Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-endo-dig and 6-exo-dig Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and Benzoxazinones
journal contributionposted on 2017-11-28, 00:00 authored by Karandeep Singh, Bhanwar Kumar Malviya, Tapta Kanchan Roy, Venus Singh Mithu, Vimal K. Bhardwaj, Ved Prakash Verma, Swapandeep Singh Chimni, Siddharth Sharma
Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study. Exposure of bis-amides to Pd(II) catalyst triggered the formation of seven-membered benzoxazepinones. This investigation established that changing the catalyst to a Echavarren’s gold(I) turned off cyclization to seven member ring and turned on 6-exo-dig annulations to afford family of six-membered benzoxazinones. To support the proposed mechanisms, quantum chemical based density functional theory calculations have been performed and validated. This novel method obtained molecular complexity up to four modular inputs and divergence of two different skeletons. 2D NMR spectroscopic techniques and single crystal X-ray diffraction established the proposed structures.
bis-amideskeletoncrystal X-ray diffractioncalculationCyclizationquantumbenzoxazinonePdsix-membereddensityannulationcyclizationcomplexitymechanismmembermethodSelective Intramolecular 7- endoSynthesipost-UgiBenzoxazepinoneExposureEchavarreninvestigation6- exoformationcatalystPost-Ugidivergenceseven-memberedbenzoxazepinone2 D NMR spectroscopic techniqueschemicalBenzoxazinoneCatalyst-Controlled Structural Divergence