Stereo- and Regioselective 1,3-Dipolar Cycloaddition of the Stable Ninhydrin-Derived Azomethine Ylide to Cyclopropenes: Trapping of Unstable Cyclopropene Dipolarophiles

A stereo-
and regioselective 1,3-dipolar cycloaddition of the stable ninhydrin-derived azomethine
ylide [2-(3,4-dihydro-2H-pyrrolium-1-yl)-1-oxo-1H-inden-3-olate, DHPO] to differently substituted cyclopropenes
has been established. As a result, an efficient synthetic protocol
was developed for the preparation of biologically relevant spiro­[cyclopropa­[a]­pyrrolizine-2,2′-indene] derivatives. DHPO has
proved to be an effective trap for such highly reactive and unstable
substrates as parent cyclopropene, 1-methylcyclopropene, 1-phenylcyclopropene,
and 1-halo-2-phenylcyclopropenes. It has also been found that 3-nitro-1,2-diphenylcyclopropene
undergoes a nucleophilic substitution reaction in alcohols and thiols
to afford 3-alkoxy- and 3-arylthio-substituted 1,2-diphenylcyclopropenes,
which can be captured as corresponding 1,3-dipolar cycloadducts in
the presence of DHPO. These new approaches provide a straightforward
strategy for the synthesis of functionally substituted cyclopropa­[a]­pyrrolizine derivatives. The factors governing regio-
and stereoselectivity have been revealed by means of quantum mechanical
calculations (M11 density functional theory), including previously
unreported Nylide–Hcyclopropene second-orbital interactions. The outcome
of this work contributes to the study of 1,3-dipolar cycloaddition,
as well as enriches chemistry of cyclopropenes and methods for the
construction of polycyclic compounds with cyclopropane fragments.