Synthesis and some cycloaddition reactions of 2-(triisopropylsilyloxy)acrolein

Article abstract of DOI:10.1021/ol006281x

(equationpresented) 2-(Triisopropylsilyloxy)acrolein is easily prepared by the reaction of triisopropylsilyl triflate and 2-methoxy-2-methyl-[1,3]dioxan-5-one in the presence of triethylamine. This dienophile reacts with selected dienes in the presence of catalytic amounts of scandium triflate to afford products that are formally 4 + 3 cycloadducts. An exception is seen in the case of butadiene, where only a 4 + 2 cycloadduct is observed.

Full text of DOI:10.1021/ol006281x

ORGANIC
LETTERS
2
000
Vol. 2, No. 17
703-2705
Synthesis and Some Cycloaddition
Reactions of
2
2-(Triisopropylsilyloxy)acrolein
Michael Harmata* and Uday Sharma
Department of Chemistry, UniVersity of Missouri-Columbia, Columbia, Missouri 65211
harmatam@missouri.edu.
Received June 30, 2000
ABSTRACT
2-(Triisopropylsilyloxy)acrolein is easily prepared by the reaction of triisopropylsilyl triflate and 2-methoxy-2-methyl-[1,3]dioxan-5-one in the
presence of triethylamine. This dienophile reacts with selected dienes in the presence of catalytic amounts of scandium triflate to afford
products that are formally 4 + 3 cycloadducts. An exception is seen in the case of butadiene, where only a 4 + 2 cycloadduct is observed.
The preparation of seven-membered rings via a 4 + 3
cycloaddition reaction of an allylic cation with a diene is of
current interest since it results in a rapid increase in molecular
synthesis of 2-(acyloxy)acroleins and demonstrated their use
in Diels-Alder reactions with a number of dienophiles.6
The use of 2-(silyloxy)acroleins and related compounds
in the 4 + 3 cycloaddition reaction has also been examined,
but not extensively and with limited success to date. For
example, Sasaki and co-workers demonstrated that treatment
1
complexity from relatively simple starting materials. Some
7
recent advances in this area deal with the use of heteroatom-
2
stabilized allylic cations as dienophiles in the reaction. In
particular, vinyl oxocarbenium ions are being studied with
increasing frequency.3
4
of aldehyde 1 with 1 equiv of SnCl in the presence of a
slight excess of cyclopentadiene afforded the cycloadduct 2
As part of our program involving the development of
vinyloxocarbenium ions in 4 + 3 cycloaddition reactions,
in 72% yield as a 2.7:1 mixture of endo and exo isomers,
respectively (Scheme 1). To the best of our knowledge,
4
7a
particularly with respect to the development of asymmetric
4
+ 3 cycloaddition reactions, we took an interest in
exploring oxygen-substituted acroleins as dienophiles.
The study of such species in the context of Diels-Alder
reactions is reasonably well-established.5 A recent example
comes from the Funk group, who developed an efficient
Scheme 1
-7
(
1) For recent reviews of the 4 + 3 cycloaddition reaction, see: (a)
Harmata, M. Tetrahedron 1997, 53, 6235. (b) Harmata, M. In AdVances in
Cycloaddition; Lautens, M., Ed.; JAI: Greenwich, CT, 1997; Vol. 4, pp
this is the best example of this type of reaction reported to
date.
4
1-86. (c) Rigby, J. H.; Pigge, F. C. Org. React. 1997, 51, 351. (d) Cha,
J.; Oh, J. Curr. Org. Chem. 1998, 2, 217.
2) Harmata, M. In Recent Research DeVelopments in Organic Chemistry;
Transworld Research Network: Trivandrum, 1997; Vol. 1, pp 523-35.
3) For some recent examples, see: (a) Stark, C. B. W.; Pierau, S.;
(
(5) For some examples and leading references, see: (a) Ochoa, M. R.;
Arias, M. S.; Aguilar, R.; Delgado, F.; Tamariz, J. Tetrahedron 1999, 55,
14535. (b) Dudones, J. D.; Sampson, P. J. Org. Chem. 1997, 62, 7508. (c)
Creary, X.; Inocencio, P. A.; Underiner, T. L.; Kostromin, R. J. Org. Chem.
1985, 50, 1932. (d) Ireland, R. E.; Obrecht, D. M. HelV. Chim. Acta 1986,
69, 1273. (e) Ardecky, R. J.; Kerdesky, F. A. J.; Cava, M. P. J. Org. Chem.
1981, 46, 1483. (f) Brodsky, L.; Agosta, W. C. J. Org. Chem. 1974, 39,
2928.
(
Wartchow, R.; Hoffmann, H. M. R. Chem. Eur. J. 2000, 6, 684. (b) Pierau,
S.; Hoffmann, H. M. R. Synlett 1999, 213. (c) Lee, J. C.; Jin, S.-J.; Cha, J.
K. J. Org. Chem. 1998, 63, 2804.
(4) (a) Harmata, M.; Jones, D. E. J. Org. Chem. 1997, 62, 1578. (b)
Harmata, M.; Jones, D. E.; Kahraman, M.; Sharma, U.; Barnes, C. L.
Tetrahedron Lett. 1999, 40, 1831.
1
0.1021/ol006281x CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/03/2000

These results stimulated our interest in captodative alkenes
such as 1 which we believe still have untapped potential in
Table 2. Cycloadducts from the Scandium Triflate Catalyzed
Reaction of 4 with Various Dienes
4
+ 3 cycloaddition chemistry. In the hope of taking
advantage of recent progress in the development of new
Lewis acid catalysts which have emerged over the past
decade, we began a study of the synthesis and chemistry of
8
alkenes related to 1. This report deals with the preparation
of the triisopropylsilyl congener (4) of 1 and some prelimi-
nary cycloaddition results.
Our synthesis of the target compound 4 was inspired by a
6
method reported by Funk. In his approach, the enol(ate) of
2,2-dimethyl-5-dioxinone is functionalized at oxygen and the
resulted alkene thermolyzed to afford the target aldehyde
via a retro-Diels-Alder reaction. While this elegant approach
would no doubt have proven viable, we sought to use a
starting material that was more readily available. A report
by Giese and co-workers suggested that dioxinone 3, easily
prepared from commercially available dihydroxyacetone and
9
trimethyl orthoacetate, would be suitable. Thus, we chose
to investigate the generation of 4, starting with this com-
pound.
To our delight, we found that simply stirring a benzene
solution of dioxinone 3 in the presence of TIPSOTf and
triethylamine for 12 h afforded the desired aldehyde in 72%
yield. Aldehydes 5 and 6 could be prepared in the same
fashion, albeit in lower yields under the same reaction
conditions (Scheme 2). The use of trimethylsilyl triflate
Scheme 2
afforded no isolable product.10 While further optimization
studies and mechanistic investigations are required, this
method represents a particularly convenient way of producing
aldehydes of this type relatively quickly.
With 4 in hand, we began investigating its ability to engage
in various Lewis acid mediated cycloaddition processes. Our
initial studies used furan as the diene and a small number of
titanium Lewis acids. Results are summarized in Table 1.
Treatment of a mixture of 4 and furan with 1.1 equiv of
titanium tetrachloride afforded the cycloadduct 7 as a single
stereoisomer in 88% yield. The stereochemical assignment
is based on precedent and comparison of NMR data with
similar compounds of known stereochemistry.4 Neither
titanium tetraisopropoxide nor dichlorotitanium diisopro-
poxide afforded any cycloadduct under the same conditions.
Since the latter Lewis acid lacked activity, we were
concerned that related Lewis acids, such as those based on
TADDOL, would not be effective and therefore sought other
reagents that would effect cycloaddition in catalytic amounts
Table 1. Reaction of 4 with Furan in the Presence of Titanium
Lewis Acids
Lewis acid
conditions
yield (%)
TiCl4
Ti(OiPr)4
TiCl2(OiPr)2
0.1 M, CH2Cl2, -78 °C
0.1 M, CH2Cl2, -78 °C
0.1 M, CH2Cl2, -78 °C
88
NR
NR
11
and under relatively mild conditions.
We chose to explore scandium triflate as the catalyst.12
Though not without limitations, this catalyst turned out to
2704
Org. Lett., Vol. 2, No. 17, 2000

work out quite well in affording cycloadducts between 4 and
yield. At present, it appears that only certain cyclic dienes
are the useful substrates if one wishes to access 4 + 3
cycloadducts in good to excellent yields.
1
3
various dienes. The results are summarized in Table 2.
The general reaction procedure consisted of treating a 0.2
M solution of 4 in dichloromethane with 10 mol % scandium
triflate in the presence of 2.5 equiv of diene at 0 °C while
warming the reaction to room temperature over the course
of 2 h. With furan this produced the cycloadduct 7 as a single
stereoisomer in 90% yield. With both cyclopentadiene and
cyclohexadiene the yields and stereoselectivities were lower,
perhaps indicative of a stepwise mechanism.14 2,5-Dimeth-
ylfuran afforded a reasonable yield of the cycloadduct 10 as
a single isomer.
Several acyclic dienes were examined as well. The reaction
worked well with butadiene, but led to only the 4 + 2
cycloaddition product 11. A mixture of 4 + 3 and 4 + 2
cycloaddition adducts was observed with 2,3-dimethylbuta-
diene, both in relatively low yields. Isoprene gave only a 4
The mechanism of the reaction of 4 with dienes is not
absolutely clear. The reactions involving 4 + 2 cycloaddi-
tions or 4 + 3 cycloadditions with high levels of simple
diastereoselectivity might be regarded as concerted processes.
On the other hand, the occurrence of stereoisomers as in the
case of cyclopentadiene or the production of mixtures as with
2,3-dimethylbutadiene suggests the possibility of an inter-
mediate which can afford both 4 + 2 and 4 + 3 cycloadducts
or 4 + 3 cyloadducts with eroded diastereoselectivity. Further
work is necessary to distinguish all of the possibilities.
In summary, we have developed a concise route to
2-(silyloxy)acroleins and have demonstrated the successful
4 + 3 and 4 + 2 cycloaddition reaction of one such
compound under mild conditions using catalytic amounts of
a Lewis acid. Broadening the scope of the reaction, finding
an appropriate chiral Lewis acid catalyst, and applying the
process in synthesis constitute our next goals in this area.
+
3 cycloadduct as a mixture of regioisomers, but in low
(
6) Funk, R. L.; Yos, K. J., III. J. Org. Chem. 1996, 61, 2598.
(7) (a) Sasaki, T.; Ishibashi, Y.; Ohno, M. Tetrahedron Lett. 1982, 23,
1
6
693. (b) Blackburn, C.; Childs, R. F.; Kennedy, R. A. Can. J. Chem. 1983,
1, 1981.
Acknowledgment. This work was supported by the
Petroleum Research Fund, administered by the American
Chemical Society. We thank the National Science Foundation
for partial support of the NMR (PCM-8115599) facility at
the University of MissourisColumbia and for partial funding
for the purchase of a 500 MHz spectrometer (CHE-89-
08304).
(8) (a) Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic
Synthesis; CRC: Boca Raton, 1996. (b) Lewis Acid Reagents. A Practical
Approach; Yaammoto, H., Ed.; Oxford University: Oxford, 1999.
9) M u¨ ller, S. N.; Batra, R.; Senn, M.; Giese, B.; Kisel, M.; Shadyro, O.
J. Am. Chem. Soc. 1997, 119, 2795.
10) However, treatment of ketone 3 with TMSCl, triethylamine, and
DMAP in refluxing dichloromethane gave the corresponding TMS enol
ether.
(
(
(11) For a review of TADDOL Lewis acids and their applications, see:
Gawronski, J.; Gawronska, K. Tartaric and Malic Acids in Synthesis;
Wiley: New York, 1999; Chapter 12.
Supporting Information Available: General procedures
for the synthesis of 4 and its cycloaddition reaction with
dienes and copies of proton and carbon spectra of 4-14.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
12) Kobayashi, S. In Lanthanides: Chemistry and Use in Synthesis;
Kobayashi, S., Ed.; Springer, 1999; pp 64-118.
13) Dienes which did not afford good yields of cycloadducts upon
reaction with 4 in the presence of scandium triflate: N-carbomethoxypyrrole,
-methoxyfuran, 2-methylfuran, and 1,3-cycloheptadiene.
14) (a) Cramer, C. J.; Barrows, S. E. J. Org. Chem. 1998, 63, 5523. (b)
Cramer, C. J.; Barrows, S. E. J. Phys. Org. Chem. 2000, 13, 176.
(
2
(
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