Studies of stereoselectivity in cycloaddition of cyclic dienes to 2-azabicyclo[2.2.2]octene derivatives; through-space effects on 15N NMR shifts of bicyclic amines and lactams

Only two of the four possible facial approaches of cyclohexa-1,3-diene to the double bond in 2-methyl-5,6-benzo-2-azabicyclo[2.2.2]oct-7-en-3-one 7 are observed, giving exo,endo- and endo,endo-Diels–Alder cycloadducts and at atmospheric pressure (exo- and endo-defined here by reference to the benzo- and etheno-bridges, respectively). Hydride reduction of the carbonyl in provides an indirect route to , which is formally derived from 2-methyl-5,6-benzo-2-azabicyclo[2.2.2]oct-7-ene but which is inaccessible directly owing to thermal retro-cycloaddition of . X-Ray crystal structures confirm the stereochemical assignments. Cycloaddition of cyclopentadiene to follows a similar path and the results are compared with corresponding studies on 7-azabicyclo[2.2.1]heptene analogues where only exo-facial attack is observed. Through-space interactions with proximate etheno- and ethano-bridges give rise to substantial upfield 15N NMR shifts of amino and lactam nitrogen.