Investigation of Lewis Acid-Catalyzed Asymmetric Aza-Diels-Alder Reactions of 2H-Azirines

Article abstract of DOI:10.1021/jo0352326

Asymmetric Diels-Alder reactions with 2H-azirines as dienophiles have been studied. Diastereoselective reactions with an enantiopure azirine 1b, bearing a chiral auxiliary, gave substituted bi- and tricyclic tetrahydropyridines in high yield and stereoselectivity, under the influence of a Lewis acid. The novel enantioselective [4+2] cycloaddition reaction of 3-benzyl-2H-azirine carboxylate with cyclopentadiene was investigated with various chiral Lewis acid complexes and provided the corresponding tetrahydropyridines in moderate to low yield and enantioselectivity.

Full text of DOI:10.1021/jo0352326

In vestiga tion of Lew is Acid -Ca ta lyzed Asym m etr ic
Aza -Diels-Ald er Rea ction s of 2H-Azir in es
Åsa Sjo¨holm Time´n and Peter Somfai*
Department of Chemistry, Organic Chemistry, Royal Institute of Technology (KTH),
SE-100 44 Stockholm, Sweden
somfai@kth.se
Received August 22, 2003
Asymmetric Diels-Alder reactions with 2H-azirines as dienophiles have been studied. Diastereo-
selective reactions with an enantiopure azirine 1b, bearing a chiral auxiliary, gave substituted bi-
and tricyclic tetrahydropyridines in high yield and stereoselectivity, under the influence of a Lewis
acid. The novel enantioselective [4+2] cycloaddition reaction of 3-benzyl-2H-azirine carboxylate
with cyclopentadiene was investigated with various chiral Lewis acid complexes and provided the
corresponding tetrahydropyridines in moderate to low yield and enantioselectivity.
SCHEME 1
In tr od u ction
Nitrogen-containing heterocycles are versatile struc-
tures which often occur in natural products and fre-
quently show biological activity.1 During the enormous
efforts to develop stereoselective reactions, various al-
kaloids have also been found to efficiently act as both
ligands and chiral auxiliaries.2,3 Furthermore, many
structures pose great synthetic challenges and the de-
velopment of efficient and stereoselective methods for
their preparation is therefore attracting the interest of
many organic chemists.
A reaction that is efficient and often highly stereose-
lective is the Diels-Alder reaction, which in one step
generates six-membered rings with up to four new
stereogenic centers.4,5 The Diels-Alder reaction is equally
valuable for the construction of heterocycles and there
are numerous examples of oxygen- and nitrogen-contain-
ing dienes and dienophiles which have been used in this
reaction.6 Imines, which are the most commonly used
aza-dienophiles, generally require activation by an elec-
tron-withdrawing group and a Lewis acid to participate
in [4+2] cycloaddition reactions.7,8 Azirines, highly strained
three-membered unsaturated nitrogen-containing het-
erocycles with a reactive CdN bond, are more reactive
than the corresponding acyclic imines and are therefore
useful aza-dienophiles. Some examples of Diels-Alder
reactions between aryl- and alkyl-substituted azirines
and electron-poor dienes have been reported.9 Activated
azirines bearing a conjugated electron-withdrawing sub-
stituent, for example, an ester, amide, or phosphonate
group, react also with less reactive aliphatic 1,3-dienes
under thermal conditions.10,11 The products obtained in
these reactions contain a highly functionalized fused
[4.1.0] ring system that may undergo further transforma-
tions.12 Oxidation of the formed double bond, ring opening
of the aziridine ring, and reduction or hydrolysis of the
ester functionality are examples of transformations which
would lead to a great number of interesting compounds,
for instance unnatural R- as well as â-amino acids
(Scheme 1).
* Address correspondence to this author. Phone (+46)-8-790 6960.
Fax: (+46)-8-791 2333.
(1) Kleemann, A.; Engel, J .; Kutscher, B.; Reichert, D. Pharmaceuti-
cal Substances: Syntheses, Patents, Applications, 3rd ed.; Thieme:
Wu¨rtsburg, Germany, 1999.
(2) Ojima, I. Catalytic asymmetric synthesis; VCH Publishers: New
York, 1993.
(3) Seyden-Penne, J . Chiral Auxiliaries and Ligands in Asymmetric
Synthesis; Wiley: New York, 1995.
(4) Oppolzer, W. In Comprehensive Organic Synthesis; Paquette, L.
A., Ed.; Pergamon Press: Oxford, UK, 1991; Vol. 5, pp 316-399.
(5) (a) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogian-
nakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668-1698. (b) Kagan, H.
B.; Riant, O. Chem. Rev. 1992, 92, 1007-1019.
(6) Boger, D. L.; Weinreb, S. M. Hetero Diels-Alder methodology in
organic synthesis; Academic Press: New York, 1987; Vol. 47.
(7) Buonora, P.; J .-C., O.; Oh, T. Tetrahedron 2001, 57, 6099-6138.
(8) Weinreb, S. M. In Comprehensive Organic Synthesis; Paquette,
L. A., Ed.; Pergamon Press: Oxford, UK, 1991; Vol. 5, pp 401-449.
Diels-Alder reactions between azirines and several
dienes are known to give products with complete regio
(9) Anderson, D. J .; Hassner, A. Synthesis 1975, 483-495.
(10) Gilchrist, T. L. Aldrichim. Acta 2001, 34, 51-55.
(11) Davis, F. A.; Wu, Y.; Yan, H.; Prasad, K. R.; McCoull, W. Org.
Lett. 2002, 4, 655-658.
(12) Bickley, J . F.; Gilchrist, T. L.; Mendonca, R. Arkivoc 2002, 192-
204.
10.1021/jo0352326 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/19/2003
9958
J . Org. Chem. 2003, 68, 9958-9963

Asymmetric Aza-Diels-Alder Reactions of 2H-Azirines
SCHEME 2
SCHEME 3
and endo selectivity (with respect to the three-membered
ring).10 However, until now only a few attempts to control
the absolute stereochemistry in these reactions have been
reported, all of which employ substrate control.11,13 In one
case the chiral information was part of the azirine ring
itself, by an aromatic substituent in the 2-position,
affording the corresponding cycloadduct in excellent
selectivity.11 Two attempts to govern the stereochemical
outcome with chiral auxiliaries (Oppolzer’s N,N-dialkyl-
(1R)-isobornyl-10-sufonamide and (S)-phenylethylamide)
attached to the 3-position of the azirine, i.e., a chiral
azirine ester and amide, respectively, have been de-
scribed, both resulting in low or no selectivity.13
Azirines show an inherent sensitivity toward acid-
catalyzed decomposition. Despite this, previous work in
our laboratory has shown it possible to enhance the
reactivity of the azirines in Diels-Alder reactions by
coordination to a Lewis acid.14,15 It is well-known that
Lewis acids often increase not only the rate of the Diels-
Alder reactions but also the selectivities.4 This proved
to be true also for 2H-azirines substituted with a chiral
auxiliary and the preliminary results were reported in a
communication.16 The most optimal approach to asym-
metric synthesis and stereochemically pure compounds
is, however, the use of chiral catalysts. This methodology
has, as far as we know, not previously been applied to
the cycloaddition reactions of azirines. Herein will be
reported our results from the investigations of the
asymmetric [4+2] cycloadditions of 2H-azirines with
various dienes.
TABLE 1. Lew is Acid -Ca ta lyzed Diels-Ald er Rea ction s
of Azir in e 1b w ith Dien es 5, 8a , 8b, a n d 11
dea yield
entry diene
LA
T (°C)
-75 to -40 6, 7
6, 7
-100 to -90 6, 7
products (%) (%)
1
2
5
5
30
96
87
90
MgBr2‚OEt2 -100
ZnCl2‚OEt2
56b
31b
3
5
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
8a
8a
8a
8b
8b
8b
11
11
11
11
11
11
11
11
11
11
rt
-77
-78
9a , 10a
20 100c
MgBr2‚OEt2
ZnCl2‚OEt2
9a , 10a
9a , 10a
80
99
-75 to -40 9b, 10b 30
80b
99
MgBr2‚OEt2
ZnCl2‚OEt2
-75
-77
9b, 10b 97
9b, 10b 34
99
-78 to -40 12, 13
8
85
58
99
MgBr2‚OEt2 -100
ZnCl2‚OEt2 -100
MgI2‚(OEt2)x -78 to -40
MgBr2
MgCl2
YbCl3
Mg(OTf)2
ZnCl2‚OEt2
BF3‚OEt2
12, 13
12, 13
e
88b,d
99
78 100d
10 100d
15 100d
31 100d
17f 100
-100 to -72 12, 13
-78 to -40 12, 13
-73
12, 13
-100 to -72 12, 13
g
-77
-77
12, 13
12, 13
19
54b
a
b
Determined by 1H NMR. After chromatography. c Based on
unreacted azirine. Including ring-opened aziridine. e Only ring-
d
opened aziridine was obtained. f Opposite major diastereomer
g
compared to entries 10-16 and 18. 10 mol %.
Resu lts a n d Discu ssion
8-phenylmenthol was the auxiliary of choice, and with
MgBr2‚OEt2 excellent de was obtained.
Au xilia r y Con tr olled Diels-Ald er Rea ction s. To
study the substrate-controlled reaction, enantiomerically
pure 2H-azirines 1a and 1b were chosen as substrates
(Scheme 2). The dienophiles were reacted with 1-meth-
oxy-1,3-butadiene (2) under thermal conditions as well
as in the presence of a series of Lewis acids17 to give 3a ,4a
and 3b,4b, respectively,16,18 with complete regioselectivity
and endo selectivity. It was clear from this study that
The obtained results encouraged us to determine the
scope of this reaction with an additional set of dienes.
Danishefsky’s diene (5), cyclohexadiene (8a ), 2-(trimeth-
ylsilyloxy)-1,3-cyclohexadiene (8b), and cyclopentadiene
(11) were therefore selected and reacted with azirine 1b
(Scheme 3 and Table 1).
Cycloaddition of Danishefsky’s diene with 1b afforded
6 in 96% de in the presence of MgBr2‚OEt2 and in 87%
de with ZnCl2‚OEt2 (entries 2 and 3). These results
should be compared to 30% de obtained under thermal
conditions (entry 1). It is clear that both Lewis acids
greatly influence the stereochemical outcome in a positive
way. In addition, the reaction time was significantly
shortened to less than 10 min with MgBr2‚OEt2 compared
to several days without Lewis acid. However, the yield
of 6 and 7 after chromatography was unsatisfactory,
which might be due to hydrolysis of the TMSO group.
The reaction between azirine 1b and cyclohexadiene in
(13) (a) AÄ lvares, Y. S. P.; Alves, M. J .; Azoia, N. G.; Bickley, J . F.;
Gilchrist, T. L. J . Chem. Soc., Perin Trans. 1 2002, 1911-1919. (b)
Gilchrist, T. L.; Mendonc¸a, R. Arkivoc 2000, 1, 769-778.
(14) Ray, C. A.; Risberg, E.; Somfai, P. Tetrahedron 2002, 58, 5983-
5987.
(15) Ray, C. A.; Risberg, E.; Somfai, P. Tetrahedron Lett. 2001, 42,
9289-9291.
(16) Sjo¨holm Time´n, Å.; Fischer, A.; Somfai, P. Chem. Commun.
2003, 1150-1151.
(17) Motoyama, Y.; Nishiyama, H. In Lewis Acids in Organic
Synthesis; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1, p 59-88.
(18) The absolute configuration of 3a and 4a has not been deter-
mined.
J . Org. Chem, Vol. 68, No. 26, 2003 9959

Sjo¨holm Time´n and Somfai
SCHEME 4
F IGURE 1.
the presence of MgBr2‚OEt2 gave no expected product
despite complete consumption of the azirine (entry 5). For
this diene ZnCl2‚OEt2 proved to be a valuable comple-
ment and cycloadducts 9a :10a were obtained as a 90:10
mixture in quantitative yield. This was a considerable
increase in selectivity compared to the uncatalyzed
reaction (compare entry 4 with entry 6). For the TMSO-
substituted cyclohexadiene 8b MgBr2‚OEt2 was the Lewis
acid of choice affording 9b in 97% de in excellent yield,
while no influence on the stereoselectivity was observed
for ZnCl2‚OEt2 (entries 8 and 9). Despite this, an increase
in reaction rate was noticed for both Lewis acids. In the
presence of ZnCl2‚OEt2 or MgBr2‚OEt2 the reaction of 1b
and cyclopentadiene was completed after less than 10
min at -100 °C. Also in this case MgBr2‚OEt2 was
superior to ZnCl2‚OEt2 providing the product in good
diastereoselectivity (entries 11 and 12). Another magne-
sium salt, MgI2‚(OEt2)x, also facilitated the cycloaddition
reaction with a de of 78% (entry 13). However, to our
surprise MgBr2 and MgCl2 did not exert any appreciable
stereoselectivity (entries 14 and 15). A small selectivity
was observed with YbCl3 and Mg(OTf)2 although the
latter with opposite diastereomer 13 as major product
(entries 16 and 17). Worth noting is that the formed
cycloadducts can be separated by standard flash chro-
matography; this also makes reactions with less than
excellent selectivities useful.
acids are needed. However, we found that 10 mol % of
ZnCl2‚OEt2 was sufficient for complete conversion of 1b
in 4.5 h at -77 °C in the reaction with 11, compared to
days for the corresponding reaction in the absence of
Lewis acid. This indicates catalytic behavior, albeit with
low stereoselectivity (entry 18). A monodentate Lewis
acid, BF3‚OEt2, was applied but no product was obtained
although all azirine was consumed (entry 19).
The obtained configuration of the major 8-phenylmen-
thol-derived cycloadducts can be rationalized as follows.22
It is assumed that the carbonyl group is aligned with the
axial C(1) hydrogen in the cyclohexane ring and the
phenyl group oriented parallel to the azirine nuclei. If
the azirine ring is locked in an s-cis conformation by a
chelating Lewis acid, the Re-face becomes shielded by the
phenyl group and the cycloaddition therefore takes place
on the Si-face of the azirine (Figure 1).
En a n tioselective Diels-Ald er Rea ction s. The de-
velopment of catalytic enantioselective aza-Diels-Alder
reactions with imines as dienophiles has only recently
been addressed,7,23 and to the best of our knowledge, the
use of azirines as dienophiles in these reactions has not
yet been reported. There are a few obstacles with imines
as dienophiles in catalytic enantioselective Diels-Alder
reactions that have to be considered to achieve useful
reactions: the Lewis basic nitrogens in both imines and
product (vide supra), the flexible E/Z conformations
which generate several possible reactive conformers, the
low reactivity, and unstable substrates. However, azir-
ines have the potential to overcome some of the men-
tioned drawbacks, such as fewer conformations, due to a
cyclic imine moiety with the lone pair electrons in a well-
defined position, and a higher reactivity. On the other
hand, the acid sensitivity of the azirines as well as of
the products requires fine-tuned Lewis acid-ligand
complexes which have to be potent enough to promote
the cycloadditions but not destroy the azirine and the
aziridine.
In this study a wide range of Lewis acidic metals and
ligands, which have previously shown excellent results
in Diels-Alder reactions, have been screened together
with benzyl-2H-azirine-3-carboxylate 15 as dienophile
and cyclopentadiene (11) (Scheme 5 and Figure 2).3,22-25
Some representative results are collected in Table 2.
The uncatalyzed reaction proceeded smoothly, and
clean conversion of azirine 15 into 16 was obtained in
less than 15 min at room temperature. Product formation
was evident after 15 min also at lower temperatures (-40
and -78 °C), and the cycloadducts predominated after
The strained aziridine moiety in 12 and 13 was found
to easily undergo stereoselective ring opening by YbCl3
and all the magnesium halides, of which MgI2‚(OEt2)x
was the most effective reagent for this transformation
(Scheme 4).
Compound14a , obtained from major isomer 12, was
recrystallized and the absolute configuration determined
by X-ray crystallography.16 The other major cycloaddition
products 3b, 6, 9a , and 9b were assigned in analogy. A
few Lewis acids were then investigated to find a way to
limit the undesired ring-opening reaction.19 None of them
showed the same ability to affect the stereoselectivity as
did MgBr2‚OEt2 and MgI2‚(OEt2)x. For the magnesium-
based Lewis acids the etherate complexes are most
efficient (compare entries 11 and 14). The reason for this
still remains unclear, but might be due to different
solubility. It is known that zinc halides, which are
sparingly soluble in CH2Cl2, become more potent Lewis
acids due to increased solubility when complexed to
ether.20 Despite the etherate complex, MgBr2‚OEt2 is not
completely soluble under the present reaction conditions.
The basicity of the formed cycloaddition products is
believed to exceed that of the corresponding azirines,21
leading to deactivation or inhibition of the Lewis acid.
As a consequence, stoichiometric amounts of the Lewis
(22) Corey, E. J . Angew. Chem., Int. Ed. 2002, 41, 1650-1667.
(23) J ørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558-3588.
(24) Azirine 15 was prepared by thermolysis from the corresponding
vinyl azide.27 The vinyl azide was obtained in two steps, using a slightly
modified literature procedure, starting from benzyl acrylate. Gilchrist,
T. L.; Mendonca, R. Synlett 2000, 1843-1845.
(19) In addition to Mg(OTf)2 (presented in Table 1), also Yb(OTf)3,
Ti(OiPr)4, and SnCl4 were screened.
(20) Mayr, H.; Striepe, W. J . Org. Chem. 1985, 50, 2995-2998.
(21) Alcami, M.; Mo´, O.; Ya´nez, M. J . Am. Chem. Soc. 1993, 115,
11074-11083.
(25) Cernerud, M.; Skrinning, A.; Be´rge`re, I.; Moberg, C. Tetrahe-
dron: Asymmetry 1997, 8, 3437-3441.
9960 J . Org. Chem., Vol. 68, No. 26, 2003

Asymmetric Aza-Diels-Alder Reactions of 2H-Azirines
SCHEME 6 a
F IGURE 2. Ligands used in the Diels-Alder reactions of
azirine 15.
SCHEME 5
a
Reagents and conditions: (a) TMSCl, Et3N, CH3CN, PhMe.28
(b) acryloyl chloride, CuCl2, PhMe.28 (c) Br2, CH2Cl2; a : rt, 81%;
b: 50 °C, 95%. (d) NaN3, DMF; a : 60 °C, 56%; b: 85 °C, 65%. (e)
CH2Cl2, 150 °C, 20 min; a and b: >95%. (f) Acryloyl chloride, Et3N,
DMAP, CH2Cl2, 0 °C.29
TABLE 2. En a n tioselective Diels-Ald er Rea ction s of
Azir in e 15 w ith Cyclop en ta d ien e
T
(°C)
eea
(%)
yieldb
(%)
entry
LA
AlMe3
ligand
to 52%, while the yield was essentially the same (entry
6). Both the reaction conducted at -40 °C and the one at
-60 °C were considerably faster than the aluminum-
catalyzed reactions, with no azirine remaining after 40
min and 4 h, respectively. For some combinations of
Lewis acids and ligands the reactions were slow and
azirine was still present after prolonged reaction times.
Yet, for other combinations the azirine was consumed
directly, leaving no desired product after workup. The
low to moderate yields obtained after purification in all
reactions employing chiral catalysts indicated degrada-
tion of either the azirine and/or the product. This may,
thus, be caused by decomposition during chromatogra-
phy,26 by the Lewis acids, or simply by decomposition of
the unstable azirine over time.
Syn th esis of Ch ir a l Azir in es 1a a n d 1b. The
auxiliary derivatized azirines 1a and 1b were synthesized
in good yields via the corresponding acrylates, which were
converted into the dibromides and then further into the
vinyl azides (Scheme 6). The vinyl azides were then
cleanly transformed into the corresponding azirines by
thermolysis at 150 °C in CH2Cl2 for 20 min.27 No puri-
fication was necessary and the azirines were immediately
used in the cycloaddition reactions.
1
2
3
4
5
6
7
8
-40
-35
-40
-40
-40
-60
-60
-60
75
41
27
17
18
19
19
19
20
21
51
35
AlMe3
Mg(ClO4)2
Mg(ClO4)2
Mg(ClO4)2
AlMe3
c
c
32
52
12
19
22
25
22
20
AlMe3
a
b
Determined by chiral HPLC, Chiralcel, OD-H. After chro-
matography. c In the presence of 4 Å molecular sieves.
1.5 h at -40 °C (entry 1). The reactions were, therefore,
conducted with a stoichiometric amount of catalyst to
limit the background reaction. Of all the Lewis acids
screened, AlMe3 together with especially oxygen-contain-
ing but also nitrogen-containing ligands proved to be
most successful (entries 2, 3, 7, and 8). (S)-BINOL (17)
gave together with AlMe3 16 in 50% enantiomeric excess
(ee) and 41% yield (entry 2). Both the selectivity and yield
dropped slightly when using TADDOL (18) as ligand
(entry 3). With bissulfonamide ligands 20 and 21 low
selectivities and yields were obtained (entries 7 and 8).
Aluminum-based Lewis acids are among those considered
to be strongly acidic, particularly compared to magne-
sium and zinc Lewis acids, which showed excellent
results in the auxiliary controlled Diels-Alder reactions.
Despite the acidity of AlMe3, its complexes did not affect
the reactivity of the cycloaddition in a positive way. In
an attempt to increase the reaction rate, AlMe3 was
exchanged for AlMe2Cl in the reactions using ligands 17
and 18, but no product was obtained in either case.
Ligand 19 was then investigated together with Cu(OTf)2,
Zn(OTf)2, Mg(ClO4)2, MgI2‚(OEt2)x, and FeCl3. Depending
on the Lewis acid employed the azirine remained un-
changed or was rapidly consumed without any ap-
preciable formation of 16. However, cycloadduct 16 was
obtained in 32% ee and 22% yield when a combination
of powdered 4 Å molecular sieves and a catalyst formed
from ligand 19 and Mg(ClO4)2 was applied (entry 5). At
a lower reaction temperature, -60 °C, the ee increased
Con clu sion s
Herein is described a novel Lewis acid-catalyzed asym-
metric [4+2] cycloaddition reaction of 2H-azirines with
various dienes affording adducts comprising a fused
tetrahydropyridine-aziridine moiety. The enantioselec-
tive Diels-Alder reaction of benzyl-2H-azirine-3-carboxy-
late has, under the investigated reaction conditions, not
(26) Loss of product was observed on both silica and aluminum
oxide.
(27) Sjo¨holm Time´n, Å.; Risberg, E.; Somfai, P. Tetrahedron Lett.
2003, 44, 5339-5341.
(28) Thom, C.; Kocienski, P. Synthesis 1992, 582-586.
(29) Whitesell, J . K.; Liu, C.-L.; Buchanan, C. M.; Chen, H.-H.;
Minton, M. A. J . Org. Chem. 1986, 51, 551-553.
J . Org. Chem, Vol. 68, No. 26, 2003 9961

Sjo¨holm Time´n and Somfai
1H), 2.55 (B-part of split ABq, J ) 17.4, 2.0 Hz, 1H), 2.18 (s,
1H), 2.09 (s, 1H), 2.04-2.16 (m, 2H), 1.89 (m, 3H), 1.33-1.47
(m, 2H), 1.13 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 170.1, 124.3, 123.0, 84.7, 65.4, 56.5, 53.1, 48.8, 47.9, 44.2,
42.3, 38.1, 32.7, 27.3, 26.5, 22.9, 20.6, 19.9; HRMS (FAB+)
calcd for C18H27N2O4S (M + H) 367.1692, found 367.1707.
given useful levels of enantioselectivity and yield. On the
other hand, the auxiliary controlled Diels-Alder reac-
tions of azirine 1b proved to produce the cycloaddition
products in a highly efficient way. The high levels of
stereoselectivity and yields obtained in the reactions with
a variety of dienes, the easy separations of the formed
diastereomers, and the convenient preparation of the
chiral azirines as well as removal of the auxiliary from
the adducts12 make this a valuable method for the
asymmetric synthesis of fused nitrogen-containing het-
erocycles. We find, at this stage, the auxiliary based
approach superior to the enantioselective approach.
Analytical data for the m in or isom er : [R]25 -7 (c 0.27,
D
1
CH2Cl2); H NMR (500 MHz, CDCl3) δ 5.68 (m, 1H), 5.46 (m,
1H), 4.90 (br s, 1H), 3.98 (dd, J ) 7.7, 4.8 Hz, 1H), 3.63 (s,
3H), 3.48 (A-part of ABq, J ) 13.6 Hz, 1H), 3.38 (B-part of
ABq, J ) 13.6 Hz, 1H), 2.93 (dd, J ) 18.0, 6.2 Hz, 1H), 2.35
(br dd, J ) 18.3, 2.2 Hz, 1H), 2.19 (s, 1H), 2.05 (m, 1H), 2.01
(s, 1H), 1.86-1.98 (m, 4H), 1.32-1.42 (m, 2H), 1.18 (s, 3H),
0.98 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.3, 124.3, 123.0,
84.8, 66.2, 56.6, 53.9, 48.2, 47.6, 45.1, 41.7, 38.6, 33.4, 28.2,
26.3, 23.0, 21.4, 19.9; HRMS (FAB+) calcd for C18H27N2O4S
(M + H) 367.1692, found 367.1688.
Exp er im en ta l Section
This Experimental Section contains general procedures for
the Lewis acid mediated Diels-Alder reactions of azirines 1a ,
1b, and 15 and analytical data of all cycloadducts. A general
procedure for the ring-opening reaction of aziridines 12a , 12b,
and 12c and analytical data of the corresponding products 14a ,
14b, and 14c are also reported. For general experimental
details and procedures for preparation of 25a , 25b, 26a , 26b,
1a , and 1b and their analytical data, seethe Supporting
Information.
Cycloa d d u cts 6 a n d 7. 6 and 7 were prepared from azirine
1b and diene 5 as described for 3b and 4b and obtained as
a colorless oil. Analytical data for 6: [R]25 +44 (c 0.27,
D
CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.24-7.31 (m, 4H), 7.12
(m, 1H), 4.88 (br s, 1H), 4.83 (td, J ) 10.8, 4.5 Hz, 1H), 4.46
(m, 1H), 3.59 (s, 3H), 2.37 (br d, J ) 18.1 Hz, 1H), 2.01 (m,
1H), 1.88-1.94 (m, 4H), 1.60-1.68 (m, 2H), 1.41-1.52 (m, 1H),
1.34 (s, 3H), 1.24 (s, 3H), 1.08 (app qd, J ) 12.6, 3.8 Hz, 1H),
0.97 (q, J ) 12.0 Hz, 1H), 0.86 (d, J ) 6.5 Hz, 3H), 0.79-0.89
(m, 1H), 0.21 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 170.7,
151.2, 148.1, 128.0, 125.5, 125.2, 99.2, 87.9, 75.6, 56.4, 50.4,
41.7, 39.9, 38.9, 34.6, 31.3, 29.4, 27.3, 26.8, 26.7, 26.4, 21.8,
0.1; HRMS (FAB+) calcd for C27H42NO4Si (M + H) 472.2883,
found 472.2877.
Gen er a l P r oced u r e for Lew is Acid -Med ia ted Diels-
Ald er Rea ction of 2H-Azir in es 1a a n d 1b F or m in g Cy-
cloa d d u cts 3b a n d 4b. Freshly prepared azirine 1b (20 mg,
67 µmol) and ZnCl2‚OEt2 (47 µL, 134 µmol) were stirred in
dry CH2Cl2 (1.3 mL) at -100 °C for 20 min before addition of
1-methoxybutadiene (13 µL, 134 µmol). Complete consumption
of 1b was indicated by TLC after 10 min and NaHCO3 (aq, 1
mL) was added. The two-phase mixture was then vigorously
stirred at room temperature for 20 min before filtration
through an Extrelute tube, which was rinsed with CH2Cl2 (15
mL). The resulting organic phase was evaporated and the
diastereoselectivity determined by 1H NMR. The crude product
was purified by flash chromatography (SiO2, pentane-EtOAc)
to afford cycloadducts 3b (14 mg,37 µmol, 56%) and 4b (2 mg,
Analytical data for 7: [R]25 -85 (c 0.41, CH2Cl2); 1H NMR
D
(500 MHz, CDCl3) δ 7.23-7.30 (m, 4H), 7.07 (br t, J ) 7.2 Hz,
1H), 4.96 (td, J ) 10.7, 4.3 Hz, 1H), 4.85 (br s, 1H), 4.43 (m,
1H), 3.59 (s, 3H), 2.06-2.11 (m, 2H), 1.91 (br d, J ) 18 Hz,
1H), 1.79 (m, 2H), 1.74 (s, 1H), 1.67 (s, 1H), 1.66 (m, 1H), 1.41-
1.51 (m, 1H), 1.33 (s, 3H), 1.20 (s, 3H), 1.14 (app qd, J ) 12.8,
3.6 Hz, 1H), 0.98 (app q, J ) 12.2 Hz, 1H), 0.87 (d, J ) 6.7 Hz,
3H), 0.85-0.93 (m, 1H), 0.21 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 170.6, 151.8, 148.2, 127.9, 125.4, 125.0, 98.9, 88.0,
75.1, 56.5, 50.3, 41.7, 39.6, 38.7, 34.5, 31.3, 28.9, 28.7, 26.5,
26.4, 24.0, 21.8, 0.2; HRMS (FAB+) calcd for C27H42NO4Si (M
+ H) 472.2883, found 472.2898.
4 µmol, 6%) as oils. Analytical data for 3b: [R]25 +61 (c 0.43,
D
CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.23-7.31 (m, 4H), 7.12
(br t, J ) 6.8 Hz, 1H), 5.57 (m, 1H), 5.36 (m, 1H), 4.83 (td, J
) 10.8, 4.5 Hz, 1H), 4.72 (br s, 1H), 3.60 (s, 3H), 2.27 (br dd,
J ) 18.6, 2.3 Hz, 1H), 2.02 (ddd, J ) 12.3, 20.8, 3.5 Hz, 1H),
1.91 (s, 1H), 1.90 (s, 1H), 1.87-1.95 (m, 2H), 1.64 (m, 2H),
1.42-1.52 (m, 1H), 1.33 (s, 3H), 1.24 (s, 3H), 1.03-1.14 (m,
1H), 0.96 (app q, J ) 11.1 Hz, 1H), 0.86 (d, J ) 6.5 Hz, 3H),
0.80-0.90 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 171.0, 151.4,
128.0, 125.5, 125.0, 124.0, 123.4, 85.7, 75.5, 56.4, 50.5, 41.7,
39.8, 37.9, 34.5, 31.2, 29.1, 27.5, 26.8, 26.1, 21.8, 21.5; HRMS
(FAB+) calculated for C24H34NO3 (M + H) 384.2539, foun:
384.2537.
Cycloa d d u cts 9a a n d 10a . 9a and 10a were prepared from
azirine 1b and diene 8a as described for 3b and 4b and
obtained as a colorless oil. Analytical data for 9a : [R]25 +40
D
(c 0.23, CH2Cl2); IR (neat) νmax 2952, 2921, 1727, 1229; 1H NMR
(400 MHz, CDCl3) δ 7.26 (m, 4H), 7.13 (m, 1H), 5.97 (m, 1H),
5.56 (m, 1H), 4.90 (td, J ) 10.6, 4.3 Hz, 1H), 3.79 (m, 1H),
2.31 (m, 1H), 2.07 (ddd, J ) 12.2, 10.6, 3.5 Hz, 1H), 1.81-1.90
(m, 2H), 1.62-1.74 (m, 2H), 1.51 (s, 1H), 1.40-1.51 (m, 1H),
1.30 (s, 3H), 1.24 (s, 1H), 1.22 (s, 3H), 1.19-1.27 (m, 1H), 1.09
(app qd, J ) 12.6, 3.5 Hz, 1H), 0.97 (app q, J ) 12.1 Hz, 1H),
0.87 (d, J ) 6.5 Hz, 3H), 0.82-1.01 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 171.3, 151.9, 130.9, 127.9, 125.4, 125.2, 124.9,
74.9, 52.3, 50.5, 41.7, 39.7, 39.3, 34.6, 31.2, 29.1, 28.6, 28.0,
Analytical data for 4b: [R]25D -87 (c 0.47, CH2Cl2); IR (neat)
ν
max 2955, 2922, 1716, 1256, 1113; 1H NMR (400 MHz, CDCl3)
δ 7.22-7.31 (m, 4H), 7.07 (br tt, J ) 7.1, 1.3 Hz, 1H), 5.55 (m,
1H), 5.34 (m, 1H), 4.95 (td, J ) 10.8, 4.5 Hz, 1H), 4.69 (br s,
1H), 3.60 (s, 3H), 2.17 (br dd, J ) 18.7, 6.1 Hz, 1H), 2.08 (ddd,
J ) 12.3, 10.8, 3.8 Hz, 1H), 1.77 (s, 1H), 1.75-1.84 (m, 3H),
1.71 (s, 1H), 1.66 (m, 1H), 1.42-1.52 (m, 1H), 1.33 (s, 3H), 1.20
(s, 3H), 1.08-1.18 (m, 1H), 0.98 (app q, J ) 12.1 Hz, 1H), 0.87
(d, J ) 6.5 Hz, 3H), 0.84-0.94 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 171.0, 151.9, 127.9, 125.4, 125.0, 124.2, 123.0, 85.7,
75.1, 56.5, 50.3, 41.7, 39.6, 37.9, 34.5, 31.3, 28.8, 28.4, 26.5,
24.1, 21.8, 21.2; HRMS (FAB+) calcd for C24H34NO3 (M + H)
384.2539, found 384.2542.
26.6, 24.9, 24.1, 21.8, 20.4; HRMS (FAB+) calcd for C25H34
NO2 (M + H) 380.2590, found 380.2591.
-
Analytical data for 10a : [R]25D -63 (c 0.30, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.25 (m, 4H), 7.13 (m, 1H), 6.14 (m, 1H),
5.57 (m, 1H), 4.98 (td, J ) 10.6, 4.5 Hz, 1H), 3.80 (m, 1H),
3.12 (m, 1H), 2.06 (ddd, J ) 12.3, 10.6, 3.5 Hz, 1H), 1.73-1.89
(m, 3H), 1.30 (s, 3H), 1.25-1.59 (m, 4H), 1.20 (s, 3H), 1.09 (s,
1H), 1.01 (s, 1H), 0.97-1.13 (m, 3H), 0.86 (d, J ) 6.5 Hz, 3H),
0.78-0.90 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 172.0, 151.2,
131.0, 128.0, 125.5, 125.23, 125.17, 75.2, 52.5, 49.7, 41.6, 40.0,
38.6, 34.4, 31.3, 29.6, 27.0, 26.9, 26.5, 24.1, 21.7, 20.5; HRMS
(FAB+) calcd for C25H34NO2 (M + H) 380.2590, found 380.2587.
Cycloa d d u cts 3a a n d 4a . 3a and 4a were prepared from
azirine 1a and diene 2 as described for 3b and 4b and obtained
as a colorless semisolid. Analytical data for the m a jor
isom er : [R]25D +139 (c 0.32, CH2Cl2); IR (neat) νmax 1687, 1328,
Cycloa d d u cts 9b a n d 10b. 9b and 10b were prepared from
azirine 1b and diene 8b as described for 3b and 4b and
1
1134, 1109; H NMR (400 MHz, CDCl3) δ 5.69 (m, 1H), 5.48
(m, 1H), 4.89 (br s, 1H), 3.89 (dd, J ) 7.6, 5.0 Hz, 1H), 3.60 (s,
3H), 3.43 (s, 2H), 2.70 (A-part of split ABq, J ) 17.9, 6.0 Hz,
obtained as a colorless oil. Analytical data for 9b: [R]25 +68
D
1
(c 0.41, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.23-7.29 (m,
9962 J . Org. Chem., Vol. 68, No. 26, 2003

Asymmetric Aza-Diels-Alder Reactions of 2H-Azirines
4H), 7.12 (m, 1H), 4.95 (td, J ) 10.6, 4.5 Hz, 1H), 4.49 (dd, J
) 6.3, 2.5 Hz, 1H), 3.81 (m, 1H), 2.66 (q, J ) 2.6 Hz, 1H), 2.00
(ddd, J ) 12.2, 10.6, 3.5 Hz, 1H), 1.77-1.87 (m, 2H), 1.54 (s,
1H), 1.50-1.62 (m, 3H), 1.42 (s, 1H), 1.41-1.49 (m, 1H), 1.34
(s, 3H), 1.26 (s, 3H), 1.20-1.31 (m, 2H), 0.98 (app q, J ) 12.1
Hz, 1H), 0.97-1.07 (m, 1H), 0.85 (d, J ) 6.5 Hz, 3H), 0.75-
0.87 (m, 1H), 0.25 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 171.1,
154.1, 151.0, 127.9, 125.5, 125.4, 96.8, 75.0, 52.8, 50.5, 41.8,
40.0, 39.4, 35.4, 34.5, 31.3, 28.7, 27.1, 26.8, 26.2, 25.5, 21.8,
21.1, 0.1; HRMS (FAB+) calcd for C28H42NO3Si (M + H)
468.2934, found 468.2933.
1H), 3.60 (s, 2H), 3.31 (dd, J ) 5.5, 2.8 Hz, 1H), 2.15 (m, 1H),
2.05 (m, 1H), 1.97 (ddd, J ) 11.6, 5.5, 3.5 Hz, 1H), 1.53-1.68
(m, 3H), 1.49 (s, 3H), 1.42 (s, 1H), 1.37-1.42 (m, 1H), 1.30 (s,
3H), 0.93-1.08 (m, 2H), 0.89 (d, J ) 6.3 Hz, 3H), 0.76-0.91
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 171.3, 150.7, 137.1,
132.8, 128.1, 125.7, 125.5, 78.0, 55.7, 51.6, 50.1, 49.4, 46.1, 40.6,
40.3, 34.5, 31.3, 29.5, 27.4, 26.9, 25.0, 21.8; HRMS (FAB+)
calcd for C24H33INO2 (M + H) 494.1556, found 494.1551.
(-)-8-P h en ylm en th ol-Der ived Aza -bicyclo[3.2.1]octen e
14a . 14a was obtained as colorless crystals. Analytical data:
mp 120-121 °C; [R]25 -50 (c 0.71, CH2Cl2); 1H NMR (400
D
Analytical data for 10b: [R]25D -96 (c 0.2, CH2Cl2); 1H NMR
(500 MHz, CDCl3) δ 7.25 (m, 4H), 7.13 (m, 1H), 4.97 (td, J )
10.7, 4.3 Hz, 1H), 4.49 (dd, J ) 6.4, 2.7 Hz, 1H), 3.79 (m, 1H),
3.02 (br d, J ) 2.1 Hz, 1H), 2.05 (ddd, J ) 12.2, 10.6, 3.4 Hz,
1H), 1.78 (m, 3H), 1.49-1.57 (m, 2H), 1.38-1.47 (m, 1H), 1.30
(s, 3H), 1.25-1.35 (m, 2H), 1.24 (s, 1H), 1.20 (s, 3H), 1.08 (app
q, J ) 12.2 Hz, 1H), 1.00 (s, 1H), 0.97-1.11 (m, 1H), 0.85 (d,
J ) 6.4 Hz, 3H), 0.75-0.88 (m, 1H), 0.24 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 171.7, 154.3, 151.2, 128.0, 125.5, 125.2,
96.9, 75.2, 53.1, 49.6, 41.6, 40.0, 38.8, 35.9, 34.4, 31.3, 29.7,
27.1, 26.9, 26.4, 25.4, 21.7, 21.0, 0.1; HRMS (FAB+) calcd for
MHz, CDCl3) δ 7.31 (m, 4H), 7.18 (m, 1H), 6.36 (dd, J ) 5.5,
2.5 Hz, 1H), 6.13 (dd, J ) 5.5, 2.8 Hz, 1H), 4.91 (td, J ) 10.8,
4.3 Hz, 1H), 3.77 (br t, J ) 3.0 Hz, 1H), 3.60 (d, J ) 13.8 Hz,
1H), 3.36 (d, J ) 13.8 Hz, 1H), 3.24 (dd, J ) 5.3, 2.5 Hz, 1H),
2.11 (m, 1H), 2.04 (m, 2H), 1.46 (s, 3H), 1.45-1.58 (m, 4H),
1.38 (m, 1H), 1.30 (s, 3H), 0.93-1.07 (m, 2H), 0.88 (d, J ) 6.3
Hz, 3H), 0.80 (app qd, J ) 12.3, 3.5 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 169.7, 150.5, 135.9, 132.9, 128.1, 125.8, 125.4,
78.0, 61.7, 55.7, 50.3, 49.6, 48.1, 45.8, 40.9, 40.3, 34.4, 31.3,
29.8, 27.4, 24.5, 21.8; HRMS (FAB+) calcd for C24H33BrNO2
(M + H) 446.1695, found 446.1703.
C
28H42NO3Si (M + H) 468.2934, found 468.2953.
(-)-8-P h en ylm en th ol-Der ived Aza -bicyclo[3.2.1]octen e
14c. 14c was obtained as a colorless oil (3 mg, 55%). [R]25
Cycloa d d u cts 12 a n d 13. 12 and 13 were prepared from
D
1
azirine 1b and diene 11 as described for 3b and 4b and
-42 (c 0.18, CH2Cl2); H NMR (500 MHz, CDCl3) δ 7.35 (m,
obtained as a colorless oil. Analytical data for 12: [R]25 +51
4H), 7.17 (tt, J ) 6.6, 1.9 Hz, 1H), 6.37 (dd, J ) 5.8, 2.7 Hz,
1H), 6.13 (dd, J ) 5.8, 2.7 Hz, 1H), 4.89 (td, J ) 10.4, 4.1 Hz,
1H), 3.79 (m, 1H), 3.59 (d, J ) 13.7 Hz, 1H), 3.18 (d, J ) 13.7
Hz, 1H), 3.13 (dd, J ) 5.3, 2.7 Hz, 1H), 1.97-2.10 (m, 3H),
1.55 (m, 1H), 1.44 (s, 3H), 1.43-1.50 (m, 2H), 1.39 (m, 1H),
1.30 (s, 3H), 1.26 (br s, 1H), 0.94-1.05 (m, 2H), 0.88 (d, J )
6.3 Hz, 3H), 0.79 (app qd, J ) 12.5, 3.6 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 169.3, 150.4, 135.7, 132.9, 128.1, 125.8,
125.4, 77.9, 66.8, 55.9, 50.4, 49.2, 47.8, 44.4, 41.0, 40.3, 34.5,
D
(c 0.42, CH2Cl2); IR (neat) νmax 2953, 2918, 1724, 1238; 1H NMR
(400 MHz, CDCl3) δ 7.23-7.30 (m, 4H), 7.13 (br t, J ) 6.8 Hz,
1H), 5.95 (m, 1H), 5.54 (br dd, J ) 5.3, 2.3 Hz, 1H), 4.93 (td,
J ) 10.8, 4.5 Hz, 1H), 3.99 (br s, 1H), 2.52 (m, 1H), 2.36 (d, J
) 2.8 Hz, 1H), 2.06 (ddd, J ) 12.3, 3.8 Hz, 1H), 1.88 (m, 2H),
1.76 (app dq, J ) 13.4, 3.4 Hz, 1H), 1.59-1.69 (m, 2H), 1.51
(s, 1H), 1.43-1.52 (m, 1H), 1.32 (s, 3H), 1.22 (s, 3H), 1.12 (app
qd, J ) 12.8, 3.3 Hz, 1H), 0.96 (app q, J ) 12.0 Hz, 1H), 0.86
(d, J ) 6.5 Hz, 3H), 0.83-0.93 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 171.6, 151.8, 133.3, 127.9, 127.6, 125.4, 125.0, 75.0,
66.1, 60.5, 50.5, 43.5, 43.4, 43.2, 41.6, 39.6, 34.5, 31.2, 28.4,
26.5, 24.5, 21.8; HRMS (FAB+) calcd for C24H32NO2 (M + H)
366.2433, found 366.2426.
31.3, 29.9, 27.4, 24.5, 21.8; HRMS (FAB+) calcd for C24H33
ClNO2 (M + H) 402.2200, found 402.2191.
-
Gen er a l P r oced u r e for th e Ch ir a l Lew is Acid -Med i-
a ted Diels-Ald er Rea ction of 2H-Azir in e 15 F or m in g
Cycloa d d u cts 16.14 A solution of AlMe3 in Hexanes (2 M, 114
µL, 0.23 mmol) was added dropwise to a solution of (S)-BINOL
(65 mg, 0.23 mmol) in CH2Cl2 (2 mL) at room temperature.
The Lewis acid-ligand mixture was stirred at room temper-
ature for 30 min before being cooled to -35 °C. A solution of
15 (35 mg, 0.20 mmol) in CH2Cl2 (2 mL) was added before
addition of diene 11 (17 µL, 0.21 mmol). NaHCO3 (aq, 1 mL)
was added after 24 h and the two-phase mixture was then
vigorously stirred at room temperature for 20 min before
filtration through an Extrelute tube, which was rinsed with
CH2Cl2 (15 mL). The organic phase was concentration in vacuo
and purified by flash chromatography (SiO2, pentane-EtOAc)
to afford cycloadducts 16 as an oil in 41% yield. The enantio-
meric excess was determined by HPLC (Chiralcel OD-H,
hexane:i-PrOH, 90:10, 0.6 mL/min).
Analytical data for 13: [R]25D -98 (c 0.23, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.21-7.26 (m, 4H), 7.10 (br tt, J ) 6.4,
2.1 Hz, 1H), 6.11 (m, 1H), 5.58 (dd, J ) 5.0, 2.3 Hz, 1H), 4.96
(td, J ) 10.6, 4.3 Hz, 1H), 3.99 (br s, 1H), 3.33 (m, 1H), 2.04
(m, 2H), 1.87 (m, 1H), 1.71 (m, 2H), 1.56-1.66 (m, 2H), 1.39-
1.51 (m, 1H), 1.31 (s, 3H), 1.26 (s, 1H), 1.20 (s, 3H), 1.00-1.13
(m, 2H), 0.86 (d, J ) 6.5 Hz, 3H), 0.79-0.90 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 172.6, 151.4, 133.2, 127.9, 125.4, 125.0,
75.2, 66.1, 60.7, 50.1, 44.4, 43.0, 42.0, 41.6, 39.8, 34.5, 31.3,
27.5, 26.7, 25.7, 21.7; HRMS (FAB+) calcd for C24H32NO2 (M
+ H) 366.2433, found 366.2428.
Gen er a l P r oced u r e for th e Syn th esis of (-)-8-P h en yl-
m en th ol-Der ived Aza -bicyclo[3.2.1]octen es 14a , 14b, a n d
14c. Aziridine 12 (10 mg, 27 µmol) was added to a suspension
of MgI2‚OEt2 (22 mg, 60 µmol) in CH2Cl2 (1 mL) at -65 °C.
TLC indicated complete consumption of the aziridine after 2
h and NaHCO3 (aq, 0.5 mL) was added. The two-phase mixture
was stirred before filtration through an Extrelute tube, which
was rinsed with CH2Cl2 (15 mL). The resulting organic phase
was concentrated before purification by preparative HPLC
(Zorbax Rx-SIL, hexane:i-PrOH, 99:1), which gave 14b as a
Ack n ow led gm en t. The authors appreciate financial
support provided by the Swedish Research Council.
Su p p or tin g In for m a tion Ava ila ble: Procedures for the
synthesis of dibromides 25a and 25b, vinyl azides 26a and
26b, and azirines 1a and 1b, and their analytical data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
colorless oil (8 mg, 45%). Analytical data: [R]25 -91 (c 0.55,
D
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.32 (m, 4H), 7.18 (m,
1H), 6.35 (dd, J ) 5.8, 2.8 Hz, 1H), 6.15 (dd, J ) 5.8, 2.8 Hz,
1H), 4.94 (td, J ) 10.6, 4.3 Hz, 1H), 3.79 (br t, J ) 3.0 Hz,
J O0352326
J . Org. Chem, Vol. 68, No. 26, 2003 9963