Nucleophilicity Parameters of Stabilized Iodonium Ylides for Characterizing Their Synthetic Potential

Kinetics and mechanisms
of the reactions of the β-dicarbonyl-substituted
iodonium ylides 1­(a–d) with several π-conjugated
carbenium and iminium ions have been investigated. All reactions proceed
with rate-determining attack of the electrophile at the nucleophilic
carbon center of the ylides to give iodonium ions, which rapidly expel
iodobenzene and undergo different subsequent reactions. The second-order
rate constants k2 for the reactions of
the iodonium ylides with benzhydrylium ions correlate linearly with
the electrophilicity parameters E of the benzhydrylium
ions and thus follow the linear free energy relationship log k(20 °C) = sN(N + E) (eq 1), where electrophiles are characterized
by one parameter (E), while nucleophiles are characterized
by two parameters: the nucleophilicity N and the
susceptibility sN. The nucleophilicity
parameters 4 < N < 8 for iodonium ylides 1­(a–d) derived from these correlations show that substituting
hydrogen for Ph-I+ at the carbanionic center of Meldrum’s
acid or dimedone, respectively, reduces the nucleophilicity by approximately
10 orders of magnitude. The iodonium ylides 1­(a–d) thus have nucleophilicities similar to those of pyrroles, indoles,
and silylated enol ethers and, therefore, should be suitable substrates
in iminium-activated reactions. Good agreement of the measured rate
constant for the cyclopropanation of the imidazolidinone-derived iminium
ion 10a with the iodonium ylide 1a with
the rate constant calculated by eq suggests
a stepwise mechanism in which the initial nucleophilic attack of the
iodonium ylide at the iminium ion is rate-determining. The reaction
of cinnamaldehyde with iodonium ylide 1a catalyzed by
(5S)-5-benzyl-2,2,3-trimethyl-imidazolidin-4-one
(11a, MacMillan’s first-generation catalyst) gives
the corresponding cyclopropane with an enantiomeric ratio of 70/30
and, thus, provides proof of principle that iodonium ylides are suitable
substrates for iminium-activated cyclopropanations.