ASYMMETRIC HETERO-DIELS-ALDER REACTIONS AND ENE REACTIONS CATALYZED BY CHIRAL COPPER(II) COMPLEXES

A new copper(II) bisoxazoline-catalyzed reaction of glyoxylate esters with dienes leading to the hetero Diet-Alder product and the ene product in high yield and with a high enantiomeric excess (ee) has been developed. The hetero Diels-Alder product:ene product ratio is in the range 1:0.6 to 1:1.8 and is dependent on both the chiral ligand attached to the metal, the glyoxylate ester, and the reaction temperature. The scope of the copper(II) bisoxazoline-catalyzed reaction of glyoxylate esters with dienes is demonstrated by the reaction of a variety of different dienes with ethyl and isopropyl glyoxylate, and it is shown that a simple substrate such as 1,3-butadiene reacts to give the hetero Diels-Alder product in 55% yield with an ee of 87%. Furthermore, the synthetic application of the reaction is demonstrated by the synthesis of a highly interesting synthon for sesquiterpene lactones in high yield and diastereoselectivity, and with a very high ee from 1,3-cyclohexadiene and ethyl glyoxylate using a copper(II) bisoxazoline as the catalyst. A mechanism for the hetero Diels-Alder reaction, which accounts for the enantioselectivity in the reactions, is proposed.