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
摘要:
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-2lambda(5)-phospholes containing a 1,3-cyclohexadiene or 1,4-cyclohexadiene system with moderate to excellent regio- and stereocontrol. The heterocycles were readily hydrolyzed, affording gamma-(N-alkylamino)diphenylphosphinic acids with the functionalities linked to a cyclohexadiene substructure.