Synthesis, structural analysis, and reactivity of bridged orthoamides by intramolecular Schmidt reaction.
Intramolecular Schmidt reactions can be reliably steered toward bridged heterocycles containing orthoamides in high yields. The ketal tether enhances the control of regioselectivity in the migration of the bond distal to the reactive azide nucleophile, thus providing the first examples of the intramolecular Schmidt reaction proceeding with a complete regioselectivity en route to bridged products. The method is broad in scope and allows for systematic study of compounds that are analogous to elusive tetrahedral intermediates of amide addition reactions. Some initial reactivity and structural profiling of these compounds are also reported.
Department of Medicinal Chemistry, University of Kansas, Structural Biology Center, 2121 Simons Drive, West Campus, Lawrence, Kansas 66047, USA.
Michal
M
Szostak
Jeffrey
J
Aubé
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000577:Amides; D006571:Heterocyclic Compounds