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Enantioselective synthesis of α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines via chiral phosphoric acid catalysis.

ABSTRACT: An enantioselective Friedel-Crafts reaction of cyclic α-diaryl N-acyl imines with indolizines catalyzed by a chiral spirocyclic phosphoric acid has been developed. The asymmetric transformation proceeds smoothly to afford α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines in good yields with up to 98% ee under mild conditions.

SUBMITTER: Zhong J

PROVIDER: S-EPMC9284663 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines via chiral phosphoric acid catalysis.

Zhong Jialing J Pan Rihuang R Lin Xufeng X

RSC advances 20220715 32

An enantioselective Friedel-Crafts reaction of cyclic α-diaryl N-acyl imines with indolizines catalyzed by a chiral spirocyclic phosphoric acid has been developed. The asymmetric transformation proceeds smoothly to afford α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines in good yields with up to 98% ee under mild conditions. ...[more]

PMID: 35919132

Similar Datasets

Enantioselective synthesis of α-tetrasubstituted (1-indolizinyl) (diaryl)-methanamines via chiral phosphoric acid catalysis† † Electronic supplementary information (ESI) available. CCDC 2167990 (3p). For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d3ra07636a

Project description: Not available

| S-EPMC10759308 | biostudies-literature

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis

Project description:Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid–catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction. A de novo access to chiral α,α-disubstituted ketones by visible-light photoactivation and phosphoric acid catalysis is developed.

| S-EPMC10275591 | biostudies-literature

Enantioselective Intramolecular Allylic Substitution via Synergistic Palladium/Chiral Phosphoric Acid Catalysis: Insight into Stereoinduction through Statistical Modeling.

Project description:The mode of asymmetric induction in an enantioselective intramolecular allylic substitution reaction catalyzed by a combination of palladium and a chiral phosphoric acid was investigated by a combined experimental and statistical modeling approach. Experiments to probe nonlinear effects, the reactivity of deuterium-labeled substrates, and control experiments revealed that nucleophilic attack to the π-allylpalladium intermediate is the enantio-determining step, in which the chiral phosphate anion is involved in stereoinduction. Using multivariable linear regression analysis, we determined that multiple noncovalent interactions with the chiral environment of the phosphate anion are integral to enantiocontrol in the transition state. The synthetic protocol to form chiral pyrrolidines was further applied to the asymmetric construction of C-O bonds at fully substituted carbon centers in the synthesis of chiral 2,2-disubstituted benzomorpholines.

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Enantioselective Tandem Cyclization of Alkyne-Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis.

Project description:Reported is the enantioselective synthesis of tetracyclic indolines using silver(I)/chiral phosphoric acid catalysis. A variety of alkyne-tethered indoles are suitable for this process. Mechanistic studies suggest that the in situ generated silver(I) chiral phosphate activates both the alkyne and the indole nucleophile in the initial cyclization step through an intermolecular hydrogen bond and the phosphate anion promotes proton transfer. In addition, further modifications of the cyclization products enabled stereochemistry-function studies of a series of bioactive indolines.

| S-EPMC5997581 | biostudies-literature

Chiral spirocyclic phosphoric acid-catalyzed enantioselective synthesis of heterotriarylmethanes bearing an amino acid moiety.

Project description:We present herein an enantioselective protocol for the chiral phosphoric acid-catalyzed addition of 3-arylisoxazol-5-amines to highly reactive 3-methide-3H-pyrroles to provide a diverse range of heterotriarylmethanes bearing an amino acid moiety in good yields (up to 97%) and high enantioselectivities (up to 93% ee) under mild conditions. The chiral spirocyclic phosphoric acid is crucial in converting the initial 1H-pyrrol-3-yl carbinols into reactive 3-methide-3H-pyrroles and obtaining the good enantiocontrol, thereby facilitating the desired enantioselective transformation.

| S-EPMC10285616 | biostudies-literature

Metal-free, visible-light induced enantioselective three-component dicarbofunctionalization and oxytrifluoromethylation of enamines via chiral phosphoric acid catalysis.

Project description:Using diverse carbon-centered radical precursors and electron-rich (hetero)aromatics and alcohols as nucleophiles, a visible-light driven chiral phosphoric acid (CPA) catalyzed asymmetric intermolecular, three-component radical-initiated dicarbofunctionalization and oxytrifluoromethylation of enamines was developed, which provides a straightforward access to chiral arylmethylamines, aza-hemiacetals and γ-amino acid derivatives with excellent enantioselectivity. As far as we know, this is the first example of constructing a chiral C-O bond using simple alcohols via visible-light photocatalysis. Chiral phosphoric acid played multiple roles in the reaction, including controlling the reaction stereoselectivity and promoting the generation of radical intermediates by activating Togni's reagent. Mechanistic studies also suggested the importance of the N-H bond of the enamine and indole for the reactions.

| S-EPMC8790774 | biostudies-literature

Enantioselective Synthesis of α,α-Disubstituted Lactones via a Chiral Bronsted Acid Catalyzed Intramolecular Cyclization.

Project description: Not available

| S-EPMC5198840 | biostudies-literature

Synthesis of Lactams via a Chiral Phosphoric Acid-Catalyzed Aniline Cyclization.

Project description:The enantioenriched lactams disclosed in this work are synthesized concisely in four steps. In the penultimate reaction, a benzylamine species complexes with a chiral phosphoric acid to produce benzo-fused δ-lactams equipped with an all-carbon quaternary stereocenter. Partial and full reductions were carried out on the ester and amide moieties, and a Suzuki-Miyaura cross-coupling expanded the molecule from the aromatic ring. Finally, our method was successful at a >1 g scale, indicating that the method has important practical use.

| S-EPMC11382273 | biostudies-literature

Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization.

Project description:Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses significant challenges, due to the difficulty in controlling both chiral C─O axes, and their more flexible conformations. Herein, an efficient protocol for catalytic enantioselective synthesis of axially chiral diaryl ethers is presented using organocatalyzed asymmetric Povarov reaction-enabled desymmetrization, followed by aromatizations. This method yields a wide range of novel quinoline-based diaryl ether atropoisomers in good yields and high enantioselectivities. Notably, various aromatization protocols are developed, resulting in a diverse set of polysubstituted quinoline-containing diaryl ether atropisomers. Thermal racemization studies suggested excellent configurational stabilities for these novel diaryl ether atropisomers (with racemization barriers up to 38.1 kcal mol-1). Moreover, this research demonstrates for the first time that diaryl ether atropisomers lacking the bulky t-Bu group can still maintain a stable configuration, challenging the prior knowledge in the field. The fruitful derivatizations of the functional group-rich chiral products further underscore the value of this method.

| S-EPMC11425261 | biostudies-literature

Chiral phosphoric acid-catalyzed enantioselective construction of structurally diverse benzothiazolopyrimidines.

Project description:A highly efficient catalytic enantioselective [4+2] cycloaddition was developed between 2-benzothiazolimines and enecarbamates. A wide range of benzothiazolopyrimidines bearing three contiguous stereogenic centers was obtained in high to excellent yields and with excellent diastereo- and enantioselectivities (d.r. > 98 : 2 and up to >99% ee). Furthermore, this chiral phosphoric acid-catalyzed strategy was scalable and enabled access to a new class of optically pure Lewis base isothiourea derivatives.

| S-EPMC6461124 | biostudies-literature