Application of the silicon-tether strategy for controlling the regioselectivity and diastereoselectivity of intramolecular nitrone cycloadditions for aminopolyol synthesis

Article abstract of DOI:10.1021/ja000248o

Highly regioselective and diastereoselective intramolecular chiral nitrone cycloaddition reactions with a vinyl group tethered by a silicon atom have been developed as a general method for the synthesis of stereodefined amino polyols. This strategy featur

Full text of DOI:10.1021/ja000248o

J. Am. Chem. Soc. 2000, 122, 7633-7637
7633
Application of the Silicon-Tether Strategy for Controlling the
Regioselectivity and Diastereoselectivity of Intramolecular Nitrone
Cycloadditions for Aminopolyol Synthesis
Teruhiko Ishikawa,* Takayuki Kudo, Kazunori Shigemori, and Seiki Saito*
Contribution from the Department of Bioscience and Biotechnology, Faculty of Engineering,
Okayama UniVersity, Tsushima, Okayama, Japan 700-8530
ReceiVed January 24, 2000. ReVised Manuscript ReceiVed May 8, 2000
Abstract: Highly regioselective and diastereoselective intramolecular chiral nitrone cycloaddition reactions
with a vinyl group tethered by a silicon atom have been developed as a general method for the synthesis of
stereodefined amino polyols. This strategy features a series of one-pot reactions involving (1) DIBAH reduction
of the carbonyl groups of chiral R- or â-hydroxy carbonyl compounds, in which the hydroxy group is protected
as diphenylvinylsilyl ethers, at -78 °C to give an aldehyde, (2) condensation of the aldehyde with
N-benzylhydroxylamine to furnish nitrone (-78 °C f rt), and (3) intramolecular [3 + 2] dipolar cycloaddition
reaction between the nitrone and the silicon-tethered vinyl group (rt f 70 °C, 3-15 h) to give isoxazolidine
derivatives as direct precursors for amino polyols. Since the cycloaddition reaction is concerted in nature and
passes through a fused-bicyclic transition state, the substituents, the nitrone substrate, and the silicon atom
bias the stereochemical course of this addition, resulting in highly diastereoselective and synthetically useful
transformations.
Introduction
asymmetric aminohydroxylation8 has appeared as a method for
introducing the 1,2-amino alcohol functionality directly to
carbon-carbon double bonds. Although these reactions are quite
effective, the complete carbon chains required for the target
amino sugars must be prepared either before or after the
reactions. Thus, other versatile concepts that satisfy simultaneous
introduction of both the carbon chain and the amino alcohol
functionality are desirable. We have succeeded in realizing such
objectives by means of the silicon-tether strategy for controlling
the regioselectivity and diastereoselectivity of intramolecular
nitrone cycloadditions.9 New oxygen- and nitrogen-bearing
stereogenic centers are introduced in a 1,2-fashion following
the nitrone cycloaddition step by application of the Tamao
oxidation.10
The outline of our concept is shown in Scheme 1. This plan
features a series of reactions involving (1) DIBAH reduction
of the carbonyl function of 2, itself prepared by silylation of
the hydroxy group of chiral hydroxy carbonyl compounds (1),
to an aldehyde group at -78 °C, (2) condensation of the
aldehyde with N-benzylhydroxylamine to give nitrone 3
(-78 °C f rt), and (3) intramolecular [3 + 2] dipolar
cycloaddition reaction between the nitrone (3) and the vinyl
group on the silicon atom to furnish isoxazolidine derivatives
(4) (rt f 70 °C, 3-15 h). Ten chiral compounds (1a-j) were
used as substrates for this series of reactions. On the basis of
Polyhydroxylated alkaloids and amino sugars are important
classes of compounds which are ubiquitous in nature and play
an important role in biological functions such as recognition,
transport, adhesion, etc. in the form of glycoproteins, oligosac-
charides, or glycolipids.1 Other compounds of biological interest
sometimes contain amino polyol functions or amino sugars
attached to aglycons as illustrated by HIV protease inhibitors
and macrolide and anthracycline antibiotics.2 The search for
effective mimetics or large-scale production of these glycocon-
jugates by organic or chemical-enzymatic synthesis requires an
efficient and practical synthetic route to stereodefined amino
sugars. In the early 1980s, specific amino sugars were targeted,
and diastereoselective inter- or intramolecular nitrone-olefin
cycloaddition reactions,3 Henry reactions,4 or intramolecular
amino Michael addition reactions5 have been employed as key
steps in their total synthesis. However, these methods are not
always highly stereoselective for a broad range of substrates.
Asymmetric epoxidation6 and dihydroxylation7 followed by
the appropriate nucleophilic carbon-nitrogen bond formation
has became one of the more widely applied strategies for
enantiocontrolled synthesis of amino alcohols. More recently,
(1) (a) Springer, T. A. Nature 1990, 346, 425-434. (b) Sharon, N.; Lis,
H. Science 1989, 246, 227-234.
(2) See, for example: Masamune, S.; Bates, G. S.; Corcoran, J. W.
Angew. Chem., Int. Ed. Engl. 1977, 16, 585-607.
(3) (a) Wovkulich, P. M.; Uskokovi′c, M. R. J. Am. Chem. Soc. 1981,
103, 3956-3958. (b) DeShong, P.; Leginus, J. M. J. Am. Chem. Soc. 1983,
105, 1686-1688. See also: DeShong, P.; Dicken, C. M.; Leginus, J. M.;
Whittle, R. R. J. Am. Chem. Soc. 1984, 106, 5598-5602.
(4) Hanessian, S.; Kloss, J. Tetrahedron Lett. 1985, 26, 1261-1264. See
also: Rosini, G. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 2, pp 321-340. Shibasaki,
M.; Gro¨ger, H. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. III, pp 1075-
1090.
(6) For reviews, see: (a) Finn, M. G.; Sharpless, K. B. In Asymmetric
Synthesis; Morrison, J. D., Ed.; Academic: Orlando, 1985; Vol. 5, pp 247-
308. (b) Rossiter, R. E. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic: Orlando, 1985; Vol. 5, pp 193-246.
(7) For reviews, see: (a) Johnson, R. A.; Sharpless, K. B. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993; pp 227-
272. (b) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483-2547.
(8) (a) Goossen, L. J.; Liu, H.; Dress, K. R.; Sharpless, K. B. Angew.
Chem. Int. Ed. 1999, 38, 1080-1083 and references therein. Acetamido-
glycosylation with glycal donors also has gained entry to this category,
see: Bussolo, V. D.; Liu, J.; Huffman, L. G., Jr.; Gin, D. Y. Angew. Chem.,
Int. Ed. 2000, 39, 204-207.
(5) Hirama, M.; Shigemoto, T.; Tamazaki, Y.; Ito, S. J. Am. Chem. Soc.
1985, 107, 1797-1798.
10.1021/ja000248o CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/29/2000

7634 J. Am. Chem. Soc., Vol. 122, No. 32, 2000
Ishikawa et al.
Chart 1. Structural Types (A-F) of Chiral Hydroxy
Scheme 1
Carbonyl Compounds (1): These Were Synthesized Using
Standard Methods, As Outlined in the Supporting
Information, or Are Commercially Available in the Cases of
1b and 1e
(1) the concerted nature of nitrone-olefin [3 + 2] cycloaddi-
tion,11 (2) the fused bicyclic architecture of the transition states,
(3) the geometrical homogeneity (Z) of the nitrone CdN
bond,3b,12 and (4) the steric influence exerted by the phenyl
groups on the silicon atom and the substituents on the carbon
chain of 3, it was expected that a highly diastereoselective
transformation should result. If so established, the stereodefined
isoxazolidines 4 would serve as precursors for variety of chiral
amino polyols (6) via oxidation of the Si-C bond10 and
reductive cleavage of the N-O bond.13
Results and Discussion
available methyl (2S)-2,3-O-isopropylidene-2,3-dihydroxypro-
panoate was converted to methyl (2S)-2-O-benzyl-2,3-dihydroxy-
propanoate (C-type: 1d) via a series of routine reactions
involving acetonide deprotection, selective primary hydroxy
protection (TBDMS), secondary hydroxy protection (benzyl),
and final deprotection of the TBDMS group. Evans asymmetric
aldol protocol16 was employed for the synthesis of syn-aldols
(E-type: 1h,i). Esterification of (R)-mandelic acid and TBDMS-
protection of (R)-pantolactone led to 1c (B-type) and 1j (F-
type), respectively. The remaining chiral hydroxy compounds
1b (B-type) and 1e (C-type) are commercially available and
were used as received.
Cycloaddition Reactions and Absolute Structure Deter-
mination. Hydroxy carbonyl compounds 1a-i were converted
to the corresponding R- or â-O-diphenylvinylsilyl derivatives
(2a-i) using a standard method [Ph2(CH2dCH)Si-Cl/imidazole/
THF/rt, 1 h]. A typical one-pot procedure for the intramolecular
nitrone cycloaddition reaction is as follows. To a solution of
2a-i in toluene was added DIBAH (toluene solution, 1.0 equiv)
at -78 °C. The reaction mixture was stirred at -78 °C for
30 min followed by the addition of BnNHOH (1.5-3.0 equiv).
Without isolating nitrone intermediates (3), the resulting mixture
was warmed to room temperature and stirred at that temperature
in the case of B-type substrates leading to the cycloadducts
of a bicyclo[3.3.0] backbone (4b,c) or at elevated temperature
(70 °C) in the case of A- and C-E-type substrates leading to
the cycloadducts of a bicyclo[4.3.0] framework (4a,d-i).
Purification or diastereomer separation for these cycloadducts
was conducted by means of silica gel column chromatography.
Chiral r- or â-Hydroxy Carbonyl Compounds. Six classes
(A-F) of chiral R- or â-hydroxy carbonyl compounds were
used in this work as shown in Chart 1. The conversion of
(S)-malic acid to ethyl (3S)-3-O-tert-butyldimethylsilyl-3,4-
dihydroxybutanate (A-type: 1a) was reported from our labora-
tory.14 This â-hydroxy ester (1a) and commercially available
ethyl (3R)-3-hydroxybutanoate were employed as precursors to
2,3-anti-disubstituted esters 1f and 1g (D-type), respectively,
which were prepared using Fra´ter’s procedure.15 Commercially
(9) To the best of our knowledge, this is the first example of generalized
silicon-tether strategy for an intramolecular nitrone-olefin cycloaddition
reaction. For only one fragmentary example of the reaction of this class,
see: (a) Rong, J.; Roselt, P.; Plavec, J.; Chattopadhyaya, J. Tetrahedron
1994, 50, 4921-4936. For intermolecular nitrone-vinylsilane cycloaddition
reactions, see: (b) Padwa, A.; MacDonald, J. G. J. Org. Chem. 1983, 48,
3189-3195. (c) DeShong, P.; Leginus, J. M. J. Org. Chem. 1984, 49, 3421-
3423. (d) DeShong, P.; Leginus, J. M.; Lander, S. W., Jr. J. Org. Chem.
1986, 51, 574-576. For the silicon-tether strategy for intramolecular [3 +
2] cycloaddition reactions other than nitrones, see: (e) Righi, P.; Marotta,
E.; Landuzzi, A.; Rosini, G. J. Am. Chem. Soc. 1996, 118, 9446-9447. (f)
Denmark, S. E.; Hurd, A. R.; Sacha, H. J. J. Org. Chem. 1997, 62, 1668-
1674. (g) Garner, P.; Cox, P. B.; Anderson, J. T.; Protasiewicz, J.; Zaniewski,
R. J. Org. Chem. 1997, 62, 493-498. (h) Young, D. G. J.; G.-Bengoa, E.;
Hoveyda, A. H. J. Org. Chem. 1999, 64, 692-693. (i) Marrugo, H.;
Dogbe´avou, R.; Breau, L. Tetrahedron Lett. 1999, 40, 8979-8983.
(10) For reviews, see: (a) Tamao, K. In AdVances in Silicon Chemistry;
Larson, G. L., Ed.; Vol. 3, Jai Press: 1996; pp 1-62. (b) Fleming, I.
Chemtracts, Org. Chem. 1996, 9, 1-64. (c) Jones, G. R.; Landais, Y.
Tetrahedron 1996, 52, 7599-7662. See also: (d) Tamao, K.; Ishida, N.;
Tanaka, T.; Kumada, M. Organometallics 1983, 2, 1694-1696.
(11) Saito, S.; Ishikawa, T.; Moriwake, T. J. Org. Chem. 1994, 59, 4375-
4377 and references therein.
(12) Saito, S.; Ishikawa, T.; Kishimoto, N.; Kohara, T.; Moriwake, T.
Synlett 1994, 282-284.
(14) Saito, S.; Ishikawa, T.; Kuroda, A.; Koga, K.; Moriwake, T.
Tetrahedron 1992, 48, 4067-4086. See also: Saito, S.; Hasegawa, T.; Inaba,
M.; Nishida, R.; Fujii, T.; Nomizu, S.; Moriwake, T. Chem. Lett. 1984,
1389-1392.
(15) Fra´ter, G. HelV. Chim. Acta 1979, 62, 2825-2828.
(16) Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982,
104, 1737-1739.
(13) It is well-known that an N-O bond of isoxazolidine can easily be
cleaved, see: Dondoni, A.; Mercha´n, F. L.; Merino, P.; Tejero, T. Synth.
Commun. 1994, 24, 2551-2555. The combination of Pearlman’s catalyst
and hydrogen is also known to work well in this transformation. For
simultaneous introduction of a Boc group into a nitrogen atom under such
conditions, see ref 23.

Si-Tether Strategy for Nitrone Cycloadditions
J. Am. Chem. Soc., Vol. 122, No. 32, 2000 7635
Scheme 2
Chart 2. Absolute Configuration of the Major Cycloadducts
(4): Yield, % (% de), and Typical JH-H Values
3
3
Careful NMR analysis involving JH-H values and NOESY
or NOEDIF data for predominant (4a,d,e,h,i) or exclusive (4f,g)
cycloadducts made the unambiguous determination of their
absolute structures possible. Two- or one-dimensional NOE data
clearly indicated that they are cis-fused. The spin-coupling
constants between hydrogens on fused carbons (J1,5) were
observed in the range of 6.1-8.8 Hz for these cycloadducts,
which are reasonably compatible with the conclusion based on
the NOE data. The typical cis-J1,5 value seems to be 6.1 Hz as
observed for 4a in this bicyclo[4.3.0] system. The largest J1,5
value (8.8 Hz) observed for 4h can be explained by assuming
that 4h adopts a twist chair conformation in order to relieve
1,3-type nonbonded repulsion between the C(9)-axial methyl
group and the C(4)-C(5) σ-bond, for which the dihedral angle
[ H(1)-C(1)-C(5)-H(5)] become nearly zero.
Although 4b,c were difficult to purify because of the inclusion
of a vinylsilane-derived contaminants even after column chro-
matography, the cis-fused structures for the major products were
assured on the basis of careful NMR analysis involving NOE
3
and JH-H measurements. Under such a situation, however,
diastereoselectivity was difficult to determine. This analysis was
performed at the stage of derivatives 5b,c obtained through
Tamao oxidation10 and subsequent acetylation (Scheme 2): both
1H and 13C NMR spectra indicated that they are exclusive
products. These results are summarized in Chart 2 [chemical
yields (% de)] together with some critical NMR data.
The Origin of Diastereoselectivity. On the basis of the
stereostructures of the cycloadducts in Chart 2, we considered
the transition state structures illustrated as ALsEL in Chart 3
to be reasonable, together with the corresponding disfavored
higher energy transition states AH1, AH2, and BH-EH.
First of all, the important role of the phenyl groups on the
silicon atom should be mentioned: AH1 is presented to draw
attention to the fact that transition states of this class must be
the highest energy ones because of severe 1,3-diaxial type
interaction between one of the phenyl groups on the silicon atom
and the nitrone group. Hence AH1 should be ruled out. Indeed,
the absolute structures of minor diastereomers never have their
origin in AH1-type transition states. Therefore, although not
indicated in Chart 3, similar transition states with respect to
type C-E should be also ruled out.
Model considerations indicate that bicyclo[3.3.0] or -[4.3.0]
transition states leading to trans-fused cycloadducts would not
be feasible because the interatomic distance between the oxygen
atom of the nitrone and the carbon atom of the dipolarophile is
improbably long. Those transition states (AH2-EH) leading to
alternative cis-fused cycloadducts would suffer from steric
constraints involving the axial “Z” substituents, while AL-EL
would be free from such disadvantages: transition state BL
leading to 4b or 4c minimizes the torsional strain between the
Z substituent and the nitrone moiety; CL avoids not only an
A(1,3)-type destabilizing interaction between the nitrone moiety
and the Z group but also is free from 1,3-diaxial-type destabiliz-
ing interactions between the Z group and the vinyl group on
the silicon atom (CH).
The moderate diastereomeric excess (60% de) observed in
the case of 2a may be a consequence of the rather longer O-Si
bond length17 by which the 1,3-diaxial interaction between the
Z group (TBSOCH2 in this case) and the axial phenyl group on
the silicon atom at the transition state (AH2) may become weak
in comparision to that for the normal carbocyclic structure. Thus,
the proportion of the route to a minor cis-fused isomer via AH2
becomes significant.
The anti-aldols 1f and 1g can afford exclusive cycloadducts
4f and 4g, respectively, because both substituents Z1 and Z2
are equatorially arranged in the lowest energy bicyclic transition
state (DL); there seems to be no chance of the 1,2-diaxial
transition state DH being utilized. On the other hand, syn-aldols
(17) Typical bond length of Si-O ) 1.633 ( 0.005 Å. See: Gordon,
A. J.; Ford, R. A. The Chemist Companion; Wiley: New York, 1972; pp
107-108.

7636 J. Am. Chem. Soc., Vol. 122, No. 32, 2000
Chart 3. Transition State Structures
Ishikawa et al.
Scheme 3
1h and 1i led only to cis-fused cycloadducts but with different
diastereofacial senses (4h and 4i). As a consequence of the A
value difference between a phenyl and methyl (2.80-1.74 )
1.06 kcal/mol),18 1h preferred EL to EH (Z1 ) Ph, Z2 ) Me)
with a diastereomeric excess of 71%. Particularly interesting is
the case of 1i where a diastereomeric excess as high as 96%
was observed: 1i preferred EH to EL (Z1 ) CH3CHdCH-, Z2
) Me). Such a high % de is surprising because the A value
difference between methyl and 1-propenyl is estimated to be
small.19 At the corresponding transition state (EH) leading to 4i
the propenyl group apparently prefers an axial (Z1 in EH)
disposition judging from the stereochemistry of 4i.20
the formation of 4-(trimethylsilyl)-substituted isoxazolidines (4),
which are the direct precursors of the targeted 1,2-amino alcohol
functionality.21 Aside from the regiochemical problem, the
intermolecular reactions (eq 2) also exhibited an unacceptable
level of stereochemical control. Careful NMR analysis of 8
indicated that it consists of four diastereoisomers in a 3:3:1:1
ratio.22 Thus, the intramolecular cycloaddition reaction of chiral
nitrones with unsubstituted vinylsilane via the silicon-tether
strategy is required to achieve concurrent access to the 1,2-
amino alcohol functionality following Tamao oxidation.10
Application and Prospect for Amino Sugar Synthesis.
Chiral γ-lactone 1j can be used as a substrate for the present
protocol. In this case the introduction of the diphenylvinylsilyl
ether followed DIBAH reduction and nitrone formation. From
this nitrone (2j), trans-fused cycloadduct (4j-trans) was exclu-
sively formed in 80% yield. No nuclear Overhauser effect
between the two hydrogens on the fused carbons was observed
at all. The NMR signal of hydrogen at C(1) appeared at 3.43
ppm as a triplet with a J1,5 value of 8.9 Hz which strongly
suggests that three contiguous protons attached to C(10), C(1),
and C(5) are trans to each other. These results clearly indicated
that the cycloadduct should be a trans-fused bicyclo[5.3.0]
Regiochemical Aspect of Silicon-Tether Strategy. Inter-
molecular cycloaddition reactions between nitrones and unsub-
stituted vinylsilanes such as trimethylvinylsilane were reported
by DeShong.9c In this case the cycloaddition proceeded with
completely reversed regiochemical sense in comparison to that
of the intramolecular examples reported here to give 5-(tri-
methylsilyl)-substituted isoxazolidine (eq 1, Scheme 2). This
regioselectivity appears to be general for the intermolecular
reactions. Indeed, when unsubstituted trimethylvinylsilane was
reacted with chiral nitrone (7), 5-(trimethylsilyl)-substituted
isoxazolidine (8) was obtained (72%) as shown in eq 2. Thus,
only the present intramolecular silicon-tether strategy can realize
(18) Eliel, E. L.; Wilen, S. H.; Mander L. N. Stereochemistry of Organic
Compounds; Wiley: New York, 1994; pp 695-698.
(19) A value for -CHdCHCH3 is not available from the exhaustive
listing in ref 18. However, we can roughly estimate that the
A
value difference (∆∆G°) between Me (A value ) 1.74 kcal/mol) and
-CHdCHCH3 may be small. The A value for the CH2dCH- group
is 1.68 kcal/mol.
(20) At present we have no other plausible idea than an attractive CH/π
interaction to explain why 1-propenyl and phenyl groups arrange cis in a
1,3-diaxial fashion in transition state EH: see Nishio, M.; Hirota, M.;
Umezawa, Y. The CH/π Interaction: EVidence, Nature, and Consequences;
Wiley-VCH: New York, 1998.
(21) Cycloadducts with the regiochemistry of 4 may be obtained in
the intermolecular cycloaddition if substituted vinylsilanes such as â-tri-
methylsilylstyrene is used as a dipolarophile: see ref 9d.
(22) This ratio was conveniently determined by the signal intensity of
the methyl carbons on the stereocenter (see Supporting Information).

Si-Tether Strategy for Nitrone Cycloadditions
J. Am. Chem. Soc., Vol. 122, No. 32, 2000 7637
Chart 4. Possible Amino Polyols
Scheme 4
structure. This result is highly surprising because we expected
that nitrone 2j(Z) might lead to an alternative product 4j-cis
through transition state FH.
Inspection of models suggests that transition state FH might
be avoided because it should suffer from severe torsional strain
between the substituents on the stereogenic center and the
neighboring geminal dimethyl groups (Scheme 3, Newmann
projection, right). We also had the additional insight that 2j(Z)
could not lead to 4j-trans because the interatomic distance
between the oxygen atom of the (Z)-nitrone and the carbon atom
of the dipolarophile is too long to achieve an effective overlap
of molecular orbitals. However, we realized that trans-selectivity
might be realized if the (Z)-nitrone isomerized to the (E)-isomer
(2j(E)) under the reaction conditions (105 °C for 53 h).23 If
this is the case, the reaction might proceed through the transition
state (FL), which features a gauche conformation around the
C(2)-C(3) bond (Scheme 3; Newmann projection, left) and
is free from torsional strain, to furnish 4j-trans exclusively. A
final assessment of this analysis, however, must await future
systematic studies.
obtained in this work would lead to amino polyols of the nine
basic structural types shown in Chart 4.
Conclusions. The silicon-tether strategy for controlling
the regioselectivity and diastereoselectivity of intramolecular
nitrone-olefin cycloadditions has been developed. Chiral R-
or â-hydroxy carbonyl compounds are amenable to the present
protocol to give silabicyclic isoxazolidine derivatives in a highly
regio- and stereoselective manner. The phenyl groups on the
silicon atom play a role in differentiating the two π-faces of
the reaction partners, largely through nonbonded interaction.
The silicon-tether strategy resulted in regioselectivity opposite
to that observed in the case of intermolecular cycloaddition
reaction using trimethylvinylsilane as a dipolarophile, which is
crucial for the introduction of the oxygen- and nitrogen-bearing
stereogenic centers in a 1,2-fashion.
The carbon-silicon bonds in 4a-j can be cleaved by using
the Tamao protocol10 to introduce the stereodefined hydroxyl
group. For example, 4e led to isoxazoline 5e in 66% overall
yield via the oxidative cleavage of the carbon-silicon bond of
4e and subsequent acetylation of two hydroxyl groups. The final
reductive cleavage24 of the N-O bond using catalytic hydro-
genolysis afforded 6e (Scheme 4). Thus, the cycloadducts
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Education,
Science, Sports, and Culture, Japan. We are also grateful to the
SC-NMR Laboratory of Okayama University for high-field
NMR experiments.
Supporting Information Available: Experimental details
involving synthetic procedures, physical constants, spectroscopic
data, and NMR spectra (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
(23) LeBel discussed the possibility of nitrone syn-anti interconversion
when a solution of the nitrone in EtOH or toluene was heated at reflux,
see: LeBel, N. A.; Banucci, E. G. J. Org. Chem. 1971, 36, 2440-2448.
(24) Saito, S.; Nakajima, H.; Inaba, M.; Moriwake, T. Tetrahedron Lett.
1989, 30, 837-838.
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