Formation and HERON reactivity of cyclic 'N,N'-dialkoxyamides

Abstract

Cyclic 'N,N'-dialkoxyamides have been made, for the first time, by hypervalent iodine oxidation of β- and y-hydroxyhydroxamic esters 17, 19, and 21. The fused y-lactam products, 'N'-butoxy- and 'N'-benzyloxybenzisoxazolones (22a and 22b), are stable while alicyclic y-lactam and δ-lactam products, 24 and 25, although observable by NMR spectroscopy and ESI-MS are unstable at room temperature, undergoing HERON reactions. The y-lactam 24 undergoes exclusive ring opening to give a butyl ester-functionalised alkoxynitrene 28. The δ-lactam 25, instead, undergoes a HERON ring contraction to give butyrolactone (27). The structures of model y- and δ-lactams 6, 7, and 8 have been determined at the B3LYP/6-31G(d) level of theory and the y-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 (EA = 113 kJ mol⁻¹) and ring contraction of 8 (EA = 145 kJ mol⁻¹) are predicted well, when compared with the HERON rearrangement of 5 (EA = 178 kJ mol⁻¹).