No abstract

The kinetics of the '-lithiations of /V,Ai-dimethyl-2,4,6-triisopropylbenzamide (4) and (V,7V-diethyl-2,4,6-triisopropylbenzamide (5) by seobutyllithium (j-BuLi) in cyclohexane have been investigated. Direct observation of the reactant amide, the intermediate amide-lithium reagent complex(es), and the '-lithiated products by stopped-flow infrared spectroscopy was used to investigate the initial rate constants as a function of reactant concentrations. At constant amide concentration the initial rate constant decreases sharply with increasing concentration of J-BuLi. This behavior is also observed in the presence of tetramethylethylenediamine (TMEDA). The major interaction of TMEDA with s-BuLi in cyclohexane is shown by cryoscopic measurements to be an addition of TMEDA to aggregated J-BuLi. Semiquantitative schemes constructed on the basis of the kinetic data suggest the presence of at least two reactive complexes and that complexes with more ligands are more reactive. The implications of these results are discussed.

Efficient and practical access to chiral aminocyclopropanes is secured by the title reaction (see example). Both E and Z enamides undergo the cyclopropanation with high diastereoselectivity (d.r. up to >95:5). The application of this methodology to the synthesis of biologically significant aminocyclopropanes illustrates the potential of chiral enamides as useful building blocks for stereoselective organic synthesis.

[reaction: see text] A short and unique approach to (+/-)-lycoramine as one of the galanthamine-type alkaloids has been efficiently developed. The alternative advantage lies in that three stereocenters, including a crucial quaternary carbon center, were constructed with high diasteroselectivity via a key one-step NBS-mediated semipinacol rearrangement of the allylic alcohol.