A versatile asymmetric synthesis of bicyclic
pyrazolidinones through alkaloid-catalyzed formal [3 + 2]- and [3 + 2
+ 2]-cycloadditions of ketenes with azomethine imines is described.
The methodology was found to be tolerant of ketene and a variety of
monosubstituted ketenes (R = alkyl, OAc). The products were
formed in good to excellent yields (71-99% for 24 examples, 39
examples in all), with good to excellent diastereoselectivity in many
cases (dr 3:1 to 27:1 for 22 examples), and with excellent
enantioselectivity for most examples (≥93% ee for 34 products). In
the case of most disubstituted ketenes, the reaction proceeded
through a [3 + 2 + 2]-cycloaddition to form structurally interesting
bicyclic pyrazolo-oxadiazepinediones with moderate
diastereoselectivity (dr up to 3.7:1) and as racemic mixtures (3
examples). The method represents the first unambiguous example
of an enantioselective reaction between ketenes and a 1,3-dipole.