Mechanism of the diastereoselective, boron trifluoride-catalyzed cyclization of olefinic tosylhydrazones to stereolabeled, bridgehead-substituted azoalkanes

Article abstract of DOI:10.1021/ja00111a005

For the first time 1,4-dialkylated 2,3-diazabicyclo[2.2.1]hept-2-enes (5a-c) with stereolabels at the C-7 position have been prepared via the intramolecular cyclization of stereolabeled γ,δ-unsaturated tosylhydrazones under acidic conditions. The stereochemically labeled olefinic carbonyl compounds 3, required for the preparation of the tosylhydrazones 4, were made by syn carbometalation of the appropriate terminal alkynes 1a,b(D) with dialkylcuprates in THF at 0 °C. Hydrolysis of the ketal functionality in the resulting linear alkenes 2 afforded the desired ketones 3. Although the boron trifluoride-catalyzed cyclization of the tosylhydrazones 4 led in all cases to mixtures of stereochemically labeled azoalkanes, the process is highly diastereoselective in that the initial synlanti diastereomeric ratio of the tosylhydrazones 4 dictates the stereochemistry of the final azoalkanes 5. Thus, in the deuterium-labeled substrates, the syn tosylhydrazone of (E)-4a(D) affords the azoalkane syn-5a(D) through the orthogonal syn-A arrangement of the tosylhydrazone and olefin functionalities, while the anti tosylhydrazone of (E)-4a(D) leads to the azoalkane anti-5a(D) through the parallel anti-B arrangement, irrespective of the stereolabeled olefin geometry. A delicate balance of steric effects in the orthogonal and parallel conformers for the syn and anti diastereomers of the tosylhydrazones seems to control the observed diastereoselectivity.