Catalytic and Enantioselective Route to Medium-Ring Heterocycles. Asymmetric Zirconium-Catalyzed Ethylmagnesation of Seven- and Eight-Membered Rings

A variety of medium-ring heterocycles, prepared
efficiently by the Ru-catalyzed diene metathesis method,
undergo asymmetric catalytic ethylmagnesation to afford nonracemic
unsaturated alcohols and amides in excellent
enantiomeric purity (>98% ee). Noteworthy features of these
studies are as follows:  (i) Eight-membered unsaturated
tosyl amides are readily prepared by transition-metal-catalyzed
metathesis. (ii) With six-, seven-, and
eight-membered
N-containing substrates the presence of an electron-withdrawing Ts unit
is required for efficient carbomagnesation
(corresponding alkylamines are inert). Chiral medium-ring
heterocycles are resolved by the Zr-catalyzed C−C bond-forming reaction to afford recovered starting materials in up to >99%
ee. The kinetic resolution data indicate that
simple steric models can reliably predict the sense of the asymmetric
induction in the asymmetric carbomagnesation
or kinetic resolution. However, experimental results presented
herein also illustrate that the observed levels
of
enantioselectivity cannot be predicted on the basis of such
paradigms.