through Xꢀray crystallographic analysis of one representative compound 4g
(CCDC 1472710). The information about the relative stereochemistry obtained from the Xꢀray
crystallographic analysis of compound 4g (see supporting information) enables us to assign the
2
3
4
relative configuration of C , C and C centers of the pyran ring as R, R and S respectively.
In this present endeavor we have also successfully evaluated the synthetic application of these
synthesized 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates by converting them into highly
functionalized pyranooxazolone and pyrrole derivatives by devising fluoride ion and acid
catalyzed ring opening of aziridine moiety. For the fluoride ion catalyzed transformation,
tetrabutylammonium fluoride was employed as suitable reagent owing to its solubility in organic
solvents. Further strong hydrogen bonding affinity of fluoride ion and its speciality in providing
clean reaction by maintaining neutral reaction environment make it a better choice of reagent for
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 2. Substrate scope to synthesize 3ꢀcyanoꢀ2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl
a
carboxylates
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2a, 92%, 30 min
2
b, 90%, 30 min
2c, 93%, 30 min
2
2
d, 94%, 30 min
Br
O
CN
O
NH
O
O
O
Cl
2e, 96%, 30 min
2
f, 95%, 30 min
2g, 89%, 30 min
h, 90%, 60 min
O
CN
NH
O
O
O
O
2
j, 90%, 60 min
2
k, 88%, 60 min
2l, 90%, 60 min
2i, 88%, 60 min
O
O
Cl
CN
NH
O
O
O
2
m, 92%, 60 min
2p, 95%, 30 min
2n, 84%, 60 min
2
o, 90%, 30 min
2q, 94%, 30 min
2r, 90%, 30 min
ACS Paragon Plus Environment

Page 11 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
a
Reaction conditions: 1 (1 mmol), PhIO (1.5 mmol), carboxylic acids (2 mmol), Et N (1 mmol)
3
b
DCM (5 mL), r.t. Isolated yield and reaction time.
this purpose. Some selective 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates were
transformed into pyranooxazolones in presence of one equivalent of tetrabutylammonium
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
fluoride in dioxane medium at room temperature. The transformation was very fast (~30 min)
3
(
when R = methyl, benzyl) and almost quantitatively afforded a well decorated
pyranooxazolone scaffold bearing angular functionality (Table 4, entry 5aꢀd). Applying this
method 2e, 2f, 2d, 4f and 2a were successfully transformed into 5a-e respectively. The
transformation is equally efficient for both the ester and nitrile derivative of 2ꢀoxaꢀ7ꢀ
azabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates (Table 4, entry 5aꢀe). They were (5aꢀe) well
1
13
characterized by H NMR, C NMR, IR, HRMS and elemental analysis data and their structural
motif was fully confirmed through Xꢀray crystallographic analysis of a single crystal of
compound 5c (CCDC 1472711). One very interesting structural feature (see supporting
information) of this pyranooxazolone molecular scaffold is that the pꢀnitrophenyl, nitrile and
benzyl groups are in syn relationship to each other. Literature reviews suggest that both this type
of pyranooxazolones and their synthetic route are new.
Furthermore, when some selective 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates were
treated with pꢀtoluenesulphonic acid (10 mol%) in refluxing methanol they were transformed
into well functionalized pyrrole derivatives. In all cases the conversion took place in short
reaction time (~2h) and the products are obtained in excellent yields (Table 5, 6aꢀd). 2a, 2d, 2f,
2g were converted to 6a-d respectively by applying this protocol and when compound 2d was
subjected to same pꢀTsOH catalyzed reaction in ethanol medium , pyrrole 6e was obtained in
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 3. Substrate scope to synthesize ethyl 1ꢀ(carbethoxy)ꢀ2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀeneꢀ
a
6ꢀcarboxylates
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4c, 86%, 30 min
4
a, 88%, 30 min
4b, 90%, 30 min
4d, 82%, 60 min
4f, 90%, 60 min
4
e, 80%, 60 min
4g, 84%, 60 min
4h, 82%, 60 min
4j, 88%, 60 min
4i, 80, 60 min
a
Reaction conditions: 3 (1 mmol), PhIO (1.5 mmol), carboxylic acids (2 mmol), Et N (1 mmol)
3
b
DCM (5 mL), r.t. Isolated yield and reaction time.
good yield. However this conversion is very efficient only for cyano derivatives of 2ꢀoxaꢀ7ꢀ
ACS Paragon Plus Environment

Page 13 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
azabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates which possess cyclohexanone fragment fused with the
pyran moiety.
a
Table 4. Synthesis of pyranooxazolones
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5b, 96%, 30 min
5
a, 98%, 30 min
5
c, 92%, 30 min
5d, 96%, 30 min
b
5
e , 50%, 30 min
a
b
o
Reaction conditions: 2 or 4 (1 mmol), nBu NF (1 mmol), Dioxane (2 mL), r.t. heated at 60 C.
4
b
Isolated yield and reaction time.
1
13
Compounds 6aꢀe are also fully characterized by H NMR, C NMR, IR, HRMS and elemental
analysis data and confirmation of the structural motif was done by single crystal Xꢀray
crystallographic analysis of compound 6a (CCDC 1472712). Interestingly product pyrroles
evolved via acid catalyzed transformation, features a quaternary carbon atom, attached with both
a nitrile and a methoxy carbonyl group at the same time and the –CN group is in syn relationship
3
2
with the aryl group of the C atom. In case of compound 6a the relative configuration of C and
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
C center of the pyrrole ring can be assigned as R and S respectively from the Xꢀray crystal
structure of it (see supporting information).
a
Table 5. Synthesis of pyrroles
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
a, 90%, 2h
6b, 88%, 2h
6c, 87%, 2h
6d, 90%, 2h
6
e, 74%, 2h
a
o
b
Reaction conditions: 2 (1 mmol), PTSA (10 mol%), alcohol (3 mL), 80 C. Isolated yield and
reaction time.
A mechanism for the formation of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates is depicted
in scheme 3. Based on the fact that iodobenzene diacetate undergoes ligand exchange in presence
13
of carboxylic acids, we tentatively assume that the initial reaction between iodosyl benzene and
carboxylic acid have produced the species PhI(OCOR) (I) which then acted as the actual reagent
2
in this reaction. Initially I attacks the amino group of the starting material (1) leading to the
formation of Nꢀiodo intermediate II. The carboxylic acid released in this step is consumed by
ACS Paragon Plus Environment

Page 15 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
triethylamine to produce an ion pair which could serve as a source of carboxylate ion. Attack by
the double bond, assisted by the pyran oxygen atom, to the electrophilic nitrogen center
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Mechanism for the synthesis of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates
generates the intermediate III by releasing iodobenzene and carboxylate ion. The attachment of
the pyran oxygen atom with the enamine moiety is crucial for the formation of 2ꢀoxaꢀ7ꢀ
azabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates since it assists in the formation and stabilization of the
2
intermediate III. Subsequently, attack by the carboxylate ion to the C center of the pyran ring
of III takes place which ultimately generates 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylate
2
. The Xꢀray crystal structure of compound 4g (see supporting information) explains the relative
stereochemistry in the pyran fused NHꢀaziridine scaffold and clearly displays the syn
4
relationship between the aziridine ring and 4ꢀnitrophenyl substituent of C center of pyran ring.
This syn orientation in the product aziridine molecules undoubtedly indicates that the attacking
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 4. Stereochemical course of the aziridination reaction
carboxylate ion has approached from the opposite side of 4ꢀnitrophenyl group. This in turn
establishes the diastereoselective nature of this particular reaction. During the nucleophilic attack
1
4
(carboxylate ion), the large group (R ) of the C carbon atom controls the facial selectivity.
1
Carboxylate ion prefers αꢀattack, i.e., the attack from the opposite side of R , hence leads to the
ACS Paragon Plus Environment

Page 17 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
formation of 2 as the exclusive diastereomer. The β attack which is sterically hindered does not
take place at all under the imposed experimental condition.
The stereochemical course of this aziridination reaction is described in scheme 4. The starting
pyran compounds are racemates since they have synthesized applying achiral methodology.
When a starting pyran derivative 1 is treated with 1.5 eq. of iodosylbenzene in presence of 2 eq.
of a carboxylic acid and 1 eq. of triethylamine, it’s corresponding enantiomers 1a and 1b results
in the formation of the intermediates IIIa and IIIb following the same mechanistic pathway as
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
proposed in scheme 3. In the next step, subsequent attack by the carboxylate ion to the C center
of the pyran ring of both IIIa and IIIb takes place to generate the final aziridine product. Now,
during the neucleophilic attack of carboxylate ion, the preferred approach is controlled by steric
1
factor and takes place from the opposite side of the R group. Consequently the intermediate IIIa
and IIIb rapidly transformed into the product 2a and 2d respectively. The formation of 2b and 2c
is sterically forbidden and they have not formed at all during the course of reaction. Now, 2a and
2d possess enantiomeric relationship to each other. On the other hand, 2a and 2d possess
diastereomeric relationship with 2b and 2c respectively. Thus the reaction follows the
diastereoselective pathway and eventually transforms the racemic pyran compound to the
corresponding pyran fused NHꢀaziridine racemate in diastereoselective manner.
Plausible mechanisms for the fluoride ion and acid catalyzed transformations of the 2ꢀoxaꢀ7ꢀ
azabicyclo[4.1.0]heptꢀ3ꢀenyl carboxylates are also depicted in scheme 5 and 6 respectively.
Acidic nature of the H of the aziridine ring in 2 facilitates its abstraction by the fluoride ion to
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
R1
R1
O
E
E
R
O
nBu NF
4
N
NH
N
O
R
E
O
O
O
R
R1
O
2
O
O
H
(IV)
intramolecular
rearrangement
plausible orientaion of
carboxylate group
nBu NFH
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
R1
R1
intramolecular
rearrangement
E H
N
E H
N
R
O
O
O
R
O
O
O
5
(
V)
Scheme 5. Mechanism for the synthesis of pyranooxazole
generate intermediate IV. This negatively charged species IV then immediately undergo
intramolecular rearrangement with concomitant proton abstraction to generate V. During this
step the plausible orientation of the carboxylate group in intermediate IV is depicted in scheme
3. V then follows second intramolecular rearrangement pathway in which migration of the R
group takes place to the αꢀposition of the positively charged oxygen atom, which ultimately
afford the compound 5.
Scheme 6. Mechanism for the synthesis of pyrroles
ACS Paragon Plus Environment

Page 19 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In case of acid catalyzed ring opening reaction (scheme 6), the aziridine ring of 2 is first opened
+
up in presence of H ion resulting in the formation of intermediate VI which then undergoes acid
catalyzed ring opening and generates VII. VII on tautomerization changes into its keto form
VIII which then transformed into IX in presence of acid. Finally IX undergoes acid catalyzed
cyclization to assume the product 6 i.e. fused pyrrole derivative.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CONCLUSION
In conclusion, an advanced protocol of intramolecular aziridination reaction has been developed
to synthesize 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl carboxylate from their corresponding 4ꢀHꢀ
pyrans and spiropyrans using iodosylbenznene as the exclusive oxidant in presence of various
aromatic as well as aliphatic carboxylic acids and triethylamine. Regardless of its broader
substrate scope this methodology offers a very simple, robust and diastereoselective route to
construct pyran fused NHꢀaziridine molecular scaffolds. Well functional group tolerance of the
oxidant makes this protocol suitable to introduce high skeletal and stereochemical diversity in
the product NHꢀazridines. Their potent synthetic efficacy has been discovered by efficiently
transforming them into biologically relevant novel pyranooxazolone and pyrrole derivatives
under mild reaction conditions.
EXPERIMENTAL SECTION
12a
General procedure for the synthesis of 4-H-pyrans
Triethylamine (1 drop) was added to a solution of aromatic aldehydes (2 mmol), malononitrile
or ethyl 2ꢀcyanoacetate) (2 mmol), and 1,3ꢀdiketones (2 mmol) in EtOH (5ml) and the reaction
(
mixture was refuxed for 15 min. The precipitate thus appeared was filtered off, washed with
water (5×10 ml) and EtOH (3×5 ml), and finally recrystallized from EtOH. The crystallized pure
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
12aꢀj
compounds
were then subjected for the synthesis of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl
carboxylates.
12a
General procedure for the synthesis of spiropyran
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Triethylamine (1 drop) was added to a solution of ninhydrin (2 mmol), malononitrile (2 mmol),
and dimedone (2 mmol) in EtOH (5ml) and the reaction mixture was refuxed for 15 min. The
precipitate thus formed was filtered off, washed with water (5×10 ml) and EtOH (3×5 ml), and
12k
finally recrystallized from EtOH. The crystallized pure compound was then subjected for the
synthesis of 2ꢀoxaꢀ7ꢀazabicyclo[4.1.0]heptꢀ3ꢀenꢀ1ꢀyl carboxylates.
General procedure for the synthesis of 2-oxa-7-azabicyclo[4.1.0]hept-3-en-1-yl carboxylate
2
a-r and 4a-j
To a stirring suspension of iodosylbenzene (1.5 mmol) in 5mL DCM was added carboxylic acid
2 mmol) and stirred for 5 min at rt followed by addition of triethylamine (1 mmol) and stirred
(
for another 2 min. Finally 2ꢀaminoꢀ4ꢀHꢀpyrans (1 mmol) were added in the reaction mixture and
stirred for the stipulated time (Table 2 and 3) until the total consumption of the starting material
(
monitored by TLC) was observed. After completion of the reaction, the mixture was diluted
with DCM(10mL) and washed with saturated sodium bicarbonate solution (10mL×3 times). The
combined organic layers were dried over sodium sulphate and subjected to column
chromatographic separation (20ꢀ 50% ethylacetate in petroleum ether) to get the pure products.
The same procedure was applied in case of 2ꢀamino spiropyran. All the synthesized compounds
1
13
were characterized by spectral ( H NMR, C NMR, IR, HRMS and elemental analysis) data, and
Xꢀray crystallographic analysis (4g).
ACS Paragon Plus Environment

Page 21 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
7
a-cyano-6-oxo-7-phenyl-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
4-
nitrobenzoate 2a
Yield: 396 mg, 92%; white solid; Mp: 208ꢀ210 C; IR (KBr): 3214, 2956, 2832, 2245, 1750,
o
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ1 1
1
710, 1680, 1632, 1530, 1350, 1091, 987 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 2.07 (d,
3 4
J=4.8 Hz, 2H), 2.30ꢀ2.41 (m, 3H), 2.60 (d, J=4.8 Hz, 2H), 4.61 (s, 1H), 7.21ꢀ7.25 (m, 2H), 7.30ꢀ
1
3
7
.36 (m, 3H), 8.26ꢀ8.35 (m, 4H); C NMR (75 MHz; CDCl ; Me Si): δ 20.2, 27.9, 36.8, 36.9,
3 4
3
8.9, 88.8, 110.2, 116.0, 123.9, 127.4, 128.1, 129.0, 131.6, 132.5, 136.3, 151.5, 161.6, 165.4,
+
195.7; HRMS (ESIꢀTOF) m/z Calcd for [C H N O +H] : 432.1190, found: 432.1215 and
2
3
17
3
6
+
[
C H N O +Na] : 454.1010, found: 454.1016.
23 17 3 6
7
a-cyano-6-oxo-7-phenyl-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
4-
methoxybenzoate 2b
Yield: 374 mg, 90%; white solid; Mp: 190ꢀ200 C; IR (KBr): 3254, 2938, 2844, 2243, 1726,
o
ꢀ
1 1
1
675, 1630, 1605, 1166, 1100, 937, 606 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ 1.91 (s,
6 4
2
H), 2.26 (d, J=3.9 Hz, 2H), 2.53 (s, 2H), 3.85 (s, 3H), 4.33 (s, 1H), 5.84 (s, 1H), 7.13 (d, J=8.7
13
Hz, 2H), 7.20ꢀ7.32 (m, 5H), 8.02 (d, J=8.7 Hz, 2H); C NMR (75 MHz; DMSO d ; Me Si): δ
6
4
24.9, 32.6, 40.7, 41.7, 60.8, 84.2, 93.4, 114.5, 118.8, 119.7, 121.4, 123.9, 132.1, 132.8, 133.2,
1
33.4, 133.9, 136.4, 137.3, 143.1, 167.4, 169.6, 170.7, 200.6; Anal. Calcd for C H N O : C,
24 20 2 5
6
9.22; H, 4.84; N, 6.73%. Found: C 69.20; H 4.86; N 6.70%.
7a-cyano-6-oxo-7-phenyl-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
2-
chlorobenzoate 2c
o
Yield: 391 mg, 93%; white solid; Mp: 182ꢀ184 C; IR (KBr): 3277, 2922, 2890, 2243, 1751,
ꢀ1 1
1
672, 1632, 1369, 1188, 1099, 1088, 1025, 918, 743 cm ; H NMR (300 MHz; CDCl ; Me Si):
3 4
δ 1.91ꢀ2.07 (m, 2H), 2.19ꢀ2.36 (m, 2H), 2.40 (s, 1H), 2.45ꢀ2.60 (m, 2H), 4.50 (s, 1H), 7.14ꢀ7.33
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
(
m, 6H), 7.45ꢀ7.46 (d, J=3.6 Hz, 2H), 7.92ꢀ7.95 (d, J=7.8 Hz, 1H); C NMR (75 MHz; CDCl3;
Me Si): δ 19.8, 27.7, 36.6, 38.7, 88.3, 109.8, 115.8, 126.0, 126.7, 127.1, 127.14, 127.2, 127.6,
4
1
28.6, 131.4, 132.1, 134.2, 135.1, 136.3, 161.2, 165.3, 195.6; HRMS (ESIꢀTOF) m/z Calcd for
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
[
C H ClN O +H] : 421.0950, found: 421.0931 and [C H ClN O +Na] : 443.0769, found:
23 17 2 4 23 17 2 4
443.0748.
7
a-cyano-7-(4-nitrophenyl)-6-oxo-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
7
d
2
-phenylacetate 2d
o
Yield: 419 mg, 94%; white solid; Mp: 204ꢀ206 C; IR (KBr): 3114, 2956, 2826, 2243, 1788,
ꢀ1
1
1
653, 1632, 1515, 1347, 1236, 1091, 995 cm ; H NMR (300 MHz; DMSOꢀd ; Me Si): δ 2.02
6 4
(
s, 2H), 2.27ꢀ2.55 (m, 5H), 3.83 (s, 2H), 4.41 (s, 1H), 7.30ꢀ7.39 (m, 7H), 8.16ꢀ8.18 (d, J=8.7 Hz,
1
3
2H); C NMR (75 MHz; DMSOꢀd ; Me Si): δ 15.3, 23.2, 31.5, 32.0, 34.5, 35.6, 83.3, 104.8,
6
4
1
10.6, 119.1, 123.1, 124.05, 124.1, 124.6, 126.6, 139.5, 142.7, 161.4, 163.4, 191.0; Anal. Calcd
for C H N O : C 64.72; H 4.30; N 9.43%. Found: C 64.74; H 4.32; N 9.40%.
24 19
3
6
7
a-cyano-6-oxo-7-phenyl-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
acetate
7d
2
e
o
Yield: 311 mg, 96%; offꢀwhite solid; Mp: 132ꢀ134 C; IR (KBr): 3175, 2963, 2238, 1791, 1631,
ꢀ1 1
1
238, 1229, 1152, 1100, 1063, 936 cm ; H NMR (300 MHz; DMSOꢀd ; Me Si): δ 1.90 (s, 2H),
6 4
13
2
.24 (s, 5H), 2.50 (s, 2H), 4.26 (s, 1H), 5.67 (s, 1H), 7.17ꢀ7.33 (m, 5H); C NMR (75 MHz;
DMSOꢀd ; Me Si): δ 20.3, 20.7, 28.0, 36.0, 37.1, 88.5, 109.8, 116.8, 127.5, 128.2, 128.6, 138.5,
6
4
+
1
3
7
66.0, 168.1, 196.0; HRMS (ESIꢀTOF) m/z Calcd for [C H N O +H] : 325.1183, found:
18 16 2 4
25.1188.
-(2-chlorophenyl)-7a-cyano-6-oxo-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
7d
acetate 2f
ACS Paragon Plus Environment

Page 23 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
ꢀ1
Yield: 341 mg, 95%; white solid; Mp 142ꢀ144 C; IR (KBr):cm ; 3217, 2956, 2937, 2244, 1788,
ꢀ
1 1
1
668, 1626, 1234, 1175, 1102, 1064, 768 cm ; H NMR (300 MHz; CDCl3; Me Si): δ 1.90ꢀ1.98
4
(
m, 2H), 2.18 (s, 3H), 2.22ꢀ2.26 (t, J=6.2 Hz, 2H), 2.36 (s, 1H), 2.48ꢀ2.51 (t, J=5.3 Hz, 2H), 5.06
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(
s, 1H), 6.85ꢀ6.88 (d, J=7.5 Hz, 1H), 7.04ꢀ7.16 (m, 2H), 7.36ꢀ7.39 (d, J=7.8 Hz, 1H); C NMR
(75 MHz; CDCl3; Me Si): δ 19.8, 20.1, 27.5, 34.4, 35.2, 36.5, 87.8, 110.6, 115.6, 126.2, 128.5,
4
1
28.8, 129.4, 133.7, 134.3, 165.5, 166.9, 195.1; HRMS (ESITOF) m/z Calcd for
[
C H ClN O +H]+ : 359.0793, found: 359.0799.
1
8
15
2
4
7a-cyano-6-oxo-7-(thiophen-2-yl)-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-1a(1H)-yl
-nitrobenzoate 2g
Yield: 389 mg, 89%; pale yellow solid; Mp: 180ꢀ182 C; IR (KBr):cm ; 3188, 2954, 2840, 2246,
3
o
ꢀ1
ꢀ1 1
1786, 1688, 1632, 1528, 1352, 1234, 1091, 930 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ
6
4
1
.80 (s, 2H), 2.19 (s, 2H), 2.43 (s, 2H), 4.65 (s, 1H), 6.20 (s, 1H), 6.91 (s, 2H), 7.30 (s, 1H), 7.83
1
3
(
s, 1H), 8.37 (d, J=6 Hz, 1H), 8.52 (d, J=6 Hz, 1H), 8.64 (s, 1H); C NMR (75 MHz; DMSO d ;
6
Me Si): δ 19.8, 27.6, 35.0, 35.2, 36.7, 88.9, 110.0, 116.0, 124.4, 125.2, 126.0, 126.6, 128.5,
4
1
29.6, 131.4, 135.9, 140.4, 148.2, 161.4, 164.7, 195.5; Anal. Calcd for C H N O S: C 57.66; H
21 15 3 6
3.46; N 9.61%. Found: C 57.64; H 3.44; N 9.64%.
7
-(4-bromophenyl)-7a-cyano-6-oxo-7a,8-dihydro-6H-chromeno[3',4':5,6]pyrano[2,3-
b]azirin-8a(7H)-yl 4-chlorobenzoate 2h
Yield: 495 mg, 90%; offꢀwhite solid; Mp: 220ꢀ222 C; IR (KBr): 3310, 2241, 1768, 1712, 1645,
o
ꢀ1
1
1
6
3
3
489, 1384, 1241, 1108, 701, 564 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ 4.76 (s, 1H),
6 4
.43 (s, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.29ꢀ7.38 (m, 2H), 7.49 (d, J=8.1 Hz, 2H), 7.60ꢀ7.68 (m,
1
3
H), 7.78 (d, J=6.9 Hz, 1H), 8.04 (d, J=8.4 Hz, 2H); C NMR (75 MHz; DMSO d ; Me Si): δ
6
4
5.9, 90.0, 100.4, 113.7, 115.9, 116.9, 121.5, 123.3, 125.2, 126.1, 130.1, 130.8, 131.8, 132.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
2
7
33.6, 136.9, 140.8, 152.4, 155.2, 159.9, 162.6; Anal. Calcd for C H BrClN O : C 56.80; H
2
6
14
2
5
.57; N, 5.10%. Found: C 56.78; H 2.59; N, 5.12%.
-(4-bromophenyl)-7a-cyano-6-oxo-7a,8-dihydro-6H-chromeno[3',4':5,6]pyrano[2,3-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
b]azirin-8a(7H)-yl 3-nitrobenzoate 2i
Yield: 493 mg, 88%; pale yellow solid; Mp: 230ꢀ232 C; IR (KBr): 3320, 2241, 1768, 1720,
o
ꢀ1 1
1645, 1530, 1489, 1384, 1330, 1241, 762 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ 4.87
6 4
(s, 1H), 6.60 (s, 1H), 7.32 (d, J=8.1 Hz, 2H), 7.39ꢀ7.52 (m, 2H), 7.58 (d, J=8.4 Hz, 2H), 7.72 (t,
J=7.8 Hz, 1H), 7.89 (d, J=8.1 Hz, 1H), 7.97 (t, J=8.1 Hz, 1H), 8.52 (d, J=7.8 Hz, 1H), 8.66 (d,
13
J=8.4 Hz, 1H), 8.80 (s, 1H); C NMR (75 MHz; DMSO d ; Me Si): δ 35.9, 90.1, 100.5, 115.9,
6
4
1
16.9, 121.5, 123.3, 124.9, 125.2, 128.9, 130.1, 130.8, 131.8, 133.7, 136.4, 136.8, 148.6, 152.4,
+
155.1, 161.8; HRMS (ESIꢀTOF) m/z Calcd for [C H BrN O +H] : 560.0088, found: 560.0113.
26
14
3
7
7a-cyano-7-(4-nitrophenyl)-6-oxo-7a,8-dihydro-6H-chromeno[3',4':5,6]pyrano[2,3-b]azirin-
8a(7H)-yl 4-chlorobenzoate 2j
o
Yield: 348 mg, 90%; offꢀwhite solid; Mp: 216ꢀ218 C; IR (KBr): 3291, 2244, 1752, 1720, 1678,
ꢀ1
1
1661, 1636, 1239, 1118, 949 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ 2.24 (s, 3H), 4.77
6 4
1
3
(s, 1H), 6.01 (s, 1H), 7.25 (s, 5H), 7.75 (d, J=7.2 Hz, 3H), 7.94ꢀ7.97 (m, 1H); C NMR (75
MHz; DMSO d ; Me Si): δ 20.7, 35.8, 89.3, 116.3, 119.6, 126.3, 126.5, 128.0, 128.7, 128.9,
6
4
1
30.8, 131.7, 134.5 135.2, 137.8, 150.2, 168.1, 177.6, 182.7; Anal. Calcd for C H N O : C
22 14 2 5
68.39; H 3.65; N 7.25%. Found: C 68.37; H 3.63; N 7.28%.
9
a-cyano-9-(4-nitrophenyl)-3,8-dioxo-3,8,9,9a-tetrahydrobenzo[6,7]chromeno[2,3-b]azirin-
a(1H)-yl 4-chlorobenzoate 2k
1
o
Yield: 465 mg, 88%; yellow solid; Mp: 222ꢀ224 C; IR (KBr): 3298, 2246, 1756, 1722, 1678,
ꢀ1
1
1661, 1636, 1534, 1350, 1295, 1101, 701 cm ; H NMR (300 MHz; CDCl and DMSO d ;
3 6
ACS Paragon Plus Environment

Page 25 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Me Si): δ 4.80 (s, 1H), 5.26 (s, 1H), 7.42 (d, J=8.4 Hz, 2H), 7.51 (d, J=8.1 Hz, 2H), 7.66ꢀ7.68
4
1
3
(
m, 2H), 7.82 (d, J= 2.4 Hz,1H), 7.99ꢀ8.05 (m, 3H), 8.16 (d, J=8.4 Hz, 2H); C NMR (75 MHz;
DMSO d ; Me Si): δ 35.1, 89.8, 115.7, 118.8, 124.0, 126.0, 126.4, 126.6, 130.2, 130.9, 131.5,
6
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
32.3, 134.7, 135.2, 140.9, 145.3, 147.5, 150.5, 162.4, 177.4, 182.7; HRMS (ESIꢀTOF) m/z
+
Calcd for [C H ClN O +Na] : 550.0412, found: 550.0428.
2
7
14
3
7
9
-(2-chlorophenyl)-9a-cyano-3,8-dioxo-3,8,9,9a-tetrahydrobenzo[6,7]chromeno[2,3-
b]azirin-1a(1H)-yl 4-chlorobenzoate 2l
Yield: 466 mg, 90%; yellow solid; Mp: 212ꢀ214 C; IR (KBr): 3291, 2242, 1752, 1720, 1678,
o
ꢀ1
1
1
661, 1636, 1239, 1094, 714 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 2.87 (s, 1H), 5.62 (s,
3 4
1
H), 7.10 (s, 1H), 7.19 (d, J=7.2 Hz, 1H), 7.28 (d, J=3Hz, 1H), 7.48ꢀ7.57 (m, 3H), 7.73 (d, J=3.3
1
3
Hz, 2H), 7.94 (d, J=3.9 Hz, 1H), 8.04ꢀ8.08 (m, 2H), 8.13 (d, J=2.7 Hz, 1H); C NMR (75 MHz;
CDCl ; Me Si): δ 35.8, 36.0, 89.2, 115.3, 120.0, 125.3, 126.7, 127.0, 129.3, 129.5, 129.9, 130.1,
3
4
1
30.4, 131.5, 131.9, 133.8, 134.0, 134.8, 141.8, 150.1, 162.3, 182.2; Anal. Calcd for
C H Cl N O : C 62.69; H 2.73; N, 5.42%. Found: C 62.66; H 2.75; N, 5.40%.
27
14
2
2
5
9
-(2-chlorophenyl)-9a-cyano-3,8-dioxo-3,8,9,9a-tetrahydrobenzo[6,7]chromeno[2,3-
b]azirin-1a(1H)-yl 2-phenylacetate 2m
Yield: 457 mg, 92%; yellow solid; Mp: 208ꢀ210 C; IR (KBr): 3180, 2244, 1754, 1735, 1670,
o
ꢀ1 1
1
661, 1636, 1350, 1295, 1239, 1094, 949, 701 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ
6 4
3.97ꢀ4.13 (m, 2H), 5.29 (s, 1H), 6.45 (s, 1H), 7.23 (s, 2H), 7.36 (s, 6H), 7.59 (d, J=7.2 Hz, 1H),
13
7
.82 (s, 3H), 8.03 (d, J=5.7 Hz, 1H); C NMR (75 MHz; DMSO d ; Me Si): δ 34.2, 36.5, 89.4,
6
4
1
19.6, 126.3, 126.5, 127.7, 127.8, 128.7, 129.0, 129.7, 130.0, 130.8, 131.3, 131.5, 132.9, 134.6,
1
35.2, 150.5, 169.2, 177.4, 182.6; Anal. Calcd for C H ClN O : C 67.68; H 3.45; N 5.64%.
2
8
17
2
5
Found: C 67.66; H 3.48; N 5.62%.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
a-cyano-6-oxo-7-(thiophen-2-yl)-7a,8-dihydro-6H-chromeno[3',4':5,6]pyrano[2,3-b]azirin-
8a(7H)-yl 4-chlorobenzoate 2n
o
Yield: 401 mg, 84%; offꢀwhite solid; Mp: 214ꢀ216 C; IR (KBr): 3235, 2254, 1755, 1729, 1638,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ꢀ1 1
1379, 1228, 1090, 755, 708 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 2.86 (s, 1H), 5.04 (s,
3 4
1H), 6.96 (t, J=4.4 Hz, 1H), 7.09 (d, J=3.3 Hz, 1H), 7.17ꢀ7.26 (m, 3H), 7.43 (d, J=8.1 Hz, 2H),
1
3
7
.51 (t, J=7.8 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 8.00 (d, J=8.1 Hz, 2H); C NMR (75 MHz;
CDCl ; Me Si): δ 36.5, 37.1, 89.4, 100.4, 113.4, 115.2, 116.8, 123.1, 124.5, 125.2, 125.9, 127.1,
3
4
127.2, 129.4, 131.9, 133.1, 137.5, 141.9, 152.6, 159.9, 162.2; Anal. Calcd for C H ClN O S: C
2
4
13
2
5
6
7
1
0.45; H 2.75; N, 5.87%. Found: C 60.43; H 2.77; N, 5.85%.
-benzoyl-7a-cyano-4,4-dimethyl-6-oxo-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-
a(1H)-yl 3-nitrobenzoate 2o
o
Yield: 439 mg, 90%; white solid; Mp: 188ꢀ190 C; IR (KBr): 3240, 2959, 2840, 2244, 1743,
ꢀ1 1
1
660, 1605, 1533, 1350, 1260, 1200, 1168, 1094, 934 cm ; H NMR (300 MHz; CDCl ; Me Si):
3 4
δ 1.05 (s, 6H), 2.22 (s, 2H), 2.29ꢀ2.47 (m, 2H), 3.20 (s, 1H), 5.19 (s, 1H), 7.49 (t, J=7.4 Hz, 2H),
.58ꢀ7.68 (m, 2H), 8.09 (d, J=7.5 Hz, 2H), 8.35 (d, J=7.5 Hz, 1H), 8.44 (d, J=8.1 Hz, 1H), 8.86
7
1
3
(s, 1H); C NMR (75 MHz; CDCl ; Me Si): δ 27.8, 28.4, 32.6, 34.1, 38.1, 41.2, 50.0, 88.1,
3
4
108.3, 115.2, 125.4, 129.0, 129.1, 129.2, 130.2, 134.6, 135.3, 135.8, 148.5, 161.6, 164.4, 196.0,
+
196.1; HRMS (ESIꢀTOF) m/z Calcd for [C H N O +Na] : 510.1272, found: 510.1251.
2
6
21
3
7
7-benzoyl-7a-cyano-4,4-dimethyl-6-oxo-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-
a(1H)-yl cyclohexanecarboxylate 2p
Yield: 426 mg, 95%; white solid; Mp: 136ꢀ138 C; IR (KBr): 3272, 2966, 2928, 2840, 2242,
1
o
ꢀ1
1
1740, 1668, 1605, 1250, 1208, 1168, 1094, 934 cm ; H NMR (300 MHz; CDCl ; Me Si): δ
3 4
1
.11 (s, 6H), 1.24ꢀ1.32 (m, 3H), 1.52 (d, J=10.8 Hz, 2H), 1.77 (s, 2H), 1.99 (d, J=12.6 Hz, 2H),
ACS Paragon Plus Environment

Page 27 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2
.25 (s, 2H), 2.32ꢀ2.52 (m, 3H), 2.97 (s, 1H), 5.16 (s, 1H), 7.55 (t, J=7.7 Hz, 2H), 7.66 (d, J=7.5
1
3
Hz, 1H), 8.15 (d, J=7.8 Hz, 2H); C NMR (75 MHz; CDCl ; Me Si): δ 25.1, 25.5, 27.7, 28.3,
3
4
28.5, 32.5, 34.1, 38.3, 41.2, 42.4, 50.0, 87.1, 108.0, 115.5, 129.1, 134.4, 135.4, 164.6, 172.9,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
1
95.9, 196.2; HRMS (ESIꢀTOF) m/z Calcd for [C H N O +H] : 449.2071, found: 449.2068,
2
6
28
2
5
+
and [C H N O +Na] : 471.1890, found: 471.1869.
26
28
2
5
7
1
-benzoyl-7a-cyano-4,4-dimethyl-6-oxo-3,4,5,6,7,7a-hexahydrochromeno[2,3-b]azirin-
a(1H)-yl 4-methoxybenzoate 2q
o
Yield: 444 mg, 94%; white solid; Mp: 184ꢀ186 C; IR (KBr): 3272, 2959, 2932, 2864, 2244,
ꢀ1
1
1
743, 1660, 1605, 1373, 1260, 1200, 1168, 1094, 934, 767, 612 cm ; H NMR (300 MHz;
CDCl ; Me Si): δ 1.03 (s, 6H), 2.20 (s, 2H), 2.26ꢀ2.46 (m, 2H), 3.02 (s, 1H), 3.79 (s, 3H), 5.16
3
4
(s, 1H), 6.87 (d, J=9.0 Hz, 2H), 7.48 (t, J=7.7 Hz, 2H), 7.58 (t, J=7.4 Hz, 1H), 7.98 (d, J=9.0 Hz,
13
2
4
1
4
H), 8.09 (d, J=7.8 Hz, 2H); C NMR (75 MHz; CDCl ; Me Si): δ 27.7, 28.5, 32.5, 34.2, 38.4,
3
4
1.2, 50.0, 55.6, 87.7, 108.1, 114.2, 115.5, 119.4, 129.1, 129.1, 132.7, 134.4, 135.5, 163.0, 164.7,
+
64.8, 196.0, 196.2; HRMS (ESIꢀTOF) m/z Calcd for [C H N O +Na] : 495.1527, found:
27
24
2
6
95.1529.
7a-cyano-4,4-dimethyl-1',3',6-trioxo-1,1',3,3',4,5,6,7a-octahydro-1aH-spiro[chromeno[2,3-
b]azirine-7,2'-inden]-1a-yl 4-chlorobenzoate 2r
o
Yield: 453 mg, 90%; offꢀwhite solid; Mp: 220ꢀ222 C; IR (KBr): 3247, 2967, 2939, 2833, 2249,
ꢀ1 1
1790, 1752, 1713, 1665, 1644, 1369, 1249, 1214, 942, 720 cm ; H NMR (300 MHz; DMSO d ;
6
Me4Si): δ 0.98 (d, J=5.4 Hz, 3H), 1.04 (s, 3H), 1.98ꢀ2.50 (m, 3H), 2.58ꢀ2.74 (m, 1H), 6.86 (d,
1
3
J=6.0 Hz, 1H), 7.69ꢀ7.74 (m, 2H), 8.05ꢀ8.10 (m, 6H); C NMR (75 MHz; DMSO d ; Me4Si): δ
6
2
6.4, 28.8, 32.8, 35.6, 49.4, 54.8, 87.9, 109.3, 113.8, 124.2, 125.9, 130.1, 132.3, 137.3, 137.8,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 40
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
40.8, 141.1, 161.9, 169.0, 193.9, 196.6, 196.8; HRMS (ESIꢀTOF) m/z Calcd for
+
[
C H ClN O +H] : 503.1004, found: 503.1033.
27 19
2
6
ethyl
1a-((4-nitrobenzoyl)oxy)-6-oxo-7-phenyl-1,1a,3,5,6,7-hexahydrochromeno[2,3-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
b]azirine-7a(4H)-carboxylate 4a
Yield: 421 mg, 88%; offꢀwhite solid; Mp: 202ꢀ204 C; IR (KBr): 3290, 2967, 2833, 1740, 1713,
o
ꢀ1
1
1642, 1611, 1530, 1350, 1200, 1093, 941 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 1.27 (t,
3 4
J=7.1 Hz, 3H), 2.05 (s, 2H), 2.34ꢀ2.46 (m, 2H), 2.58 (d, J=4.2 Hz, 2H), 4.21ꢀ4.26 (m, 2H), 5.07
1
3
(s, 1H), 7.25 (s, 5H), 8.23 (d, J=7.8 Hz, 2H), 8.33 (d, J=6.6 Hz, 2H); C NMR (75 MHz; CDCl ;
3
Me Si): δ 14.1, 20.3, 28.1, 35.9, 37.2, 48.4, 63.4, 90.0, 112.1, 123.9, 127.0, 128.1, 128.2, 131.4,
4
133.0, 138.8, 151.3, 161.9, 165.2, 167.2, 196.5; HRMS (ESIꢀTOF) m/z Calcd for
+
+
[C H N O +H] : 479.1449, found: 479.1441 and [C H N O +Na] : 501.1268, found:
2
5
22
2
8
25 22
2
8
501.1255.
ethyl 1a-((cyclohexanecarbonyl)oxy)-6-oxo-7-phenyl-1,1a,3,5,6,7-hexahydrochromeno[2,3-
b]azirine-7a(4H)-carboxylate 4b
o
Yield: 396 mg, 90%; white solid; Mp: 120ꢀ122 C; IR (KBr): 3280, 2980, 2940, 2826, 1740,
ꢀ1 1
1715, 1642, 1611, 1200, 1093, 950 cm ; H NMR (300 MHz; DMSO d ; Me Si): δ 1.20ꢀ1.34
6
4
(m, 8H), 1.57 (s, 1H), 1.64 (s, 2H), 1.78 (s, 2H), 1.90 (t, J=5.9 Hz, 2H), 2.24 (s, 2H), 2.39 (s,
1
H), 4.10 (s, 1H), 4.13ꢀ4.21 (m, 2H), 4.73 (s, 1H), 7.07 (d, J=7.5 Hz, 2H), 7.12ꢀ7.24 (m, 3H);
1
3
C NMR (75 MHz; DMSO d ; Me4Si): δ 19.0, 25.0, 29.4, 30.1, 32.6, 33.0, 33.1, 41.0, 41.7,
6
46.4, 52.5, 67.5, 93.9, 115.6, 131.4, 132.8, 132.9, 144.6, 170.6, 171.7, 177.2, 201.0; Anal. Calcd
for C H NO : C 68.32; H 6.65; N 3.19%. Found: C 68.30; H 6.63; N 3.21%.
25 29
6
ethyl
7-(4-bromophenyl)-1a-(2,2-diphenylacetoxy)-4,4-dimethyl-6-oxo-1,1a,3,5,6,7-
hexahydrochromeno[2,3-b]azirine-7a(4H)-carboxylate 4c
ACS Paragon Plus Environment

Page 29 of 40
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
Yield: 542 mg, 86%; offꢀwhite solid; Mp: 140ꢀ142 C; IR (KBr): 3330, 2967, 2939, 2833, 1735,
ꢀ1 1
1
720, 1642, 1243, 1093, 1051, 1029, 950, 744, 668 cm ; H NMR (300 MHz; CDCl ; Me Si): δ
3 4
.
99ꢀ1.06 (m, 9H), 2.11 (s, 2H), 2.30 (s, 2H), 2.64 (s, 1H), 3.85ꢀ3.92 (m, 2H), 4.77 (s, 1H), 4.96
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(
s, 1H), 7.00 (d, J=7.8 Hz, 2H), 7.16ꢀ7.29 (m, 12H); C NMR (75 MHz; CDCl ; Me Si): δ 13.9,
3
4
28.0, 28.4, 31.7, 35.6, 41.6, 48.2, 50.9, 56.0, 63.1, 89.5, 110.4, 120.8, 127.6, 128.2, 128.3, 128.4,
28.5, 128.6, 128.7, 128.8, 129.9, 131.1, 136.9, 137.1, 138.0, 163.8, 166.6, 169.6, 196.4; Anal.
Calcd for C H BrNO : C 64.77; H 5.12; N 2.22%. Found: C 64.75; H 5.10; N 2.25%.
1
3
4
32
6
ethyl
8a-((4-chlorobenzoyl)oxy)-7-(4-nitrophenyl)-6-oxo-8,8a-dihydro-6H-
chromeno[3',4':5,6]pyrano[2,3-b]azirine-7a(7H)-carboxylate 4d
o
Yield: 462 mg, 82%; offꢀwhite solid; Mp: 180ꢀ182 C; IR (KBr): 3315, 1740, 1642, 1529, 1349,
ꢀ1 1
1200, 1093, 1051, 1029, 941, 746 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 1.29 (t, J=7.1 Hz,
3
4
3
7
1
1
H), 3.12 (s, 1H), 4.19ꢀ4.36 (m, 2H), 5.36 (s, 1H), 7.27ꢀ7.33 (m, 2H), 7.45ꢀ7.60 (m, 4H), 7.69ꢀ
.75(m, 1H), 7.87 (d, J=7.8 Hz, 1H), 8.02 (d, J=8.4 Hz, 2H), 8.13 (d, J=8.4 Hz, 1H), 8.25 (s,
1
3
H); C NMR (75 MHz; CDCl ; Me Si): δ 14.1, 37.5, 48.4, 63.9, 90.4, 101.0, 113.9, 116.7,
3
4
22.7, 123.1, 123.7, 124.4, 125.6, 129.2, 129.4, 131.7, 132.7, 135.0, 140.0, 141.5, 148.3, 152.6,
155.8, 160.8, 162.6, 166.1; Anal. Calcd for C H ClN O : C 59.74; H 3.40; N 4.98%. Found: C
2
8
19
2
9
5
9.72; H 3.42; N 4.96%.
ethyl
8a-(benzoyloxy)-7-(4-nitrophenyl)-6-oxo-8,8a-dihydro-6H-
chromeno[3',4':5,6]pyrano[2,3-b]azirine-7a(7H)-carboxylate 4e
o
Yield: 423 mg, 80%; offꢀwhite solid; Mp: 170ꢀ172 C; IR (KBr): 3350, 1745, 1640, 1540, 1350,
ꢀ1
1
1
190, 1093, 1050, 1029, 941, 745 cm ; H NMR (300 MHz; CDCl ; Me Si): δ 1.25ꢀ1.33 (m,
3 4
3
H), 3.00 (d, J=9.3 Hz, 1H), 4.18ꢀ4.30 (m, 2H), 5.30 (d, J=9.6Hz, 1H), 7.17ꢀ7.65 (m, 8H), 7.82
13
(
t, J=8.4 Hz, 1H), 7.93 (t, J=8.4 Hz, 1H), 8.07 (t, J=8.4 Hz, 1H), 8.18 (d, J=10.5 Hz, 1H); C
ACS Paragon Plus Environment