Organocatalytic stereoselective [8+2] and [6+4] cycloadditions

Abstract

Cycloadditions that involve more than six π electrons are termed higher-order cycloadditions and are an excellent tool for solving complex synthetic challenges, as they provide direct access to polycyclic scaffolds that contain medium-sized rings. They have interesting synthetic potential for the discovery of new bioactive molecules and in natural product synthesis. It is peculiar that stereocontrolled [8+2] and [6+4] cycloadditions have been largely neglected for the past 50 years. Here we demonstrate a cross-dienamine activation of 2-cyclopentenone and the unprecedented endocyclic linear-dienamine activation of 2-cyclohexenones and 2-cycloheptenones. These dienamine intermediates undergo aminocatalytic stereoselective [8+2], [6+4] and formal [4+2] cycloadditions with various heptafulvenes. The periselectivities of the cycloadditions are controlled based on the ring size of the 2-cycloalkenones and the substitution patterns of the heptafulvenes. The chiral products obtained undergo various chemical and photochemical single-step transformations that give access to other classes of all-carbon polycyclic scaffolds.

Organocatalyzed Synthesis of [3.2.1] Bicyclooctanes

“…Very recently Jørgensen has described the first catalytic stereoselective intermolecular [6 + 4] cycloaddition (Scheme 18) [37]. This reaction is included into the so-called higher-order cycloadditions, excellent tools for solving synthetic challenges [37,38].…”

“…This reaction is included into the so-called higher-order cycloadditions, excellent tools for solving synthetic challenges [37,38]. The novel organocatalytic asymmetric higher-order cycloaddition paves the way for further development in this area for the [3.2.1] bicyclic systems.…”

Catalytic Asymmetric [8+3] Annulation Reactions of Tropones or Azaheptafulvenes with meso‐Aziridines

“…However, the wider application of such reactions was hampered by the lack of periselectivity and other competing side reactions. Moreover, enantioselective versions of these transformations are limited and only several of them were achieved recently –. Among them, enantioselective [8+3] cycloadditions of tropones remain scarce.…”

The Game of Electrons: Organocatalytic Higher‐Order Cycloadditions Involving Fulvene‐ and Tropone‐Derived Systems

“…The ability to generate electron‐rich dienamines through the HOMO‐rising aminocatalytic principle has also been utilized for the development of higher‐order cycloadditions. In 2017, cycloadditions between various dienamines derived from 2‐cycloalkenones 69 a – c under aminocatalytic conditions and tropone 36 a or heptafulvene derivatives 68 a,b were studied in details by Jørgensen and co‐workers (Schemes and ) . This work led to the development of enantioselective [6+4]‐, [8+2]‐ or [4+2]‐cycloadditions through aminocatalysis using primary amines derived from the cinchona alkaloids.…”