3
the isolation of acetophenone during the above process (Scheme
5).
In summary we have successfully carried out a one-pot, three
component rhodium catalysed dehydrogenation/1,3-dipolar
cycloaddition reaction to form fused ring heterocycles in good
yields.
Coordination of rhodium to the nitrogen atom followed by
insertion into the CH bond generates organometallic
species Iminium complex then undergoes
which undergoes
α
A
.
B
deprotonation furnishing the 1,3-dipole
the cycloaddition reaction with maleimide.10,14
C
Acknowledgments
We thank Leeds University for support.
We further probed the formation of spirocycle 4. Initially it
was thought that spirocyclic product 4 could arise from the
Michael addition of piperidine with N-methylmalemide followed
by rhodium catalysed cycloaddition with N-methylmalemide
(Scheme 4). To test this hypothesis piperidine (1 mmol) and N-
methylmalemide (1 mmol) were reacted in toluene (15 ml) for
16 hours to produce Michael product 11. N-methylmalemide (2
mmol), triethylamine (10 mol%) and RhCl(PPh3)3 (10 mol%)
were then added to the reaction vessel and heated to 110˚C for a
further 16 hours which failed to provide the spirocyclic
cycloadduct 4. Only staring materials were recovered, probably
due to strong chelation between the piperidine nitrogen and the
imide carbonyl group to rhodium.
Notes and references
1
2
3
Zhao, Y.; Liu, L.; Sun, W.; Lu, J.; McEachern, D.; Li, X.; Yu, S.;
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.
,
7
.
2009, 2371-2372;
2009
.
,
,
8
9
.
,
,
,
,
Another proposed mechanism for the formation of
spirocyclic cycloadduct 4 is shown in Scheme 5. At this
stage, it must be emphasised that the proposed mechanism is
merely tentative and is the subject of ongoing research.
,
,
,
.
,
O
+
[M]
O
,
,
Me
N
, 1, 97-99.
Me
N
O
N
N
[M]
O
O
O
O
.
,
.
, 4
N
[M-H]
H
N
1
,
B
1,2 Proton
transfer
Diallo, O.; Pages, C.; Vincendeau, S. Organometallics 2006, 25,
Me
N
2943-2948.
H
O
O
H
O
N
O
O
N
Me
N
N
Me
H
O
N
O
Me
4
O
Scheme 5
Metal catalysed insertion into the α−CH bond generates the
iminium ion species B and metal hydride. The metal hydride can
act as a nucleophile to produce acetophenone and 1-piperideine.
1-Piperideine then undergoes Michael addition with N-methyl
maleimide to form a zwitterionic species which undergoes 1,2-
proton transfer to generate the 1,3-dipole which reacts with N-
methyl maleimide to produce spirocyclic cycloadduct 4. 1-
Piperideine could also arise via the metal catalysed
dehydrogenation of piperidine. However, this possibility was
ruled out by using preformed staring material 1 in the above
process. Further evidence to support the above mechanism was