A Novel Sc(OTf)3‐Catalyzed (2+2+1)‐Cycloannulation/Aza‐Friedel–Crafts Alkylation Sequence toward Multicyclic 2‐Pyrrolines. Issue 53 (22nd August 2018)

• Record Type: Journal Article
• Authors: Schlegel, Marcel; Coburger, Peter; Schneider, Christoph
• Is Part Of: Chemistry. Volume 24:Issue 53(2018)
• Page Start: 14207
• Page End: 14212
• Publication Date: 2018-08-22
• Subjects: 1-azaallyl cations -- aza-Friedel–Crafts reaction -- Lewis acid catalysis -- multicomponent reactions -- tertiary alcohols; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201802478
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The rapid assembly of molecular complexity continues to be at the forefront of novel reaction development. In the pursuit of that goal, we herein report a novel Sc(OTf)3 ‐catalyzed, one‐pot multicomponent reaction that furnishes complex multicyclic 2‐pyrrolines with excellent overall yields and perfect diastereocontrol. This process is based on our previously established (2+2+1)‐cycloannulation of in situ generated 1‐azaallyl cations, 1, 3‐dicarbonyls and primary amines. The newly formed and highly reactive aminal moiety is readily substituted with indoles and pyrroles both as external and internal π‐nucleophiles to provide densely functionalized N‐heterocycles with four new σ‐bonds and two vicinal quaternary stereogenic centers. In addition, DFT calculations have been conducted to further characterize the intermediate 1‐azaallyl cations. Abstract : Creating complexity : A highly chemo‐ and diastereoselective synthesis of densely functionalized, multicyclic 2‐pyrrolines by Sc(OTf)3 ‐catalyzed multicomponent reactions of in situ‐generated 1‐azaallyl cations was established. A sequential dehydration/C−C‐coupling/enaminone‐aminal formation/aza‐Friedel–Crafts reaction was initiated to furnish complex N‐heterocycles with excellent yields in a one‐pot operation.