ABSTRACT
A conceptual strategy for a formal α-alkylation of α-methylene ketones was developed. Diverse 1° and 2° alkyl substituents were generated in the α-position of various ketones via synthesis of enaminone (step 1) and treatment with organomagnesium (step 2) with subsequent catalytic hydrogenation (step 3, 1° alkyl) or organocopper reagents (step 4, 2° alkyl). Tolerance toward ester, Boc-protected amine, and α-fluoro-substituted ketone moieties was demonstrated. The suitability of the method for late-stage natural product modification was shown.
ABSTRACT
A one-step synthesis of functionalized 3-azabicyclo[3.2.0]heptanes by [2+2]-photochemical intermolecular cycloaddition of N-benzylmaleimide to alkenes was elaborated. The obtained compounds were easily transformed into the bi- and tricyclic analogues of piperidine, morpholine, piperazine, and GABA, which are advanced building blocks for drug discovery.
ABSTRACT
In the context of drug discovery, novel spirocyclic pyrrolidines have been synthesized in two steps from common three- to seven-membered-ring (hetero)alicyclic ketones. The key transformation is a reaction between an electron-deficient exocyclic alkene and an in situ generated N-benzyl azomethine ylide. The developed method has been used to synthesize the central diamine core of the known antibacterial agents Sitafloxacin and Olamufloxacin.
