Highly stereoselective hydroxy-directed Diels-Alder reaction

Article abstract of DOI:10.1021/jo020664m

The successful stereocontrol of the Diels-Alder reaction of semicyclic dienes possessing a secondary and tertiary allylic magnesium alkoxide alcohol functionality and activated dienophiles such as methyl acrylate, methacrolein, acrolein, and N-phenylmalei

Full text of DOI:10.1021/jo020664m

High ly Ster eoselective Hyd r oxy-Dir ected Diels-Ald er Rea ction
Louis Barriault,* J ermaine D. O. Thomas,† and Roxanne Cle´ment
Department of Chemistry, 10 Marie Curie, University of Ottawa, Ottawa, Canada, K1N 6N5
lbarriau@science.uottawa.ca
Received October 21, 2002
The successful stereocontrol of the Diels-Alder reaction of semicyclic dienes possessing a secondary
and tertiary allylic magnesium alkoxide alcohol functionality and activated dienophiles such as
methyl acrylate, methacrolein, acrolein, and N-phenylmaleimide is described.
In tr od u ction
The creation of multiple carbon-carbon bonds with
regio- and stereoselectivity makes the Diels-Alder reac-
tion a spearhead in the development of efficient syntheses
of natural and nonnatural products.1 The π-facial dia-
stereoselectivity of the Diels-Alder reaction has been the
subject of many synthetic and theoretical studies over
the last 20 years.2 Different theoretical models such as
orbital interactions3 and steric,4 torsional,5 and electronic
effects6 have been considered to explain the π-facial
selectivity of perturbed dienes.
Independent research by Overman7 and Frank8 has
shown that heteroatomic substitutions at the R-allylic
position on semicyclic dienes can control the diastereo-
selectivity in [4+2] cycloaddition (eq 1, Scheme 1). Allylic
ether substituents (R ) CH3, Si(alkyl)) are considered
anti directors, thereby favoring the endo-anti product
formation (dr > 25:1). When R ) H, the endo-syn product
F IGURE 1. General mechanism for the tethered Diels-Alder
reaction.
was isolated in 10-36% yield depending on the nature
of the solvents used. Carreno et al. reported a similar
ratio with a diene possessing an allylic alcohol at the â
position (eq 2).9
Problems of regio- and π-facial selectivity are amplified
when employing a nonsymmetrical dienophile such as
methyl vinyl ketone.10 To solve this problem of selectivity,
our approach is based on using a temporary tether, thus
transforming an intermolecular Diels-Alder reaction into
an intramolecular process by linking the dienophile and
the diene together (Figure 1).
† Current address: Pfizer, Ann Arbor, MI.
Temporary metal tethers in cycloaddition reactions
have been the subject of many studies.11 Pioneer work of
Tamao and Ito clearly demonstrated the usefulness of
silicon as a disposable tether in Diels-Alder reactions.12
Although the silyl acetal linkage of the diene and
dienophile perfectly controls the regiochemistry, ad-
ditional transformations are necessary to install and/or
remove the anchor unit. Recently, other metal-based
temporary tethers such as Mg,13 Zn,14 B,15 and Al13 have
proven to be effective when using nonactivated dieno-
(1) For review, see: (a) Nicolaou, K. C.; Snyder, S. A.; Montagnon,
T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668. (b)
Corey, E. J . Angew. Chem., Int. Ed. 2002, 41, 1650.
(2) (a) Yadav V. K.; Senthil, G.; Babu, G.; Parvez, M.; Reid, J . L. J .
Org. Chem. 2002, 67, 1109. (b) Letourneau, J . E.; Wellman, M. A.;
Burnell, J . D. J . Org. Chem. 1997, 62, 7272. (c) Wellman, M. A.; Burry,
L. C.; Letourneau, J . E.; Bridson, J . N.; Miller, D. O.; Burnell, J . D. J .
Org. Chem. 1997, 62, 939. (d) Crisp, G. T.; Gebauer, M. G. J . Org.
Chem. 1996, 61, 8425. (e) Gandolfi, R.; Amade, M. S.; Rastelli, A.;
Bagatti, M.; Montanari, D. Tetrahedron Lett. 1996, 37, 517. (f) Fallis,
A. G.; Lu, Y.-F. Adv. Cycloaddit. 1993, 3, 1 and references therein.
(3) Gleiter, R.; Ginsburg, D. Pure Appl. Chem. 1979, 51, 1301.
(4) (a) Burnell, J . D.; Valenta, Z. Can, J . Chem. 1991, 69, 179. (b)
Tsuji, T.; Ohkita, M.; Nishida, S. J . Org. Chem. 1991, 56, 997. (c)
Ishihara, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561. (d)
Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994, 116,
2812. (e) Corey, E. J .; Sarshar, S.; Lee, D. H. J . Am. Chem. Soc. 1994,
116, 12089. (f) Xidos, J . D.; Poirier, R. A.; Pye, C. C.; Burnell, J . D. J .
Org. Chem. 1998, 63, 105.
(9) Carreno, M. C.; Urbano, A.; Di Vitta, C. J . Org. Chem. 1998, 63,
8320.
(10) Kawamata, T.; Harimaya, K.; Iitaka, Y.; Inayama, S. Chem.
Pharm. Bull. 1989, 37, 2307.
(5) (a) Houk, K. N.; Li, Y.; Evanseck, J . P. Angew. Chem., Int. Ed.
Engl. 1992, 31, 682. (b) Coxon, J . M.; Froese, R. D. J .; Ganguly, B.;
Marchand, A. P.; Morokuma, K. Synlett 1999, 1681. (c) Brown, F. K.;
Houk, K. N.; Burnell, J . D.; Valenta, Z. J . Org. Chem. 1987, 52, 3050.
(d) Brown, F. K.; Houk, K. N. J . Am. Chem. Soc. 1985, 107, 1971.
(6) (a) Paquette, L. A.; Branan, B. M.; Rogers, R. D.; Bond, A. H.;
Lange, H.; Gleiter, H. J . Am. Chem. Soc. 1995, 117, 5992. (b) Coxon,
J . M.; Fong, S. T.; McDonald, D. Q.; Steel, P. J . Tetrahedron Lett. 1993,
34, 163. (c) Roush, W.; Brown, B. B. J . Org. Chem. 1992, 57, 3380. (d)
Kahn, S. D.; Hehre, W. J . J . Am. Chem. Soc. 1987, 109, 663.
(7) Fisher, M. J .; Hehre, W. J .; Kahn, S. D.; Overman, L. E. J . Am.
Chem. Soc. 1988, 110, 4625.
(11) For review, see: Shea, K. J .; Zandi, K. S.; Gauthier, D. R.
Tetrahedron 1998, 54, 2289 and references therein.
(12) (a) Tamao, K.; Kobayashi, K.; Ito, Y. J . Am. Chem. Soc. 1989,
111, 6478. (b) Stork, G.; Chan, T. Y.; Breault, G. A. J . Am. Chem. Soc.
1992, 114, 7578. (c) Sieburth, S.; Fensterbamk, L. J . Org. Chem. 1992,
57, 5279.
(13) Stork, G.; Chan, T. Y. J . Am. Chem. Soc. 1995, 117, 6595.
(14) Olsson, R.; Bertozzi, F.; Fredj, T. Org. Lett. 2000, 2, 1283.
(15) (a) Batey, R. A.; Thadani, A. N.; Lough, A. J . J . Am. Chem.
Soc. 1999, 121, 450. (b) Nicolaou, K. C.; Ueno, H.; Liu, J .-J .; Nantermet,
Z.; Yang, Z.; Renaud, J .; Paulvannan, K.; Chadha, R. J . Am. Chem.
Soc. 1995, 117, 653. (c) Shimada, S.; Osoda, K.; Narasaka, K. Bull.
Chem. Soc. J pn. 1993, 66, 1254-1257. (d) Narasaka, K.; Shimada, K.;
Osoda, N.; Iwasawa, N. Synthesis 1991, 1171
(8) Datta, S. C.; Franck, R. W.; Tripathy, R.; Quigley, G. J .; Huang,
L.; Chen, S.; Sihaed, A. J . Am. Chem. Soc. 1990, 112, 8472.
10.1021/jo020664m CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/14/2003
J . Org. Chem. 2003, 68, 2317-2323
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Barriault et al.
SCHEME 1. In ter m olecu la r Diels-Ald er Rea ction w ith Sem icyclic Dien es
SCHEME 2. Syn th esis of Typ e I Dien esa
a
Reagents and conditions: (a) I2, pyridine, Et2O. (b) CH2dCRMgBr, ZnBr2, Pd(PPh3)4, THF-DMF. (c) R′MgBr, Et2O, -78 °C. (d)
NaBH4, CeCl3-7H2O, MeOH.
SCHEME 3. Syn th esis of Typ e II Dien esa
a
Reagents and condtiions: (a) CH2dCRMgBr, THF -78 °C. (b) R′MgBr, Et2O, -78 °C. (c) DHP, t-Buli, THF, -78 to 0 °C. (d)
CH2dCHMgBr, THF, -78 °C.
philes. All of these reactions require harsh conditions and
high temperatures to form the metal-alkoxide diene
species and involve dienes possessing a primary alcohol.
The use of Lewis acids in the control of the Diels-Alder
reactions has also been well studied.16 However, there is
a conspicuous paucity of examples in the literature for
their use with dienes possessing a tertiary alcohol. To
address the issue of employing a metal-based temporary
tether to control the diastereoselectivity of the Diels-
Alder reaction, two types of semicyclic dienes were
prepared.
Resu lts a n d Discu ssion
The synthesis of the type I dienes began with R
iodination of 2-cyclohexenone 1 to give iodoenone 2 in
85% yield (Scheme 2).17 Palladium-catalyzed cross cou-
pling under Negishi conditions18 provided ketodienes 32a
and 419 in 90% and 92% yield, respectively. Subsequent
Grignard addition with phenyl-, allyl-, or vinylmagne-
sium bromide afforded dienes 5-8 in modest yields. In
the same vain, ketone dienes 3 and 4 were exposed to
Luches’ reduction condition to furnish the corresponding
(17) J ohnson, C. R.; Adams, J . P.; Braun, M. P.; Senanayake, C. B.
W. Tetrahedron Lett. 1992, 33, 919.
(18) (a) Pour, M.; Ngishi, E. Tetrahedron Lett. 1996, 37, 4679. (b)
Negeshi, E.; Owczarczyk, Z. R.; Swanson, D. Tetrahedron Lett. 1991,
32, 4453.
(16) (a) Oppolzer, W. Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Paquette, L. A., Eds.; Pergamon: Oxford, UK, 1991;
Vol. 5, Chapter 4.1.4, pp 339-345. (b) First example of Diels-Alder
accelerated by Lewis acid: Yates, P.; Eaton, P. J . Am. Chem. Soc. 1960,
82, 4436.
(19) Laredo, G. C.; Maldonada, L. A. Heterocycles 1987, 25, 179.
2318 J . Org. Chem., Vol. 68, No. 6, 2003

Hydroxy-Directed Diels-Alder Reaction
TABLE 1. Hyd r oxy-Dir ected Diels-Ald er w ith P h MgBr
SCHEME 4. Tem p or a r y Teth er ed Diels-Ald er
Rea ction
alcohols 99 and 1020 in 81% and 85% yield, respectively.
Due to their instability, these dienes were used within
2-3 h after a quick purification on silica gel doped with
triethylamine.
The second set of dienes (type II) was synthesized as
outlined in Scheme 3. This synthetic sequence started
with isopropyl enol ether 11, followed by addition of vinyl-
and isopropenylmagnesium bromide and 6-lithio-3,4-
dihydro-2H-pyrane to give and ketones 12 ,21 13, and 14,
respectively, in 29-48% yield. With use of the same
conditions previously described, nucleophilic addition
with vinyl-, isopropyl-, and phenylmagnesium bromide
was performed on 12, 13, and 14 to afford the desired
semicyclic dienes 15-18 in 43-84% yield. The docu-
mented success of aluminum-based Lewis acids in the
Diels-Alder reaction influenced our decision to begin the
investigation with AlMe3, AlMeCl2, and AlMe2Cl. It was
envisaged that an Al-alkoxide species 19 would be
generated after mixing the Lewis acid with diene 5
(Scheme 4). Upon addition of methyl acrylate the complex
20 would be formed and then undergo a [4+2] cycload-
dition with complete stereocontrol to give cycloadduct 21.
The success we anticipated was not achieved. The
aluminum-based Lewis acids under investigation all
failed. In each case, a black, viscous substance was
produced with the addition of the Lewis acid at -78 or
-90 °C. Upon the addition of methyl acrylate, no cyclo-
addition products were isolated. The 1H NMR of the crude
mixture showed complete degradation of the diene. The
instability of these dienes restricted the choice of Lewis
acid and conditions in the development of this methodol-
ogy. The futility of the Al Lewis acids meant that the
tether would have to be made via other means.
a
b
Yields were calculated after purification on silica gel. dr
values were determined by 300- and 500-MHz 1H NMR of the
crude reaction mixture.
We then turned our attention to the formation of a
magnesium alkoxide tether. This type of tether has been
used by Kanemasa and co-workers in the stereocontrol
of metal-assisted 1,3-dipolar cycloaddition of an alken-
oxymagnesium bromide and an electron-deficient dieno-
phile.22 Recently, Ward reported intramolecular Diels-
Alder reactions by self-assembly of dienoxymagnesium
bromide and methyl acrylate.23
F IGURE 2. Proposed mechanism for the hydroxy-Diels-Alder
reaction.
A solution of diene 6 in toluene was treated with 2
equiv of phenylmagnesium bromide (1.0 M in THF) at
(22) (a) Kanemasa, S.; Okuda, K.; Yamamoto, H.; Kaga, S. Tetra-
hedron Lett. 1997, 38, 4095. (b) Kanemasa, S.; Nishiuchi, M.; Ka-
mimura, A.; Hori, K. J . Am. Chem. Soc. 1994, 116, 2324. (c) Kanemasa,
S.; Nishiuchi, M. Tetrahedron Lett. 1993, 34, 4011.
(20) Werner, H.; Rouh, R. J . J . Org. Chem. 1985, 50, 618
(21) (a) Strekowski, L.; Kong. S.; Battiste, M. A. J . Org. Chem. 1988,
53, 901. (b) Hayakawa, K. S.; Ohsuti, S.; Kanematsu, K. Tetrahedron
Lett. 1986, 27, 947.
(23) Ward, D. E.; Abaee, M. S. Org. Lett. 2000, 2, 3937.
J . Org. Chem, Vol. 68, No. 6, 2003 2319

Barriault et al.
TABLE 2. Hyd r oxy Dir ected Diels-Ald er Rea ction w ith Dien es Typ e I
a
b
Yields were calculated after purification on silica gel. dr values were determined by 300- and 500-MHz 1H NMR of the crude reaction
mixture.
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Hydroxy-Directed Diels-Alder Reaction
TABLE 3. Hyd r oxy-Dir ected Diels-Ald er Rea ction w ith Dien es Typ e II
a
b
Yields were calculated after purification on silica gel. dr values were determined by 300- and 500-MHz 1H NMR of the crude reaction
mixture.
-78 °C to form in situ the magnesium alkoxide 21
(Scheme 4). Three equivalents of methyl acrylate was
added and the reaction mixture was slowly warmed to
room temperature. After the mixture was stirred for 3
h, the desired cycloadduct 21 was isolated in 65% yield
as the sole diastereomer. Application of this method to
other dienes was performed and the results of the
cycloaddition reactions are depicted in Table 1. The
reaction gave yields ranging from 30% (entry 4) to 85%
(entry 2). In all entries, the regio- and diastereoselectivity
ratio was greater than 25:1 for both the type I (entries 1
and 2) and type II dienes (entries 3 and 4). The reaction
proves to be tolerant for a variety of substituents at the
tertiary alcohol.
The high regio- and diastereoselectivity can be ratio-
nalized by the proposed transition state depicted in
Figure 2. In the case of the type I dienes, the endo-facial
approach of the dienophile is governed by the complex-
ation of the magnesium alkoxide 26 with the dienophile
carbonyl, i.e., syn to the tertiary alcohol (Figure 2). The
endo approach of the dienophile can occur via two
possible transition states A and B. In transition state A,
an eight-membered-ring intermediate is formed whereas
in transition state B a nine-membered-ring intermediate
is formed. Transition state A is favored due to less strain
when the dienophile approaches the diene. The exclusive
formation of 27 over 28 is thus readily explained.
In the case where type II dienes such as 29 are used,
the same analysis is applied. The dienophile can ap-
proach in two ways to give transition state intermediates
C or D. Cycloadduct 30 is formed via a seven-membered-
ring transition state C whereas cycloadduct 31 would
result from the more strained eight-membered-ring
transition state D. Cycloadduct 31 was never observed
in the crude reaction mixture. Although the results with
PhMgBr were successful, they were not entirely satisfac-
tory because of the irreproducibility of the reaction yields.
It was discovered that the yield of the reaction was closely
related to the quality and the concentration of the
PhMgBr being used. In general, the use of a freshly
prepared solution of PhMgBr (1-1.5 M in THF) gave good
yields. However, as the Grignard reagent aged, the yields
diminished. The inconsistency of the yields with PhMgBr
necessitated an alternative means of forming the semi-
cyclic diene magnesium alkoxide. Vedejs and collabora-
tors reported the formation of magnesium alkoxides using
MgBr2‚Et2O and Et3N.24 Applying this method to the
tertiary alcohol 5, we discovered that the sequence of
addition of these reagents is imperative to the success of
the reaction. The successful method involves addition of
4 equiv of Et3N to a solution of MgBr2‚Et2O (2 equiv) in
dichloromethane at room temperature. This mixture
must be stirred until a pink color persists. The diene is
then added and stirred for 20 min. Finally, the dienophile
is added and the reaction is allowed to proceed with
stirring. The results of the MgBr2‚Et2O mediated reaction
are shown in Tables 2 and 3.
(24) Vedejs, E.; Daugulis, O. J . Org. Chem. 1996, 61, 5702.
J . Org. Chem, Vol. 68, No. 6, 2003 2321

Barriault et al.
TABLE 4. Hyd r oxy-Diels-Ald er Rea ction w ith Oth er Lew is Acid s
Excellent diastereoselectivity was observed in most
cases. It was discovered, however, that a prolonged
exposure to MgBr2-OEt2 and Et3N resulted in epimer-
ization at C5 of cycloadduct 33 (Table 2, entry 2). The
aldehyde 34 also epimerized under MgBr2-OEt2 and
Et3N conditions (12 h) to give a mixture of R/â at C5 of
1:7. To circumvent this, triethylamine was replaced by
2,6-lutidine and the diastereoselectivity was improved to
12:1 (entry 3) and >25:1 (entry 4). As was the case with
PhMgBr, the reactions with MgBr2‚Et2O and triethyl-
amine or 2,6-lutidine were highly regio- and diastereo-
selective. This method provided good and reproducible
yields. The reaction maintained its tolerance to a variety
of substituents on the tertiary alcohol and was shown to
be successful with semicyclic dienes having a secondary
allylic alcohol (Table 2, entries 8-13). To further dem-
onstrate the scope of the reaction, acrolein (Table 2,
entries 4, 9, and 12), methacrolein (Table 2, entries 1, 6,
7, 10, and 13), and N-phenylmaleimide (Table 3, entry
3) were used as dienophiles in addition to methyl acry-
late. These dienophiles worked remarkably well with
yields as high as 82%. The relative stereochemistry of
cycloadducts 23 and 24 was established by X-ray crystal-
lography, which supported, without ambiguity, the pro-
posed mechanism and transition states depicted in Figure
2.25
the reaction. The results are summarized in Table 4.
MgCl2 gave similar yields to MgBr2‚OEt2 (Table 4, entries
1 and 7) whereas MgI2 provided a substantially lower
yield (entry 2). Surprisingly, Mg(OTf)2 did not lead to any
cycloaddition products. Only starting material was re-
covered (entry 6). It was discovered that zinc bromide
and triethylamine gave the desired product but the yield
was considerably lower (entry 3). When semicyclic dienes
of type I and type II were exposed to MgBr2‚OEt2, MgCl2,
MgI2, and ZnBr2 and methyl acrylate in dichloromethane
without triethylamine or 2, 6-lutidine, a complex mixture
resulted from which it was not possible to isolate the
desired cycloadducts. These experiments confirmed with-
out ambiguity the crucial role of the Lewis bases for the
formation of the corresponding magnesium alkoxide 26
and 29 as depicted in Figure 2.
Su m m a r y
The results presented in this study show the successful
development of a method that controls the regio- and
stereoselectivity of the Diels-Alder reaction with PhMg-
Br or MgBr2‚OEt2 and triethylamine of semicyclic dienes
possessing a secondary and tertiary allylic alcohol func-
tionality in the R or â position and activated dienophiles
We also investigated the effect of different halogens
on the magnesium, as well as that of other metals, on
(25) 23 was reduced to the corresponding alcohol with DibalH in
THF to provide crystalline material.
2322 J . Org. Chem., Vol. 68, No. 6, 2003

Hydroxy-Directed Diels-Alder Reaction
at 0 °C. The reaction was stirred for 15 min then cooled to
-78 °C. After an additional 15 min of stirring, the dienophile
(methyl acrylate) (1 equiv) was added via syringe. The tem-
perature was slowly raised to room temperature and the
reaction was monitored by TLC until complete. A solution of
saturated aqueous NH4Cl was then added, followed by extrac-
tion with ether (3×). The combined organic layers were dried
with MgSO4, filtered, and concentrated under vacuum. The
crude product was then purified by flash chromatography (10-
20% EtOAc in hexanes) to provide the desired cycloadduct.
Meth od B. Triethylamine (4 equiv) was added to a mixture
of MgBr2‚OEt2 (2 equiv) in CH2Cl2 (2 M) and stirred until the
initial pale yellow color turned slightly pink. At this time, a
solution of the diene (1 equiv) in CH2Cl2 (0.5 M) was added
via cannula. The reaction was stirred for 20 min, then the
dienophile (2 equiv) was added, via syringe. The mixture was
stirred and the reaction was monitored to completion by TLC.
A solution of saturated aqueous NH4Cl was then added,
followed by extraction (3×) with CH2Cl2. The combined organic
layers were dried over MgSO4, filtered, and concentrated under
vacuum. The crude product was purified by flash column
chromatography (10-20% EtOAc in hexanes) to provide the
desired cycloadduct.
such as methyl acrylate, methacrolein, acrolein, and
N-phenylmaleimide. In the case of the PhMgBr-controlled
reactions, optimal results were obtained when a freshly
prepared bottle of the Grignard reagent was used. The
reactions with magnesium bromide diethyl etherate and
triethylamine show an improvement in yields of the
PhMgBr reactions. Various Lewis acids were examined,
among which only MgBr2‚OEt2, MgCl2, MgI2, and ZnBr2
with the conjunct use of triethylamine or 2,6-lutidine
proved to yield the expected Diels-Alder products in high
regio- and diastereoselectivity. The simplicity and ef-
ficiency of this method has a tremendous potential in
organic synthesis, and is presently being used in our
laboratory in the total synthesis of natural products.
Exp er im en ta l Section
All reactions were carried out under dry N2 atmosphere in
flame-dried glassware equipped with a magnetic stir bar and
a rubber septum, unless otherwise indicated. THF and Et2O
were freshly distilled from sodium/benzophenone. Dichlo-
romethane, triethylamine, and DMF were freshly distilled
from CaH2. ZnBr2 was flame dried under vacuum (1 mmHg).
MgBr2‚OEt2 was prepared from Mg and dibromoethane in THF
and stored in a glovebox (O2 < 1 ppm and H2O < 1 ppm). The
other commercially available reagents were used directly,
unless otherwise indicated. Reactions were monitored by thin-
layer chromatography (TLC) analysis of aliquots, using alu-
minum sheets precoated (0.2 mm layer thickness) with silica
gel 60 F254 (E. Merck). Flash chromatography was carried out
on 230-400 mesh silica gel 60. For purification of compounds
containing tertiary alcohol functionality, the silica gel was
doped with 2% Et3N. TLC plates were viewed under UV light
and stained with phosphomolybdic acid or p-anisaldehyde
staining solutions. GC/MS used a cross linked 5% PH ME
Ack n ow led gm en t. We thank the Natural Science
and Engineering Research Council of Canada (NSERC),
Canada Foundation for Innovation, Ontario Innovation
Trust, Premier’s Research Excellence Award (PREA),
Bristol Myers Squibb (Candiac, Canada), Merck-Frosst
Canada, and the University of Ottawa for generous
funding. R.C. thanks NSERC for an undergraduate
summer scholarship. We are grateful to Effiette Sauer
and Irina Denissova for their useful comments in the
preparation of this paper.
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and spectroscopic data for compounds
1
siloxane column (30 m × 0.25 mm, 0.25 µm film). H and 13C
1
2-18, 21-25, and 32-45 and copies of H and 13C NMR for
NMR spectra were recorded on a 300- or 500-MHz spectrom-
eter. IR spectra were recorded on a FTIR spectrometer.
Gen er al P r ocedu r e for Diels-Alder Reaction s: Meth od
A. Phenylmagnesium bromide (1.2 equiv) was added, via
syringe, to a 0.1 M solution of the diene (1 equiv) in toluene
all new compounds; ORTEP views of 23 reduced as an alcohol
and 24. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O020664M
J . Org. Chem, Vol. 68, No. 6, 2003 2323