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4.6 Synthesis of α-Alkylidene Cyclopentenones via a Rhodium(I)-Catalyzed Allenic
Cyclocarbonylation Reaction
During our investigations of the Mo(CO)6-mediated cyclocarbonylation reaction of
amino-ester tethered allenynes, a number of issues were encountered: (1) the reaction was not
entirely selective for the proximal double bond of the allene, affording up to 20% of the
undesired 4-alkylidene cyclopentenone particularly in the reaction of sterically encumbered
amino acids; (2) the desired α-alkylidene cyclopentenones were obtained as mixtures of
diastereomers with unpredictable diastereoselectivity depending on the nature of the amino-acid
side chain (Schemes 4.30 and 4.32); and (3) because Mo(CO)6 is used in stoichiometric amount,
purification issues were encountered upon scale-up during library synthesis. In addition,
generating large amounts of unidentified molybdenum waste posed an environmental concern.
However, the amino-acid derived α-alkylidene cyclopentenones obtained via this protocol
proved extremely useful in the synthesis of a library of tricyclic pyrroles and can potentially be
used in other DOS applications. For these reasons, we have recently begun investigating the
possibility to conduct a catalytic cyclocarbonylation reaction selective for the proximal double
bond of the allene.
In 2003, Shibata reported that IrCl(CO)(PPh3)2 (Vaska’s complex) selectively catalyzes
the formation of α-alkylidene cyclopentenone 316 from trisubstituted allenyne 315. 223 It was
demonstrated that the course of the reaction with the proximal double bond of the allene is
sterically influenced by the substitution pattern of the allene, since disubstituted substrate 317
gave a mixture of cyclocarbonylation products with 318c dominating.
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