N-Benzyl-N-(methoxymethyl)-
N-trimethylsilylmethylamine (1) is a valuable reagent for in situ
generation of the N-benzyl azomethine ylide (2). It is generally
preferred over alternative silylmethylamine precursors6–8 because
of ease of handling and use. The ylide (2) is most conveniently
generated from (1) using a catalytic amount of trifluoroacetic acid
as described by Achiwa.Alternative catalysts include LiF,
TBAF,Me3SiOTf–CsF, or Me3SiI–CsF. Mechanistic studies
provide evidence that the reactive intermediate generated from
(1) with either CF3CO2H or F? is a 1,3-dipolar species. Reaction
of (2) with alkenes provides an efficient convergent route
to pyrrolidine derivatives. Alkynes afford 3-pyrrolines which can
be converted into pyrroles.The ylide (2) reacts most readily with
electron deficient alkenes and alkynes since this pairing results in
a narrow dipole HOMO–dipolarophile LUMO energy gap.Examples
of suitable dipolarophiles include unsaturated esters,
ketones, imides,nitriles,and sulfones. Cycloaddition occurs
with complete cis stereospecificity (eq 1) which is consistent
with a concerted mechanism. Dipolarophiles containing
an endocyclic double bond afford fused bicyclic pyrrolidines,
whereas substrates with an exocyclic double bond provide access
to spirocyclic systems.
