Hydrogen-Bond-Driven Electrophilic Activation for Selectivity Control: Scope and Limitations of Fluorous Alcohol-Promoted Selective Formation of 1,2-Disubstituted Benzimidazoles and Mechanistic Insight for Rationale of Selectivity

摘要

Hydrogen-bond-driven electrophilic activationnfor selectivity control during competitive formation of 1,2-ndisubstituted and 2-substituted benzimidazoles from o-phenylenediaminenand aldehydes is reported. The fluorous alcoholsntrifluoroethanol and hexafluoro-2-propanol efficiently promotenthe cyclocondensation of o-phenylenediamine with aldehydesnto afford selectively the 1,2-disubstituted benzimidazoles at rtnin short times. A mechanistic insight is invoked by NMR, massnspectrometry, and chemical studies to rationalize the selectivity. The ability of the fluorous alcohols in promoting the reactionnand controlling the selectivity can be envisaged from their better hydrogen bond donor (HBD) abilities compared to that of thenother organic solvents as well as of water. Due to the better HBD values, the fluorous alcohols efficiently promote the initialnbisimine formation by electrophilic activation of the aldehyde carbonyl. Subsequently the hydrogen-bond-mediated activation ofnthe in situ-formed bisimine triggers the rearrangement via 1,3-hydride shift to form the 1,2-disubstituted benzimidazoles.