Cross‐conjugated Trienamine Catalysis with α′‐Alkylidene 2‐Cyclohexenones: Application in β,γ‐Regioselective Aza‐Diels–Alder Reaction

Abstract

Endo-type cross-conjugated trienamines between highly congested α'-alkylidene 2-cyclohexenones and a chiral primary amine catalyst serve as HOMO-raised dienophiles in inverse-electron-demand aza-Diels-Alder cycloadditions with a number of 1-azadiene substrates. The reactions exhibit exclusive β,γ-regioselectivity, and multifunctional products with high molecular complexity are efficiently constructed in excellent diastereo- and enantioselectivity (>19:1 d.r., up to 99 % ee).

Organocatalytic Asymmetric Transformations Involving the Cyclic Imine Moiety in Indole and Isoindole Related Heterocycles

“…The combination of Cat. 29′ and salicylic acid could also effectively promote the asymmetric IED aza‐DA cycloadditions between 2d and highly congested α′‐alkylidene 2‐cyclohexenones 89 , which was recently described by the Chen laboratory . The β,γ‐regioselective [4+2] annulation proceeded through the in situ generation of HOMO‐raised endo ‐type cross‐trienamine intermediate 90 from 89 and Cat.…”

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…The same team [173] has recently implemented a conceptually different version of the trienamine catalysis for the IED aza‐DAR with participation of cyclic 2,2′‐dienones 154 as active dienophile precursors. In the presence of the 9‐amino‐9‐deoxyepiquinine XVIIb /salicylic acid (SA) catalytic system, these substrates reversibly produced the trienamine species containing two endo ‐ and one exo ‐cyclic C=C bonds which could serve as HOMO‐raised dienophiles in asymmetric reactions with saccharin‐ or 2‐vinyl‐benzo[ d ]oxa(thia)zole‐based 1‐aza‐dienes 148 and 155 (Scheme 56).…”

Polyenals and Polyenones in Aminocatalysis: A Decade Building Complex Frameworks from Simple Blocks

“…In 2017, an endo ‐type cross conjugated trienamine catalysis by using dienones was reported by Chen et al α'‐Alkylidene 2‐cyclohexenone substrates 124 proceeded in an inverse electron‐demand aza‐Diels–Alder cycloaddition with 3‐styryl‐1,2‐benzoisothiozole‐1,1‐dioxide 125 in the presence of cinchona‐based primary amine Cat.19 , leading to the fused heterocyclic frameworks 126 with a β,γ‐regioselectivity, endo ‐diastereoselectivity and good to excellent enantioselectivity (Scheme ) …”