Dispersion and Steric Effects on Enantio-/Diastereoselectivities in Synergistic Dual Transition-Metal Catalysis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(4), P. 1971 - 1985

Published: Jan. 20, 2022

Comprehensive computational studies were carried out to explore the mechanisms of enantioselective Cu/Pd and stereodivergent Cu/Ir dual-catalytic syntheses α,α-disubstituted α-amino acids (α-AAs). A chiral copper azomethine ylide undergoes facile α-allylation with racemic π-allylpalladium species or stereopure π-allyliridium complex stereoconvergently stereodivergently furnish single/double stereocenters, respectively. Stereoselectivity at α-center is controlled by facial selectivity respect prochiral nucleophile. Despite apparently similar transition-state assemblies, models distortion/interaction analyses disclose versatile modes stereoinduction wherein can face-selectively intercept metal−π-allyl intermediates utilizing attractive dispersion interactions and/or sterically caused distortions. Generation β-stereocenter in system relies on a stereospecifically generated allyliridium electronically branched-to-linear selectivity, while dual yields linear monochiral product due steric factors π–π stacking interactions. The demonstrate molecular level how ligand-encoded information transferred α-/β-sites resulting α-AAs mode regio-/stereoselection altered differences transition-metal-stabilized coupling partners. To facilitate stereoselective catalysis, suite analytical tools extract controlling for asymmetric induction demonstrated.

Language: Английский

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Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(5), P. 2368 - 2378

Published: Jan. 31, 2022

α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones presence of a base, can serve as effective metalloradicophiles Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation alkenes. With D2-symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin optimal supporting ligand, system efficiently activate different α-alkynyldiazomethanes at room temperature highly broad range This catalytic radical process provides general synthetic tool stereoselective construction alkynyl cyclopropanes high yields with both diastereoselectivity and enantioselectivity. Combined computational experimental studies offer several lines evidence support underlying stepwise mechanism Co(II)-catalyzed olefin involving unique α-metalloradical intermediate that is associated two resonance forms α-Co(III)-propargyl γ-Co(III)-allenyl radical. The resulting enantioenriched cyclopropanes, showcased stereospecific transformations, may valuable building blocks organic synthesis.

Language: Английский

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Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(12)

Published: Dec. 5, 2023

London dispersion (LD) interactions are the main contribution of attractive part van der Waals potential. Even though LD effects driving force for molecular aggregation and recognition, role these omnipresent in structure reactivity had been largely underappreciated over decades. However, recent years considerable efforts have made to thoroughly study their potential as a chemical design element structures catalysis. This was possible through fruitful interplay theory experiment. review highlights results advances utilizing structural motif understand utilize intra- intermolecularly LD-stabilized systems. Additionally, we focus on quantification fundamental reactions.

Language: Английский

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From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(16), P. 7465 - 7478

Published: April 14, 2022

A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated germylated) α-diazoacetate derivatives. number control experiments combination detailed computational studies provide compelling evidence that an interligand hydrogen bond between −NH group amidate ester carbonyl reactive rhodium carbene intermediate plays a quintessential role stereodetermining transition state. The penalty for distorting this array outweighs steric arguments renders two four conceivable transitions states unviable. Based on mechanistic insight, design parent catalyst is revisited herein: placement appropriate peripheral substituents allows high levels diastereocontrol imposed upon cyclopropanation, which original lacks. Because new complexes allow either trans- or cis-configured stannylated cyclopropanes made selectively excellent optical purity, transformation also marks rare case diastereodivergent catalysis. products are amenable stereospecific cross coupling aryl halides alkenyl triflates; these transformations appear first examples formation stereogenic quaternary carbon centers by Stille reaction; carbonylative achieved. Moreover, tin/lithium exchange affords lithium enolates, can intercepted variety electrophilic partners. virtues inherent flexibility methodology illustrated efficient synthesis salinilactones, extremely scarce bacterial metabolites signaling function involved self-regulatory growth inhibition producing strain.

Language: Английский

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Unraveling Atomic Contributions to the London Dispersion Energy: Insights into Molecular Recognition and Reactivity

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: 20(5), P. 1923 - 1931

Published: Feb. 7, 2024

We present a general framework that enables quantification with atomic resolution of the overall London dispersion energy, which can be readily integrated currently available energy decomposition schemes. This approach used to determine contribution individual atoms and functional groups molecular recognition, conformational preferences, stability, reactivity. Its efficacy across diverse realms chemistry biology is demonstrated application balances in solution, asymmetric organocatalytic transformations, subcomplex F1FO ATP synthase.

Language: Английский

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Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

Chemical Science, Journal Year: 2021, Volume and Issue: 12(33), P. 11181 - 11190

Published: Jan. 1, 2021

This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective high induction could be achieved using either (R)-pantolactone as a chiral auxiliary tetracarboxylate catalysts. For meta- para-substituted heteroaryldiazoacetates optimum catalyst was Rh2(R-p-Ph-TPCP)4. In case ortho-substituted heteroaryldiazoacetates, Rh2(R-TPPTTL)4. reaction substrates, 2-chloropyridine required an additive in presence 4 Å molecular sieves 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Under optimized conditions, conducted variety heterocycles, such pyridines, pyrazines, quinolines, indoles, oxadiazoles, thiophenes pyrazoles.

Language: Английский

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Catalytic Diastereo‐ and Enantioselective Cyclopropanation of gem‐Dihaloalkanes and Terminal Olefins

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: May 11, 2023

Chiral cyclopropane derivatives are essential in synthetic chemistry and drug discovery. Their synthesis commonly relies on asymmetric cyclopropanation of diazo compounds, potentially explosive needing stabilizing substituents. Thus, catalytic transformations non-stabilized carbenes or carbenoids remain a formidable challenge. Herein, we report the unprecedented chromium-catalyzed readily available gem-dihaloalkanes terminal olefins. Distinct from previous approaches, serve as suitable precursors for carbenoids, furnishing various functionalized chiral cyclopropanes. Mechanistic studies, including radical trapping, non-linear effect, UV/Vis spectroscopy, provide insights into process, featuring radical-polar crossover.

Language: Английский

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Exploring the Limits of Intramolecular London Dispersion Stabilization with Bulky Dispersion Energy Donors in Alkane Solution

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(4), P. 2093 - 2097

Published: Jan. 23, 2023

We present an experimental study of a cyclooctatetraene-based molecular balance disubstituted with increasingly bulky tert-butyl (tBu), adamantyl (Ad), and diamantyl (Dia) substituents in the 1,4-/1,6-positions for which we determined valence-bond shift equilibrium n-hexane (hex), n-octane (oct), n-dodecane (dod). Computations including implicit explicit solvation support our temperature-dependent NMR measurements indicating that more sterically crowded 1,6-isomer is always favored, irrespective solvent, free energy quite insensitive to substituent size.

Language: Английский

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Silver(I)/Dirhodium(II) Catalytic Platform for Asymmetric N–H Insertion Reaction of Heteroaromatics

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 733 - 741

Published: Dec. 27, 2023

Transition-metal-catalyzed enantioselective N–H insertion reactions of carbene species offer a powerful and straightforward strategy to produce chiral nitrogen-containing compounds. Developing highly selective using indole variants can meet synthetic demand. Herein we present an asymmetric reaction into bonds the aromatic heterocycles donor/acceptor-substituted diazo compounds based on heteronuclear catalytic platform. Although previously developed catalysis comprising silver catalyst or dirhodium(II,II) paddlewheel complexes with without phosphoric acid showed modest performance, unique combination widely available Rh2(OAc)4 silver(I) phosphate dimer [(S)-TRIP-Ag]2 enabled (up 98% ee). Moreover, Ag/Rh system facilitated regioselective C–H functionalization protic indoles. Mechanistic investigation density functional theory indicated that in situ-generated Ag–Rh trimetallic enolate is protonated environment.

Language: Английский

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Overview of Transition Metal Catalyzed Multicomponent Reactions Based on Trapping of Allylic Electrophiles

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(4)

Published: Jan. 11, 2024

Abstract Multicomponent reactions provide an excellent approach toward quaternary carbon centres utilizing convergent chemical in a highly selective manner under one‐pot conditions. The reactivity of substrates and metal catalysts is carefully controlled, precluding the formation side‐products. In this context, transition catalyzed onium ylides generated via diazo precursors nucleophiles with third component (an electrophile) have garnered significant attention. Using allylic precursor as electrophilic partner provides opportunities to construct all‐carbon centres. Furthermore, presence allyl fragment multicomponent product serves pivotal handle for carrying out subsequent modifications. Several recent studies employed Rh, Pd, dual Rh/Pd catalytic systems involving alkylation that proceed synergistic or relay pathway. Although not significantly successful, few cases, asymmetric induction achieved through chiral phosphoric acids phosphine ligands. Limited substrate catalyst scope underlying mechanistic complexities posed formidable challenges, slowing advancement reactions. This review details using readily available like compounds, carbonates, (R‐OH, R‐NH 2 , etc .) forming complex organic compounds. Our primary objective discuss issues may facilitate progress field.

Language: Английский

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