Diastereoselective Synthesis of 3,4-Benzomorphan Derivatives via Tandem [5 + 1]/Hemiaminalization of (2-Aminoaryl)divinyl Ketones

Abstract

A novel tandem formal [5 + 1]/hemiaminalization reaction based on the readily available (2-aminoaryl)divinyl ketones and various nucleophiles has been developed. The reaction represents a highly efficient and convenient methodology for the synthesis of 3,4-benzomorphan derivatives with high diastereoselectivity, and three new bonds and two rings are successively formed in one step under mild, metal-free conditions.

Triple Nucleophilic Attack of Nitromethane on (2-Iminoaryl)divinyl Ketones: A Domino Synthetic Strategy for Hexahydrophenanthridinones

“…On the basis of these results (Table , Schemes and ), our previous work, , and related literatures, ,− we proposed two possible pathways (Scheme , taking the formation of hexahydrophenanthridin-9­(5 H )-one 3aa as an example). Path A may involve (1) a base-promoted intermolecular Michael addition of (2-iminoaryl)­divinyl ketone 2aa and nitromethane (attack at the less hindered enone moiety of 2aa ) to provide intermediate I , (2) a consecutive intramolecular Michael addition of intermediate I by selective attack at the less hindered face to generate cyclohexanone intermediate II in a diastereoselective manner, , and (3) an intramolecular aza-Henry reaction of II to furnish hexahydrophenanthridin-9­(5 H )-one 3aa . − When (4-chlorobenzylidene)­amino)­phenyl)-6,6-dimethylhepta-1,4-dien-3-one 2ai bearing a bulky tert -butyl group was employed in this reaction, tetrahydroquinoline 4ai was obtained in 60% yield (Scheme ). Although the bulky tert -butyl group in acceptors often affects the orientation of certain reactions, , this result is consistent with Xu’s work (Scheme , eq 2) .…”

“…For example, synthesis of cyclohexanone derivatives with divinyl ketones as acceptors via double Michael addition (Scheme , eq 1) or use of iminochalcones gave nitrotetrahydroquinolines through a tandem Michael/nitro-Mannich sequence (Scheme , eq 2) . Recently, we developed a novel and general tandem double Michael addition/hemiaminalization reaction of (2-aminoaryl)­divinyl ketones 1 with nitromethane, which act as a binucleophile for the direct and convenient synthesis of 3,4-benzomorphans in one step under mild base conditions (Scheme , eq 3) . To our best knowledge, it is hardly ever seen that nitromethane acts as a triple donor (trinucleophile) toward three differently reactive acceptors presented in the same molecule to create polycyclic compounds.…”

Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems

“…Presumably, these protocols could be readily adapted to the preparation of the non-racemic forms of these heterocycles through, for example, the enantioselective 1,2reduction of the starting enones 7 and 10. Given the extensive and ongoing interest in benzomorphans and related systems, 18 the processes outlined in Schemes 4 and 5 should be of considerable utility in a range of settings.…”

A Domino Aza-Prins/Friedel–Crafts Reaction for the Synthesis of Benzomorphans

“…In addition, closely related morphan scaffolds can be found in natural products such as strychnochromine and aspernomine. 2 Benzomorphans are therefore interesting targets and several syntheses have been published. 2,3 The Prins reaction is the acid-catalyzed addition of aldehydes to alkenes and was developed almost a century ago.…”

“…2 Benzomorphans are therefore interesting targets and several syntheses have been published. 2,3 The Prins reaction is the acid-catalyzed addition of aldehydes to alkenes and was developed almost a century ago. 4 It allows the formation of C-C bonds and gives acetals, diols, and allyl or homoallyl alcohols, depending on the reaction conditions.…”