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

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(4), С. 1971 - 1985

Опубликована: Янв. 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.

Язык: Английский

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Stereodivergent synthesis of enantioenriched azepino[3,4,5-cd]-indoles via cooperative Cu/Ir-catalyzed asymmetric allylic alkylation and intramolecular Friedel–Crafts reaction

Chemical Science, Год журнала: 2022, Номер 13(17), С. 4801 - 4812

Опубликована: Янв. 1, 2022

A stereodivergent synthesis of azepino[3,4,5- cd ]-indoles bearing three stereogenic centers was established via synergistic dual-metal catalysis followed by acid-promoted epimerization, and up to all eight stereoisomers could be predictably achieved.

Язык: Английский

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Catalytic Enantioselective [3+2] Cycloaddition of N‐Metalated Azomethine Ylides

Chemistry - A European Journal, Год журнала: 2023, Номер 29(28)

Опубликована: Март 7, 2023

Abstract Asymmetric [3+2] cycloaddition reactions are fascinating and powerful methods for the synthesis of enantioenriched pyrrolidines up to four stereocentres. Pyrrolidines important compounds both biology organocatalytic applications. This review summarizes most recent advances in enantioselective by cycloadditions azomethine ylides using metal catalysis. It has been organized type catalysis used further arranged complexity nature dipolarophile. The presentation each reaction highlights their advantages limitations.

Язык: Английский

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Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1298 - 1298

Опубликована: Янв. 20, 2024

The present review contains a representative sampling of mechanistic studies, which have appeared in the literature last 5 years, on 1,3-dipolar cycloaddition reactions, using DFT calculations. Attention is focused insights into 1,3-dipoles propargyl/allenyl type and allyl such as aza-ylides, nitrile oxides azomethyne ylides nitrones, respectively. important role played by various metal–chiral–ligand complexes use chiral eductors promoting site-, regio-, diastereo- enatioselectivity reaction are also outlined.

Язык: Английский

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Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(1)

Опубликована: Сен. 30, 2022

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes alkynes has been developed. Notably, Hünig's base together with simple ethanol successfully applied as the hydrogen sources instead commonly used Hantzsch esters in this catalytic photoredox reaction. This approach considerable advantages for straightforward synthesis stereodefined multiple substituted alkenes bearing an azaarene motif, such excellent regioselectivity (>20 : 1 >30 examples) stereoselectivity E/Z), broad substrate scope good functional group compatibility under mild reaction conditions, which utilized concise natural product monomorine I. reasonable pathway involving protolysis cobaltacyclopentene intermediate proposed based on mechanistic studies.

Язык: Английский

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New Insights and Predictions into Complex Homogeneous Reactions Enabled by Computational Chemistry in Synergy with Experiments: Isotopes and Mechanisms

Accounts of Chemical Research, Год журнала: 2022, Номер 55(8), С. 1109 - 1123

Опубликована: Апрель 6, 2022

Homogeneous catalysis and biocatalysis have been widely applied in synthetic, medicinal, energy chemistry as well synthetic biology. Driven by developments of new computational methods better computer hardware, has become an essentially indispensable mechanistic "instrument" to help understand structures decipher reaction mechanisms catalysis. In addition, synergy between experimental deepens our understanding, which further promotes the rational design catalysts. this Account, we summarize or deeper insights (including isotope, dispersion, dynamical effects) into several complex homogeneous reactions from systematic studies along with subsequent different groups. Apart uncovering some reactions, a few predictions (such excited-state heavy-atom tunneling, steric-controlled enantioswitching, geminal addition mechanism) based on were verified ensuing experiments.The Zimmerman group developed photoinduced triplet di-π-methane rearrangement form cyclopropane derivatives. Recently, study predicted first (carbon) quantum tunneling one rearrangement, rates 12C/13C kinetic isotope effects (KIEs) can be enhanced at low temperatures. This unprecedented recently KIE Singleton group. Such combined should open up opportunities discover more rare other reactions. found unexpectedly large secondary values five-coordinate Fe(III)-catalyzed hetero-Diels-Alder pathway, even substantial C-C bond formation, due non-negligible equilibrium effect (EIE) derived altered metal coordination. Therefore, these cannot reliably reflect transition-state for pathway. Furthermore, density functional theory (DFT) quasi-classical molecular dynamics (MD) simulations demonstrated that coordination mode and/or spin state iron electric field affect (e.g., dynamically stepwise process, entrance/exit channels).Moreover, unveiled mechanism account uncommon Ru(II)-catalyzed geminal-addition semihydrogenation hydroboration silyl alkynes. Our proposed key gem-Ru(II)-carbene intermediates double migrations same alkyne carbon crossover experiments. Additionally, DFT MD suggested hydrogen migration may directly quickly gem-Ru-carbene structures, thereby "bypassing" second step. extensive revealed origin enantioselectivity Cu(I)-catalyzed 1,3-dipolar cycloaddition azomethine ylides β-substituted alkenyl bicyclic heteroarenes enabled dual both substrates. promoted reversal corresponding monocyclic heteroarene substrates regiospecific less reactive internal C═C diene substrate. These proven collaborators. Finally, are also presented. Overall, hope interactive enrich understanding aid development.

Язык: Английский

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Copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of 1,3-enynes and azomethine ylides

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 4, 2023

Herein, we report a copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 1,3-enynes, which provides series chiral poly-substituted pyrrolidines in high regio-, diastereo-, enantioselectivities. Both 4-aryl-1,3-enynes 4-silyl-1,3-enynes serve as suitable dipolarophiles while 4-alkyl-1,3-enynes are inert. Moreover, the method is successfully applied construction both tetrasubstituted stereogenic carbon centers spiro pyrrolidines. The DFT calculations also conducted, imply concerted mechanism rather than stepwise mechanism. Finally, various transformations started from pyrrolidine bearing triethylsilylethynyl group centered on alkyne achieved, compensates for inertness present reaction.

Язык: Английский

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Copper-catalyzed asymmetric [4 + 1] annulation of yne-allylic esters with pyrazolones

Chinese Chemical Letters, Год журнала: 2024, Номер unknown, С. 110114 - 110114

Опубликована: Июнь 1, 2024

Язык: Английский

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Copper-Catalyzed Asymmetric Conjugate Addition of Alkene-Derived Nucleophiles to Alkenyl-Substituted Heteroarenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9611 - 9620

Опубликована: Июль 22, 2022

We herein report the copper-catalyzed asymmetric conjugate addition of β-substituted alkenyl heteroarenes, one most challenging Michael acceptors, with alkenes as latent nucleophiles. Diverse chiral heteroarenes bearing two vicinal stereocenters were obtained in good to excellent yields, generally enantioselectivity, and a level diastereoselectivity. The products can be readily transformed into other valuable acyclic enantioenriched structures three contiguous via amine catalysis. Mechanistic studies, including an isotope labeling experiment, nonlinear effect study, kinetic experiments, initial-rate kinetics implemented, experimental results indicated that hydrocupration step might turnover-limiting step. Moreover, origin preferential alkene presence Ph-BPE-ligated CuH catalyst was also elucidated some control experiments.

Язык: Английский

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Electron-rich benzofulvenes as effective dipolarophiles in copper(i)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

Chemical Science, Год журнала: 2023, Номер 14(20), С. 5460 - 5469

Опубликована: Янв. 1, 2023

A series of benzofulvenes without any electron-withdrawing substituents were employed as 2π-type dipolarophiles for the first time to participate in Cu(i)-catalyzed asymmetric 1,3-dipolar cycloaddition (1,3-DC) reactions azomethine ylides. An intrinsic non-benzenoid aromatic characteristic from serves a key driving force activation electron-rich benzofulvenes. Utilizing current methodology, wide range multi-substituted chiral spiro-pyrrolidine derivatives containing two contiguous all-carbon quaternary centers formed good yield with exclusive chemo-/regioselectivity and high excellent stereoselectivity. Computational mechanistic studies elucidate origin stereochemical outcome chemoselectivity, which thermostability these products is major factor.

Язык: Английский

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