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

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

doi:10.1002/chem.201700845

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

Chemistry. 2017 Jun 27;23(36):8678-8684. doi: 10.1002/chem.201700845. Epub 2017 Jun 5.

Authors

Alessandro Bosmani¹, Sandip A Pujari¹, Céline Besnard², Laure Guénée², Amalia I Poblador-Bahamonde¹, Jérôme Lacour¹

Affiliations

¹ Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211, Geneva 4, Switzerland.
² Laboratory of Crystallography, University of Geneva, Quai Ernest Ansermet 24, 1211, Geneva 4, Switzerland.

PMID: 28406541
DOI: 10.1002/chem.201700845

Abstract

In the context of Tröger base chemistry, regio- and stereoselective C_sp3 -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.

Keywords: C−H functionalization; Tröger base; asymmetric synthesis; azides; enantiospecificity; iminium intermediates.