Practical procedures for the preparation of N-tert-butyldimethylsilylhydrazones and their use in synthetic organic chemistry

Hydrazones serve as intermediates in numerous reactions of synthetic utility, including such important transformations as the Wolff-Kishner reduction and the Barton vinyl iodide preparation. The synthesis of hydrazones from carbonyl-containing compounds, however, is frequently problematic, and methods that involve hydrazones as intermediates often suffer as a consequence. In this work we develop practical chemistry for the preparation of N-tert -butyldimethylsilylhydrazone (TBSH) derivatives from aldehydes and ketones by condensation with equimolar amounts of 1,2-bis(tert-butyldimethylsilyl)hydrazine (BTBSH) and a catalytic quantity of scandium trifluoromethanesulfonate (typically, 0.01 mol %). We show that these products are formed with higher efficiencies (typically >95% yield) than are simple hydrazones, that they exhibit greatly enhanced stabilities (they can be stored and subjected to routine laboratory manipulations without evident decomposition), and that they undergo a number of synthetically useful transformations. Optimized procedures are provided for the use of TBSH derivatives in a Wolff-Kishner-type reduction protocol that proceeds at low temperature (23--100°C) and in a single reaction flask. Similarly, protocols for the use of TBSH derivatives as precursors to vinyl halides and gem-dihalides are described in detail. These reactions typically proceed in higher yield and under milder conditions than the corresponding transformations employing simple hydrazones as substrates. We also describe a new method for the synthesis of diazoalkanes by the oxidation of TBSH derivatives with (difluoroiodo)benzene, a reagent heretofore unexplored in the context of hydrazone oxidation. When conducted in the presence of a carboxylic acid substrate, the oxidation leads to efficient esterification in situ. In addition to greatly extending the range of diazoalkanes that are now available for esterifications, this new protocol offers significant advantages with regard to safety, for diazo intermediates are neither isolated nor achieve appreciable concentrations during the reaction.