Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(5), С. 2884 - 2900

Опубликована: Янв. 25, 2023

The involvement of planar carbocation intermediates is generally considered undesirable in asymmetric catalysis due to the difficulty gaining facial control and their intrinsic stability issues. Recently, suitably designed chiral catalyst(s) have enabled a guided approach nucleophiles one prochiral faces carbocations affording high enantiocontrol. Herein, we present vital mechanistic insights from our comprehensive density functional theory (B3LYP-D3) study on Ir-phosphoramidite-catalyzed reductive deoxygenation racemic tertiary α-substituted allenylic alcohols. catalytic transformation relies synergistic action phosphoramidite-modified Ir catalyst Bi(OTf)3, first leading formation an Ir-π-allenyl intermediate through turn-over-determining SN1 ionization, followed by face-selective hydride transfer Hantzsch ester analogue yield enantioenriched product. Bi(OTf)3 was found promote significant number ionic interactions as well noncovalent (NCIs) with substrates (allenylic alcohol ester), thus providing access lower energy route compared pathways devoid Bi(OTf)3. In nucleophilic addition, induction depend efficacy such key NCIs. curious case reversal enantioselectivity, when α-substituent allenyl changed methyl cyclopropyl, identified originate change mechanism enantioconvergent pathway (α-methyl) dynamic kinetic (α-cyclopropyl). These molecular could lead newer strategies tame enantioselective reactions using suitable combinations catalysts additives.

Язык: Английский

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Design Approaches That Utilize Ionic Interactions to Control Selectivity in Transition Metal Catalysis

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

The attractive force between two oppositely charged ions can constitute a powerful design tool in selective catalysis. Enzymes make extensive use of ionic interactions alongside variety other noncovalent interactions; recent years have seen synthetic chemists begin to seriously explore these catalyst designs that also incorporate reactive transition metal. In isolation, single interaction exhibits low directionality, but many successful systems they exist additional which provide high degree organization at the selectivity-determining state. Even situations with key interaction, directionality is not always detrimental, and even be advantageous, conferring generality catalyst. This Review explores approaches utilize control selectivity metal It divided into halves: first, occurs outer sphere complex, using ligand or bound an anion; second, bears formal charge, associated counterion.

Язык: Английский

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Controlling Stereoselectivity with Noncovalent Interactions in Chiral Phosphoric Acid Organocatalysis

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Chiral phosphoric acids (CPAs) have emerged as highly effective Brønsted acid catalysts in an expanding range of asymmetric transformations, often through novel multifunctional substrate activation modes. Versatile and broadly appealing, these benefit from modular tunable structures, compatibility with additives. Given the unique types noncovalent interactions (NCIs) that can be established between CPAs various reactants─such hydrogen bonding, aromatic interactions, van der Waals forces─it is unsurprising catalyst systems become a promising approach for accessing diverse chiral product outcomes. This review aims to provide in-depth exploration mechanisms by which impart stereoselectivity, positioning NCIs central feature connects broad spectrum catalytic reactions. Spanning literature 2004 2024, it covers nucleophilic additions, radical atroposelective bond formations, highlighting applicability CPA organocatalysis. Special emphasis placed on structural mechanistic features govern CPA-substrate well tools techniques developed enhance our understanding their behavior. In addition emphasizing details stereocontrolling elements individual reactions, we carefully structured this natural progression specifics broader, class-level perspective. Overall, findings underscore critical role catalysis significant contributions advancing synthesis.

Язык: Английский

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Cooperative Asymmetric Dual Catalysis Involving a Chiral N-Heterocyclic Carbene Organocatalyst and Palladium in an Annulation Reaction: Mechanism and Origin of Stereoselectivity

ACS Catalysis, Год журнала: 2023, Номер 13(2), С. 1133 - 1148

Опубликована: Янв. 3, 2023

The increasing number of examples on cooperative dual catalysis involving organocatalysts and transition metal catalysts indicate their wider acceptance utility in synthetic applications. In such reactions, the concurrent activation substrates is likely to present mechanistic complexities. one studies, designed for intermolecular annulation aimed at making a biologically important class benzazepines, chiral N-heterocyclic carbenes engage an enal form Breslow intermediate (nucleophilic partner) Pd(0) activates rac-vinyl benzoxazinanone as Pd-π-allyl (electrophile). Given current importance lack molecular insights origin high enantio-/diastereoselectivities cooperativity catalytic we have undertaken detailed computational investigation using density functional theory. kinetically most accessible from (S)- (R)-vinyl found be Cre Csi (where re si denote open prochiral faces through which nucleophile can add), respectively. An energetically favorable change configuration Cre, via PPh3-induced π–σ–π isomerization, suggests that enantioconvergent mechanism was responsible enrichment desired species. Ready availability higher energy state (TS) alternative nucleophilic addition ee (computed >99%, experimental 99%). Improved shape complementarity between electrophile preferred C–C bond formation TS well noncovalent interactions (C–H··· π, π···π, H-bonding) therein dictates diastereoselectivity. intramolecular C–N final annulated product turnover-determining TS. Molecular energetic features, obtained our computations, are concert with several observations, even beyond sense extent stereoselectivities.

Язык: Английский

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Rhodium-catalyzed diastereoselective synthesis of highly substituted morpholines from nitrogen-tethered allenols

Chemical Communications, Год журнала: 2023, Номер 59(29), С. 4376 - 4379

Опубликована: Янв. 1, 2023

Rhodium-catalyzed intramolecular cyclization of nitrogen-tethered allenols was investigated for the synthesis functionalized morpholines.

Язык: Английский

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Synergistic Palladium/Chiral Phosphoric Acid-Catalyzed Kinetic Resolution via Stereoselective Intramolecular Substitution of Unactivated Allylic Alcohols

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(9), С. 5813 - 5826

Опубликована: Апрель 7, 2023

This paper reports the kinetic resolution of racemic secondary alcohols (O-nucleophiles) via stereoselective intramolecular allylic substitution. The reaction was enabled by synergistic palladium and chiral phosphoric acid catalysis produced cis-1,3-disubstituted 1,3-dihydroisobenzofurans with a selective factor up to 60.9 diastereomeric ratio 7.8:1. Asymmetric synthesis compound antihistaminic activity demonstrated as application this methodology.

Язык: Английский

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Nickel-Catalyzed Asymmetric Hydroamination of Branched 1,3-Diene: Mechanism and Origin of Regio- and Enantioselectivities

ACS Catalysis, Год журнала: 2024, Номер 14(16), С. 11990 - 12005

Опубликована: Июль 26, 2024

Selective hydrofunctionalization of feedstock molecules such as 1,3-diene has received notable attention in recent years. In particular, nickel-catalyzed hydrofunctionalizations have served valuable examples chemo-, regio-, and enantioselective transformations conjugated dienes. However, the mechanistic understanding origin observed selectivities several reactions continue to remain rather limited. Herein, we provide molecular insights derived through a comprehensive density functional theory (B3LYP-D3) investigation focusing on stereoinduction promising Ni-catalyzed intermolecular hydroamination branched 1,3-dienes (2-phenyl-1,3-diene) by benzylamine (BnA) presence trifluoroethanol (TFE) additive. The most preferred pathway is identified considering different likely catalyst–substrate combinations well timing sequence activation substrates. discernible role TFE found be Ni-bound form an electrophilic Ni-π-allyl alkoxy intermediate, which outer-sphere nucleophilic addition BnA energetically likely. addition, transition states enjoy explicit noncovalent interactions with 2:1 BnA-TFE cluster. relative Gibbs energies for 3,4-addition intermediate indicate clear preference re prochiral face leading R enantiomer hydroaminated product over potentially competitive achiral 1,4-addition product. lowest energetic span 16.7 kcal/mol noted pathway, turnover-determining step. predicted regio- enantioselectivities are very good agreement experimental report, δE consistent reaction conditions employed.

Язык: Английский

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Role of Chiral Skeleton in Chiral Phosphoric Acids Catalyzed Asymmetric Transfer Hydrogenation: A DFT Study

Catalysts, Год журнала: 2023, Номер 13(1), С. 98 - 98

Опубликована: Янв. 3, 2023

Chiral phosphoric acids (CPAs) have received considerable attention due to their high activity for enantioselective transformations. However, the role of various chiral skeletons CPAs in regulating mechanism and enantioselectivity asymmetric transfer hydrogenation has remained unclear. Density functional theory (DFT) calculations are performed elucidate on acidity, mechanism, enantioselectivity, kinetic stabilities transition states (TSs) Asymmetric Transfer Hydrogen (ATH) reaction catalyzed by five CPAs. We found that acidity is strongly dependent skeleton. The origin ATH arises from differential noncovalent interactions between TSs Moreover, shape size catalyst pocket depending play key roles stability ATH. This study might facilitate design computationally screening guide strategic choice CPA reduce experimental workload.

Язык: Английский

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Molecular Understanding and Practical In Silico Catalyst Design in Computational Organocatalysis and Phase Transfer Catalysis—Challenges and Opportunities

Molecules, Год журнала: 2023, Номер 28(4), С. 1715 - 1715

Опубликована: Фев. 10, 2023

Through the lens of organocatalysis and phase transfer catalysis, we will examine key components to calculate or predict catalysis-performance metrics, such as turnover frequency measurement stereoselectivity, via computational chemistry. The state-of-the-art tools available potential energy and, consequently, free energy, together with their caveats, be discussed examples from literature. various highlight challenges related mechanism, transition state theory, solvation involved in translating calculated barriers a metric stereoselectivity. Examples literature that validated theoretical models showcased. Lastly, relevance opportunity afforded by machine learning discussed.

Язык: Английский

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A photoactivated chiral molecular clamp rotated by selective anion binding

Chemical Science, Год журнала: 2024, Номер 15(38), С. 15790 - 15798

Опубликована: Янв. 1, 2024

A molecular clamp with photoactivated chiral properties is reported. Selective anion binding achieved rational tuning of the conformations and chiroptical properties, including circular dichroism circularly polarized luminescence.

Язык: Английский

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