Zinc(II)-catalysed asymmetric hetero-Diels–Alder reactions of conjugated dienes with glyoxylate

Abstract

The zinc(II)-catalysed hetero-Diels–Alder reaction of the conjugated dienes 2,3-dimethylbuta-1,3-diene and cyclohexa-1,3-diene with ethyl glyoxylate has been studied in the presence of different C₂-symmetric bisoxazolines. The zinc(II)-catalysed reaction of 2,3-dimethylbuta-1,3-diene with ethyl glyoxylate gives both the hetero-Diels–Alder and ene products, the former being the major product with an enantiomeric excess up to 87%. The hetero-Diels–Alder∶ene ratio is relatively independent of the catalytic system and the solvent and is in the range 1∶0.5–1∶0.8. For the zinc(II)-catalysed reaction of cyclohexa-1,3-diene with ethyl glyoxylate, the hetero-Diels–Alder product is formed in up to 84% isolated yield and with an enantiomeric excess up to 65%. The enantiomeric excess for this reaction is very dependent on the solvent, with MeNO₂ generally lowering the enantiomeric excess compared with CH₂Cl₂. Based on the absolute stereochemistry of the hetero-Diels–Alder products and semi-empirical calculations on different bisoxazoline–zinc(II)–ethyl glyoxylate intermediates the mechanism for the reaction is discussed.