Introduction
tert -Butoxy-bis(dimethylamino)methane [Bredereck’s reagent, t -BuOCH(NMe2 )2 ] (Figure 1) is a useful reagent for α-methylation, α-methylenation, and α-amination of several carbonyl systems or compounds with an active CH group.
Figure 1 Bredereck’s reagent (1 ).
Compared to the conventional methods to insert a methyl, methylene or amine groups at the position α to a carbonyl group, Bredereck’s reagent has the advantage of generating a strong basic alkoxide (t -BuO- ) in situ and the corresponding iminium ion by thermal decomposition. After the Mannich reaction between the carbonyl substrate and the iminium ion formed in situ, β-elimination of dimethylamine from the adduct in the final step affords the condensation product which can be transformed into various types of compounds as shown below. These factors combine to make Bredereck’s reagent the reagent of choice for α-methylation, α-methylenation, and α-amination of carbonyl compounds.
Preparation Bredereck’s reagent is commercially available in pure form and can be used either in solution (e.g. DMF, benzene, toluene) or as a solvent and reagent. The reagent can also be prepared from the reaction of alcohol-free alkoxides and secondary amines, or from the reaction of Villsmeier reagent with sodium alkoxides.
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