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4.5 Diversification of α-Alkylidene Cyclopentenones
4.5.1 Studies Towards the Synthesis of Tricyclic Pyrroles
Although the amino-ester derived α-alkylidene cyclopentenones could potentially serve
as useful tools to study biological systems, we were somewhat concerned with the reactivity of
the exocyclic enone moiety towards nucleophilic reagents, which may lead to non-specific
alkylation of biomolecules. It was reasoned that the reactivity of the enone could instead be
utilized in various Michael-type additions to increase the molecular complexity of the newly
obtained cyclopentenones. 197 More specifically, umpolung 198 addition of an aldehyde to the
enone via a Stetter reaction would yield a 1,4-diketone B resulting in increase of molecular
complexity (Scheme 4.39). 199, 200 Moreover, this 1,4-dicarbonyl moiety is synthetically versatile
and could, in principle, be utilized in a Paal-Knorr reaction to afford furan C under acidic
conditions or pyrrole D in presence of an amine. 201, 202 Additionally, aldol condensation was
envisioned under basic conditions, affording enone E (Scheme 4.39). 203
Scheme 4.39 Diversification potential of α-alkylidene cyclopentenones.
N
R1 P
MeO2C A
O
H
O
R 2
Stetter
reaction
N O
R1 P
MeO2C O
B
112
R 2
H +
R 3 -NH 2
OH -
P N
R1 MeO2C P N
R1 MeO2C P N
R1 MeO2C C
D
E
O
R 2
N R3
R 2
R 4
O