Quinone methides, generation lactones

A number of carbonates and lactones have been shown to give rise to quinone methide intermediates on irradiation.90-92 For example, Padwa and coworkers92 demonstrated that 3-phenylisocoumaranone (146) will extrude a molecule of carbon monoxide when irradiated in methanol to generate ort/zo-quinone methide (24) with moderate efficiency ( = 0.058, Eq. 1.39). This intermediate is subsequently trapped by the methanol solvent to give 147. 

However, there are two problems with these unconjugated lactones lack of selectivity and limited stability of the inhibitor in biological buffers. Coumarin carboxylates have been developed to improve selectivity toward a given serine protease (Section 11.4.1). On the other hand, the amide bond is chemically and enzymatically much more stable than the ester one. This raised the question of whether a starting functionalized lactam behaved like the previous lactones and generated in situ a quinonimine methide, the aza-analogue of the quinone methide (Section 11.5). 

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