Synthesis of Allene Substituted Nipecotic Acids by Allenylation of Terminal Alkynes

5 years ago

Synthesis of Allene Substituted Nipecotic Acids by Allenylation of Terminal Alkynes

Maren Schaarschmidt, Klaus T. Wanner

The relative reactivities of several secondary amines serving as hydride donors in propargylic amines undergoing a [1,5]-hydride transfer reaction to yield the respective terminal and 1,3-disubstituted allenes were studied. For this study, a two-step procedure was employed. At first, the synthesis of propargylic amines via the Cu^I-catalyzed aldehyde-alkyne-amine reactions (A³ coupling) was accomplished. The obtained propargylic amines were subsequently transformed to the desired allenes under CdI₂ or ZnI₂ catalysis. As a result, among the various secondary amines employed, differing in steric bulk, electronic nature, and conformational properties, allyl(tert-butyl)amine was found to be the best hydride donor for the synthesis of terminal allenes. For the synthesis of 1,3-disubstituted allenes, the propyne derivatives containing either a allyl(tert-butyl)amine or a 1,2,3,6-tetrahydropyridine unit in propargylic position performed best. Finally, with the developed procedure, nipecotic acid derivatives containing an N-allenyl substituent were synthesized with good yields using either ZnI₂ as catalyst for the preparation of 1-substituted or CdI₂ for the synthesis of 1,3-disubstitued allenes.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00630

DOI: 10.1021/acs.joc.7b00630