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The Journal of Organic Chemistry
Page 2 of 10
or hexahelicenes are not optically resolvable due to the lack of
corresponding steric hindrance. The presence of pyran ring in
oxahelicenoids offers a larger in plane turn angle for the overall
helicity (Figure 1).15-20 For the synthesis of such oxa-helical
molecules, there is no data on the use of Diels Alder approach
so far, which is more commonly used for synthesizing
carbohelicenes.21-23 Indeed, there are very few reports of the
synthesis of such molecules.15-20 Moreover, the stereochemical
study of pyran ring containing [5] and [7]helicenes was the least
addressed area in the helicene chemistry. With these
considerations, we aimed to construct [5] and [7]oxahelicenoids
via the Diels Alder approach and study its structural and
stereochemical properties.
derivative 17, the initial protection of one of the phenolic groups
1
2
3
4
5
6
7
8
of 2,7-naphthalene diol was necessary before the cyclisation
reaction of 15 in the presence of 80% sulfuric acid to result in
the cyclized product 16.
After the successful synthesis of sterically crowded
bichromene systems, we employed the π4 + π2 cycloaddition,
i.e. the Diels-Alder reaction between the corresponding diene
bichromene derivatives and suitable highly reactive dienophile
for the synthesis of [5] and [7] oxahelicenoids.
9
12
13
O
12a
O
11
14
15
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
10b
16b
10
7
16
1
10a
16a
9
8
16c
16d
6b
6a
2
3
Results and discussion
O
6
O
4a
5
4
8
In this article, we report a straightforward access to pyran ring
containing [5] and [7]oxaheliceoids through the Diels-Alder
approach. Also, we present unusual stepwise mechanism in the
reaction of sterically crowded bichromenes with benzyne to
give the anti cycloadduct, which is not typical for the Diels-
Alder chemistry. Density functional theory (DFT) and
crystallographic studies weigh in favours of this intriguing
pathway. For the synthesis of [5] and [7] oxahelicenoids by this
method the corresponding suitable diene and dienophile are
required. In this case, the bichromene derivatives are considered
to be an ideal hetero-annular diene for the present work. It is of
note that the introduction of hetero (oxygen) atom in
bichromene not only changes the geometrical features of
helicenoid but also activates the peripheral (aryl) ring for
electrophilic functionalization in the targeted helicenoids.
X-ray of 18
18
16
15
14a 14
17
O
O
20b
13
18 16a
O
R
20c
12a
20d
12
9
12b
20a
20
R
R
19
2
11
10
1
20f
8b
R
O
8a
3
20e
8
O
O
6a
4
4a
7
6
5
R=H=19
R=OMe= 20
R=H=12
R=OMe= 17
Carbon labelling in
[7]oxahelicenoids
Scheme 2. Benzyne mediated synthesis of [5] and
[7]oxahelicenoids, 18-20
Just a few reports were found for the preparation of [5]-
carbohelicenes involving the cycloaddition reaction where 1,4-
benzoquinone, N-phenylmaleimide and other reactive
dienophiles were employed to undergo the reaction with the
diene systems23c,28
.
However, the newly synthesized
We first embarked on the preparation of oxa bichromene
systems 8, 12, and 17 as suitable dienes by following Scheme
1. Initially phenol 5 upon Michael addition with acrylonitrile in
triethyl amine as the base instead of triton B, by slight
modification in reported methodology24, afforded the
corresponding acryl aryl ether 6 with excellent yield (95%)
much better than the reported yield. The cyclization of 3-
phenoxypropanenitrile has been carried out using reported25
procedure to obtain chroman-4-one, 7. Then, 7 was subjected to
HgCl2 - Al (aluminium amalgam) to initiate the coupling
bichromene derivatives, 8, 12 and 17 failed to react with all
these dineophiles. However, benzyne alone was found to
undergo the reaction with these three bichromene diene systems
to afford [5] and [7]oxaheliceneoid, 18-20 (Scheme 2). Though
the reaction appears to be a classical π4 + π2 Diels-Alder
cycloaddition, the failure of reaction with dienophiles other
than benzyne created some doubt upon the standard concerted,
cis-syn addition pathway in the presence of benzyne29a,b as a
dienophile.
reaction to produce 2H,2'H-4,4'-bichromene 8 in good yield27.
The UV spectra showed the absorption range from 325 nm
for [5]oxahelicenoids to 360nm for dibromo[7]oxahelicenoid.
The helicenoids were found to be fluorescence active with
stokes shifts in the range of 55-80nm (SI, figure S78-S105) The
UV absorption for [5]oxahelicenoids is comparable with the
corresponding [5]carbohelicene.28a
O
O
OH
O
CN
Acrylonitrile
TEA, reflux
AlCl3, EDC
reflux
Al, HgCl2
Benzene-Ethanol
reflux
O
6
5
7
O
8
O
CN
O
OH
Al, HgCl2
O
O
Acrylonitrile
To investigate the mechanistic aspects and exclusive
selectivity of benzyne as a dienophile in this reaction, the
stereochemistry of [5] and [7]-helicenoids, have been
comprehensively investigated. 1H and 13C NMR analyses
showed that all dienes 8, 12, 17 and helicenoids 18-20 are
symmetrical in nature (see SI). It is noticed that syn forms of
adducts, 18-20, are expected to possess Cs symmetry and the
anti form of the same adducts are expected to possess C2
symmetry. In both these possibilities, the 1H & 13C NMR were
are expected to be symmetric in nature. This apparently is the
major reason for the lack of comprehensive stereochemical
assignment and proposed mechanism for the reactions leading
to the synthesis of crowded helicenes so far. Thus, to confirm
the stereochemistry of the products unambiguously, the
corresponding crystallographic study was needed. Whilst a
suitable single crystal was obtained in the case of 18, for the [7]-
TEA
Reflux
Benzene-Ethanol
reflux
80% H2SO4
O
11
9
10
12
OMe
OH
OH
OMe
OMe
O
Al, HgCl2
Acrylonitrile
DMS
O
TEA
Reflux
Benzene
Ethanol
reflux
CN
CN
O
NaOH
80% H2SO4
O
OH
O
O
MeO
17
13
14
15
16
Scheme 1. Synthesis of bichromenes 8,12 and 17 containing
diene scaffold
The 3-(naphthalen-2-yloxy)propanenitrile, 10, was prepared
following a reported procedure26 by replacing Triton B with
triethyl amine, which gave better yield (90%). Reported
procedure26 was followed for the preparation of 2,3-dihydro-
1H-benzo[f]chromen-1-one, 11. Other two bichromenes 12, 17
were prepared similarly.27 In the preparation of chromene
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