S. Krompiec et al. / Tetrahedron Letters 49 (2008) 6071–6074
6073
N
N
Ar
Ar
Ar
Cl
O
CH3
O
OH
Et3N
+
+
N
Q
CH2Cl2
H3C
Q
Q
CH3
cis- and trans-
A
cis- and trans-B
Q = 9-carbazolyl, Ph3Si
Scheme 6. Cycloaddition of 2,6-dichlorobenzonitrile oxide to 9-(1-propenyl)carbazole and triphenyl(1-propenyl)silane.
N
Y
Ar
Et3N
O
Ar
Cl
OH
+
N
CH2Cl2
Q
Q
Y
X
X
a) Q = PhO, t-BuO, Me3SiO, Me2N, (i-Pr)2N, p-MeC6H4N(COMe), 9-carbazolyl, t-BuS,
Ph3CS, Me3Si, Ph3Si; X ,Y = H
b) Q, X = -OCH2CH2CH2O-, Y = H (2-vinyl-1,3-dioxane)
c) Q, Y = -OCH2OCH2OCH2-; X = H (4,7-dihydrodioxepine)
Scheme 7. Reagents and conditions: rt, 24 h, ArCNO/Q-allyl/Et3N = 1:2:3. Conversion: 100% (in all cases); isolated yields: 60–80%. Synthesis of isoxazolines via cycloaddition
of 2,6-Cl2C6H3CNO to allylic systems.
The failure of the reaction in the case of trityl-(1-propenyl) sul-
fide (Q = Ph3CS, entry 12) probably results from steric interactions.
If the trityl group is located further from the reaction center, as in
allyl trityl sulfide, cycloaddition proceeds unhindered (Scheme 7).
A strong steric effect, which controlled the regioselectivity, was ob-
served previously in the reactions of cycloaddition reactions of
benzonitrile oxide to MeCH@CHCO(Y) systems.16 We have ob-
served that regioisomer A was also the only product of dipolar
cycloaddition to allylic systems—Scheme 7.
In these cases, the regioselectivity is controlled by the inductive
effect of Q strengthened by the hyperconjugation effect. In the case
of allyl systems, even if Q is an electron donor (Q = Me3Si) and
therefore counteracts the hyperconjugation effect, the formation
of one regioisomer is observed (thus the CH3 hyperconjugation
effect is dominant). Importantly, our results show that there are
no exceptions to the above interpretation, the regioselectivity of
the cycloadditions of all 14 systems of type QC(X)@CHCH2Y and
13 systems of type QCH(X)CH@CHY we studied can be explained
with resonance and Q inductive effects and the hyperconjugation
effects of the –CH2– or –CH3 groups. Interestingly, the formation
of the mixture of cis (cis-A and/or cis-B in Schemes 1 and 6) and
trans (trans-A and/or trans-B on Schemes 1 and 6) isomers inde-
pendently of (E)- or (Z)-configuration of the QCH@CHCH3 substrate
used (entries 2, 7, and 8) indicates that the cycloaddition of ArCNO
to these systems cannot be a concerted reaction. This means that
this is a two-step reaction and rotation around the QC–CCH3 bond
is possible in the intermediate. As a result, both stereoisomers are
formed and not just one, as expected in concerted reactions.
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This work was supported by the Ministry of Science and Higher
Education as a research Grant (No. 3 T09A 147 29) for the years
2005–2008.
´
Supplementary data
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Supplementary data associated with this article can be found, in
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