4-Cyanomethyl-ortho-quinone tautomerism and the structure of the dienophile in Gatesʹ morphine synthesis

Oxidation of (3,4-dihydroxyphenyl)acetonitrile gives (3-hydroxy-4-oxo-cyclohexa-2,5-dienylidene)acetonitrile via the isomeric ortho-quinone ((3,4-dioxo-cyclohexa-2,5-dienylidene)acetonitrile). This para-quinomethane product is formed as a mixture of diastereoisomers and with an initial composition of Z/E 4:1. Over 24 h this mixture equilibrates to a composition of Z/E 5:4. The para-quinomethane reacts with morpholine to give (3,4-dihydroxyphenyl)-morpholin-4-yl-acetonitrile. Similar oxidation of (3,4-dihydroxynaphthalen-1-yl)acetonitrile also gives a para-quinomethane derivative and not the 1,2-naphthoquinone as previously described. The reactivity of this para-quinomethane derivative as a 1,3-dienophile in a key step of the Gatesʹ morphine synthesis is attributed to formation of its conjugate acid.