I2 as an efficient catalyst in ionic Diels-Alder reactions of α,β-unsaturated acetals

Article abstract of DOI:10.1016/S0040-4039(03)00387-3

A variety of protected and unprotected α,β-unsaturated aldehydes react with 1,3-dienes in the presence of I₂ to give the corresponding cycloadducts.

Full text of DOI:10.1016/S0040-4039(03)00387-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3001–3003
I2 as an efficient catalyst in ionic Diels–Alder reactions of
a,b-unsaturated acetals
Subhash P. Chavan,* Pallavi Sharma, G. Rama Krishna and Mahesh Thakkar
Division Of Organic Chemistry: Technology, National Chemical Laboratory, Pune-411008, India
Received 22 October 2002; revised 29 January 2003; accepted 7 February 2003
Abstract—A variety of protected and unprotected a,b-unsaturated aldehydes react with 1,3-dienes in the presence of I2 to give the
corresponding cycloadducts. © 2003 Elsevier Science Ltd. All rights reserved.
The Diels–Alder reaction1 finds immense utility in the
synthetic arena by virtue of its operational simplicity,
generality and stereoselective construction of six-mem-
bered rings. Although the Diels–Alder reaction is a very
powerful tool for six-membered ring annulation, it is
often limited by polymerization of the diene as well as
dienophiles under the reaction conditions. A useful
variant of the Diels–Alder reaction, developed by
Gassman et al.2 employs acetals or orthoesters of the
a,b-unsaturated dienophile so as to avoid the problem
of polymerisation or isomerisation under thermal con-
ditions. Thus, in the Lewis acid-catalysed ionic Diels–
Alder reaction, powerful dienophiles are generated by
transient formation of a carbocation, the most powerful
carbon-based electron-withdrawing group known, adja-
cent to the vinyl moiety which finally gives a neutral
adduct. Thus the masked dienophiles furnish 4p+2p
cycloadducts in high yields and under milder reaction
conditions.
15–30 min and shows high selectivity in almost all the
cases.
I2 has been reported earlier in the context of Diels–
Alder reactions wherein it activates substrates like N-
allyl enamides and lactam derivatives,8a anilide and
maleimide derivatives8b via the formation of cationic
intermediates arising from iodolactonisation, to give the
cycloadducts. In all the above, the presence of a suit-
ably placed olefin is critical and crucial for the success
of the reaction. Aditionally, an excess (2 equiv.) of
iodine has to be employed to effect the Diels–Alder
reaction.
Herein we report that iodine can also catalyse all kinds
of masked a,b-unsaturated dienophiles bearing no acti-
vating group, with equal ease. It was observed that the
Diels–Alder reactions of acrolein acetal were efficiently
catalysed by iodine to furnish the adducts in 15–30 min,
with high selectivity.
A number of acids and Lewis acids, viz. TfOH,2a
TMSOTf,2b BF3·Et2O,2c CF3SO3H,2d CF3SO3Si(CH3)3,2e
TiCl4–Ti(OiPr)4,3 electro-generated acid,4 LiClO4,5
Thus, when a mixture of the 2,2-dimethylpropylene
acetal of acrolein 3 and cyclopentadiene (1:2) in dry
dichloromethane at 0°C was treated with 0.1 equiv. of
I2, the adduct 8 was obtained in excellent yield after
quenching the reaction with Et3N and purification by
column chromatography. The product was obtained as
a mixture of endo and exo isomers 12.6:1. The doublets
Nafion-H6a and recently InCl3 have been studied as
6b
catalysts to effect 4p+2p cycloaddition reactions. A
variety of protic acids are also known to catalyse the
reaction.
Recently our group has reported the use of FeCl3 and
FeCl3 adsorbed on silica gel7 as an efficient catalyst in
the ionic Diels–Alder reaction. In continuation of our
efforts in search of a better catalyst, we found that I2
had the potential to catalyse this reaction. In the pres-
ence of iodine the reaction goes to completion within
1
at l 3.7 and l 4.2 in the H NMR spectrum indicated
the ratio of endo and exo isomers.
To demonstrate the generality of our protocol a variety
of protected a,b-unsaturated dienophiles substituted at
various positions were subjected to reaction with both
cyclic and acyclic dienes. Moderate to excellent yields
were obtained as shown in Table 1. As shown in Table
* Corresponding author.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00387-3

3002
S. P. Cha6an et al. / Tetrahedron Letters 44 (2003) 3001–3003
Table 2.
Table 1.
1, acetals of both ketones and aldehydes participated
smoothly to give appreciable yields. It is noteworthy
that the yield from the reaction of 3 with cyclopentadi-
ene in the presence of I2 is far better than that reported
using electro-generated acids.4
As shown in entries 7–9 reaction with cyclohexadiene
resulted in almost exclusive formation of endo isomers
in all cases. The protocol developed works equally well
for both acyclic and cyclic acetals. Variously substi-
tuted dienophiles react to different exents to furnish the
corresponding cycloadducts in varying yields, although
the selectivity remains unaffected.
Interestingly, it was observed that under the above
mentioned reaction conditions, I2 also effectively
catalyses the Diels–Alder reaction of unprotected
dienophiles (Table 2), which are known to undergo
polymerisation under most of the reported reaction
conditions, in good to moderate yields.
In conclusion, this study clearly demonstrates the
efficiency of I2 to catalyse ionic Diels–Alder reactions
of protected dienophiles as well as those of unprotected
dienophiles with dienes for cycloadduct formation with
high selectivity and good yields over short reaction
times.
Acknowledgements
We thank the CSIR, New Delhi (India) for the award
of fellowships to P.S., G.R.K. and M.T. Funding from
YSA (CSIR), New Delhi, India to S.P.C. is gratefully
acknowledged.
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