Regio- and stereoselectivity of diethylaluminum azide opening of trisubstituted epoxides and conversion of the 3 degrees azidohydrin adducts to isoprenoid aziridines

The regioisomer ratios (3 degrees,2 degrees /2 degrees,3 degrees ), and in some cases the stereochemistry, of vicinal azidohydrins formed in reactions of 11 trisubstituted terpene epoxides with Et(2)AlN(3) in toluene are reported. The more highly substituted azide usually predominated (3 degrees,2 degrees /2 degrees,3 degrees ratios >or= 40:1 to 2.5-1) in accord with a Markovnikov orientation and an S(N)1-like transition state. Reversed regioisomer ratios were observed with 6,7-epoxygeranyl acetate (1:2.5) and cis-1,2-epoxylimonene (1:3.3 to 1:10). The tertiary azido diols from 2,3-epoxygeraniol, 2,3-epoxyfarnesol, and 2,3-epoxynerol were formed as single isomers with inversion of configuration at C3 (>or= 35-40:1 for the C(10) azido diols). The regioselectivity was affected by the presence and proximity of oxy functional groups on the epoxide substrate (OH, OAc, and OSi-tBuMe(2)), the equivalents of Et(2)AlN(3), and additives (EtOAc or EtOH). The results and trends are rationalized by consideration of the structural and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion intermediates and transition states, together with the nucleophilicity of the azide donor. Six of the 3 degrees,2 degrees azidohydrins were converted to the corresponding aziridines by primary-selective silylations of four azido diols, mesylations, and reductive cyclizations with LiAlH(4).