´
180
J. G. Sosnicki / Tetrahedron Letters 50 (2009) 178–181
O
Supplementary data
1.
4 (0.075 equiv.)
80 oC PhMe, 5 h
Ph
Ph
O
Cl
Descriptions of analytical and synthetic methods, yields and
physical data on the new compounds are available. Supplementary
data associated with this article can be found, in the online version,
NH
Ph
N
Ph
Ph
N
Ph
S
2. LR (0.6 equiv.)
80 oC PhMe, 1 h
"one-pot"
1f (75%)
3f (76%)
Scheme 3. Synthesis of 1,6-diphenyl-5,6-dihydro-1H-pyridine-2-thione (3f) via the
References and notes
one-pot RCM/thionation procedure.
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´
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NOE
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trans-diallyl
trans-diallyl
cis-diallyl
648.
R= H, Ph
´
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Scheme 4. The mixture of trans-diallyl and cis-diallyl rotamers of NMe and NCy
derivatives (left). Single trans-diallyl rotamers of NH and NPh derivatives (right).
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example (Scheme 3). In this case, the starting dialkenoic amide
1f was obtained from acryloyl chloride and N-phenyl-N-(1-phenyl-
but-3-en-1-yl)amine. The successful synthesis of 3f indicates the
potential of this strategy in the synthesis of N,6-disubstituted thi-
one analogs without the necessity of isomerization. In both, the
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used, respectively.
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In order to explain the differences in the reactivity of the open
chain diallylic amides 1a–d, their structures were analyzed using
1H, 13C NMR, 1H, 1H COSY, 13C, 1H COSY and 1H, 1H NOESY spectro-
scopy in CDCl3 and toluene-d6 solutions. We found that the NMe
and NCy diallylic compounds exist in solution as mixtures of
trans-diallyl and cis-diallyl rotamers (Table 1, Scheme 4). Exchange
signals between rotamers present in the 1H, 1H NOESY spectra ta-
ken at room temperature indicate a low barrier to rotation around
the N–CO bond in both amides 1b and 1c, which explains their
good reactivity in RCM. As a result of the low barrier to rotation,
the trans-diallyl rotamer, which is unfavorable for RCM, can be
converted easily into the reactive cis-diallyl form under the reac-
tion conditions. As concluded from the 1H, 13C NMR and 1H, 1H
NOESY spectra, the NH and NPh diallylic precursors exist only in
the more stable trans-diallylic form, which is unsuitable for the
ring closing reaction, therefore their reactivity in cyclization is low-
er. The NH derivative gave no cyclic product, probably because in
toluene its barrier to rotation around the N–CO bond is much high-
er than the other N-substituted analogs. The observations of the
rotational behavior of amides 1a–d are in good agreement with
the experimental and theoretical data obtained for similar amide
models in a more specific investigation.19
In conclusion, we have presented a new, easy, and relatively
inexpensive approach to N-substituted and N,6-disubstituted 5,6-
dihydro-1H-pyridine-2-thiones including derivatives possessing a
quinolizidine ring system. The synthesis is based on RCM of dialk-
enoic amides followed by thionation with Lawesson’s reagent and
ˇ
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isomerization of the b,c-unsaturated thiolactams (3,6-dihydro-1H-
pyridine-2-thiones), if necessary. This strategy for the synthesis of
5,6-dihydro-1H-pyridine-2-thiones is a promising approach com-
plementary to other methods leading to valuable Michael accep-
tors. Additionally, a new and significant dependence of the RCM
of diallylic amides on the barrier to N–CO rotation (trans-diallyl
vs cis-diallyl) is described.
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Acknowledgment
17. For a comparative study, NPh and NCy derivatives of 3,6-dihydro-1H-pyridine-
2-one were subjected to isomerization with an equimolar amount of DBU for 5
Financial support by the National Committee for Scientific Re-
search (KBN, Grant No. 3 T09A 106 28) is gratefully acknowledged.
days. As a result, an inseparable mixture of both b,c- and a,b-unsaturated