Role of Cinchona Alkaloids in the Enantio- and Diastereoselective Synthesis of Axially Chiral Compounds

• DOI: 10.1021/acs.accounts.2c00515
• Publication Date: 2022-12-08T03:36:16Z
• Authors: Chiara Portolani; Giovanni Centonze; Paolo Righi; Giorgio Bencivenni
• Keywords: Stereocenter; Atropisomer; Desymmetrization; Axial Chirality; Kinetic resolution; Cinchona; Chirality; Cinchona Alkaloids

ConspectusAsymmetric synthesis using organic catalysts has evolved since it was first realized and defined. Nowadays, can be considered a valid alternative to transition metal catalysis for synthesizing chiral molecules. According the literature, number of asymmetric organocatalytic processes associated with atropisomer rapidly increased over past 10 years because organocatalysis addresses challenges posed by most widespread strategies used preparing axially molecules satisfactory results.These strategies, useful prepare wide range C–C, C–heteroatom, N–N atropisomers, vary from kinetic resolution direct arylation, desymmetrization, central-to-axial chirality conversion. In this field, our contribution focuses on determining novel methods during which, in cases, construction one or more stereogenic centers other than axis occurred. To efficiently address challenge, we exploited ability based cinchona alkaloid scaffold realize enantioselective transformations. Desymmetrization N-(2-tert-butylphenyl) maleimides that pursued C–N atropisomers. The main principle is presence rotationally hindered single bond owing large tert-butyl group. Following peculiar reactivity type substrate as powerful electrophile dienophile, several transformations.First, investigated vinylogous Michael addition 3-substituted cyclohexenones, where two contiguous stereocenters were concomitantly remotely formed stereocontrolled primary amine catalyst. Subsequently, desymmetrization via an Diels–Alder reaction activated unsaturated ketones enabled highly atropselective transformation efficient diastereoselectivity, thereby simultaneously controlling four elements. Employing bases allowed us desymmetrizations carbon nucleophiles, such 1,3-dicarbonyl compounds, cyanoacetates, oxindoles. These reactions, performed different types catalysts, highlighted versatility strategy pro-axially maleimides.Hereafter, studied Friedel–Crafts alkylation naphthols indenones, method conformationally restricted diastereoisomeric indanones. We selective Knoevenagel condensation This provided access enantioenriched olefins containing oxindole core. initiated intense program computational investigation mechanism processes. An understanding catalytic activity well role played acidic cocatalyst experimental work achieved.Recently, have garnered interest frontiers synthesis. As observed recent publications, there considerable development emerging topic field focused hydrazide atropisomers developing one-pot sequential protocol reactions high stereocontrol