Asymmetric Synthesis of Functionalized Dihydronaphthoquinones Containing Quaternary Carbon Centers via a Metal-Free Catalytic Intramolecular Acylcyanation of Activated Alkenes

Abstract

A novel metal-free catalytic annulation was developed through a Lewis base-catalyzed asymmetric allylic alkylation and the ensuing unprecedented asymmetric intramolecular acylcyanation of alkenes. This protocol provides a unique and facile access to prepare enantioenriched densely functionalized dihydronaphthoquinones accompanied by enantiomerically pure 3,3-disubstituted phthalides bearing quaternary carbon centers.

CF3-Substituted Mollugin 2-(4-Morpholinyl)-ethyl ester as a Potential Anti-inflammatory Agent with Improved Aqueous Solubility and Metabolic Stability

“…Lithiation of 17a – b , which was followed by quenching with anhydrous DMF, provided aldehyde 18a – b in good yields. Subsequent treatment of formylbenzamide 18a – b with trimethylsilyl cyanide in the presence of KCN and 18-crown-6 gave the corresponding key intermediates 19a – b [ 22 ]. Hauser annulation of cyanophthalide 19a – b with methyl acrylate and LiOtBu yielded the fluorinated 1,4-naphthoquinol 13a , d , which further underwent cyclization and transesterification to yield 15a , d .…”

Cyanide Anions as Nucleophilic Catalysts in Organic Synthesis

“…A related reaction sequence leading to tetralin-1,4-diones like compound 27 with a quaternary stereocenter is depicted in Scheme 7. 28 The lactone 26 with an ,-unsaturated ester moiety in the side chain is transformed by conjugate addition of a cyanide ion to give an ester enolate, which adds to the carbonyl group of the lactone furnishing intermediate 28. The oxabicyclic structure is then cleaved by elimination of the catalytic cyanide from the cyano-…”

Recent advancements in synthetic methodologies of 3-substituted phthalides and their application in the total synthesis of biologically active natural products

“…4.1.1 Metal-free catalytic annulation to develop enantioriched highly functionalized dihydronaphthoquinones. A metalfree catalytic annulation is developed by Zhuang and coworkers, 94 which involves Lewis base-mediated asymmetric allylic alkylation and a novel asymmetric intramolecular acyl cyanation of alkenes. This route provides a novel method to obtain enantioriched highly functionalized dihydronaphthoquinones 160 and chiral 3,3-disubstituted phthalides 158 having quaternary carbon centers (Schemes 29 and 30).…”