chromium - Nozaki-Hiyama-Kishi reaction - oxazolines - enantioselective ketone allylation
Significance
<P>As an extension of the author’s previously reported enantioselective Nozaki-Hiyama-Kishi
reaction (J.-Y. Lee, J. J. Miller, S. S. Hamilton
Org. Lett. 2005,
7, 1837-1839), this communication highlights the first example of a chromium-catalyzed
enantioselective addition of allylic bromides to ketones. The ligand used is synthesized
in three steps from a protected valine. For aryl ketones, the scope is broad and encompasses
various substitution types (electron-withdrawing, -donating, or neutral) and placements
(
ortho,
meta, or
para) on the aromatic ring with good to excellent ee values and yields. Halide-substituted
aryl ketones are also well tolerated. Methylallyl- and crotylbromides can also be
used as the nucleophilic components; modest diastereoselection (3.8:1) is seen for
crotylbromide addition. Poor enantiomeric ratios are observed for aliphatic ketones
and the facial selectivity is reversed.</P>
Comment
<P>Asymmetric addition of allyl nucleophiles to carbonyls is a popular method for
constructing enantioenriched homoallylic alcohols, although this method is largely
limited to aldehydes. The present report using ketones is thus a valuable contribution
to this area. Moreover, using allylic halides as the allyl source had not been reported
in a catalytic version of this transformation. The success of the asymmetric process
was attributed to modular catalyst design; systematic changes were made to the ligand
template and the modified ligands were tested until good ee values were obtained.
The authors concluded that the oxazoline module of the ligand has little effect on
asymmetric induction, whereas the proline module and the relative stereochemistries
of the proline and amide modules have a large effect. The relative configurations
of stereocenters in the ligand affect both the enantioselectivity and the absolute
configuration of the product.</P>
