MgBr2-mediated ionic Diels-Alder reaction of acetals of α,β-unsaturated aldehydes and ketones with 1,3-dienes

Article abstract of DOI:10.1080/00397910701410814

A facile, mild, and efficient methodology for the ionic Diels-Alder reaction of acetals of α,β-unsaturated ketones and aldehydes as dienophiles with various 1,3-dienes employing MgBr2 as the Lewis acid catalyst to furnish corresponding Diels-Alder adducts

Full text of DOI:10.1080/00397910701410814

Synthetic Communicationsw, 37: 2337–2343, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410814
MgBr2-Mediated Ionic Diels–Alder
Reaction of Acetals of a,b-Unsaturated
Aldehydes and Ketones with 1,3-Dienes
Subhash P. Chavan, Krishna S. Ethiraj, and
Shubhada W. Dantale
Division of Organic Chemistry: Technology, National Chemical
Laboratory, Pune, India
Abstract: A facile, mild, and efficient methodology for the ionic Diels–Alder reaction
of acetals of a,b-unsaturated ketones and aldehydes as dienophiles with various
1,3-dienes employing MgBr2 as the Lewis acid catalyst to furnish corresponding
Diels–Alder adducts at ambient temperature is described.
Keywords: acetals, catalysts, Diels–Alder reactions, dienes
The Diels–Alder reaction is one of the most efficient and widely utilized
reactions for the stereoselective construction of six-membered rings. Often
the Diels–Alder reactions employ harsh conditions, thereby leading to
polymerization of dienes and dienophiles. A variety of modified methods
have been proposed in the Diels–Alder cycloadditions to overcome problems
such as polymerization and isomerization encountered in the thermal
reactions. Lewis acids,[1] certain lanthanide complexes,[2] and high-pressure
techniques[3] have been utilized to avoid polymerization and isomerization.
Highly reactive dienophiles such as acrolein and methyl vinyl ketone often
undergo polymerization even at low temperature. However, they are stable
Received in the USA December 4, 2006
Address correspondence to Subhash P. Chavan, Division of Organic Chemistry:
Technology, National Chemical Laboratory, Pune 411 008, India. E-mail: sp.
chavan@ncl.res.in
2337

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S. P. Chavan, K. S. Ethiraj, and S. W. Dantale
when stored as corresponding acetals. Normally a,b-unsaturated acetals require
high temperatures for cycloaddition reactions. However, in the presence of a
suitable reagent, they can be made to undergo facile cycloaddition via the inter-
mediacy of allyl cations,[4] which serve as strong dienophiles.
Ionic Diels–Alder reactions of acetals of a,b-enones and a,b-enals with
various 1,3-dienes has been reported, employing triflic acid dissolved in
1,1,2-trichloro-1.2,2-trifluoro ethane,[4] electrogenetrated acid,[5] TiCl4 with
Ti(Oi-Pr)4,[6] and LiClO4 with 1 mol% camphor sulphonic acid.[7] In addition,
reactions of triethylorthopropiolate[8] or triethyl orthoacrylate[9] to 1,3-dienes
using trimethylsilyl triflate to furnish the corresponding cycloadducts are
also well documented. Cycloaddition of 1-vinyl-4-methyl-2,6,7-trioxabicy-
clo[2.2.2]octane to 1,3-dienes has been carried out using BF3(OEt)2.[10] Lewis
acids such as TiCl4, Me3SiOTf, BF3(OEt)2. SnCl4, and GaCl3 have also been
employed for the generation of highly reactive cationic dienophiles from
2,2-dimethoxyethyl acrylates for ionic Diel–Alder reaction with various
1,3-dienes.[11–15] Recently Nafion-H[16a] and InCl3
[16b]
have been shown to
be excellent catalysts in ionic Diels–Alder reactions. Most of these
methods employ expensive reagents and require the reactions to be
performed at low temperatures.
We have recently demonstrated that FeCl3[17a] and I2[17b] act as efficient
catalysts in effecting ionic Diels–Alder reactions. Our search for milder and
efficient reagents led us to explore the utility of MgBr2 as the Lewis acid in
effecting ionic Diels–Alder reaction. This communication describes a facile
Diels–Alder reaction of various 1,3-dienes with acetals of a,b-unsaturated
ketones and aldehydes using MgBr2 as an efficient catalyst in good yields.
The oxophilic propensity of MgBr2 is well documented.[18,19] It was
decided to exploit this propensity of MgBr2 in complexing with the oxygen
of the acetal, thereby transiently generating the allyl cation, which would
undergo a Diels–Alder reaction. Initial experiments were carried out with
cyclopentadiene and acrolein acetal 1. Thus, cyclopentadiene was subjected
to the Diels–Alder reaction with acrolein acetal with MgBr2 as the Lewis acid.
After a few trials varying the amount of catalyst, solvent, and tempera-
ture, it was concluded that the best results were obtained when the reaction
was performed with 0.5 eq. of MgBr2 and dichloromethane as the solvent.
Accordingly, freshly prepared MgBr2 (from dibromoethane and Mg)
treated with a mixture of cyclopentadiene 5 and acrolein acetal 1 was
allowed to stir at room temperature in dichloromethane as the solvent and,
after usual workup, furnished the cycloadduct 6 in 80% yield as a mixture
of stereoisomers (endo:exo ¼ 6:1).
Having successfully demonstrated the utility of MgBr2 as an efficient
Lewis acid in effecting ionic Diels–Alder reaction, attention was focused
on establishing the generality of this reaction. Accordingly, cyclic and
acyclic dienes were subjected to the reaction with different dienophiles, and
moderate to good yields of the corresponding adducts were obtained. The
results of this study are summarized in Table 1.

MgBr2-Mediated Ionic Diels–Alder Reaction
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Table 1. Cycloaddition reactions of dienes and dienophiles using MgBr2 as catalyst
Time
(h)
Entry
1
Diene
Dienophile
Product
Yield (%)
80 (6:1)
4
2
4
65a
3
4
12
8
38b,c
50 (3.8:1)
5
6
7
8
2
68 (3.3:1)
72a
12
61b,c
(continued)

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S. P. Chavan, K. S. Ethiraj, and S. W. Dantale
Table 1. Continued
Time
(h)
Entry
8
Diene
Dienophile
Product
Yield (%)
66
8
Note. Reaction was carried out with 0.5 eq of MgBr2 in dichloromethane at room
temperature.
aSingle isomer.
b10 eq. of the diene were used.
cReaction mixture was initially maintained at 08C, then allowed to attain room
temperature.
From the table, it is clear that cyclic dienes participate well as compared
to the acyclic dienes. This may be ascribed to the greater reactivity of the
cyclic dienes than the reactivity of the acyclic one. Variously substituted
a,b-unsaturated acetals (1–4) were also subjected to ionic Diels–Alder
reactions. They were shown to participate well in the ionic Diels–Alder
reaction. An interesting point worthy of note is the exclusive formation of
the endo isomer when the reaction was performed with cyclohexadiene and
acetals 1 and 3. The acyclic diene isoprene (9) furnished only one regioisomer
when subjected to the treatment with acetals 1 and 3 (Table 1, entries 3 and 7).
It is interesting to note that the acyclic acetal 4 gives less yield of the cyclo-
adduct than cyclic acetal 1 (Table 1, entries 1 and 8). This may be ascribed to
the removal of ethanol from the ionic intermediate, thereby resulting in low
efficiency of recombination and hence lower yield.
In conclusion, we have demonstrated MgBr2 as a convenient, simple, and
efficient reagent to achieve high levels of stereoselective and regioselective
ionic Diel–Alder reactions at ambient temperature. Currently, we are
exploring the use of other homogeneous and heterogeneous materials to
effect such transformation under mild conditions.
EXPERIMENTAL
1. General Procedure for Ionic Diels-Alder Reaction
To the freshly prepared MgBr2 (0.5 eq.) in 10 ml of dry CH2Cl2 under a
nitrogen atmosphere, first 2 eq./10 eq. of 1,3-diene was added, followed by
1 eq. of dienophile (unsaturated acetal) in 1 ml of dry CH2Cl2. (In the case
of isoprene, temperature was lowered to 08C). The reaction mixture was

MgBr2-Mediated Ionic Diels–Alder Reaction
2341
stirred at room temperature and monitored by thin-layer chromatagraphy
(TLC). After the completion of reaction, it was quenched with 15 ml of
water and stirred until it became clear. The organic layer was separated,
and the aqueous layer was extracted with CH2Cl2 (3 ꢀ 25 ml). The organic
layer was dried with anhydrous Na2SO4, and concentration under reduced
pressure furnished a viscous residue. Column purification of the residue on
SiO2/neutral alumina furnished the Diels–Alder adduct as a viscous oil in
good yields.
2. Typical Procedure for the Preparation of 8
MgBr2 was prepared from 30 mg of magnesium turnings (1.25 mmol) and
0.47 g (2.5 mmol) of 1,2-dibromoethane. To the freshly prepared MgBr2
(1.25 mmol) in 10 ml of dry CH2Cl2, 0.40 g (5 mmol) of 1,3-cyclohexadiene
7 was added, followed by 0.25 g (2.5 mmol) of 2-vinyl-1,3-dioxalane 1. The
reaction was stirred at room temperture for 4 h and monitored by thin-layer
chromatography (TLC). After completion of the reaction and usual workup,
followed by purification by column chromatography (SiO2) using 2% ethyl
acetate–pet. Ether as eluent, the reaction furnished 0.29 g of endo-2(bicy-
clo[2.2.2]oct-5-en-2-yl) dioxolane 8 as a viscous oil in 65% yield.
IR (neat) cm21: 3075, 1975, 1330, 1120, 975, 840. 1H NMR (200 MHz):
1.15–1.4 (m, 2H), 1.40–1.85 (m, 4H), 1.85–1.95 (m, 1H), 2.55 (br s, 1H),
2.70 (br d, 1H), 3.75–4.05 (m, 4H), 4.35 (d, 1H, J ¼ 10.8 Hz), 6.20 (dd,
1H, J ¼ 5.4), 6.40 (dd, 1H, J ¼ 5.4). Mass (m/e): 180, 151, 137, 99, 79,
1
77, 73, 65, 55. All compounds were characterized by H NMR, 13C NMR,
and mass spectral analyses.
ACKNOWLEDGMENTS
Presented in part at the National Symposium in Chemistry, January 27–30,
1999, Indian Institute of Science (IISc). Banglore, India. One of us
(K. S. Ethiraj) thanks Council of Scientific and Industrial Research (CSIR),
New Delhi (India), for the award of a fellowship. Funding under Young
Scientist Award (YSA) scheme from CSIR, India, is gratefully acknowledged.
We are thankful to T. Ravindranathan for encouragement.
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