RESUMO
Efforts to substitute the cyclopropane ring in a series of aryl cyclopropylnitriles led to the discovery of an operationally simple one-pot method for Knoevenagel condensation and subsequent Corey-Chaykovsky cyclopropanation giving diastereomerically pure products as a racemic mixture of enantiomers. Method development and results for variably substituted aryl acetonitriles and aldehydes in the reaction are reported. A concise synthesis of (±)-bicifadine in two steps is provided to demonstrate the utility of the method.
Assuntos
Aldeídos/química , Ciclopropanos/química , Nitrilas/química , Estrutura Molecular , EstereoisomerismoRESUMO
A radical mediated C-H functionalization of 3,6-dichloropyridazine using primary alcohols, t-BuOOH, and TiCl3 to access alkoxy pyridazines is described. This transformation is conducted open to air and on gram scale. A subsequent cyclization step can then be employed to efficiently access diversely substituted tetrahydropyridopyridazines with multiple functional handles.
Assuntos
Radicais Livres/química , Piridazinas/síntese química , Piridinas/síntese química , Ciclização , Estrutura Molecular , Piridazinas/química , Piridinas/químicaRESUMO
The preparation of the diastereomerically pure beta-tetralone ketal 4 is reported. Intramolecular alkylidene C-H insertion followed by hydrolysis of 4 proceeded to give the enantiomerically pure cyclopentene 15. The key step in this synthesis was the bis-intramolecular cyclization of keto aldehyde 2 to give the tetracyclic intermediate 20. Enone 20 was converted over several steps to (-)-morphine 1.