Cycloaddition of nitrosoaromatics with steroidal dienes: Unexpected dependence of the chemoselectivity on the aryl ring substituent

Tandem palladium-catalyzed Stille coupling of steroidal alkenyl iodides (17 -iodo-androst-16-ene (1), 17-iodo-4-methyl-4-aza-androst-16-en-3-one (4), a nd 17-iodo-4-aza-androst-16-en-3-one (5)) with vinyltributylstannane and he tero Diels-Alder reaction of the products using nitrosobenzene or some para -substituted nitrosoaromatics (p-NO2, p-Br, p-Me, p-OMe) as dienophiles wer e investigated. Cycloaddition was regioselective in each case, but two ster eoisomers were obtained in a 2:1 ratio with unsubstituted pregnadienes as r eaction partners. Stereoselectivity was improved by the use of Lewis acid c atalysts. The similar reaction of substituted nitrosoaromatics with highly negative Hammett substituent-constants (p-OH, p-NMe2) resulted in the spont aneous dehydrogenation of the dihydro-oxazine, which was followed by the fo rmation of rearrangement products. The assignment of stereoisomers was carr ied out by various NMR techniques including H-1-H-1 COSY and NOESY experime nts.