Hydrogen-Bond-Guided Reaction of Cyclohexadienone-aldehydes with Amines: Synthesis of an Aminal Group Containing a Fused Tetracyclic Framework

Abstract

A modular approach has been developed for an efficient synthesis of an aminal group containing a new tetracyclic framework. The strategy has been devised based on selective hydrogen-bond-guided aza-Michael addition of heteroaromatic amines to cyclohexadienone-aldehydes. The reaction is highly atom economic and practical and involves stereoselective construction of four new C–N bonds and four rings. The synthetic utility of the tetracyclic product was explored. The role of a H-bond was explained with the help of experimental and density functional theory (DFT) computation studies.

Progress on the Synthesis and Applications of Aminals: Scaffolds for Molecular Diversity

“…Moving on to more complex cyclic systems we can highlight the work of Song et.a.l 32 (Scheme 11) and Chauhan et.al. 33 (Scheme 12). Despite of having only one example of aminal synthesis, the unprecedent protocol developed by Song et.al.…”

“…Aminal (62) was prepared in 63% yield from the N-benzyl-6-nitroquinolin-1-ium bromide and (E)-4-(2-(phenylamino)phenyl)but-3-en-2-one with an enantiomeric excess of 61% (Scheme 11). Also exploring the reactivity of aminopyridine derivatives, Chauhan 33 introduced a sophisticated method for constructing symmetrical and unsymmetrical fused tetracyclic systems incorporating aminal moieties. This approach relied on a selective hydrogen-bondguided aza-Michael addition of cyclohexadienone-aldehydes (63) with heteroaromatic amines (64) (Scheme 12).…”

“…Moving on to more complex cyclic systems we can highlight the work of Du and Chen 32 (Scheme 11 ) and Grellier and Kumar 33 (Scheme 12 ). Despite describing only one example of aminal synthesis, the unprecedented protocol developed by Du and Chen 32 has the potential to forge interesting new polyheterocycles possessing aminals (e.g., 62 ).…”

“…Also exploring the reactivity of aminopyridine derivatives, Grellier and Kumar 33 introduced a sophisticated method for constructing symmetrical and unsymmetrical fused tetracyclic systems incorporating aminal moieties. This approach relied on a selective hydrogen-bond-guided aza-Michael addition of cyclohexadienone-aldehydes 63 with heteroaromatic amines 64 (Scheme 12 ).…”

Catalytic Friedel–Crafts Alkylative Desymmetrization of Cyclohexa-2,5-dienones: Access to Linear and Bridged Polycyclic Pyrroles and 3-Arylpyrroles

“…On the other hand, cyclohexa-2,5-dienones are potent prochiral building blocks and have been greatly used for the construction of bicyclic and polycyclic architectures . Along this line, most of the progress was achieved with alkynyl tethered dienone 1 in the presence of external or internal nucleophiles (Scheme b). , We have also used this line for the synthesis of hydronaphtho­[1,8- bc ]­furans and tetracyclic aminals . Furthermore, cyclohexa-2,6-dienones or p -quinols are known to be an “aromatic to be” electrophilic surrogate to afford functionalized arenes and biaryls .…”