Racemic and asymmetric Diels-Alder reactions of 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes

Article abstract of DOI:10.1021/jo005619y

Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions, somewhat more than 1,3-dialkoxy-1,3-butadienes (e.g., Danishefsky's diene). The cycloadditions of the achiral and chiral dienes with several different dienophiles were examined. The reactions proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent facial selectivity in cycloadditions with α-substituted acroleins, maleic anhydride and N-phenylmaleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were obtained with ee's ranging from 22% to >98%.

Full text of DOI:10.1021/jo005619y

J . Org. Chem. 2000, 65, 9059-9068
9059
Ra cem ic a n d Asym m etr ic Diels-Ald er Rea ction s of
1-(2-Oxa zolid in on -3-yl)-3-siloxy-1,3-bu ta d ien es
J acob M. J aney,† Tetsuo Iwama, Sergey A. Kozmin, and Viresh H. Rawal*
Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637
v-rawal@uchicago.edu
Received August 24, 2000
Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily
available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the
1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions,
somewhat more than 1,3-dialkoxy-1,3-butadienes (e.g., Danishefsky’s diene). The cycloadditions of
the achiral and chiral dienes with several different dienophiles were examined. The reactions
proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent
facial selectivity in cycloadditions with R-substituted acroleins, maleic anhydride and N-phenyl-
maleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were
obtained with ee’s ranging from 22% to >98%.
In tr od u ction
are easy to prepare, are stable, and readily undergo
Diels-Alder reactions to afford, for the chiral versions,
products with as high as g98% ee.
The Diels-Alder reaction continues to play a central
role in complex molecule synthesis.1 The importance of
this cycloaddition stems from its remarkable selectivity
profile: Many of these reactions proceed with high regio-,
endo-, and facial selectivities, so as to produce, in a single
step, six-membered ring products with up to four chiral
centers. The versatility of the Diels-Alder reaction has
increased with the advent of new, heteroatom-substituted
dienes, which not only are more reactive but also give
highly functionalized, useful products.2 Finally, asym-
metric variants have made the Diels-Alder reaction all
the more important, enabling the synthesis of complex
products in enantiomerically enriched form.3-6 We de-
scribe here the results of an extensive study on the
synthesis and Diels-Alder reactivity of achiral and chiral
1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes. Such dienes
We recently reported on the preparation and Diels-
Alder reactivity of 1-amino-3-siloxy-1,3-butadienes (2).
These dienes are easily prepared from vinylogous amides
(1) and exhibit extraordinary reactivity and versatility
in [4 + 2] cycloadditions (Scheme 1).7-9 This methodology
was incorporated into a new strategy to Aspidosperma
alkaloids, culminating in the synthesis of (()-taberso-
nine.10 In an effort to expand the utility of amino siloxy
dienes, we explored chirally modified versions of these
dienes. Specifically, we found that the cycloaddition of a
diene possessing the C2-symmetric trans-2,5-diphen-
ylpyrrolidine unit (4) proceeded with remarkably high
diastereofacial selectivity with several different dieno-
philes and yielded, after eliminative workup, a variety
of substituted cyclohexenones with 88% to >98% ee.11,12
The advantage of C2 symmetry in the amine was that
the same steric environment was maintained near the
diene, regardless of rotation of the auxiliary about the
nitrogen-carbon bond. Although this chemistry repre-
sented one of the most direct and general methods for
† Recipient of the Pfizer Undergraduate Summer Research Fellow-
ship in Synthetic Organic Chemistry (1997).
(1) (a) Oppolzer, W. In Comprehensive Organic Synthesis; Pergamon
Press: New York, 1991; Vol. 5, pp 315-399. (b) Dell, C. P. J . Chem.
Soc., Perkin Trans. 1 1998, 3873-3905.
(2) (a) Petrzilka, M.; Grayson, J . I. Synthesis 1981, 753-786. (b)
Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; Wiley:
New York, 1990.
(3) (a) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1984, 23, 876-
889. (b) Paquette, L. A. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: New York, 1984; Vol. 3, pp 455-501. (c) Taschner,
M. J . Asymmetric Diels-Alder Reactions; J AI Press, Inc.: Greenwich,
1989; Vol. 1, pp 1-101.
(4) Chirally modified dienophiles: (a) Jurczak, J.; Bauer, T.; Chapuis,
C. In Stereoselective Synthesis; Houben-Weyl, 4th ed.; Helmchen, G.,
Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.; Verlag: Stuttgart,
1995; Vol. E21c, pp 2735-2871. (b) Ru¨ck-Braun, K.; Kunz, H. Chiral
Auxiliaries in Cycloadditions; Wiley-VCH: New York, 1999.
(5) Chiral dienes: (a) Krohn, K. Angew. Chem., Int. Ed. Engl. 1993,
32, 1582-1584. (b) Enders, D.; Meyer, O. Liebigs Ann. 1996, 1023-
1035. (c) Barluenga, J .; Sua´rez-Sobrino, A.; Lo´pez, L. A. Aldrichim.
Acta 1999, 32, 4-15.
(6) Catalyzed asymmetric reactions: (a) Narasaka, K. Synthesis
1991, 1-11. (b) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007-
1019. (c) Oh, T. Reilly, M. Org. Prep. Proc. Int. 1994, 26, 129-158. (d)
Dias, L. C. J . Braz. Chem. Soc. 1997, 8, 289-332. For an in-depth
discussion of catalytic asymmetric DA reactions, see: (e) Evans, D.
A.; J ohnson, J . S. In Comprehensive Asymmetric Catalysis; J acobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol.
III, pp 1177-1235.
(7) For the chemistry of achiral amino siloxy dienes, see: (a) Kozmin,
S. A.; Rawal, V. H. J . Org. Chem. 1997, 62, 5252-5253. (b) Kozmin,
S. A.; J aney, J . M.; Rawal, V. H. J . Org. Chem. 1999, 64, 3039-3052.
(8) Kozmin, S. A.; Green, M. T.; Rawal, V. H. J . Org. Chem. 1999,
64, 8045-8047.
(9) Examples of the Diels-Alder reaction with related 1-amino-3-
siloxydienes: (a) Smith, A. B., III; Wexler, B. A.; Tu, C.-Y.; Konopelski,
J . P. J . Am. Chem. Soc. 1985, 107, 1308-1320. (b) Kuehne, M. E.;
Bornmann, W. G.; Earley, W. G.; Marko, I. J . Org. Chem. 1986, 51,
2913-2927. (c) Comins, D. L.; Al-awar, R. S. J . Org. Chem. 1992, 57,
4098-4103. (d) Ludwig, C.; Wistrand, L.-G. Acta Chem. Scand. 1989,
43, 676-679. (e) Danieli, B.; Lesma, G.; Luzzani, M.; Passarella, D.;
Silvani, A. Tetrahedron 1996, 52, 11291-11296.
(10) Application to tabersonine synthesis: Kozmin, S. A.; Rawal,
V. H. J . Am. Chem. Soc. 1998, 120, 13523-13524.
(11) (a) Kozmin, S. A.; Rawal, V. H. J . Am. Chem. Soc. 1997, 119,
7165-7166. (b) Kozmin, S. A.; Rawal, V. H. J . Am. Chem. Soc. 1999,
121, 9562-9573.
(12) Two preparative procedures have been accepted for publication
in Organic Syntheses, one for the synthesis of amino siloxy diene 2 (R
) Me) and the other for the use of this diene in
a Diels-Alder
reaction: Kozmin, S. A.; He, S.; Rawal, V. H. Org. Synth. 2000, 78, in
press.
10.1021/jo005619y CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/06/2000

9060 J . Org. Chem., Vol. 65, No. 26, 2000
J aney et al.
Sch em e 1
Sch em e 2
reported oxazolidinone containing dienes 6, which under-
went cycloadditions with N-phenylmaleimide with good
to high diastereoselectivities.14f In our own work, we have
incorporated the advantageous properties of the oxazo-
lidinone auxiliary to amino siloxy dienes, which possess
many of the same advantages of 1,3-dialkoxy-1,3-buta-
dienes, such as Danishefsky’s diene, including the pos-
sibility of generating a cyclohexenone upon hydrolysis.
the preparation of enantiomerically enriched 4- and 4,5-
disubstituted cyclohexenones, it suffered from the incon-
venience associated with the preparation of the required
auxiliary.
Among other readily available auxiliaries for our amino
siloxy dienes,13,14 the amide or carbamate linkage on the
diene was attractive since such dienes have been found
to afford high endo selectivity with several dieno-
philes.14a,f,15,16 The carbonyl group on the amide nitrogen
was expected to preferentially adopt the anti conforma-
tion, away from the dienyl moiety. The alkyl group on
the amide would then occupy the position proximal to
the diene, such that a chiral element on the alkyl group
would block one face of the diene. This approach was first
demonstrated by Smith and co-workers through diene 5,
which showed excellent diastereoselectivity in some
Diels-Alder reactions.14a Subsequently, Stevenson et al.
Resu lts a n d Discu ssion
Ach ir a l Dien es. Before exploring the chemistry of
chiral 1-oxazolidinone substituted siloxy dienes (e.g., 7),
we first prepared and explored the reactivity of the
parent, achiral oxazolidinone substituted diene 10. Of the
routes examined, that shown in Scheme 2 is the most
straightforward and highest yielding. The condensation
of 2-oxazolidinone (8) with 3-butyn-2-one (prepared in
situ by J ones oxidation of 3-butyn-2-ol) in the presence
of N-methylmorpholine (NMM) in CH2Cl2 at room tem-
perature afforded the desired vinylogous amide 9 in
quantitative yield.17 Deprotonation of 9 using potassium
(13) For examples of chiral alkoxy dienes, see: (a) David, S.;
Eustache, J .; Lubineau, A. J . Chem. Soc., Perkin Trans. 1 1974, 2274-
2278. (b) David, S.; Lubineau, A.; Vatele, J .-M. J . Chem. Soc., Chem.
Commun. 1975, 701-702. (c) David, S.; Lubineau, A.; Vatele, J .-M. J .
Chem. Soc., Perkin Trans. 1 1976, 1831-1837. (d) David, S.; Lubineau,
A.; Thieffry, A. Tetrahedron 1978, 34, 299-304. (e) Trost, B. M.;
Godleski, S. A.; Genet, J . P. J . Am. Chem. Soc. 1978, 100, 3930-3931.
(f) David, S.; Eustache, J .; Lubineau, A. J . Chem. Soc., Perkin Trans.
1 1979, 1795-1798. (g) Trost, B. M.; O’Krongly, D.; Belletire, J . L. J .
Am. Chem. Soc. 1980, 102, 7595-7596. (h) Bednarski, M.; Danishefsky,
S. J . Am. Chem. Soc. 1983, 105, 6968-6969. (i) Gupta, R. C.; Harland,
P. A.; Stoodley, R. J . J . Chem. Soc., Chem. Commun. 1983, 754-756.
(j) Gupta, R. C.; Harland, P. A.; Stoodley, R. J . Tetrahedron 1984, 40,
4657-4667. (k) Gupta, R. C.; Slawin, A. M. Z.; Stoodley, R. J .; Williams,
D. J . J . Chem. Soc., Chem. Commun. 1986, 668-670. (l) Bednarski,
M.; Danishefsky, S. J . Am. Chem. Soc. 1986, 108, 7060-7067. (m)
Gupta, R. C.; Slawin, A. M. Z.; Stoodley, R. J .; Williams, D. J . J . Chem.
Soc., Chem. Commun. 1986, 1116-1118. (n) Lubineau, A., Queneau,
Y. J . Org. Chem. 1987, 52, 1001-1007. (o) Gupta, R. C.; Raynor, C.
M.; Stoodley, R. J .; Slawin, A. M. Z.; Williams, D. J . J . Chem. Soc.,
Perkin Trans. 1 1988, 1773-1785. (p) Siegel, C.; Thornton, E. R.
Tetrahedron Lett. 1988, 29, 5225-5228. (q) Gupta, R. C.; Larsen, D.
S.; Stoodley, R. J .; Slawin, A. M. Z.; Williams, D. J . J . Chem. Soc.,
Perkin Trans. 1 1989, 739-749. (r) Tucker, J . A.; Houk, K. N.; Trost,
B. M. J . Am. Chem. Soc. 1990, 112, 5465-5471. (s) Tripathy, R.;
Carroll, P. J .; Thornton, E. R. J . Am. Chem. Soc. 1991, 113, 7630-
7640. (t) Boehler, M. A.; Konopelski, J . P. Tetrahedron 1991, 47, 4519-
4538.
(14) For examples of chiral amino dienes, see: (a) Menezes, R. F.;
Zezza, C. A.; Sheu, J .; Smith, M. B. Tetrahedron Lett. 1989, 30, 3295-
3298. (b) Enders, D.; Meyer, O.; Raabe, G. Synthesis 1992, 1242-1244.
(c) Barluenga, J .; Aznar, F.; Valdes, C.; Martin, A.; Garcia-Granda,
S.; Martin, E. J . Am. Chem. Soc. 1993, 115, 4403-4404. (d) Schlessing-
er, R. H.; Pettus, T. R. R. J . Org. Chem. 1994, 59, 3246-3247. (e)
Enders, D.; Meyer, O.; Raabe, G.; Runsink, J . Synthesis 1994, 66-72.
(f) Murphy, J . P.; Nieuwenhuyzen, M.; Reynolds, K.; Sarma, P. K. S.;
Stevenson, P. J . Tetrahedron Lett. 1995, 36, 9533-9536. (g) Barluenga,
J .; Aznar, F.; Martin, A.; Vazquez, J . T. J . Am. Chem. Soc. 1995, 117,
9419-9426. (h) Barluenga, J .; Aznar, F.; Ribas, C.; Valdes, C.;
Fernandez, M.; Cabal, M.-P.; Trujillo, J . Chem. Eur. J . 1996, 2, 805-
811. (i) Barluenga, J .; Canteli, R.-M.; Florez, J .; Garcia-Granda, S.;
Gutierrez-Rodriguez, A.; Martin, E. J . Am. Chem. Soc. 1998, 120,
2514-2522.
(15) For examples of the synthesis of 1-N-acylamino-1,3-dienes,
see: (a) Oppolzer, W.; Frostl, W. Helv. Chim. Acta 1975, 58, 587-589.
(b) Overman, L. E.; Taylor, G. F.; J essup, P. J . Tetrahedron Lett. 1976,
3089-3092. (c) Overman, L. E.; Clizbe, L. A. J . Am. Chem. Soc., 1976,
98, 2352-2354, 8295. (d) Overman, L. E.; Taylor, G. F.; Petty, C. B.;
J essup, P. J . J . Org. Chem. 1978, 43, 2164-2167. (e) Oppolzer, W.;
Bieber, L.; Francotte, E. Tetrahedron Lett. 1979, 981-984. (f) Oppolzer,
W.; Bieber, L.; Francotte, E. Tetrahedron Lett. 1979, 4537-4540. (g)
Overman, L. E.; Clizbe, L. A.; Freerks, R. L.; Marlowe, C. K. J . Am.
Chem. Soc. 1981, 103, 2807-2815. (h) Zezza, C. A.; Smith, M. B. J .
Org. Chem. 1988, 53, 1161-1167. Several of the papers in this group
also discuss the Diels-Alder reactivity of the dienes.
(16) For examples of the Diels-Alder reaction of 1-N-acylamino-
1,3-dienes, see: (a) Oppolzer, W.; Keller, K. J . Am. Chem. Soc. 1971,
93, 3836-3837. (b) Oppolzer, W.; Frostl, W. Helv. Chim. Acta 1975,
58, 590-593. (c) Oppolzer, W.; Frostl, W.; Weber, H. P. Helv. Chim.
Acta 1975, 58, 593-595. (d) Overman, L. E.; Taylor, G. F.; Houk, K.
N.; Domelsmith, L. N. J . Am. Chem. Soc. 1978, 100, 3182-3189. (e)
Overman, L. E.; J essup, P. J . J . Am. Chem. Soc. 1978, 100, 5179-
5185. (f) Stork, G.; Morgans, D. J . J . Am. Chem. Soc. 1979, 101, 7110-
7111. (g) Overman, L. E.; Freerks, R. L.; Petty, C. B.; Clizbe, L. A.;
Ono, R. K.; Taylor, G. F.; J essup, P. J . J . Am. Chem. Soc. 1981, 103,
2816-2822. (h) Overman, L. E.; Lesuisse, D.; Hashimoto, M. J . Am.
Chem. Soc. 1983, 105, 5373-5379. (i) Rawal, V. H.; Michoud, C.;
Monestel, R. F. J . Am. Chem. Soc. 1993, 115, 3030-3031. (j) Rawal,
V. H.; Iwasa, S. J . Org. Chem. 1994, 59, 2685-2686.
(17) Lee, E.; Kang, T. S.; J oo, B. J .; Tae, J . S.; Li, K. S.; Chung, C.
K. Tetrahedron Lett. 1995, 36, 417-420.

Reactions of 1-(2-Oxazolidinon-3-yl)-3-siloxy-1,3-butadienes
J . Org. Chem., Vol. 65, No. 26, 2000 9061
Sch em e 3
Sch em e 4
Sch em e 5
hexamethyldisilazide (KHMDS) in tetrahydrofuran (THF)
at -78 °C and trapping of the resulting enolate with tert-
butyldimethylsilyl chloride (TBSCl) gave the desired
diene 10, a white solid, in 94% yield. Larger scale
preparation of 10 was carried out more conveniently
using NaHMDS, which is available commercially from
Aldrich as a 1 M solution in THF. With either base, the
crude product is formed in high purity and can be used
without purification.
The Diels-Alder reaction of diene 10 was examined
with three different dienophiles (Scheme 3). Diene 10
reacted with N-phenylmaleimide at -20 °C to room
temperature to produce cycloadduct 11 in 78% yield, with
essentially complete endo selectivity, with no detectable
1
signals from the exo isomer in the H NMR spectrum of
counterpart, diene 2. The reduced reactivity of diene 10
is a natural consequence of having an electron-withdraw-
ing group on nitrogen. Interestingly, the oxazolidinone
diene (10) is still very reactive in Diels-Alder chemistry.
In a simple competition experiment using methacrolein
as the dienophile, the oxazolidinone-siloxy diene was
found to be somewhat more reactive than the TBS-
derivative of Danishefsky’s diene (1-methoxy-3-(tert-
butyldimethylsiloxy)-1,3-butadiene) in Diels-Alder re-
actions.7a,8 To get more precise data on the relative
reactivity of the oxazolidinone diene, the second-order
rate constant was determined for its reaction with
methacrolein in CDCl3 (K2 ) 1.2 × 10-5) and C6D6 (K2 )
5.4 × 10-6, see the Supporting Information). For the
purpose of comparison, the kinetics of the TBS derivative
of Danishefsky’s diene were redetermined (K2 ) 4.3 ×
10-6 in CDCl3).8,18 The data confirm that despite the
presence of the electron-withdrawing group on the ni-
trogen at C1, diene 10 is still very reactive, about three
times more reactive than TBS-Danishefsky’s diene.
Ch ir a l Dien es. The success of the achiral diene en-
couraged us to examine the cycloaddition of chiral oxa-
zolidinone-derived dienes. Three chiral dienes (18a -c)
were synthesized, using procedures that paralleled those
used for the preparation of achiral diene 10 (Scheme 5).
The phenyl-substituted oxazolidinone (16a ), required for
the reaction mixture. The reaction with methacrolein
required slightly higher temperature and afforded cy-
cloadduct 12 in 99% yield, again with total endo selectiv-
ity. As was the case with the parent amino siloxy dienes,7
the cycloaddition with methyl acrylate was less diaste-
reoselective. The cycloaddition took place at 60-70 °C
and provided in 88% yield a 3:1 mixture of endo/exo
diastereomers.
Effective protocols were developed for the selective
hydrolysis of the cycloadduct (Scheme 4). Treatment of
the methacrolein adduct (12) with trifluoroacetic acid at
room temperature for 1 h yielded the desilylated cyclo-
hexanone product (14) in 91% yield, with the oxazolidi-
none intact. The different signals in the 1H NMR of
1
cyclohexanone 14 were assigned using H COSY experi-
ments, and the C-3 proton was observed at δ 4.16 as a
ddd multiplet with coupling constants J ) 12 (axial), 5
(equatorial), and 1.5 (long range with CHO) Hz. The
coupling constants are consistent with the chair confor-
mation of 14, in which the oxazolidinone sits in the
equatorial position and the aldehyde occupies the axial
position. Reduction of 12 with LiAlH4 in ether at room
temperature produced the amino alcohol, which was then
treated with 49% aqueous HF in acetonitrile to afford
the 4,4-disubstituted cyclohexenone product (15) in 80%
overall yield.
Kin etics. As anticipated, the Diels-Alder reaction
conditions required for the oxazolidinone siloxy diene
were more vigorous than for its amino siloxy diene
(18) The rate constant redetermined for TBS version of Danishef-
sky’s diene was slightly different from that reported earlier (see ref
8).

9062 J . Org. Chem., Vol. 65, No. 26, 2000
J aney et al.
Sch em e 6
diene 18a , was prepared in 84% overall yield by a
modification of the reported procedure.19 (R)-Phenylgly-
cine was reduced using LiBH4/TMSCl in THF, and the
resultant (R)-phenylglycinol was heated with diethyl
carbonate in the presence of a catalytic amount of
K2CO3 to yield (R)-4-phenyl-2-oxazolidinone 16a . Oxazo-
lidinones 16b and 16c, which are commercially available,
can be prepared analogously from the corresponding
commercially available amino alcohols. As before, treat-
ment of the oxazolidinones with 3-butyn-2-one gave vin-
ylogous amides 17 in 88-97% yield. The chiral oxazoli-
dinone-derived dienes 18a -c were obtained upon treat-
ment of vinylogous amides 17a -c with NaHMDS in THF
at -78 °C for 1 h followed by silylation with TBSCl and
allowing the reaction mixture to warm to room-temper-
ature overnight. The phenyloxazolidinone substituted
diene 18a was obtained in quantitative yield, and the
crude product was clean by NMR. Crystallization of the
crude diene from ether and hexanes afforded pure 18a
as pale yellow crystals in 76% yield. Silylation of the
enolate of vinylogous amide 17b proceeded smoothly to
afford the isopropyl-substituted derivative 18b in reason-
ably pure state. On the other hand, silylation of the
1-amino-2-indanol derivative 17c with TBSCl did not go
to completion, possibly due to the steric hindrance of the
indanyl group. The 1H NMR spectrum of the reaction
mixture showed a 1:2 mixture of 17c and 18c ac-
companied by minor byproducts. Diene 18c was also less
stable compared with dienes 18a and 18b and gradually
decomposed during storage in a refrigerator.
To evaluate the reactivity and diastereofacial selection
capability of the three chiral auxiliaries, we examined
the Diels-Alder reactions of chiral dienes 18a -c with
methacrolein (Scheme 6). In general, the chiral dienes
(18) were comparable in reactivity to their achiral
counterpart, diene 10. The cycloadditions were carried
out in toluene at 35 °C (bath temp.), and the cycloadducts
19 were transformed directly into cyclohexenone 20. The
crude cycloadducts, which can be isolated in high purity
in quantitative crude yield (>17:1, endo/exo by NMR for
19a ), were treated with LiAlH4 to reduce both the
oxazolidinone and aldehyde carbonyls, and the resulting
amino diol was hydrolyzed with 49% aqueous HF in
acetonitrile to cyclohexenone 20 in 49-67% overall yields.
In all three cases cyclohexenone 20 was obtained en-
riched in the (S)-enantiomer,11 as determined by 1H NMR
analysis of the corresponding (S)-MTPA ester.20 The best
diastereoselectivity was obtained using the aminoin-
F igu r e 1. Probable low energy transition states leading to
20.
danol-derived diene 18c, which yielded cyclohexenone 20
in 96% ee. The phenylglycinol containing diene gave
lower, but still quite good, diastereoselectivity. The
asymmetric induction observed for the cycloadditions
with methacrolein can be rationalized by considering the
two endo transition states, A and B (Figure 1, illustrated
for diene 18a ). As discussed earlier, the s-trans rotamer
of the oxazolidinone is expected to be of lower energy,
presumably to avoid steric interaction between the car-
bonyl oxygen and the hydrogen at C2.14a,f Of the two
transition states, A is expected to be favored for steric
reasons, with the dienophile approaching the diene from
the face away from the aryl group. The higher diaste-
reoselectivity with diene 18c is presumably due to more
efficient shielding of the diene upper face by the aromatic
ring of the indanyl group compared to the phenyl group.
The Diels-Alder reaction of diene 18a was then
examined with several different dienophiles in order to
determine the scope of this methodology (Table 1). In all
cases the intermediate cycloadducts were not isolated,
but were converted directly to cyclohexenone derivatives
21-25 by the reduction-hydrolysis protocol. The Diels-
Alder reaction of ethacrolein proceeded at 35 °C as before
in excellent yield and with high endo and facial selectivi-
ties. After LAH reduction and HF hydrolysis, the ex-
pected cyclohexenone (21) was isolated in 65% overall
yield. The ee of this compound, as determined by 1H NMR
analysis of the corresponding (S)-MTPA ester, was 92%
(S), comparable to that observed for the methacrolein
adduct (entry 1).11,20 The cycloaddition reaction with
methyl acrylate proceeded with much lower endo/exo
selectivity. The endo/exo mixture was subjected to the
reduction-hydrolysis protocol to afford enone 22, with
55% ee (entry 2). The cycloadditions of both diethyl
fumarate and dimethyl maleate were low yielding. The
latter, in particular, reacted very sluggishly and even
after 4d at 65 °C only a small amount of the cycloadduct
was observed. The unreactivity of maleate with these
(19) Nicolas, E.; Russell, K. C.; Hruby, V. J . J . Org. Chem. 1993,
58, 766-770.
(20) Ward, D. E.; Rhee, C. K. Tetrahedron Lett. 1991, 32, 7165-
7166.

Reactions of 1-(2-Oxazolidinon-3-yl)-3-siloxy-1,3-butadienes
J . Org. Chem., Vol. 65, No. 26, 2000 9063
Ta ble 1. Th e Diels-Ald er Rea ction of Dien e 18a w ith Va r iou s Dien op h iles
dienes stands in contrast to our previous experience
with the parent amino siloxy diene and its chiral ver-
sion.7,8,11
Sch em e 7
On the other hand, maleic anhydride reacted cleanly
with the diene 18a . The reaction was started at -45 °C
and allowed to warm to room temperature overnight (11
h) to afford the cycloadduct as essentially a single
stereoisomer in quantitative crude yield (entry 5). Un-
fortunately, after the reduction-hydrolysis sequence the
final cyclohexenone product (24) was isolated in only 32%,
due in large measure to the difficulty associated with
extracting the amino triol intermediate from the alumi-
num residues arising from the LAH reduction, as well
as to the overall high water solubility of enone-diol 24.
However, the enantiomeric excess of 24 was excellent
by diisobutylaluminum hydride (DIBAL-H) reduction of
the enone (Scheme 7). The H NMR analysis of Mosher
1
esters 27 revealed the presence of only two diastereo-
mers, in exactly the same ratio as the original alcohols
(3:1), indicating >98% ee for enone 25. Cinnamaldehyde,
tiglic aldehyde and citraconic anhydride were unreactive
with diene 18a under the standard Diels-Alder condi-
tions.
1
(>98% ee), as determined by H NMR analysis of the
corresponding (S)-MTPA ester.11,20 The reaction with
N-phenylmaleimide also proceeded with high endo and
facial selectivities14f and gave, after reduction-hydrolysis
of the cycloadduct, cyclohexenone derivative 25 in 51%
yield with >98% ee. The ee of 25 was determined by
Mosher ester analysis of allylic alcohols 26 (3:1), obtained
The observed absolute asymmetric induction in the
Diels-Alder reactions above can be understood by con-

9064 J . Org. Chem., Vol. 65, No. 26, 2000
J aney et al.
Con clu sion
The results described above demonstrate that 1-(2-
oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are easily pre-
pared from readily available starting materials and are
highly reactive in Diels-Alder reactions. The chiral
versions of these dienes (18) show considerable promise
as an important surrogate to 1,3-dialkoxy-1,3-butadienes
(e.g., Danishefsky’s diene) for asymmetric synthesis. The
diastereoselectivities of the R-substituted dienophiles,
maleic anhydride, and N-phenylmaleimide were excel-
lent. However, the diastereoselectivities with methyl
acrylate and diethyl fumarate were poor. Although not
pursued due to its higher cost, the 1-amino-2-indanol-
derived diene shows even more promise for asymmetric
Diels-Alder reactions.21
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were carried out under a
nitrogen atmosphere. Common solvents were purified before
use. Tetrahydrofuran (THF) and diethyl ether (Et2O) were
purified by distillation from potassium-benzophenone ketyl.
Dichloromethane (CH2Cl2), benzene, and toluene were distilled
from calcium hydride. All reagents were reagent grade and
purified further when necessary. KHMDS was used from
newly opened 100 mL bottles, purchased from Aldrich, Inc.
Reactions were monitored by thin-layer chromatography (TLC)
using 250 µm Whatman precoated silica gel plates. Flash
column chromatography was performed over EM Science
Laboratories silica gel (230-400 mesh) or Davisil Grade 633
Type 60A (200-425 mesh, Fisher Scientific). Melting points
(mp) were measured on a Thomas-Hoover capillary melting
point apparatus and are uncorrected. Carbon and proton NMR
spectra were recorded on a Bru¨ker DRX-500 spectrometer. 1H
NMR chemical shifts are reported as δ values (ppm) relative
to internal tetramethylsilane, and splitting patterns are
designated as follows: s ) singlet, d ) doublet, t ) triplet, q
) quartet, m ) multiplet. 13C NMR chemical shifts are
reported as δ values (ppm) relative to chloroform-d (77.0 ppm).
Infrared spectra (IR) were recorded with Nicolet 20 SXB FTIR
spectrometer and are reported in reciprocal centimeters (cm-1).
Mass spectra were obtained on either a Kratos MS-30 or a
Kratos VG 70-250S mass spectrometer at The Ohio State
University Campus Chemical Instrumentation Center. Optical
rotations were measured on Perkin-Elmer 241 polarimeter at
the sodium D line (1 mL sample cell).
F igu r e 2. Possible transition states for the diastereoselective
Diels-Alder reaction.
sidering a general transition state model, shown in
Figures 2. The different examples can be classified into
two groups, those that are highly endo selective and those
that are not. Based on the proposed transition states in
Figure 2, one would expect, a priori, that endo-selective
cycloadditions would exhibit higher diastereofacial se-
lectivity than exo-selective cycloadditions. Of the two
endo transition states C and D, the latter is expected to
be much higher in energy, as it places the electron-
withdrawing group in close proximity to the phenyl group
on the oxazolidinone. By comparison, the energy differ-
ence between the two exo-transition states (E and F ) is
expected to be smaller (except for meth- and ethacrolein,
vide infra), since the more congested transition only has
a hydrogen close to the oxazolidinone phenyl group. For
reactions that give an endo-exo mixture, only a poor ee
of the final product can be expected since the two
diastereomers are expected to be enriched in the opposite
enantiomer of the final enone. The observed results are
consistent with this analysis. The high ee’s obtained from
meth- and ethacroleins, maleic anhydride, and N-phen-
ylmaleimide are consistent with the high endo selectivi-
ties of their Diels-Alder reactions with an amino siloxy
diene. The slightly lower excesses observed for meth- and
ethacrolein in this group can be understood by recogniz-
ing that, unlike the other dienophiles, even the exo
pathway for these dienophiles should exhibit high dias-
tereofacial selectivity (consider E and F , wherein H is
replaced with an R group), resulting in formation of the
opposite enantiomer of the final product. The consider-
ably lower ee’s of cyclohexenones 22 and 23 can be
attributed to the fact that the cycloadditions of methyl
acrylate and diethyl fumarate with diene 18a are not
highly endo-selective.
P r ep a r a tion of 4-(2-Oxa zolid in on -3-yl)-3-bu ten e-2-on e
(9). A solution of CrO3 (1.01 g, 10.1 mmol) in H2SO4/H2O (3.6
mL/18 mL) was added slowly over 30 min to a stirring solution
of 3-butyn-2-ol (ca. 6-9 mmol) in H2SO4/H2O (5.4 mL/18 mL)
at 0 °C. The mixture was stirred at 2-10 °C for 4 h, and then
CH2Cl2 (25 mL) was added. The reaction mixture was then
washed with saturated NaHCO3/H2O (7.5 mL/7.5 mL), and the
organic layer was dried with MgSO4 and then filtered. The
crude butynone product in ca. 25 mL of CH2Cl2 was added to
a stirring solution of 2-oxazolidinone (267 mg, 3.07 mmol) and
N-methylmorpholine (0.66 mL, 6.0 mmol) in CH2Cl2 (20 mL).
After 21 h at room temperature, the solution was concentrated
in vacuo and the residue purified by flash chromatography on
silica gel (elution with 10% methanol in ethyl acetate) to afford
the product 9 as a pale yellow solid (469 mg, 99%). The product
of larger scale reactions were purified by crystallization from
ethyl acetate and hexanes: mp 88-91 °C; 1H NMR (500 MHz,
CDCl3) δ 2.28 (s, 3H), 3.82 (t, J ) 8 Hz, 2H), 4.56 (t, J ) 8 Hz,
2H), 5.49 (d, J ) 14.5 Hz, 1H), 7.82 (d, J ) 14.5 Hz, 1H); 13C
(21) A wide of chiral oxazolidones can be prepared via the Sharpless
asymmetric aminohydroxylation methodology. For a leading recent
reference, see: Barta, N. S.; Sidler, D. R.; Somerville, K. B.; Weissman,
S. A.; Larsen, R. D.; Reider, P. J . Org. Lett. 2000, 2, 2821-2824.

Reactions of 1-(2-Oxazolidinon-3-yl)-3-siloxy-1,3-butadienes
J . Org. Chem., Vol. 65, No. 26, 2000 9065
NMR (125 MHz, CDCl3) δ 26.8, 42.0, 62.6, 110.8, 137.8, 154.6,
196.7; IR (CHCl3) 3018, 1782, 1760, 1690, 1626, 1599, 1480,
1414, 1348, 1215, 1094, 1037, 963, 755, 666 cm-1; HRMS m/z
[M+] calcd for C7H9NO3 155.0582, found 155.0594.
δ 0.17, 0.17 (each s, 3H), 0.93 (s, 9H), 1.21 (s, 3H), 1.63 (ddd,
J ) 14, 6, 2 Hz, 1H), 1.88 (ddd, J ) 14, 11, 7 Hz, 1H), 2.10
(ddd, J ) 18, 11, 6 Hz, 1H), 2.17 (ddd, J ) 18, 7, 2 Hz, 1H),
3.38 (dt, J ) 5.5, 8.5 Hz, 1H), 4.26 (dt, J ) 5.5, 8.5 Hz, 1H),
3.55 (q, J ) 8.5 Hz, 1H), 4.21 (q, J ) 8.5 Hz, 1H), 4.64 (d, J )
5.7 Hz, 1H), 4.66 (d, J ) 5.7 Hz, 1H), 9.65 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ -4.7, -4.3, 17.9, 18.6, 24.5, 25.5, 25.9,
42.4, 48.4, 53.8, 62.1, 98.3, 155.7, 158.6, 203.7; IR (CHCl3)
P r ep a r a tion of 3-(ter t-Bu tyld im eth ylsiloxy)-1-(2-ox-
azolidin on -3-yl)-1,3-bu tadien e (10). Meth od A. To a stirred,
chilled solution (-78 °C, bath) of KHMDS in toluene (0.5 M,
2.1 mL, 1.05 mmol) and THF (2.1 mL) was added dropwise a
solution of vinylogous imide 9 (155 mg, 1.00 mmol) in THF
(2.3 mL). The reaction mixture was warmed to -45 °C over
2.5 h, cooled to -78 °C, and treated with a solution of tert-
butyldimethylsilyl chloride (166 mg, 1.10 mmol) in THF (0.8
mL). The cold bath was removed, and the reaction mixture
was allowed to reach room temperature. Dilution with ether
(20 mL) followed by filtration through dry Celite and concen-
tration in vacuo gave 253 mg (94%) of diene 10 as a white
solid. Although the crude diene obtained through this proce-
dure is of high purity (by NMR) and was used directly for
cycloaddition chemistry, if desired it can be further purified
via bulb-to-bulb distillation at 200 °C and 0.15 mmHg.
Meth od B. A stirred solution of NaHMDS in THF (1.0 M,
6.6 mL, 6.6 mmol) and THF (6.6 mL) was cooled to -78 °C
(bath) and then treated dropwise over 15 min with a solution
of vinylogous imide 9 (931 mg, 6 mmol) in THF (15 mL). After
30 min, a solution of tert-butyldimethylsilyl chloride (995 mg,
6.6 mmol) in THF (1.5 mL) was added. The stirred mixture
was allowed to gradually warm to room temperature over 6 h
and then concentrated in vacuo. The resultant orange solid
was dissolved in ether, and the NaCl that precipitated was
removed by filtration through Celite. The Celite pad was
washed with more ether, and the combined filtrate was
concentrated. Hexanes was added, causing the precipitation
of the diene along with more NaCl. This solid was filtered
through Celite, which was then washed with EtOAc to dis-
solved the desired diene. The filtrate was evaporated to give
1.54 g (95% yield) of diene 10 as a light orange solid: mp 85-
87 °C; 1H NMR (500 MHz, CDCl3) δ 0.20 (s, 6H), 0.99 (s, 9H),
3.74 (t, J ) 8 Hz, 2H), 4.21 and 4.22 (each s, 1H), 4.46 (t, J )
8 Hz, 2H), 5.34 (d, J ) 14.0 Hz, 1H), 7.17 (d, J ) 14.0 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ -4.6, 18.2, 25.8, 42.5, 62.0,
93.3, 109.2, 125.0, 153.8, 155.1; IR (CHCl3) 3019, 2959, 2931,
2860, 1789, 1656, 1482, 1414, 1327, 1274, 1218, 942, 842, 753,
668 cm-1; HRMS m/z [M+] calcd for C13H23NO3Si 269.1447,
found 269.1437.
Diels-Ald er Rea ction betw een Dien e 10 a n d N-
P h en ylm a leim id e. A solution of diene 10 (500 mg, 1.86
mmol) in toluene (3 mL) cooled to -20 °C was treated with a
solution of N-phenylmaleimide (215 mg, 1.24 mmol) in toluene
(2 mL). After 1 h, the reaction mixture was warmed to room
temperature, diluted with toluene (5 mL), and stirred for
another 2 h. The solvent was removed in vacuo, and the
residue was purified by flash chromatography on silica gel (2:1
ethyl acetate-hexanes) followed by recrystallization from
toluene to give 430 mg (78%) of adduct 11 as a colorless solid.
(3aS*,4R*,7aS*)-6-(tert-Butyldimethylsilyloxy)-3a,4,7,7a-tet-
rahydro-4-(2-oxazolidinon-3-yl)-2-phenyl-1H-isoindole-1,3-(2H)-
dione: mp 135-137 °C; 1H NMR (500 MHz, CDCl3) δ 0.16 and
0.17 (each s, 3H), 0.92 (s, 9H), 2.49 (dd, J ) 16.5, 9 Hz, 1H),
2.80 (dd, J ) 16.5, 2.5 Hz, 1H), 3.36 (dt, J ) 2.5, 9 Hz, 1H),
3.59-3.69 (m, 3H), 4.30-4.36 (m, 2H), 4.77-4.79 (m, 1H),
4.94-4.95 (m, 1H), 7.24 (d, J ) 7.5 Hz, 2H), 7.39 (t, J ) 7.5
Hz, 1H), 7.46 (t J ) 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3)
δ -4.6, -4.4, 17.9, 25.5, 28.5, 38.4, 41.9, 43.5, 49.6, 62.4, 98.4,
126.1, 128.6, 129.2, 131.7, 153.2, 158.0, 175.8, 177.8; IR
(CHCl3) 3019, 1745, 1711, 1386, 1216, 842, 755 cm-1; HRMS
m/z [M+] calcd for C23H30N2O5Si 442.1924, found 442.1919.
Diels-Ald er Rea ction betw een Dien e 10 a n d Meth a c-
r olein . Methacrolein (2.46 mL, 29.6 mmol) was added to a
stirred solution of diene 10 (2.00 g, 7.40 mmol) in toluene (7.4
mL) at room temperature. The reaction mixture was heated
to 55 °C for 20 h. Concentration in vacuo afforded 2.50 g (99%)
of clean cycloadduct 12 as a pale yellow solid. Crystallization
from CH2Cl2 and hexanes afforded pure (3R*,4S*)-1-(tert-
Butyldimethylsilyloxy)-4-formyl-4-methyl-3-(2-oxazolidinon-3-
yl)-cyclohexene: mp 141-142 °C; 1H NMR (500 MHz, CDCl3)
3020, 2951, 2860, 1748, 1669, 1415, 1224, 840, 750, 668 cm-1
;
HRMS m/z [M+] calcd for C17H29NO4Si 339.1866, found
339.1855.
Diels-Ald er Rea ction betw een Dien e 10 a n d Meth yl
Acr yla te. Methyl acrylate (1.37 mL, 18.6 mmol) was added
to a solution of diene 10 (1.00 g, 3.7 mmol) in toluene (3.7 mL)
at room temperature. After 20h, the solution was heated to
60 °C (bath) and stirred for 22 h. Removal of the solvent and
analysis by 1H NMR showed presence of the diene 10. The
crude product was redissolved in toluene (4 mL), treated with
more methyl acrylate (1.37 mL, 18.6 mmol), and heated in an
oil bath (72 °C) for 21 h. The volatiles were removed in vacuo
and the residue purified by flash chromatography on silica gel
(elution with 25% hexanes in ethyl acetate) to afford 1.15 g
(88%) of a 3:1 ratio (by NMR) of endo (13a ):exo (13b) diaster-
eomers. To obtain spectroscopic data, the diastereomers were
separated by flash chromatography on silica gel (elution with
25% hexanes in diethyl ether). (3,4-cis)-1-(tert-Butyldimeth-
ylsilyloxy)-4-methyoxycarbonyl-3-(2-oxazolidinon-3-yl)cyclo-
1
hexene (13a ): mp 125-126 °C; H NMR (500 MHz, CDCl3) δ
0.15 and 0.16 (each s, H), 0.92 (s, 9H), 1.86-1.96 (m, 2H),
2.10-2.15 (m, 2H), 2.79 (ddd, J ) 10.5, 5.5, 5.0 Hz, 1H), 3.56
(q, J ) 8 Hz, 1H), 3.62-3.66 (m, 1H), 3.69 (s, 3H), 4.22-4.26
(m, 2H), 4.73 (d, J ) 5 Hz, 1H), 4.89 (t, J ) 5 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ -4.6, -4.3, 18.0, 21.5, 25.5, 28.7,
42.8, 43.5, 49.0, 51.9, 62.1, 100.3, 156.1, 158.0, 173.5; IR
(CHCl3) 3019, 2956, 2860, 1733, 1665, 1418, 1255, 1212, 1064,
862, 841, 750, 667 cm-1; HRMS m/z [M+] calcd for C17H29NO5-
Si 355.1815, found 355.1839. (3,4-trans)-1-(tert-Butyldimeth-
ylsilyloxy)-4-methyoxycarbonyl-3-(2-oxazolidinon-3-yl)cyclo-
hexene (13b): mp 116-117 °C; 1H NMR (500 MHz, CDCl3) δ
0.15 and 0.16 (each s, 3H), 0.92 (s, 9H), 1.95-2.08 (m, 3H),
2.13-2.20 (m, 1H), 2.56 (dt, J ) 4.5, 10 Hz, 1H), 3.48 (q, J )
8 Hz, 1H), 3.56 (q, J ) 8 Hz, 1H), 3.70 (s, 3H), 4.29-4.36 (m,
2H), 4.62 (t, J ) 2.2 Hz, 1H), 4.81-4.83 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ -4.5, -4.5, 17.9, 23.9, 25.5, 28.5, 40.6,
42.7, 52.1, 62.0, 102.9, 154.3, 157.8, 173.4; IR (CHCl3) 3020,
2956, 2860, 1751, 1747, 1733, 1665, 1423, 1258, 1198, 1047,
871, 841, 752, 667 cm-1; HRMS m/z [M+] calcd for C17H29NO5-
Si 355.1815, found 355.1814.
Hyd r olysis of Cycloa d d u ct 12 w ith Tr iflu or oa cetic
Acid : P r ep a r a tion of (3R*,4S*)-4-F or m yl-4-m eth yl-3-(2-
oxa zolid in on -3-yl)cycloh exa n on e (14). Neat CF3CO2H (0.5
mL) was added to cycloadduct 12 (50 mg, 0.15 mmol) at room
temperature. After 1 h, the reaction mixture was directly
purified by flash chromatography on silica gel (elution with
1:1 ethyl acetate/hexanes) to afford cyclohexanone 14, 30 mg
1
(91%), as a pale yellow solid: mp 112-116 °C; H NMR (500
MHz, CDCl3) δ 1.36 (s, 3H), 1.76 (ddd, J ) 14.5, 12.5, 5 Hz,
1H), 2.24 (ddd, J ) 14.5, 6, 4 Hz, 1H), 2.32 (dddd, J ) 16,
12.5, 6, 1 Hz, 1H), 2.46 (dddd, J ) 16, 5, 4, 2 Hz, 1H), 2.52
(ddd, J ) 15, 5, 2 Hz, 1H), 3.14 (ddd, J ) 15, 12, 1 Hz, 1H),
3.58-3.66 (m, 2H), 4.16 (ddd, J ) 12, 5, 1.5 Hz, 1H), 4.29-
4.37 (m, 2H), 9.64 (d, J ) 1.5, 1H); 13C NMR (125 MHz, CDCl3)
δ 19.9, 30.1, 37.4, 41.8, 43.1, 49.9, 56.0, 62.2, 158.7, 203.8,
206.5; IR (CHCl3) 3019, 2973, 1747, 1725, 1718, 1420, 1216,
1077, 755, 668 cm-1; HRMS m/z [M+] calcd for C11H15NO4
225.1001, found 225.1014.
LiAlH4 Red u ction -Hyd r olysis Sequ en ce of th e Cy-
cloa d d u ct 12: P r ep a r a t ion of 4-(H yd r oxym et h yl)-4-
m eth ylcycloh ex-2-en e-1-on e (15). Cycloadduct 12 (100 mg,
0.29 mmol) was dissolved in ether (10 mL) and added dropwise
to lithium aluminum hydride powder (112 mg, 3.0 mmol) at
-78 °C. The cold bath was removed, and the reaction was
allowed to warm to room temperature (4d), diluted with ether
(15 mL), and quenched by addition of a small amount of water
until hydrogen evolution ceased. Anhydrous Na2SO4 was

9066 J . Org. Chem., Vol. 65, No. 26, 2000
J aney et al.
added, and the organic layer was carefully decanted. The
remaining solid washed with ether (5 × 10 mL), and the
combined organic layers were dried over anhydrous Na2SO4
and concentrated in vacuo to afford 86 mg of the expected
alcohol, which was sufficiently pure for the next step. A
solution of the crude alcohol (86 mg) in acetonitrile (0.5 mL)
was treated with a 10% solution of HF in acetonitrile (3.8 M,
0.2 mL, 0.78 mmol, prepared from 49% aqueous HF). The
reaction mixture was stirred for 2.5 h at room temperature
and purified directly by flash chromatography on silica gel
(elution with ethyl acetate) affording 33 mg (80% from cy-
cloadduct 12) of 15 as a colorless oil. The 1H NMR spectrum
of this sample was in agreement with that reported previously
by us for this compound.11
136.5, 137.1, 155.0, 196.8; IR (CHCl3) 3020, 1778, 1770, 1665,
1638, 1602, 1407, 1218, 770, 668 cm-1; HRMS m/z [M+] calcd
for C13H13NO3 231.0895, found 231.0895.
P r ep a r a tion of (R)-4-(4-Isop r op yl-2-oxa zolid in on -3-yl)-
3-bu ten -2-on e (17b). The title compound was prepared from
1.00 g of (R)-(4-isopropyl-2-oxazolidinone (7.74 mmol) and 1.82
mL of 3-butyn-2-ol (23.2 mmol) in the same manner as
described above for vinylogous amide 17a . Purification by flash
chromatography on silica gel (elution with 1:3 ethyl acetate/
hexanes) gave 1.628 g of the product. Crystallization from ethyl
acetate (5 mL) and hexanes (10 mL) gave pure 17b in two crops
(first crop: 1.128 g, second crop: 0.284 g; total 1.412 g, 92%)
as colorless needles: mp 76.5-78 °C; [R]25 ) -75.0° (CHCl3,
D
1
c)1.00); H NMR (500 MHz, CDCl3) δ 0.86 and 0.97 (each d,
P r ep a r a tion of (R)-2-P h en ylglycin ol.19 The title com-
pound was prepared according to the reported procedure. To
a stirring solution of LiBH4 (4.67 g, 214 mmol) in THF (107
mL) was added trimethylsilyl chloride (54.4 mL, 429 mmol)
at room temperature. The resultant white suspension was
cooled to 0 °C and then treated with (R)-phenylglycine (16.2
g, 107 mmol) over 5 min. After the mixture was stirred for 1
h at 0 °C, the cold bath was removed and the mixture allowed
to stir at room temperature for 2 d. After being cooled back to
0 °C, the reaction was quenched by dropwise addition of MeOH
(80 mL) and then concentrated in vacuo. A solution of 20%
aqueous KOH (65 mL) was added the residue at 0 °C, followed
by water (40 mL) and CH2Cl2 (32 mL). The organic phase was
separated and the aqueous phase reextracted with CH2Cl2 (5
× 30 mL). The combined organic phase was dried over MgSO4
and concentrated to yield a yellow solid, which was filtered
and washed well with hexanes to give the title compound as a
pale yellow solid (13.6 g, 93%): mp 76-79 °C (lit.19 mp 76.5-
78.5 °C) for (S)-2-phenylglycinol. The product was sufficiently
pure by 1H NMR and used for the next reaction without further
purification.
J ) 7 Hz, 3H), 2.28 (s, 3H), 2.36-2.43 (m, 1H), 4.08 (dt, J )
9, 3 Hz, 1H), 4.33 (dd, J ) 9, 3 Hz, 1H), 4.37 (t, J ) 9 Hz, 1H),
5.63 (d, J ) 14.5 Hz, 1H), 7.75 (d, J ) 14.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 13.7, 17.8, 26.4, 26.6, 58.3, 63.5, 111.0,
137.4, 154.9, 197.0; IR (CHCl3) 2966, 1769, 1627, 1598, 1413,
1199 cm-1; HRMS m/z [M+] calcd for C10H15NO3 197.1052,
found 197.1054.
P r epar ation of (3a R-cis)-3,3a,8,8a-Tetr ah ydr o-3-(3-oxo-
1-bu ten yl)-2H-in d en o[1,2-d ]oxa zol-2-on e (17c). The title
compound was prepared from 1.00 g of (3aR-cis)-3,3a,8,8a-
tetrahydro-2H-indeno[1,2-d]oxazol-2-one (5.71 mmol) and 1.34
mL of 3-butyn-2-ol (17.1 mmol) in the same manner as
described above for vinylogous amide 17a . The crude product
was recrystallized from CH2Cl2 (20 mL)-ethyl acetate (5 mL)
to give 1.045 g (first crop: 0.952 g, second crop: 0.093 g) of
the pure compound as a colorless needles. The mother liquid
was purified by flash chromatography on silica gel (elution
with ethyl acetate:CH2Cl2, 1:10 to 1:2) to afford additional
0.305 g of the pure product. Total yield was 1.350 g (97%):
1
mp 204.5-206 °C; [R]25 ) -735° (CHCl3 c ) 1.04); H NMR
D
(500 MHz, CDCl3) δ 2.33 (s, 3H), 3.42 (d, J ) 3.5 Hz, 2H),
5.38 (dt, J ) 7, 3.5 Hz, 1H), 5.53 (d, J ) 7 Hz, 1H), 6.07
(d, J ) 15 Hz, 1H), 7.24 (t, J ) 7 Hz, 1H), 7.30 (d, J ) 7 Hz,
1H), 7.36 (t, J ) 7 Hz, 1H), 7.48 (d, J ) 7 Hz, 1H), 7.82 (d, J
) 15 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 26.7, 37.5, 62.6,
79.6, 111.2, 125.7, 125.9, 128.2, 130.2, 137.7, 138.1, 139.8,
154.1, 197.0; IR (CHCl3) 1763, 1625, 1261, 1196, 1035, 971,
757 cm-1; HRMS m/z [M+] calcd for C14H13NO3 243.0895, found
243.0902.
P r ep a r a tion of (R)-4-P h en yl-2-oxa zolid in on e.19 A modi-
fication of the reported procedure was used. A round-bottomed
flask fitted with a 10 cm Vigreux column, a stir bar was
charged with (R)-phenylglycinol (13.60 g, 99 mmol), diethyl
carbonate (24 mL, 198 mmol), and K2CO3 (2.10 g, 15 mmol),
and the resultant mixture heated at 130 °C for 2.5 h. The
phenylglycinol dissolved upon heating, and a white precipitate
(phenyloxazolidinone) gradually formed. EtOH was distilled
off over the course of the heating (2.5 h). After cooling, the
residue was dissolved in CH2Cl2 (200 mL), and water (100 mL)
was added. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (50 mL). The combined
organic layers were dried over MgSO4 and concentrated in
vacuo. The resultant solid was filtered and washed well
hexanes containing a small amount of ethyl acetate to afford
14.52 g (90%) of the title compound, which was sufficiently
pure by 1H NMR for use in the next reaction: mp 129-131
P r ep a r a tion of (R)-3-(ter t-Bu tyld im eth ylsiloxy)-1-(4-
p h en yl-2-oxa zolid in on -3-yl)-1,3-bu ta d ien e (18a ). A solu-
tion of vinylogous imide 17a (9.25 g, 40 mmol) in THF (280
mL) was added dropwise over 1 h to a chilled solution (dry
ice-acetone bath) of NaHMDS (1.0 M in THF, 44 mL, 44
mmol) in THF (80 mL). After 1 h at -78 °C, a solution of tert-
butyldimethylsilyl chloride (6.63 g, 44 mmol) in THF (32 mL)
was added, and the solution was allowed to warm gradually
to room temperature overnight. After removal of the volatiles
in vacuo, the resultant orange solid was dissolved in ether (100
mL), and the precipitated NaCl was removed by filtration
through Celite and washed with ether. The filtrate was
concentrated in vacuo to afford an orange solid that was
crystallized from ether (10 mL)-hexanes (40 mL) to give 10.56
g (first crop: 9.33 g, second crop: 1.23 g; total 76%) of the title
product as a pale yellow crystals: mp 77-78 °C; [R]25D ) -128°
(CHCl3, c ) 1.00); 1H NMR (500 MHz, CDCl3) δ 0.13 and 0.14
(each s, 3H), 0.95 (s, 9H), 3.98 (s, 1H), 4.10 (s, 1H), 4.13 (dd,
J ) 9, 5.5 Hz, 1H), 4.71 (t, J ) 9 Hz, 1H), 5.02 (dd, J ) 9, 5.5
Hz, 1H), 5.20 (d, J ) 14 Hz, 1H), 7.10 (d, J ) 14 Hz, 1H), 7.26
(d, J ) 7 Hz, 2H), 7.35 (t, J ) 7 Hz, 1H), 7.40 (t, J ) 7 Hz,
2H); 13C NMR (125 MHz, CDCl3) δ -4.8, -4.7, 18.2, 25.7, 58.7,
70.5, 93.5, 111.0, 124.0, 125.8, 128.8, 129.4, 137.9, 153.6, 155.5;
IR (CHCl3) 3021, 2959, 2931, 2859, 1766, 1750, 1657, 1405,
1309, 1218, 1037, 833, 762 cm-1; HRMS m/z [M+] calcd for
°C; [R]25 ) -58.4° (CHCl3, c ) 1.00) (lit.19 mp 128-130 °C,
D
[R]22 ) +58.0° (CHCl3, c ) 1.00)) for (S)-4-phenyl-2-oxazoli-
D
dinone.
P r ep a r a tion of (R)-4-(4-P h en yl-2-oxa zolid in on -3-yl)-3-
bu ten e-2-on e (17a ). A solution of CrO3 (29.3 g, 293 mmol) in
H2SO4/H2O (104 mL/522 mL) was added slowly over 40 min
to a stirring solution of 3-butyn-2-ol (20.9 mL, 267 mmol) in
H2SO4/H2O (157 mL/522 mL) at 0 °C. The mixture was stirred
at 2-10 °C for 4 h and then diluted with CH2Cl2 (725 mL).
The CH2Cl2 layer was separated, washed with saturated
NaHCO3 and water, and dried with MgSO4. The resulting
crude butynone was added to a stirring solution of (R)-4-
phenyl-2-oxazolidinone (14.52 g, 89 mmol) and N-methylmor-
pholine (19.1 mL, 174 mmol) in CH2Cl2 (580 mL). After 16 h
at room temperature, the reaction mixture was concentrated
in vacuo, and the residue purified by recrystallization (ethyl
acetate and hexanes) to give 18.10 g (88%) of the title
compound as orange crystals: mp 161-162 °C; [R]25D ) -194°
C
19H27NO3Si 345.1760, found 345.1749.
P r ep a r a tion of (R)-3-(ter t-Bu tyld im eth ylsiloxy)-1-(4-
1
(CHCl3, c ) 1.00); H NMR (500 MHz, CDCl3) δ 2.17 (s, 3H),
isop r op yl-2-oxa zolid in on -3-yl)-1,3-bu ta d ien e (18b). A so-
lution of NaHMDS (1 M in THF, 4.4 mL, 4.4 mmol) was diluted
with THF (12 mL) was cooled to -78 °C then treated dropwise
over 15 min with a solution of vinylogous imide 17b (789 mg,
4.0 mmol) in THF (10 mL). After 1 h at -78 °C, a solution of
4.24 (dd, J ) 9, 5 Hz, 1H), 4.82 (t, J ) 9 Hz, 1H), 5.08 (dd, J
) 9, 5 Hz, 1H), 5.29 (d, J ) 14.5 Hz, 1H), 7.24-7.26 (m, 2H),
7.37-7.44 (m, 3H), 7.81 (d, J ) 14.5 Hz, 1H); 13C NMR (125
MHz, CDCl3) δ 26.6, 58.1, 71.0, 112.3, 125.7, 129.3, 129.6,

Reactions of 1-(2-Oxazolidinon-3-yl)-3-siloxy-1,3-butadienes
J . Org. Chem., Vol. 65, No. 26, 2000 9067
tert-butyldimethylsilyl chloride (663 mg, 4.4 mmol) in THF (3.2
mL) was added, and the solution allowed to gradually warm
to room temperature overnight. After evaporation of the
volatiles, the resultant dark brown oil was dissolved in ether
(50 mL), and the precipitated NaCl was removed by filtration
through Celite and washed with ether. Evaporation of the
ether yielded an oil which still contained some NaCl. The
residue was redissolved in ether and filtered through Celite.
This filtration-concentration procedure was repeated two more
times and finally yielded 1.448 g of the title compound as a
brown oil. Although the product was sufficiently pure by 1H
NMR for use in subsequent steps, it still contained a small
amount of NaCl precipitate: 1H NMR (500 MHz, CDCl3) δ 0.20
and 0.21 (each s, 3H), 0.85 and 0.95 (each d, J ) 7 Hz, 3H),
0.99 (s, 9H), 2.38-2.41 (m, 1H), 4.01 (dt, J ) 8.5, 3 Hz, 1H),
4.20-4.23 (m, 3H), 4.37 (t, J ) 8.5 Hz, 1H), 5.50 (d, J ) 15
Hz, 1H), 7.05 (d, J ) 15 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ -4.7, -4.6, 13.8, 17.8, 18.2, 25.8, 26.5, 58.6, 62.9, 93.3, 109.5,
124.1, 153.9, 155.3; IR (CHCl3) 2960, 2930, 2858, 1759, 1659,
1413, 1203, 1026, 840, 781 cm-1; HRMS m/z [M+] calcd for
The structure of the major Diels-Alder cycloadduct was
1
confirmed by H and 13C NMR, IR, and HRMS spectra of the
crude reaction product. (3R,4S)-1-(tert-Butyldimethylsilyloxy)-
4-formyl-4-methyl-3-[(R)-4-phenyl-2-oxazolidinon-3-yl]cyclo-
hexene (19a ): 1H NMR (500 MHz, CDCl3) δ -0.21 (s, 3H),
-0.12 (s, 3H), 0.77 (s, 9H), 1.18 (s, 3H), 1.61-1.62 (m, 1H),
2.03-2.09 (m, 3H), 4.04 (dd, J ) 8.5, 3 Hz, 1H), 4.08 (d, J )
5.5 Hz, 1H), 4.48 (t, J ) 8.5 Hz, 1H), 4.70 (d, J ) 5.5 Hz, 1H),
4.73 (dd, J ) 8.5, 3 Hz, 1H), 7.17-7.39 (m, 5H), 9.76 (s, 1H);
13C NMR (125 MHz, CDCl3) δ -5.1, -4.5, 17.7, 18.8, 25.1, 25.4,
25.6, 49.9, 54.4, 59.2, 70.8, 99.9, 126.2, 128.4, 129.0, 141.4,
153.2, 158.5, 204.8; IR (CHCl3) 3019, 2973, 2932, 1737, 1380,
1214, 1068, 757, 669 cm-1; HRMS m/z [M+] calcd for C23H33
-
NO4Si 415.2179, found 415.2192.
P r ep a r a tion of (S)-4-(Hyd r oxym eth yl)-4-m eth ylcyclo-
h ex-2-en -1-on e (20). The Diels-Alder reaction was conducted
as described in the typical procedure with diene 18b (181 mg,
estimated to be 86% pure, 0.5 mmol) and methacrolein (207
µL, 2.5 mmol) in toluene (0.5 mL) at 35 °C for 4 d. Subsequent
reductive hydrolysis afforded the title compound (38 mg, 54%
1
C
16H29NO3Si 311.1917, found 311.1909.
overall yield). The H NMR spectrum of the final product was
P r ep a r a t ion of (3a R-cis)-3-[3-(ter t-Bu t yld im et h ylsi-
in agreement with that reported previously by us;11 the
enantiomeric excess was determined to be 79% via Mosher
ester analysis.20
loxy)-1,3-bu ta dien yl]-3,3a ,8,8a -tetr a h yd r o-2H-in d en o[1,2-
d ]oxa zol-2-on e (18c). A solution of NaHMDS in THF (1.0 M,
4.4 mL, 4.4 mmol) was diluted with THF (8 mL) and cooled to
-78 °C. A solution of vinylogous amide 17c (973 mg, 4.0 mmol)
in THF (100 mL) was then added dropwise over 1.5 h. After 1
h at -78 °C, a solution of tert-butyldimethylsilyl chloride (663
mg, 4.4 mmol) in THF (3.2 mL) was added. The reaction
mixture was allowed to warm to room-temperature overnight
and then concentrated in vacuo. The resultant dark brown oil
was dissolved in ether (50 mL), and the precipitated NaCl was
removed by filtration through Celite and washed with ether.
The filtrate was concentrated in vacuo to give a dark brown
oil. 1H NMR showed that the crude product consisted primarily
of the starting ketone and the desired diene (ketone:diene)ca.
1:2). Purification by flash chromatography on silica gel (elution
with 1:10 ethyl acetate:hexanes containing 4% Et3N) afforded
873 mg (61%) of impure diene. A second chromatographic
purification gave 432 mg (30%) of the diene as an orange oil.
Although some impurities were still present, this diene was
used for the Diels-Alder reaction: 1H NMR (500 MHz, CDCl3)
δ 0.23 (s, 6H), 1.00 (s, 9H), 3.40 (d, J ) 3.5 Hz, 2H), 4.29 and
4.31 (each s, 1H), 5.31 (dt, J ) 7, 3.5 Hz, 1H), 5.48 (d, J ) 7
Hz, 1H), 5.93 (d, J ) 15 Hz, 1H), 7.16 (d, J ) 15 Hz, 1H),
7.24-7.39 (m, 3H), 7.54 (d, J ) 7 Hz, 1H); HRMS m/z [M+]
calcd for C20H27NO3Si 357.1760, found 357.1761.
P r ep a r a tion of (S)-4-(Hyd r oxym eth yl)-4-m eth ylcyclo-
h ex-2-en -1-on e (20). The Diels-Alder reaction was conducted
as described in the typical procedure using diene 18c (89 mg,
0.25 mmol) and methacrolein (104 µL, 1.25 mmol) in toluene
(0.25 mL) at 35 °C for 4 d. Subsequent reductive hydrolysis
afforded the title compound (17 mg, 49% overall yield). The
1H NMR spectrum of the product was in agreement with that
reported previously by us;11 the enantiomeric excess was
1
determined to be 96% by H NMR analysis of the correspond-
ing Mosher ester.20
P r ep a r a tion of (S)-4-(Hyd r oxym eth yl)-4-eth ylcyclo-
h ex-2-en -1-on e (21). The Diels-Alder reaction was conducted
as described in the typical procedure using the diene 18a (173
mg, 0.5 mmol) and ethacrolein (245 µL, 2.5 mmol) in toluene
(0.5 mL) at 35 °C for 4 d. Subsequent reductive hydrolysis
afforded the title product (50 mg, 65% overall yield). The 1H
NMR spectrum of the product was in agreement with that
reported previously by us,11 and the enantiomeric excess was
determined to be 92%.20
P r ep a r a tion of (S)-4-(Hyd r oxym eth yl)cycloh ex-2-en -
1-on e (22). The Diels-Alder reaction was conducted as
described in the typical procedure using the diene 18a (346
mg, 1 mmol) and methyl acrylate (459 µL, 5 mmol) in toluene
(1 mL) at 60 °C for 4 d. Subsequent reductive hydrolysis
afforded the title product (40 mg, 63% overall yield). The 1H
NMR spectrum of the product was in agreement with that
reported previously by us,11 and the enantiomeric excess was
determined to be 55%.20
P r ep a r a tion of (4S-tr a n s)-4,5-Bis(h yd r oxym eth yl)cy-
cloh ex-2-en -1-on e (23). The Diels-Alder reaction was con-
ducted as described in the typical procedure using the diene
18a (173 mg, 0.5 mmol) and diethyl fumarate (409 µL, 2.5
mmol) in toluene (0.5 mL) at 50 °C for 3 d. Subsequent
reductive hydrolysis followed by purification was performed
by flash chromatography on silica gel twice (first elution with
ethyl acetate, then 20:1 ether:MeOH) gave the title product
(19 mg, 24% overall yield). The 1H NMR spectrum of the
product was in agreement with that reported previously by
us,11 and the enantiomeric excess was determined to be 22%.20
P r ep a r a tion of (4R-cis)-4,5-Bis(h yd r oxym eth yl)cyclo-
h ex-2-en -1-on e (24). The Diels-Alder reaction was carried
out using the typical procedure with the following modifica-
tions. To a solution of diene 18a (173 mg, 0.5 mmol) in toluene
(0.5 mL) was added a solution of maleic anhydride (49 mg,
0.5 mmol) in toluene (1.5 mL) at -45 °C (acetonitrile-CO2).
The reaction mixture was stirred for 11 h at -45 °C to room
temperature. Subsequent reductive hydrolysis followed by
purification was performed by flash chromatography on silica
gel twice (first elution with ethyl acetate, then 20:1 ether:
MeOH) gave the title product (25 mg, 32% overall yield). The
1H NMR spectrum of the product was in agreement with that
Typ ica l P r oced u r e for th e Asym m etr ic Diels-Ald er
Reaction , Followed by Redu ction an d Hydr olysis: P r epa-
r a tion of (S)-4-(Hyd r oxym eth yl)-4-m eth ylcycloh ex-2-en -
1-on e (20). To a solution of diene 18a (173 mg, 0.5 mmol) in
toluene (0.5 mL) was added methacrolein (207 µL, 2.5 mmol),
and the resulting solution was heated to 35 °C for 4 d. Excess
methacrolein and toluene were removed in vacuo using a
Kugelrohr bulb-to-bulb distillation apparatus. The resultant
solid was dissolved in THF (2-4 mL) and added to a suspen-
sion of lithium aluminum hydride (76 mg, 2.0 mmol) in THF
(2 mL, 4 mL in the case of ether) at 0 °C. After 30 min, the
cold bath was removed and the solution was allowed to warm
to room temperature over 5 h at room temperature. The
solution was cooled to 0 °C, diluted with ether (5-10 mL),
quenched by addition of a small amount of water until
hydrogen evolution ceased, and stirred vigorously for 1 h.
Anhydrous Na2SO4 was added, and the solids were removed
by filtration through Celite, and washed well with ether
followed by ethyl acetate or CH2Cl2. The filtrate was concen-
trated in vacuo and the residue dissolved in acetonitrile (2 mL)
and treated with 49% aqueous HF (0.26 mL). The reaction
mixture was stirred for 3h at room temperature then purified
directly by flash chromatography on silica gel (elution with
1:1 ethyl acetate/hexanes) to afford 20 as a colorless oil (47
1
mg, 67% overall yield from diene 18a ). The H NMR spectrum
of this sample was in agreement with that reported previously
by us.11 The enantiomeric excess was determined via Mosher
ester to be 91%.20

9068 J . Org. Chem., Vol. 65, No. 26, 2000
J aney et al.
reported previously by us,11 and the enantiomeric excess was
determined to be >98%.20
J ) 10, 1.5 Hz, 1H), 6.52 (d, J ) 8 Hz, 2H), 6.70 (t, J ) 7 Hz,
1H), 6.76 (dd, J ) 10, 3 Hz, 1H), 7.23 (t, J ) 8 Hz, 2H); 13C
NMR (125 MHz, CDCl3) δ 36.7, 37.9, 38.4, 51.4, 53.0, 111.5,
116.2, 129.2, 130.0, 147.1, 150.1, 197.5; IR (CHCl3) 3020, 1675,
The structure of the major Diels-Alder cycloadduct was
1
confirmed by H and 13C NMR, IR, and HRMS spectra of the
crude product. (3aS,4R,7aS)-6-(tert-Butyldimethylsilyloxy)-
3a,4,7,7a-tetrahydro-4-[(R)-4-phenyl-2-oxazolidinon-3-yl)-1,3-
isobenzofurandinone: 1H NMR (500 MHz, CDCl3) δ -0.21 (s,
3H), -0.12 (s, 3H), 0.79 (s, 9H), 2.38 (dd, J ) 16, 8 Hz, 1H),
2.68 (dd, J ) 16, 3 Hz, 1H), 3.43-3.47 (m, 1H), 3.81-3.85 (m,
1H), 4.10 (dd, J ) 8, 4 Hz, 1H), 4.61 (m, 2H), 4.77 (t, J ) 8
Hz, 1H), 4.88 (dd, J ) 8, 4 Hz, 1H), 7.28 (d, J ) 7 Hz, 2H),
7.35 (t, J ) 7 Hz, 1H), 7.41 (t, J ) 7 Hz, 2H); 13C NMR (125
MHz, CDCl3) δ -5.2, 17.8, 25.3, 29.0, 39.1, 41.9, 49.5, 59.3,
71.4, 97.9, 125.9, 128.9, 129.6, 140.2, 153.1, 158.4, 171.2, 173.0;
IR (CHCl3) 2929, 1772, 1756, 1648, 1416, 1222, 953, 783, 687
cm-1; HRMS m/z [M+] calcd for C23H29NO6Si 443.1764, found
443.1763.
1599, 1507, 1482, 1367, 1215, 760, 668 cm-1
.
The enantiomeric excess was determined as follows:
A
solution of the enone 25 (8.5 mg, 0.04 mmol) in CH2Cl2 (0.5
mL) at -78 °C was treated with a 1.0 M solution of diisobu-
tylaluminum hydride in CH2Cl2 (0.12 mL, 0.12 mmol). After
1.5 h, the reaction was quenched by addition of a small amount
of water, and the mixture was allowed to warm to room
temperature. The inorganic precipitate was removed by filtra-
tion through Celite and washed well with CH2Cl2 (ca. 30 mL).
The filtrate was concentrated in vacuo to give an allylic alcohol
in 8.4 mg (98%) yield as a 3:1 mixture of diastereomers. 1H
NMR analysis of the corresponding Mosher ester prepared in
situ showed no detectable change in this diasteromeric ratio,
which corresponds to >98% ee.20
P r ep a r a t ion of (3a R-cis)-2,3,3a ,4,5,7a -H exa h yd r o-5-
oxo-2-p h en yl-1H-isoin d ole (25). To a solution of diene 18a
(173 mg, 0.5 mmol) in toluene (0.5 mL) was added a solution
of N-phenylmaleimide (87 mg, 0.5 mmol) in toluene (0.75 mL)
at -45 °C (acetonitrile-CO2). The reaction mixture was
allowed to warm to room temperature over 24 h. Toluene was
removed in vacuo, and the resultant light orange oil was dis-
solved in ether (4 mL) and added to a suspension of lithium
aluminum hydride (152 mg, 4.0 mmol) in ether (2 mL) at 0
°C. The mixture was stirred for 30 min at 0 °C and then
warmed to 35-40 °C for 1 d. The reaction mixture was cooled
to 0 °C, diluted with ether (ca. 10 mL), quenched by addition
of a small amount of water (until hydrogen evolution ceased),
and stirred for 1 h. Anhydrous Na2SO4 was added. The solids
were removed by filtration through a small amount of Celite
and washed well with ether followed by ethyl acetate. The fil-
trate was concentrated in vacuo, and the residual oil was dis-
solved in acetonitrile (2 mL) and then treated with 49% aque-
ous HF (0.26 mL). After being stirred for 2 h at room temper-
ature, the solution was neutralized with saturated aqueous
NaHCO3 (30 mL) and extracted with CH2Cl2 (3 × 25 mL). The
extracts were washed with brine, dried over MgSO4, and con-
centrated in vacuo. The residue was purified by flash chrom-
atography on silica gel (elution with 1:9 ethyl acetate/hexanes)
to afford the title compound (25) as a pale yellow solid (55 mg,
The structure of the major Diels-Alder cycloadduct was
1
confirmed by H and 13C NMR, IR and HRMS spectra of the
crude product. (3aS,4R,7aS)-6-(tert-Butyldimethylsilyloxy)-
3a,4,7,7a-tetrahydro-2-phenyl-4-[(R)-4-phenyl-2-oxazolidinon-
3-yl)]-1H-isoindole-1,3-(2H)-dione: 1H NMR (500 MHz, CDCl3)
δ -0.22 (s, 3H), -0.14 (s, 3H), 0.79 (s, 9H), 2.42 (dd, J ) 16,
8 Hz, 1H), 2.73 (dd, J ) 16, 2 Hz, 1H), 3.27-3.31 (m, 1H),
3.27 (dd, J ) 9, 7 Hz, 1H), 4.06 (dd, J ) 8, 4 Hz, 1H), 4.63 (m,
1H), 4.66-4.67 (m, 1H), 4.77 (t, J ) 8 Hz, 1H), 4.96 (dd, J )
9, 4 Hz, 1H), 7.25-7.27 (m, 2H), 7.30-7.35 (m, 3H), 7.39-
7.42 (m, 3H), 7.47-7.50 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ -5.2, -5.1, 17.8, 25.3, 29.4, 38.4, 41.5, 50.1, 59.5, 71.3, 98.3,
125.9, 126.4, 128.6, 128.7, 129.2, 129.4, 131.8, 140.8, 152.4,
158.4, 176.4, 177.8; IR (CHCl3) 2969, 2798, 1758, 1713, 1468,
1382, 1293, 1204, 1071, 999, 737 cm-1; HRMS m/z [M+] calcd
for C29H34N2O5Si 518.2236, found 518.2264.
Ack n ow led gm en t. This work was supported by the
National Institutes of Health (R01-GM-55998). We
thank Pfizer Inc. for an undergraduate summer re-
search fellowship to J .M.J .
Su p p or tin g In for m a tion Ava ila ble: Kinetics data for
diene 10 and 1H NMR and 13C NMR of all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
51% overall yield from diene 18a ): mp 161-167 °C; [R]25
)
D
1
-160° (CHCl3, c ) 1.01); H NMR (500 MHz, CDCl3) δ 2.57
(dd, J ) 17, 5.5 Hz, 1H), 2.67 (dd, J ) 17, 5.5 Hz, 1H), 2.96-
3.03 (m, 1H), 3.14-3.17 (m, 2H), 3.40 (dd, J ) 9.5, 4 Hz, 1H),
3.47 (t, J ) 8.5 Hz, 1H), 3.64 (dd, J ) 9, 7 Hz, 1H), 6.06 (dd,
J O005619Y