tert-Butoxy bis(dimethyl-amino)methane (Bredereck's reagent)

Abstract

(A) α-Methylation of γ-lactams and γ-lactones: The Bredereck reagent has been employed in the preparation of 4-methylglutamic acids, non-proteinogenic amino acids and analogues with high optical purity and total diastereoselectivity 3,5-cis after hydrogenolysis of enamino lactam intermediate. (B) α-Methylenation of γ-lactams: After preparing the corresponding β-enamino carboxylic system by reaction of a pyroglutamic acid derivative with Bredereck's reagent, its reduction with DIBAL-H afforded the corresponding α-methylene γ-butyro-lactam. (C) α-Amination: Bredereck's reagent has been used as an intermediate for the nitrosation of active methylene groups, followed by reduction of the resulting oxime to afford α-amino lactones and lactams. (D) Introduction of a ketone group α to the carbonyl group: Bredereck's reagent has been employed in the preparation of β-enamino ketones, lactones, esters, substituted amides, or lactams, which after treatment with singlet oxygen using a sensitizer (BANT - bisacenaphthalenethiophene) afford the corresponding α-keto derivatives. (E) Ring-opening polymerization: Recently, Waymouth, Hedrick and co-workers have described the use of Bredereck's reagent as an organic catalyst for the ring-opening polymerization of strained cyclic esters for the synthesis of polylactides. (F) Solid-phase synthesis: The usefulness of the Bredereck's reagent was extended to the solid-phase synthesis of a library of pyrazoles, employing a germanium-based linker, via the formation of enaminones from aromatic ketones. (G) Enamine formation from active methylene compounds: 5-Acyl-6-methyl-2-pyridinones were converted to the corresponding enamines upon treatment with Bredereck's reagent. 1,6-Naphthyridones were obtained in good yields upon treatment of the enamines with ammonium acetate. (H) Indole synthesis: Indoles can be obtained from tetrahydronaphthalenes and Bredereck's reagent via enamine formation assisted by the nitro group in the benzene ring under mild conditions. © Georg Thieme Verlag Stuttgart.