An overview of the applications of chiral phosphoric acid organocatalysts in enantioselective additions to CO and CN bonds

Organic Chemistry Frontiers, Год журнала: 2022, Номер 9(22), С. 6331 - 6399

Опубликована: Янв. 1, 2022

Since 2004, chiral phosphoric acids (CPAs) have emerged as highyl efficient organocatalysts, providing excellent results in a wide reaction scope. In this review, the applications of CPA for enantioselective additions to CO and CN bonds are covered.

Язык: Английский

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Enantioselective Divergent Syntheses of Cephalotaxus Alkaloids: (−)-Cephalotaxine, (−)-Cephalotine B, and (−)-Fortuneicyclidins A and B

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(16), С. 9233 - 9241

Опубликована: Апрель 12, 2023

A new strategy focusing on the last-stage asymmetric assembly of ring D, which inherently possesses densest part stereogenic centers and functional groups in A/B/C/D system (-)-cephalotaxine, has been developed, a novel Rh-catalyzed (2 + 3) annulation tertiary enamides with enoldiazoacetates is designed explored for enantioselective construction crucial cyclopentane D bearing unique spirocyclic aza-quaternary stereocenter. Based expeditious access chiral functionalized building block tetracyclic system, concise total synthesis (-)-cephalotaxine starting from readily available homopiperonyl alcohol achieved nine steps only two column chromatography purifications. Following tactical introduction Meinwald rearrangement, divergent syntheses (-)-cephalotine B an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin unprecedented C3-C10 its 2-epimer (16 steps) have also accomplished first time.

Язык: Английский

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Organocatalytic Strategies for the Development of the Enantioselective Inverse‐electron‐demand Hetero‐Diels‐Alder Reaction

Chemistry - A European Journal, Год журнала: 2021, Номер 27(49), С. 12509 - 12520

Опубликована: Июнь 16, 2021

Cycloaddition reactions, in particular Diels-Alder have attracted a lot of attention from organic chemists since they represent one the most powerful methodologies for construction carbon-carbon bonds. In particular, inverse-electron-demand hetero-Diels-Alder reactions been an important breakthrough synthesis heterocyclic compounds. Among all their variants, organocatalytic enantioselective version has widely explored asymmetric diversely functionalized scaffolds under reaction conditions encompassed within green chemistry field is great interest. this review, profound revision on latest advances inverse-electron demand shown.

Язык: Английский

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Regiodivergent Organocatalytic Reactions

Catalysts, Год журнала: 2021, Номер 11(8), С. 1013 - 1013

Опубликована: Авг. 22, 2021

Organocatalysts are abundantly used for various transformations, particularly to obtain highly enantio- and diastereomeric pure products by controlling the stereochemistry. These applications of organocatalysts have been topic several reviews. emerged as one very essential areas research due their mild reaction conditions, cost-effective nature, non-toxicity, environmentally benign approach that obviates need transition metal catalysts other toxic reagents. Various types including amine catalysts, Brønsted acids, Lewis bases such N-heterocyclic carbene (NHC) cinchona alkaloids, 4-dimethylaminopyridine (DMAP), hydrogen bond-donating gained renewed interest because regioselectivity. In this review, we present recent advances in regiodivergent reactions governed organocatalysts. Additionally, briefly discuss pathways achieving changes conditions solvents, additives, or temperature.

Язык: Английский

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Enantioselective and Diastereodivergent Synthesis of Spiroindolenines via Chiral Phosphoric Acid-Catalyzed Cycloaddition

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(30), С. 11611 - 11619

Опубликована: Июль 23, 2021

A diastereodivergent and enantioselective synthesis of chiral spirocyclohexyl-indolenines with four contiguous stereogenic centers is achieved by a phosphoric acid-catalyzed cycloaddition 2-susbtituted 3-indolylmethanols 1,3-dienecarbamates. Modular access to two different diastereoisomers high enantioselectivities was obtained careful choice reaction conditions. Their functional group manipulation provides an efficient enantioenriched spirocyclohexyl-indolines -oxindoles. The origins this stereocontrol have been identified using DFT calculations, which reveal unexpected mechanism compared our previous work dealing enecarbamates.

Язык: Английский

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Hydroarylation of enamides enabled by HFIP via a hexafluoroisopropyl ether as iminium reservoir

Chemical Science, Год журнала: 2022, Номер 13(28), С. 8436 - 8443

Опубликована: Янв. 1, 2022

Hexafluoroisopropanol reversibly traps and releases iminium ions to greatly expand the scope of enamide hydroarylation, a mechanism that is likely common other reactions featuring carbocations in solvent.

Язык: Английский

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Unlock the C–N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation

The Journal of Organic Chemistry, Год журнала: 2023, Номер 89(1), С. 216 - 223

Опубликована: Дек. 18, 2023

The C–N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence trifluoromethanesulfonic acid (TfOH). method enables practical synthesis valuable enamides without use any metal reagent. In addition, this protocol can also be expanded to reactions sulfonamides, and late-stage functionalization on sulfonamide drugs such as Celecoxib Valdecoxib verified. Moreover, participation water assisting process identified isotope labeling experiments using D2O, disclosing a new possibility designing catalytic tactic other reactions.

Язык: Английский

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Strategies toward the Difunctionalizations of Enamide Derivatives for Synthesizing α,β-Substituted Amines

Accounts of Chemical Research, Год журнала: 2022, Номер 55(22), С. 3265 - 3283

Опубликована: Ноя. 1, 2022

ConspectusEnamide and enecarbamate derivatives containing a nucleophilic center at the β-position from their nitrogen atom as well latent electrophilic site α-position are interesting motifs in organic chemistry. This dual reactivity─analogous that of enamines─enables difunctionalization increased structural complexity. Furthermore, an electron-withdrawing group on drastically increases stability. In respect, enamides enecarbamates excellent partners for multicomponent transformations, our research primarily focuses these compounds particular.Difunctionalization generally occurs through addition electrophile to form iminium, which can subsequently react with species. Although potent, such approach is highly challenging due low stability intermediate leading undesired hydrolysis or oligomerization. Epimerization, competitivity, compatibility issues between reaction additional hindrances developing methodologies. To overcome limitations, we described many complementary strategies.To control enantioselectivity chiral phosphoric acids were found be particularly well-suited activate multiple reactants formation hydrogen bonds network, allowing organized transition state pocket. Interestingly, when deprotonated phosphates, they also play role ligands Lewis acidic metals.To avoid iminium oligomerization, successfully used stabilized α-arylated enamides. However, this was restricted simple β-position. achieve difunctionalizations α-unsubstituted derivatives, explored reversibly linked nucleophile address problem. Alternatively, devised sequential methodology resolving issue N-acyl based its trapping using temporary (alcohol thiol). agent could further displaced by desired final α-substituent under photocatalytic activation. led us design new bifunctional acid catalysts bearing chromophores merge asymmetric organocatalysis photochemistry.These photocatalysis studies incited focus radical processes manage original functionalizations would not feasible otherwise. β-Alkylation β-trifluoromethylation via visible-light-promoted transfer additions performed. As β-allylations remained unattainable precedent methods, eventually turned attention cerium(IV)-mediated oxidative single electron transfers. It allowed singly occupied molecular orbital activation substrates elicit umpolung reactivity.Thus, functionalization appears valid synthetic strategy obtaining important building blocks agrochemical, pharmaceutical, cosmetic industries, including diamines, haloamines, aminotryptamines, less accessible trifluoromethylated allylic compounds.

Язык: Английский

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Catalyst-controlled stereoselective carbon–heteroatom bond formations by N-heterocyclic carbene (NHC) organocatalysis

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(17), С. 4437 - 4458

Опубликована: Янв. 1, 2023

This review highlights recent advances in stereoselective carbon–heteroatom bond forming reactions, including C–N, C–O, C–S, C–F, C–P, etc ., that were enabled by NHC organocatalysis with a focus on new activation modes and reactive intermediates.

Язык: Английский

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Enantioselective and Regiodivergent Synthesis of Dihydro-1,2-oxazines from Triene-Carbamates via Chiral Phosphoric Acid-Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(48), С. 26504 - 26515

Опубликована: Ноя. 27, 2023

Conjugated trienes are fascinating building blocks for the rapid construction of complex polycyclic compounds. However, limited success has been achieved due to challenging regioselectivity control. Herein, we report an enantio- and diastereoselective process allowing regioselectively control functionalization NH-triene-carbamates. Synthesis chiral cis-3,6-dihydro-2H-1,2-oxazines is by a phosphoric acid catalyzed Nitroso-Diels-Alder cycloaddition involving [(1E,3E,5E)-hexa-1,3,5-trien-1-yl]carbamates. Moreover, modular access three different regioisomers with excellent diastereoselectivities high enantioselectivities obtained careful choice reaction conditions. A computational study reveals that influenced steric demand substituents at 6-position triene, as well noncovalent interactions between two partners. Utility each regioisomeric cycloadduct highlighted variety synthetic transformations.

Язык: Английский

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