Formation and HERON Reactivity of Cyclic N,N-Dialkoxyamides

Cyclic N,N-dialkoxyamides have been made, for the first time, by hypervalent iodine oxidation of beta- and gamma-hydroxyhydroxamic esters 17, 19, and 21. The fused gamma-lactam products, N-butoxy- and N-benzyloxybenzisoxazolones (22a and 22b), are stable while alicyclic gamma-lactam and delta-lactam products, 24 and 25, although observable by NMR spectroscopy and ESI-MS are unstable at room temperature, undergoing HERON reactions. The gamma-lactam 24 undergoes exclusive ring opening to give a butyl ester-functionalised alkoxynitrene 28. The delta-lactam 25, instead, undergoes a HERON ring contraction to give butyrolactone (27). The structures of model gamma- and delta-lactams 6, 7, and 8 have been determined at the B3LYP/6-31G(d) level of theory and the gamma-lactams are much more twisted than the acyclic N,N-dimethoxyacetamide (5) resulting in a computed amidicity for 6 of only 25 % that of N,N-dimethylacetamide (3). The HERON reactions of N,N-dimethoxyacetamide (5) and alicyclic models 6 and 8 have been modelled computationally. The facile ring opening of 6 (E-A = 113 kJ mol(-1)) and ring contraction of 8 (E-A = 145 kJ mol(-1)) are predicted well, when compared with the HERON rearrangement of 5 (E-A = 178 kJ mol(-1)).