Photochemical Deracemization of Lactams with Deuteration Enabled by Dual Hydrogen Atom Transfer

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such energy transfer, single electron and ligand-to-metal charge transfer have been leveraged promote stereoablation, relying on hydrogen atom which circumvent limitations imposed by triplet redox potential racemic substrates, remain underexplored. Conceptually, attractive method for tertiary stereocenter might be abstraction followed donation. However, implementing a strategy poses significant challenges, primarily because products are also reactive if chiral catalyst is unable differentiate between two enantiomers. Herein we report distinct dual photochemical δ- γ-lactams, achieving high enantioenrichment deuterium incorporation despite inherent reactivity products. Mechanistic studies reveal that benzophenone enables nonselective while tetrapeptide-derived thiol dictates enantioselectivity donation step. More importantly, pyridine-based alcohol was found play crucial roles facilitating well enhancing

Language: Английский

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C–H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(37), P. 17219 - 17231

Published: Sept. 13, 2022

Rh-catalyzed C-H insertion reactions to form β-lactones suffer from post-transition state bifurcations, with the same transition states leading ketones and ketenes via fragmentation in addition β-lactones. In such a circumstance, traditional theory cannot predict product selectivity, so we employed ab initio molecular dynamics simulations do provide framework for rationalizing origins of said selectivity. Weak interactions between catalyst substrate were studied using energy decomposition noncovalent interaction analyses, which unmasked an important role 2-bromophenyl substituent that has been used multiple β-lactone-forming reactions. Small large catalysts shown behave differently, latter providing means overcoming dynamically preferred by lowering barrier recombination fragments grip active site cavity.

Language: Английский

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How the Chalcogen Atom Size Dictates the Hydrogen‐Bond Donor Capability of Carboxamides, Thioamides, and Selenoamides

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(31)

Published: March 24, 2022

The amino groups of thio- and selenoamides can act as stronger hydrogen-bond donors than carboxamides, despite the lower electronegativity S Se. This phenomenon has been experimentally explored, particularly in organocatalysis, but a sound electronic explanation is lacking. Our quantum chemical investigations show that NH2 are more positively charged carboxamides. originates from larger density flow nitrogen lone pair group towards lower-lying π*C=S π*C=Se orbitals to high-lying π*C=O orbital. relative energies π* result overlap between chalcogen np carbon 2p atomic orbitals, which set by carbon-chalcogen equilibrium distance, consequence Pauli repulsion two bonded atoms. Thus, neither nor often-suggested polarizability steric size atom determines amide's donor capability.

Language: Английский

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Lewis Acid-Catalyzed Carbonyl-Ene Reaction: Interplay between Aromaticity, Synchronicity, and Pauli Repulsion

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(15), P. 11102 - 11110

Published: July 24, 2023

The physical factors governing the catalysis in Lewis acid-promoted carbonyl-ene reactions have been explored detail quantum chemically. It is found that binding of a acid to carbonyl group directly involved transformation greatly accelerates reaction by decreasing corresponding activation barrier up 25 kcal/mol. makes process much more asynchronous and transition state less in-plane aromatic. remarkable acceleration induced catalyst ascribed, means strain model energy decomposition analysis methods, mainly significant reduction Pauli repulsion between key occupied π-molecular orbitals reactants not widely accepted stabilization LUMO enophile.

Language: Английский

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C1‐4 Alkylation of Aryl Bromides with Light Alkanes enabled by Metallaphotocatalysis in Flow

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract The homologous series of gaseous C1‐4 alkanes represents one the most abundant sources short alkyl fragments. However, their application in synthetic organic chemistry is exceedingly rare due to challenging C−H bond cleavage, which typically demands high temperatures and pressures, thereby limiting utility construction complex molecules. In particular, formation C(sp 2 )−C(sp 3 ) bonds crucial for constructing biologically active molecules, including pharmaceuticals agrochemicals. this study, we present previously elusive coupling between (hetero)aryl bromides, achieved through a combination Hydrogen Atom Transfer (HAT) photocatalysis nickel‐catalyzed cross at room temperature. Utilizing flow technology allowed us conduct novel reaction with reduced times scalable fashion, rendering it practical widespread adoption both academia industry. Density Functional Theory (DFT) calculations unveiled that oxidative addition constitutes rate‐determining step, activation energy barrier increasing smaller radicals. Furthermore, radical isomerization observed propane butane analogues could be attributed electronic properties bromoarene partner, highlighting role selectivity transformation.

Language: Английский

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Diels–Alder Cycloaddition of Cyclopentadiene to C₆₀ and Si₆₀ and Their Endohedral Li⁺ Counterparts

The Journal of Physical Chemistry A, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Both silicon and carbon are elements located in group 14 on the periodic table. Despite some similarities between these two elements, differences reactivity important, whereas is a central element all known forms of life, barely found biological systems. Here, we investigate Diels-Alder cycloaddition reaction cyclopentadiene (CP) cyclopentasildiene (CPSi) with fullerenes C60, Li+@C60, Si60, Li+@Si60 using density functional theory methods. The results reveal distinct kinetic thermodynamic trends that govern selectivity. For [6,6] pathway kinetically thermodynamically favored, for [5,6] preferred but not kinetically. introduction lithium cations increases both C60 Si60. Energy decomposition analysis (EDA) unveils importance components interaction energy CPSi corresponding fullerenes. findings provide insights into interplay electronic structure, substrate reactivity, fullerene electrophilicity reactions.

Language: Английский

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Nature and stability of the chemical bond in H3C–XHn (XHn = CH3, NH2, OH, F, Cl, Br, I)

The Journal of Chemical Physics, Journal Year: 2025, Volume and Issue: 162(4)

Published: Jan. 27, 2025

We have quantum chemically analyzed the trends in bond dissociation enthalpy (BDE) of H3C–XHn single bonds (XHn = CH3, NH2, OH, F, Cl, Br, I) along three different pathways at ZORA-BLYP-D3(BJ)/TZ2P: (i) homolytic into H3C∙ + ∙XHn, (ii) heterolytic H3C+ −XHn, and (iii) H3C− +XHn. The associated BDEs for differ not only quantitatively but, some cases, also terms opposite C–X series. Based on activation strain analyses quantitative molecular orbital theory, we explain how these differences are caused by profoundly electronic structures of, thus bonding mechanisms between, resulting fragments pathways. demonstrate that nature strength a chemical fully defined when considering both molecule which exists from it forms or dissociates.

Language: Английский

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Reaction development: a student's checklist

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

So you've discovered a reaction. This review discusses the key areas involved in developing new reactions and provides handy checklist guide to help maximise potential of your novel transformation.

Language: Английский

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Computational study of polyhomologation: understanding reactivity with B, Al, and Ga

New Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In the polyhomologation, there is a higher reactivity (lower energy barrier) of boron toward Corey's ylide, in comparison to aluminum and gallium.

Language: Английский

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Mechanistic Study on the Asymmetric Cascade Michael Addition of Alkynone and Oxindole Catalyzed by Chiral Guanidine

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Density functional theory (DFT) calculations with the M06-2X-D3 were used to get mechanistic investigation and stereoselectivity of cascade Michael addition alkynone oxindole, catalyzed by a chiral guanidine-amide compound. The reaction proceeded through two-step synergistic process involving sequential C–C C–O bond formation, together an H-shift. Because high energy barriers 33.5 kcal mol−1 (for construction) 41.3 mol–1 construction), was difficult proceed without catalyst. guanidine catalyst facilitated generation enolized oxindole species nucleophilicity, activating both enolate via ion-pairing multiple hydrogen bonding, significantly lowering activation barriers. combination unit sulfonamide backbone created excellent semiclosed environment, promoting asymmetric induction. Due steric effects from ortho- para-substituted iPr groups in SO2Ar, bulky Cy group, backbone, SS-configuration spirocyclization product enantio- diastereoselectivity formed predominantly. E/Z selectivity formation key α,β-unsaturated ketone intermediate influenced catalyst-substrate interactions. Extension alkyl chain at 3-position substrate led more difficult, hindering construction spirooxindoles.

Language: Английский

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