fluoro-gauche effect - conformational analysis - Weitz-Scheffer epoxidation
Significance
Gilmour and colleagues report the study and application of commercially
available 2-(fluorodiphenylmethyl)pyrrolidine 2 as a secondary amine organocatalyst.
The authors hypothesized that a fluorine atom beta to the pyrrolidine nitrogen
would lead to a pronounced preference for a gauche conformation
of the iminium intermediate of type 1,
possibly resulting in enhanced asymmetric induction. Crystallographic
and computational studies were used to support this hypothesis.
As proof of principle, catalyst (S)-2 was applied to a Weitz-Scheffer
epoxidation. The observed enantioselectivity of catalyst (S)-2 proved to
be comparable to the original Jørgensen catalyst 4 (J. Am. Chem. Soc. 2005, 127, 6964)
and superior to the non-fluorinated analogue 3.
Comment
The fluorine-iminium ion gauche effect may
become a stimulating concept for catalyst design and find use in
solving problems in organocatalysis. Remarkably, computational and
X-ray studies of analogous iminium ions derived of the Hayashi-Jørgensen
prolinol silyl ethers by Seebach et al. (Helv.
Chim. Acta 2008, 91,
1999) revealed a very similar gauche N-C-C-O
torsion angle of 59˚ (structure 5),
suggesting the possibility that the OTMS group exerts the same effect.
Furthermore, it is interesting to speculate on the role of the fluorine
atom in the transannular aldol reactions catalyzed by fluoroproline
derivative 6, recently disclosed by Chandler
and List (J. Am. Chem. Soc. 2008, 130, 6737).
