Regiospecific control of additions of 4-substituted 3,5-dimethylisoxazoles to α,β unsaturated carbonyls

Transmetalation of C-5-lithiomethylisoxazoles with the lower-order cuprate reagent lithium thienylcyanocuprate (Li[ThCuCN]) in THF results in exclusive conjugate addition to α,β-unsaturated carbonyls. In contrast, transmetalation with samarium tris(hexamethyldisilazide) (Sm[HMDS]₃) in diethyl ether directs 1,2-carbonyl addition. In both cases, optimum results were realized with a 4,5-dihydro-4,4-dimethyl-Δ²-2-oxazoline substituent at the C-4 position of the isoxazole.