Stereoselective and Enantiospecific Mono- and Bis-C−H Azidation of Tröger Bases: Insight on Bridgehead Iminium Intermediates and Application to Anion-Binding Catalysis

5 years ago

Stereoselective and Enantiospecific Mono- and Bis-C−H Azidation of Tröger Bases: Insight on Bridgehead Iminium Intermediates and Application to Anion-Binding Catalysis

Jérôme Lacour, Céline Besnard, Alessandro Bosmani, Amalia I. Poblador-Bahamonde, Sandip A. Pujari, Laure Guénée

In the context of Tröger base chemistry, regio- and stereoselective Csp3−H azidation reactions are reported. Azide functional groups are introduced at either one or the two benzylic positions selectively. Mild conditions and good yields are afforded by the combination of TMSN3 and iodosobenzene PhIO. The process occurs with high enantiospecificity (es 96–99 %) and—interestingly and importantly—via bridgehead iminium intermediates as shown by mechanistic and in-silico studies. Finally, mono- and bistriazole derivatives were prepared in high yields and enantiospecificity by using copper-catalyzed alkyne azide cycloaddition (CuAAC) reactions; some of the products were used as anion-binding organocatalysts for the tritylation of amines and alcohols. Basic instinct: Regio- and stereoselective Csp3−H azidations of Tröger bases are reported. Both mono- and bisazide functionalizations are available using TMSN3 and PhIO as reagent. High enantiospecificity is achieved (es 96–99 %). Interestingly, bridgehead iminium intermediates are evidenced by mechanistic and in-silico studies. With the azido products in hand, tailored bistriazole derivatives were prepared for application in anion-binding catalysis.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201700845