Aminocatalytic [8+2] Cycloaddition Reactions toward Chiral Cyclazines

Abstract

An efficient and exceptionally stereoselective synthesis of chiral cycl[3.2.2]azines has been realized by means of the rational design and utilization of novel (E)‐3‐benzylidene‐3H‐pyrrolizines in iminium‐ion‐catalyzed [8+2] cycloaddition reactions. The presented protocol allows for the incorporation of diverse enals, including cinnamaldehydes, enolizable aldehydes, and substrates of extended conjugation. The obtained products contain both an electron‐rich alkenyl pyrrole moiety and an electron‐deficient carbaldehyde substituent, and both moieties can undergo selective transformations with retention of the stereochemical information established in the [8+2] cycloaddition.

Higher‐Order Cycloaddition Reactions for the Construction of Polycyclic Aromatic and Polycyclic Heteroaromatic Compounds

“…Chiral cyclazines can also be formed in a two‐step process from 3 H ‐pyrrolizines 34 involving a higher‐order [8+2] cycloaddition (Scheme 6a) [17] . The first step in this process is a proline‐mediated Mannich reaction of 34 with aryl aldehydes 35 delivering the 8π‐components 36 , featuring an accessible exocyclic position allowing for the envisioned [8+2] cycloaddition.…”