Electrocyclic ring-opening reactions may cause failure of enolate alkylation of 1,4-oxazin-2-one based chiral glycine equivalents

Attempted monoalkylation of 6-methyl-5,6-diphenyl-1,4-oxazin-2-one that had been designed as a chiral glycine equivalent gave even under optimized conditions only minute amounts of the desired monoalkylation product whereas an acyclic ketone was obtained repeatedly as the major product. This result indicates that the enolate of the chiral glycine equivalent is prone to an electrocyclic ring-opening reaction. This hypothesis could be further supported by additional experiments. Based on these results, it is reasonable to assume that electrocyclic ring-opening reactions are also the cause for the failure of alkylation reactions of structurally related glycine equivalents reported in the literature.