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G. J. Bodwell et al.
LETTER
Table 1
mation can be explained by a [1,5]-H shift of 19. More ex-
tended conjugation and lesser steric congestion between
one of the geminal methyl groups and the nearby aryl-H
atom in 20 may well be responsible for the readiness with
which the [1,5]-H shift occurs. AM1 calculations using
the Spartan package of software indicated that 20 is 7.9
kcal/mol lower in energy than 19.
Ketene aminal 1412 reacted with 5d under standard condi-
tions to afford the aromatized product 21 in 48% yield
(Entry 9). None of the product 22 was obtained, which
suggests that the dehydrogenation of its direct precursor
(cf. 8) occurs more quickly than a [1,5]-H shift. This pro-
cess would afford a compound that could aromatize via
the elimination of a second molecule of piperidine.
Although indoles have been reported to participate as di-
enophiles in IEDDA reactions,13 N-methylindole 11 failed
to react with 5d after 7 d in refluxing CH2Cl2 (Entry 12).
A more comprehensive investigation of the IEDDA
chemistry of 5d and its derivatives is now underway, as
are attempts at using the methodology described above in
the synthesis of heterohelicenes and heterokekulenes.
Acknowledgement
The authors gratefully acknowledge the Natural Sciences and En-
gineering Research Council (NSERC) of Canada for financial sup-
port of this work.
References and Notes
mentation with the reaction conditions (Entries 2-6), it
was found that equivalent yields could be obtained at
room temperature after just 1 h by using CH2Cl2 as the sol-
vent. The greater solubility of 5d in CH2Cl2 allowed the
reaction to be run at higher concentration than in CH3CN.
Changing the amine portion of the enamine from morpho-
line to pyrrolidine led to a significant increase in the yield
(64%, Entry 7). Again CH2Cl2 was found to be a better
solvent. Worthy of note is that the corresponding reaction
in CH3CN (Entry 8) afforded a small quantity of a by-
product 17. That this compound is the hydrogenated self-
condensation product of acetophenone may provide some
clue as to how the dehydrogenations are occurring. At this
point room temperature reaction in CH2Cl2 was chosen as
our standard reaction conditions.11
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Reaction of enamine 12 with 5d under standard conditions
(Entry 9) gave 18 (43%). With its geminal methyl groups,
enamine 13 (Entry 10) was not expected to react with 5d
to give an aromatized product, but rather diene 19 (cf. 8).
However the only product isolated was 20 (51%). Its for-
Synlett 1999, No. 4, 477–479 ISSN 0936-5214 © Thieme Stuttgart · New York