Regio- and Diastereoselective Preparation of Tetrahydrobenzo[c]-1-aza-2λ5-phospholes through Dearomatization Cyclization of Lithiated N-Benzyl-N-alkyl(diphenyl)phosphinamides. Synthesis of γ-(N-Alkylamino)phosphinic Acids

• Published in: Journal of organic chemistry Vol. 67; no. 11; pp. 3852 - 3860
• Main Authors: Fernández, Ignacio, Ortiz, Fernando López, Velázquez, Amador Menéndez, Granda, Santiago García
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 31.05.2002
• Subjects: Chemistry; Exact sciences and technology; Organic chemistry; Organometalloidal and organometallic compounds; P derivatives; Preparations and properties; Solvent effect; Substituent effect; Cyclohexane derivatives; Nitrogen phosphorus heterocycle; Lithium Organic compounds; Cyclization; Regioselectivity; Dearomatization; Organic phosphinate; Protonation; Chemical synthesis; Diastereoselectivity
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo025587+

A study of the protonation of the cycloadducts derived from the dearomatization reaction of lithiated N-alkyl-N-benzyldiphenylphosphinamides has been carried out. The regio- and stereoselectivity of the process has been analyzed in terms of the size of the N-alkyl substituent, the acidity and size of the protonating reagent, and the cosolvent used. The optimization of these variables allowed the preparation of tetrahydrobenzo[c]-1-aza-2λ5-phospholes containing a 1,3-cyclohexadiene or 1,4-cyclohexadiene system with moderate to excellent regio- and stereocontrol. The heterocycles were readily hydrolyzed, affording γ-(N-alkylamino)diphenylphosphinic acids with the functionalities linked to a cyclohexadiene substructure.