The Application of 2-Benzyl-1,4-naphthoquinones as Pronucleophiles in Aminocatalytic Synthesis of Tricyclic Derivatives

Abstract

This study demonstrates an unprecedented reactivity of 2-substituted-1,4-naphthoquinones. By applying the principle of vinylogy, they have been employed as vinylogous pronucleophiles in the organocatalytic cascade reaction for the first time. This novel catalytic activation of 1,4-naphthoquinones enables access to carboannulated naphthalen-1(4 H)-one derivatives of biological importance. The site-selectivity and stereoselectivity of a process proved possible to control by the proper choice of reaction conditions.

2-Substituted 1,4-Naphthoquinones in [6 + 4]-Cycloaddition with 8,8-Dicyanoheptafulvene

“…Initial experiment using cesium carbonate as the catalyst showed that the chemoselectivity of the reaction was problematic (Scheme ). The formation of two different by-products 4a (as a result of dimerization of 1a ) and 5a (as a result of oxidation of the benzylic position in 1a ) was observed (Scheme ). Furthermore, they proved inseparable from the main product 3a .…”

“…Silica gel (silica gel 60, 230−400 mesh, Fluka) was used for flash chromatography (FC). 2-Substituted 1,4-naphthoquinones 1a−1h 7,11 and 8,8-dicyanoheptafulvene 2 2b were synthesized according to literature procedures. General Procedure for the Synthesis of Compounds 3a−3i.…”

“…In 2018, a new reactivity of 2-benzyl-1,4-naphthoquinones has been established in our research group . In contrast to classical electrophilic reactivity of these compounds, it involved their usage as a novel group of pronucleophiles.…”

“…4 In 2018, a new reactivity of 2-benzyl-1,4-naphthoquinones has been established in our research group. 7 In contrast to classical electrophilic reactivity of these compounds, 8 it involved their usage as a novel group of pronucleophiles. Their deprotonation, possible to perform under mild and basic conditions (as a result of efficacious stabilization of the obtained dienolate through the mesomeric effect), led to the formation of the corresponding dienolates, which proved to be suitable substrates in the aminocatalytic reaction cascade (Scheme 2, eq 1).…”

Extended Enolates: Versatile Intermediates for Asymmetric C‐H Functionalization via Noncovalent Catalysis

“…Thus, Albrecht developed an enantio‐ and diastereoselective entry to carboannulated naphthalene‐1(4 H )‐one derivatives 159 through a tandem addition/intramolecular aldol condensation starting from naphthoquinone 156 (Scheme 41 ). [98] A similar strategy by Wu and Chi that ends up with an intramolecular Mannich addition reaction served to prepare tetrasubstituted cyclohexene carbaldehydes 160 , [99] while Li, Cheng and coworkers described the enantioselective Michael addition reaction of dienolates from alkylidene oxindoles 137 to enals. [100] In this same context, Zanardi's group explored the reactivity of doubly unsaturated enolizable malononitriles against enals under dual activation of both nucleophile and electrophile.…”