copper - N-H insertion reaction - chiral spiro bisoxazolines -
α-diazoesters -
α-amino acid derivatives
Significance
<P>A highly enantioselective catalytic insertion of α-diazoesters into N-H bonds is
reported. The catalyst is prepared from a Cu(I) source, a spiro-bisoxazoline ligand,
and a BARF counterion. A wide range of substituted anilines and naphthalenamines could
be used for the insertion reaction with complete conversions observed within two hours
and high yields and enantioselectivities were obtained. However, an electron-donating
group in the
para position of a phenyl-substituted aniline or a halogen at the
ortho position resulted in slightly lower enantioselectivities for unknown reasons. The
ester group on the diazoester could be changed with negligible effect; however, the
diazo substituent is more sensitive and can lead to lower yields or ee values. No
enantioselectivity was induced with
N-methylaniline and benzamide, and cyclohexylamine was inert under the reported conditions.</P>
Comment
<P>Although significant effort has been focused on diazoesters over the years, a highly
enantioselective catalytic N-H insertion has remained elusive until the present communication.
The authors note that the spiro-bisoxazoline ligand, which was developed in their
labs, provided optimal enantioselectivities compared to other spiro bisoxazolines,
with one diastereomer of the ligand exhibiting a matched combination of chiralities.
Also, the nature of the counterion significantly affects the reaction; the catalyst
with the BARF counterion has high enough activity that only 1 mol% of the catalyst
is needed. Copper(II) could also be used as the catalyst precursor; however, it provides
lower ee values. Chloroform and benzene could also be used as solvents, though using
acetonitrile resulted in significantly longer reaction times.</P>
