General protocols for the synthesis of C2-symmetric and asymmetric 2,8-disubstituted analogues of Troger's base via efficient bromine-lithium exchanges of 2,8-dibromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine

Methods for facile synthesis of symmetric and unsymmetric: fanctionalized analogues of Troger's base were developed with use of 2,8-dibromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (2) as the starting material. C-2-symmetric 2,8-disubstituted analogues of Troger's base (4a-f) were synthesized via double bromine-lithium exchange of 2 followed by quench with electrophiles. Desymmetrization via single bromine-lithium exchange of 2, followed by quench with electrophiles, afforded asymmetric analogues of Troger's base (6a-g). Further reaction of 2-bromo-8-(trimethylsilyl)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (6b) produced 7a-c via single bromine-lithium exchange and subsequent quench with electrophiles.