Heterocycles potassium hexamethyldisilazide

Recently, the ability of N-heterocyclic carbenes to promote the Staudinger reaction has been investigated using ionic liquids, in the presence of suitable base as pre-catalysts. According to the procedure suggested by Smith et al., a solution of base (potassium hexamethyldisilazide KHMDS, toluene as solvent) was added to the suspension of ionic liquid (triazolium salt) in Et O and stirred under N. Subsequently, the mixture was added of diphenylketene and of imine and stirred at room temperature before concentration in vacuo (Scheme 16.6). The order of addition of reactants is critical for the success of the synthesis [95]. 

Subsequently, the ability of enantiomerically pure N-heterocyclic carbenes (NHCs) to catalyse the enantioselective Staudinger reaction has been tested. Different NHCs, obtained via deprotonation by potassium hexamethyldisilazide KHMDS in Et O of the respective parent ionic liquids, are able to promote the cycloaddition of diphenylketene and N-tosylimide giving P-lactams in elevated yields and 55-75% e.e. (Scheme 16.7) [95]. 

The Julia reaction is remarkably versatile but it does need three steps to make the alkene addition, acylation, and reduction. A more recent version of the reaction cuts this down to one by using not a phenylsulfone but instead a sulfone carrying an electron-deficient heterocycle, for example a tetrazole. The anion of the sulfone is made with a strong base (here potassium hexamethyldisilazide, KHMDS—see p. 635) and is added to an aldehyde to give an alkene directly. 

One of the pioneering applications of iV-heterocyclic car-bene (NHC) organocatalysts in the view of synthesizing natural products is the application by Orellana and Rovis of a Stetter reaction to construct the spirocyclic core of the antibiotic FD-838 (Scheme 11.46). Applying the triazole NHC precursor and activating the catalyst with 20 mol% of potassium 1,1,1,3,3,3-hexamethyldisilazide [potassium bis (trimethylsilyl)amide] (KHMDS), compound 197 underwent the Stetter reaction in a perfect 99% ee. This simplified skeleton of the bioactive molecule was one of the first examples applying the great power of NHC catalysis toward natural product synthesis. 

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