Total Synthesis of Pyrrolidine and Piperidine Natural Products via TMSOTf-Mediated 5/6-endo-dig Reductive Hydroamination of Enynyl Amines

Stereoselective syntheses of pyrrolidines and piperidinesbearinghydrophobic chains have been achieved through a metal free, Lewisacid-mediated 5/6-endo-dig reductive hydroaminationcascade of enynyl amines. The brevity of the developed strategy allowedfor the collective stereoselective total synthesis of various alkaloids,including (& PLUSMN;)-pyrrolidine cis-225H, (& PLUSMN;)-epi-197B, (& PLUSMN;)-epi-225C, the familyof (+)-solenopsins and (+)-isosolenopsins, and the formal synthesisof (& PLUSMN;)-bgugaine and (+)-azimic acid.

Automated summary

Stereoselective syntheses of pyrrolidines and piperidines bearing hydrophobic chains were achieved through a metal-free, Lewis acid-mediated 5/6-endo-dig reductive hydroamination cascade of enynyl amines. The developed strategy allowed for the collective stereoselective total synthesis of various alkaloids, including (& PLUSMN;)-pyrrolidine cis-225H, (& PLUSMN;)-epi-197B, (& PLUSMN;)-epi-225C, the family of (+)-solenopsins and (+)-isosolenopsins, and the formal synthesis of (& PLUSMN;)-bgugaine and (+)-azimic acid.