TY - JOUR
T1 - Palladium and Lewis-Acid-Catalyzed Intramolecular Aminocyanation of Alkenes
T2 - Scope, Mechanism, and Stereoselective Alkene Difunctionalizations
AU - Pan, Zhongda
AU - Wang, Shengyang
AU - Brethorst, Jason T.
AU - Douglas, Christopher J.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/3/7
Y1 - 2018/3/7
N2 - An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover 13C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.
AB - An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover 13C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.
UR - http://www.scopus.com/inward/record.url?scp=85043265630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043265630&partnerID=8YFLogxK
U2 - 10.1021/jacs.8b01330
DO - 10.1021/jacs.8b01330
M3 - Article
C2 - 29465996
AN - SCOPUS:85043265630
SN - 0002-7863
VL - 140
SP - 3331
EP - 3338
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 9
ER -