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.…”

A DFT study of Ni-catalyzed (3 + 3)-annulation between donor–acceptor cyclopropanes and diaziridines

“…6 In terms of catalysis, transition metals 7 and small molecules can catalyze annulation reactions. 8,9 As important species for annulation, unsaturated compounds have been widely used and studied. 10 Because of distinct properties in various annulation transformations, DACs (donor–acceptor cyclopropanes) have evolved as a hot spot in organic synthesis.…”

Asymmetric higher-order [10 + n] cycloadditions of palladium-containing 10π-cycloaddends

“…Higher-order cycloaddition involving conjugated systems with more than 6π-electrons, which enables rapid construction of complicated cyclic frameworks, 1 has received considerable attention since its discovery in the 1960s. 2 In spite of its charm in organic synthesis, higher-order cycloaddition generally suffers from low reactivity, and poor periselectivity and stereoselectivity; thus a variety of pre-prepared cyclic polyenes (>4π) have been commonly utilised, including fulvenes, 3 Cr(0)-cycloheptatriene complexes, 4 tropone and its analogues, 5 and 3 H -pyrrolizines, 6 as well as amino-stabilised isobenzofulvenes, 7 in combination with diverse 2π- or 4π-systems under different conditions ( Scheme 1a ). Recently, significant progress in the field of higher-order cycloaddition reactions has been made with some well-designed carbonyl substrates, which could be activated by a suitable organocatalyst to generate several types of 6π, 8π, 10π or even 12π-cycloaddends in situ , typically featuring HOMO-raised polyenamine 8 or polyenolate species 9 ( Scheme 1b ).…”