An organocatalytic
strategy for the synthesis of tetrasubstituted
pyrrolidines with monoactivated azomethine ylides in high enantiomeric
excess and excellent exo/endo selectivity is presented. The key to
success is the intramolecular activation via hydrogen bonding through
an o-hydroxy group, which allows the dipolar cycloaddition
to take place in the presence of azomethine ylides bearing only one
activating group. The intramolecular hydrogen bond in the azomethine
ylide and the intermolecular hydrogen bond with the catalyst have
been demonstrated by DFT calculations and mechanistic proofs to be
crucial for the reaction to proceed.
An organocatalytic system is presented for the Michael addition of monoactivated glycine ketimine ylides with a bifunctional catalyst. The ketimine bears an ortho hydroxy group, which increases the acidity of the methylene hydrogen atoms and enhances the reactivity, thus allowing the synthesis of a large variety of α,γ‐diamino acid derivatives with excellent stereoselectivity.
The activation of
molecules through intramolecular hydrogen-bond
formation to promote chemical reactions appears as a suitable strategy
in organic synthesis, especially for the preparation of chiral compounds
under metal and organocatalytic conditions. The use of this interaction
has enabled reactivity enhancement of reagents, as well as stabilization
of the chemical species and enantiocontrol of the processes.
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