On the Distribution of Linear versus Angular Naphthalenes in Aromatic Tetradehydro-Diels–Alder Reactions – Effect of Linker Structure and Steric Bulk

Article abstract of DOI:10.1002/ejoc.201700588

We report here a systematic study of the aromatic tetradehydro-Diels–Alder (Ar-TDDA) reaction to elucidate the factors that have significant effects on the distribution of linear and angular naphthalene products. Two factors were studied, that is, the nat

Full text of DOI:10.1002/ejoc.201700588

A Journal of
Accepted Article
Title: On the Distribution of Linear vs. Angular Naphthalenes in
Aromatic Tetradehydro Diels-Alder Reaction: Effect of Linker
Structure and Steric bulk
Authors: Beeraiah Baire and Bhavani Shankar Chinata
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700588
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700588
Supported by

10.1002/ejoc.201700588
European Journal of Organic Chemistry
Full Paper
On the Distribution of Linear vs. Angular Naphthalenes in
Aromatic Tetradehydro Diels-Alder Reaction: Effect of Linker
Structure and Steric bulk
Bhavani Shankar Chinta and Beeraiah Baire*[a]
Abstract: We report here a systematic study on the aromatic
tetradehydro Diels-Alder (Ar-TDDA) reaction to understand the
factors which may play key role on the distribution of linear and
angular naphthalene products. Two factors such as nature of
structure of the linker and steric bulk of the substituent on the enyne
part have been studied. It is found that the structure of the linker has
tremendous role on the product distribution. The effect of steric bulk
of the substituent is dependent on the linker structure, in other words,
shows different preferences for different linkers.
respectively (Figure 1B). But in the third case (Figure 2), where
the ene component is a part of benzene ring, i.e. arenyne
there are always two products isolated in the literature, viz.
linearly fused naphthalene and angularly fused naphthalene
in varying amounts. A well accepted mechanism6 for the
formation of these two products and is shown in scheme
1
,
2
3
2
3
1.
Introduction
Cycloaddition reactions are the 100% atom-economical
protocols for the generation of poly substituted six-membered
ring systems from corresponding acyclic precursors.1 One of
the most utilized and best examined cycloaddition is the [4+2]
cyclization, known as the Diels-Alder (DA) reaction (Figure 1).2
In a classical D-A reaction the 4π-electron component is
referred to as "the diene" and the 2π- component as "the
dienophile". If one or more double bonds in each of the diene
and dienophile component are replaced by a triple bond, then
we will have more unsaturated, in other words, dehydrogenated
4π and 2π components as partners in the Diels-Alder reaction.
These are the "dehydrogenated" variants of the classical D-A
reaction and hence called as dehydro Diels-Alder (DDA)
reactions. Replacement of one double bond in each of the
diene and dienophile component by triple bond will result in an
enyne and an alkyne as 4π and 2π components respectively.
The [4+2] cycloaddition reaction between an enyne and an
alkyne is well studied. This reaction results in a cyclic allene,
which would undergo a [1,5]H shift to generate the stable
benzene/arene ring (Figure 1B). According to unsaturation,
when compared to classical Diels-Alder reaction, the above
transformation can be called as a tetradehydro Diels-Alder
reaction (TDDA), but in the literature they are commonly
referred as dehydro-Diels-Alder (DDA) reactions.3 Throughout
this manuscript we use the term TDDA reaction for this version.
Recently, new variants of dehydrogenated or unsaturated
Diels-Alder reactions namely, hexa-dehydro Diels-Alder
(HDDA) reaction4 and penta-dehydro Diels-Alder reaction5 were
also reported.
Figure 1: A) The classical [4+2] cycloaddition reaction, i.e., Diels-Alder
reaction; B) The tetradehydro Diels-Alder (TDDA) reaction
According to this, there are two pathways (a and b) possible
after the generation of the linear cyclic allene intermediate
via an initial [4+2] cycloaddition between arenyne and alkyne.
In path a, the allene can directly undergo a [1,5]H shift to give
the linear naphthalene product . On the other hand, (path b)
the same allene can also undergo an electrocyclic ring
opening process to give (Z, E)-dehydro[10]annulene
intermediate . An isomerisation of via C6-C7 -bond
rotation, will generate the isomeric (E, Z)-dehydro[10]annulene
intermediate . Next, can undergo an electrocyclic ring
closing reaction to give the angular cyclic allene , which will
4,
4
2
4
a
5
5

6
6
7
after [1,5]H shift generates the angular naphthalene 3.
Figure 2: The aromatic tetradehydro Diels-Alder reaction
Based on this mechanism we propose that, the linear vs.
angular product distribution in aromatic TDDA may depends on
factors such as,
The ene component of an enyne part in the TDDA reaction can
either be an acyclic olefin or cyclic olefin or can be a part of
aromatic(benzene) ring. First two cases will result in substituted
benzene and linearly fused tricyclic benzene derivatives
a) the nature or structure of the linker. This should have a
considerable effect on the electrocyclic ring opening and
closing processes, C-C bond rotations and sigmatropic [1,5]H
shift.
[a]
Dr. Beeraiah Baire
Department of Chemistry
Indian Institute of Technology Madras, Chennai
Tamilnadu, INDIA-600036
E-mail: beeru@iitm.ac.in
b) the steric bulk of a substituent on the linker, in particular
-
carbon of the enyne unit, will also play a critical role in
controlling the rates of both the sigmatropic [1,5]H shifts by
generating the repulsive steric hindrance with the "H" which
comes after the [1,5]H shift in both the products.
http://chem.iitm.ac.in/faculty/beeraiahbaire/
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700588
European Journal of Organic Chemistry
Full Paper
With this hypothesis, we aimed to perform a systematic study to
delineate the role of above mentioned factors on the distribution
of linear and angular products in the aromatic TDDA.
here that, different activation modes (outer vs. inner) on the
linker exhibits completely reverse preferences for the cyclized
products. The outer activation of the linkers e.g., entries 2 & 4
shows high preference for linear products, whereas the inner
activation of the linkers i.e., entries 3 & 6, provides a very high
preference for the angular products. Therefore, the product
distribution in aromatic TDDA reaction showed much
dependence on the structure of the linker and mode activation.
Table 1: Effect of linker structures on the linear vs. angular product distribution
Scheme 1: Reported mechanism for the formation of linear and angular
naphthalenes during the Ar-TDDA reaction
Results and Discussion
We initiated our study with the variation of linker structure.
Accordingly, we prepared six arenyne-alkyne substrates 8a-10a
and 11-13 which possess six different linker structures. Each
substrate was subjected to thermal heating conditions at same
temperature (150 °C) in 1,2-dichlorobenzene (1,2-DCB) and
results are presented in Table 1. In case of ether linker 8a, the
reaction (entry 1) resulted in a (1:0.54) mixture of both linear
product 14aL and angular product 14aA respectively. The
ynoate and ester linkers 9a
1,2-DCB gave (1:0.58) and (1: 8.3) ratios of corresponding
linear and angular products (15aL 15aA) and (16aL 16aA)
& 10a, upon heating at 150 °C in
:
:
respectively (entry 2 & 3, Table 1). From the above three
experiments of three differently activated oxygen based linkers,
it is clear that the externally activated substrates (like ynoates)
favour the linear products, whereas internally activated linkers
such as esters, show preference for the angular products.
We next studied the behaviour of three more linkers’ 11-13, i.e.,
tosylamide, tosylamido-ynoate and imide. When substrate 11
was subjected to reaction conditions at 150 °C (entry 4, Table
1) the preference for the angular product 17A increases when
compared with its oxygen counterpart (entry 1, Table 1). The
substrate 12 (amido-ynoate linker) provided a products ratio of
In continuation, we aimed to evaluate also the effect of steric
hindrance on the product distribution, which is created by the
bulkiness of a substituent on the linker, in particular -carbon of
(1:0.36) [18L:18A] relatively more preference towards the linear
the enyne unit. It is proposed that (Figure 3) the [1,5]H shift
from linear cyclic allene 4a to linear naphthalene 2a should be
relatively less hindered by the steric bulk of the substituent "G"
than the [1,5]H shift from angular cyclic allene 7a to angular
product than that of the oxygen linker (9a, entries 5 & 2). The
imide linker 13, under thermal conditions (entry 6, Table 1)
gave a decreased preference for the angular product 19A over
the linear product 19L (1:3.3), when compared with its oxygen
counterpart 10a, i.e., ester linker [entry 3, L:A = (1:8.3)].
naphthalene 3a. To verify this hypothesis, a study was
performed on various linkers carrying substituent's with diverse
steric bulk, on them employing standard conditions (150 °C in
1,2-DCB).
From these experiments it is observed that the product
preference trend in oxygen and nitrogen linkers of similar
connectivity is in same direction. It is noteworthy to mention
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700588
European Journal of Organic Chemistry
Full Paper
allene 7a to angular product 3a when compared with the [1,5]H
shift of the linear cyclic allene 4a to linear product 2a and hence
the preference for the angular products decreases.
Subsequently, the ester linker (internal activation) with various
substituent's was also employed to verify the steric bulk effect
(Table 3). Heating different enyne-alkynes 10a-10c at 150 °C in
1,2-DCB resulted in the highly preferred formation of angular
products 16aA-16eA over their linear counterparts 16aL-16eL
(entries 1-5). As the steric bulk increases from H to -Me to -Et
to -iPr to -tBu, there was no noticeable change observed in the
product distributions as the ratios of L:A lies between (0.12:1)
to (0.15: 1).
Table 3: Estimation of steric bulk effect with internally activated linker
Figure 3: Possible steric hindrance by a substituent on the
-carbon
(towards arenyne) of a linker
Initially an alkoxy-ynoate linker was employed (Table 2). In
case of unsubstituted linker 9b (G = H), the ratio of the products
15bL: 15bA is (1:0.31). As the steric bulk of the substitutent
increases from R = H to methyl to ethyl (entries 1-3, Table 2);
the preference for the corresponding angular products 15aA
and 15cA increases from 0.31 to 0.58 to 0.65. Surprisingly,
further increase in the steric bulk by introducing the larger
substituent's such as iso-propyl, iso-butyl, and cyclohexyl, (9d,
9e & 9f) resulted in the gradual decrease in the preference for
the corresponding angular products 15dA-15fA (entries 4-6,
Table 2). In case of tert-butyl group (the bulkiest substituent)
i.e., 9f exclusive formation of linear product 15gL was
observed, and there was no detection of the corresponding
Furthermore, we turned our attention to estimate the steric effect of
quaternary centres on the linkers. Accordingly, alkoxy-ynoate linker
with various -disusbstitutions (quaternary centres) was examined.
All these substrates 9h-9m show the preference for the linear
products 15hL-15mL over angular products 15hA-15mA similar to
the case of single substituent's (Table 2). There was no drastic
change in the distribution of products has been observed.
angular product 15gA
.
Table 2: Estimation of steric bulk effect on the product distribution with
externally activated linker
Table 4: Steric bulk effect of quaternary centres on externally activated
linker
These observations suggests that, the initial increase in the
steric hindrance might slow down the [1,5]H shift of the linear
cyclic allene 4a to linear product 2a and hence the competing
electrocyclic ring opening process is relatively more favoured
towards the formation of angular allene 7a. Therefore, the
preference for angular product 3a increases over the linear
product 2a. But after a certain threshold level of steric
hindrance, the increased steric bulk might be creating relatively
stronger hindrance for the [1,5]H shift of the angular cyclic
In continuation we performed the same study on an inactivated ether
linker with different quaternary centres (entries 1-4, Table 5).
Surprisingly, all the substrates 8b-e resulted in the exclusive
formation of corresponding linear products 14bL-14eL. There was
no detection of any of the angular products 14bA-14eA. This
supports the fact that, after certain level of steric bulk threshold,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700588
European Journal of Organic Chemistry
Full Paper
irrespective of the linker, the linear products are more preferred than
their angular counterparts.
We thank Indian Institute of Technology Madras, Chennai for the
infrastructure facility. We thank CSIR INDIA for financial support
through No.02(0209)/14/EMR-II grant. BSC thanks IIT Madras for
HTRA fellowship.
Table 5: Steric bulk effect of quaternary centres on inactivated ether
linker
Keywords: alkynes • cycloadditions • dehydrogenative Diels-Alder
reactions • enynes • linkers •
[1]
[2]
Kobayashi, S.; Jørgensen, K. A. Eds. Cycloaddition Reactions in
Organic Synthesis; Wiley-VCH: Weinheim, 2002.
(a) Norton, J. A. Chem. Rev. 1942, 31, 319. (b) Martin, J. G. and Hill, R.
K. Chem. Rev. 1961, 61, 537; (c) Brieger, G. and Bennett, J. N. Chem.
Rev. 1980, 80, 63. (d) Kagan, H. B. and Riant, O. Chem. Rev. 1992, 92,
1007. (e) Winkler, J. D. Chem. Rev. 1996, 96, 167. (f) Kumar, A. Chem.
Rev. 2001, 101, 1. (g) Takao, K.; Munakata, R. and Tadano, K. Chem.
Rev. 2005, 105, 4779. (g) Diels, O. and Alder, K. Justus Liebigs Ann.
Chem. 1928,460, 98.
[3]
(a) Michael, A. and Bucher, J. E. Chem. Zentrblt., 1898, 731. (b)
Wessig, P. and Müller G. Chem. Rev. 2008, 108, 2051. (c) Danheiser,
R. L.; Gould, A. E.; Pradilla, R. F. and Helgason, A. L. J. Org. Chem.
1994, 59, 5514. (d) Dunetz, J. R. and Danheiser, R. L. J. Am. Chem.
Soc. 2005, 127, 5776. (e) Hayes, M. E.; Shinokubo, H. and Danheiser,
R. L. Org. Lett., 2005, 7, 3917. (f) Wills, M. S. B. and Danheiser, R. L. J.
Am. Chem. Soc. 1998, 120, 9378. (g) Chinta, B. S.; Siraswar, A. and
Baire, B. Tetrahedron, asap. http://dx.doi.org/10.1016/j.tet.2016.11.015.
(h) Wessig, P.; Matthes, A. and Pick, C. Org. Biomol. Chem., 2011, 9,
7599. (i) Wessig, P. and Matthes, A. J. Am. Chem. Soc. 2011, 133,
2642. For metal catalyzed DDA reactions see, (j) Gorin, D. J.; Watson, I.
D. G. and Toste, F. D. J. Am. Chem. Soc. 2008, 130, 3736. (k)
Barluenga, J.; Ferna´ndez-Rodrı´guez, M. A.; Garcı´a-Garcı´a, P. and
Aguilar, E. J. Am. Chem. Soc. 2008, 130, 2764. (l) Saito, S.; Salter, M.
M.; Gevorgyan, V.; Tsuboya, N.; Tando, K. and Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 3970. (m) Xi, C.; Chen, C.; Lin, J. and Hong, X.
Org. Lett. 2005, 7, 347. (n) Nakao, Y.; Hirata, Y.; Ishihara, S.; Oda, S.;
Yukawa, T.; Shirakawa, E. and Hiyama, T. J. Am. Chem. Soc. 2004,
126, 15650. (o) Rubina, M.; Conley, M. and Gevorgyan, V. J. Am.
Chem. Soc. 2006, 128, 5818. (p) Xi, C.; Chen, C.; Lin, J. and Hong, X.
Org Lett., 2005, 7, 347. (q) Gevorgyan, V.; Takeda, A.; Homma, M.;
Sadayori, N.; Radhakrishnan, U. and Yamamoto, Y. J. Am. Chem. Soc.
1999, 121, 6391.
Overall the linear vs. angular product distributions during aromatic
TDDA reactions did show little dependency on the steric bulk of the
substituent, on the other hand, it depends strongly on the structure
of the linker of the enyne-alkyne unit.
Conclusions
In conclusion we have performed a systematic study to
understand the effect of two factors such as a) nature of the
linker structure, b) steric bulk created by the of the substituent
on the -carbon of enyne linker, on the distribution of linear vs.
angular naphthalene product during the aromatic tetradehydro
Diels-Alder reaction. From this study it is evident that, the
nature of the structure of linker plays a very strong role on the
product distributions, where different linkers show preference
for the different products, i.e. linear vs. angular. Within the
same linker the internal activation favours the angular products
whereas the external activation favours the linear one. The
steric bulk of the substituent on the linker does not have any
strong as well as consistent role on the product distributions.
Nevertheless no substituent linkers show high preference for
the linear naphthalenes, whereas gradual increase in steric
hindrance favours the angular product up to certain level and
then reverse the preference towards linear.
[4]
(a) Hoye, T. R.; Baire, B.; Niu, D.; Willoughby, P. H. and Woods, B.
P. Nature, 2012, 490, 208. (b) Yun, S. Y.; Wang, K.-P.; Lee, N.-K.;
Mamidipalli, P. and Lee, D. J. Am. Chem. Soc., 2013, 135, 4668. (c)
Bradley, A. Z. and Johnson, R. P. J. Am. Chem. Soc., 1997, 119, 9917.
(d) Miyawaki, K.; Suzuki, R.; Kawano, T. and Ueda, I. Tetrahedron
Lett., 1997, 38, 3943.
Experimental Section
[5]
[6]
Wang, T.; Naredla, R. R.; Thompson, S. K. and Hoye, T. R. Nature,
2016, 532, 484.
General experimental procedure for the synthesis of 1,3-
Dihydronaphtho[2,3-c]furan (14a) through tetradehydro
Diels-Alder reaction.
(a) Rodrı´guez, D.; Navarro, A.; Castedo, L.; Domı´nguez, D. and Saa´,
C. Org Lett., 2000, 2, 1497. (b) Rodrı´guez, D.; Navarro-Va´zquez, A.;
Castedo, L.; Domı´nguez, D. and Saa´, C. J. Am. Chem. Soc. 2001,
123, 9178. (c) Rodrı´guez, D.; Navarro-Va´zquez, A.; Castedo, L.;
Domı´nguez, D. and Saa´, C. J. Org. Chem. 2003, 68, 1938. (d) Ajaz,
A.; Bradley, A. Z.; Burrell, R. C.; Li, W. H. H.; Daoust, K.; Bovee, J. L.
B.; DiRico, K. J. and Johnson, R. P. J. Org. Chem. 2011, 76, 9320.
To a solution of alkyne 8 (70 mg, 0.411 mmol) in 1,2-DCB (7
mL) was taken in a reaction tube. The reaction tube was kept at
150°C. After 114 h, the reaction mixture was purified by column
chromatography (9:1, hexane:EtOAc) gave the 14L (35 mg,
0.205 mmol, 50 %) as a yellow solid.
For full details of all experiments, see the Supporting
Information.
Acknowledgements
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700588
European Journal of Organic Chemistry
Full Paper
Table of Contents
Full Paper
Key topic: Dehydrogenative Diels-Alder reactions
Bhavani Shankar Chinta and Beeraiah
Baire*
Page No. – Page No.
On the Distribution of Linear vs.
Angular Naphthalenes in Aromatic
Tetradehydro Diels-Alder Reaction:
Effect of Linker Structure and Steric
bulk
Text for Table of Contents
This article is protected by copyright. All rights reserved.