Pd-catalyzed asymmetric Larock reaction for the atroposelective synthesis of N─N chiral indoles

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 10, 2024

Atropisomeric indoles defined by a N─N axis are an important class of heterocycles in synthetic and medicinal chemistry material sciences. However, they remain heavily underexplored due to limited methods challenging stereocontrol over the short bonds. Here, we report highly atroposelective access axially chiral via asymmetric Larock reaction. This protocol leveraged powerful role phosphoramidite ligand attenuate common dissociation original reaction, forming with excellent functional group tolerance high enantioselectivity palladium-catalyzed intermolecular annulation between readily available o -iodoaniline alkynes. The multifunctionality prepared allowed diverse post-coupling transformations, affording broad array functionalized indoles. Experimental computational studies have been conducted explore reaction mechanism, elucidating enantio-determining rate-limiting steps.

Language: Английский

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

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(24), P. 3551 - 3571

Published: Dec. 7, 2022

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

Language: Английский

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Structurally divergent enantioselective synthesis of benzofuran fused azocine derivatives and spiro-cyclopentanone benzofurans enabled by sequential catalysis

Chemical Science, Journal Year: 2023, Volume and Issue: 14(39), P. 10768 - 10776

Published: Jan. 1, 2023

An important objective in organic synthesis and medicinal chemistry is the capacity to access structurally varied complex molecules rapidly affordably from easily available starting materials. Herein, a protocol for divergent of benzofuran fused azocine derivatives spiro-cyclopentanone benzofurans has been developed via chiral bifunctional urea catalyzed reaction between aurone-derived α,β-unsaturated imine ynone followed by switchable annulation reactions Lewis base catalysts (DBU PPh3) with concomitant epimerization. The skeletally diversified products were formed high yields diastereo- enantioselectivities. Computational analysis DFT accurate DLPNO-CCSD(T) employed gain deeper insights into mechanistic intricacies investigate role skeletal diversity.

Language: Английский

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Catalytic stereodivergent and simultaneous construction of axial and point chirality

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(12), P. 3308 - 3319

Published: Jan. 1, 2024

An unprecedented ligand-enabled stereodivergent construction of both N–N axial and point chirality in a single step is reported.

Language: Английский

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Atroposelective N–N Axes Synthesis via Electrochemical Cobalt Catalysis

Organic Letters, Journal Year: 2024, Volume and Issue: 26(24), P. 5063 - 5068

Published: June 12, 2024

Here, we disclosed an unprecedented cobalt electrocatalyzed atroposelective C–H activation and annulation for the efficient construction of diversely functionalized N–N axes in undivided cell. A broad range allene substrates benzamides bearing different functionalities are compatible with generating axially chiral products good yields excellent enantioselectivities (up to 92% yield 99% ee). series synthetic applications control experiments were also performed, which further expanded practicality this strategy.

Language: Английский

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