Recent advances in indole aryne cycloaddition chemistry. Part I: Total synthesis of (+/-)-cis-trikentrin B. Part II: Investigation into the regioselectivity of 6,7-indole aryne cycloadditions. Part III: Synthesis and reactions of novel tribromoindoles

cyclopentadiene.To complete the synthesis, the remaining unreacted C-5 bromo position was subjected to Stille cross-coupling to install the trans-butenyl side chain at this site.The original regiochemical observations in 6,7-indole aryne cycloadditions werewere made with N-Me-4-phenyl-6,7-dibromoindole resulting predominantly in the contrasteric regiosiomer .This phenomenon was observed by the virtue of the polarized nature of the 6,7indole aryne as revealed by computational studies involving ab initio calculations.In order to probe further into the regioselective cycloadditions of 6,7-indole arynes, a series of 6,7-dibromoindoles were synthesized to investigate the effect of 2-, 3-, 4-and 5substitution on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tert-butylfuran.The results of this investigation indicated that the degree of polarization of the 6,7-indole aryne bond depends on electronic nature and the positions of the various substituents on the pyrrole and benzene rings of the indole which in turn is responsible for imparting regioselectivity in the 6,7-indole aryne cycloadditions.The Buszek laboratories have previously demonstrated the exclusive generation of 6,7-indole arynes from 4,6,7-and 5,6,7-tribromoindoles via a remarkable selective metalhalogen exchange at C-7 for use in natural products total synthesis and library development.In connection to these previous efforts, synthesis of the 4,5,6-and 4,5,7-tribromoindoles, the remaining two members of the tribromoindole series, is described.Treatment with n-BuLi followed by quenching with various electrophiles reveals a strong preference for initial metal-halogen exchange at the C-7 position in the case of 4,5,7-tribromoindoles, and at the C-4 position in the case of the 4,5,6-tribromoindole scaffold.Exclusive generation of the 4,5indole aryne in either system followed by cycloaddition with 2-tert-butylfuran shows only a modest regiochemical preference in the cycloadducts.Finally, the 4,5-benzannulated v scaffolds were subjected to Negishi cross-coupling with dimethyl and diethylzinc to demonstrate the proof-of-concept for library development.vi