Exploring the unique reactivities of heterobicyclic tetrazoles—access to functionally diverse and versatile heterocyclic scaffolds

Abstract The benzylic hydrogen atom in oxabicyclic tetrazoles such as (6 R ,8 R )-(8-phenyl-5,6-dihydro-8 H -tetrazolo[5,1- c ][1,4]oxazin-6-yl)-alkanols ( A , X=CH 2 OH) is highly acidic, being alkylated in preference to a hydroxymethyl group with NaH and active alkyl halides. The enantioenriched products B now contain a phenyl and alkyl group on a stereogenic benzylic carbon atom. The products are subject to β-elimination to give 1-{1-[3-propenyl]-1 H -tetrazol-5-yl}-1-phenyl-alkanols. Cleavage of the propenyl chain leads to chiral non-racemic 1-phenyl-1-(1 H -tetrazol-5-yl)-alkanols C . Free-radical ‘anomeric’ azidation of the oxabicyclic tetrazoles followed by reduction and ring closure with inversion of configuration produces azabicyclic tetrazoles D as constrained functionalized piperazines.