Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(8), P. 4373 - 4505

Published: March 19, 2021

This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution decarboxylative oxidative substitutions. For each reaction, catalytic data, as well examples of their application to synthesis complex molecules, are collected. Sections which we discuss key aspects for high selectivity a comparison with other metals (with advantages disadvantages) also included. asymmetric substitution, data grouped according type nucleophile employed. Because prominent position use stabilized carbon nucleophiles heteronucleophiles, many chiral ligands have been developed. To better compare results, they presented by ligand types. reactions mainly promoted PHOX or Trost ligands, justifies organizing this section chronological order. results used.

Language: Английский

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Catalytic Enantioselective Alkylation of Prochiral Enolates

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(15), P. 9196 - 9242

Published: July 26, 2021

The asymmetric alkylation of enolates is a particularly versatile method for the construction α-stereogenic carbonyl motifs, which are ubiquitous in synthetic chemistry. Over past several decades, focus has shifted to development new catalytic methods that depart from classical stoichiometric stereoinduction strategies (e.g., chiral auxiliaries, alkali metal amide bases, electrophiles, etc.). In this way, enantioselective prochiral greatly improves step- and redox-economy process, addition enhancing scope selectivity these reactions. review, we summarize origin advancement enolate methods, with directed emphasis on union nucleophiles carbon-centered electrophiles derivatives. Hence, transformative developments each distinct class nucleophile ketone enolates, ester etc.) presented modular format highlight state-of-the-art current limitations area.

Language: Английский

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Evolution in heterodonor P-N, P-S and P-O chiral ligands for preparing efficient catalysts for asymmetric catalysis. From design to applications

Coordination Chemistry Reviews, Journal Year: 2021, Volume and Issue: 446, P. 214120 - 214120

Published: July 19, 2021

The success of phosphine-oxazoline ligands (PHOX) inspired the progress in P-oxazoline ligand families by modifying either backbone, electronic and/or steric properties phosphine group or exchanging to a phosphinite phosphite group. In this respect, structures chiral have become more diverse and new very efficient emerged, which improved catalytic performance some asymmetric transformations, with an increased versatility, both range reactions substrates/reagents. addition, most are synthesized from easily accessible amino alcohols, maintaining short synthetic route developed for PHOX ligands. New been replacing oxazoline functionality several other N-donor groups, e.g. imidazole, thiazole, oxazole, pyridine, etc., O- S-groups. This review offers critical overview utility these successful bidentate heterodonor P-N, P-O P-S applied metal-mediated processes. We illustrate how, through proper design, can be excellent source ligands, superior many than best C2-symmetric N,N P,P-ligands reported so far.

Language: Английский

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Enantioselective Reductive Conjugate Alkenylation of α,β-Unsaturated Ketones and Amides via Nickel Catalysis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(8), P. 6228 - 6235

Published: April 10, 2024

Chiral nickel complexes promoted enantioselective reductive alkenylation of a range conjugated enones, using alkenyl bromides, triflates, and tosylates. The neutral condition was compatible with sensitive groups azaheteroaryl rings. Importantly, in products can be readily converted to functionalized alkyl via iron-catalyzed hydrofunctionalization. Some examples asymmetric N-enoyl pyrroles indoles were also included.

Language: Английский

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Asymmetric Three-Component Reaction to Assemble the Acyclic All-Carbon Quaternary Stereocenter via Visible Light and Phosphoric Acid Catalysis

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(21), P. 13282 - 13291

Published: Oct. 17, 2022

Chiral acyclic all-carbon quaternary stereocenters are widely present in natural products and pharmaceuticals. However, their introduction remains a challenging topic the synthetic research community. Here, we report an efficient metal-free method for construction of chiral centers sited at α-position aldehyde or ketone moiety. This is achieved via well-designed reaction cascade involving arylalkynes, benzoquinones, electron-rich (hetero)arenes use visible light phosphoric acid catalysis. Notably, asymmetric catalytic visible-light-induced Paternò–Büchi cycloaddition/electrocyclic ring-opening/α-selective arylation α,β-unsaturated carbonyl compound cascades achieved. Moreover, works well broad range these three components (>70 examples). Furthermore, rich chemistry embedded provides variety synthetically useful building blocks that otherwise difficult to access. Lastly, origin enantioselectivity was investigated by density functional theory, revealing CH/π interactions play crucial role stereocontrol reaction.

Language: Английский

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Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 18, 2021

Abstract Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development highly efficient asymmetric catalytic methods for the construction these privileged motifs represents longstanding challenge organic synthesis. Herein, an chiral phosphoric acid catalyzed direct addition α-alkynyl acyclic ketones with allenamides has been developed, furnishing all-carbon excellent regioselectivities high enantioselectivities. Extensive detailed experimental mechanistic studies were performed to investigate mechanism this reaction. Despite novel covalent allyl phosphate intermediate was found reactions, further indicated that S N 2-type ketone nucleophiles is not very possible. Instead, more plausible involving elimination give α,β-unsaturated iminium intermediate, which underwent conjugate enol form under anion catalysis, proposed. In virtue fruitful functional groups bearing products, diverse derivatizations provided access wide array scaffolds stereocenters.

Language: Английский

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The Catalytic Asymmetric Allylic Alkylation of Acyclic Enolates for the Construction of Quaternary and Tetrasubstituted Stereogenic Centres

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(20)

Published: Jan. 29, 2024

To facilitate the discovery and development of new pharmaceuticals, demand for novel stereofunctionalised building blocks has never been greater. Whilst molecules bearing quaternary tetrasubstituted stereogenic centres are ideally suited to explore untapped areas chemical space, asymmetric construction ofsterically congested carbon remains a longstanding challenge in organic synthesis. The enantioselective assembly acyclic is even more demanding due need restrict much wider range geometries conformations intermediates involved. In this context, catalytic allylicalkylation (AAA) prochiral nucleophiles, namely enolates, become an indispensable tool access linearα-quaternary andα-tetrasubstituted carbonyl compounds. However, unlike AAA cyclic enolates with fixed enolate geometry, achieve high levels stereocontrol stereoselectivity enolisation must be considered. aim review offer acomprehensivediscussion reactions their analogues generate chiral using metal, non-metal dual catalysis, particular focus given control geometry its impact on stereochemical outcome reaction.

Language: Английский

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Computational insights into the synergistic interplay of ligand and fluorine effects in palladium-catalyzed regiodivergent decarboxylative allylic alkylation

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(10), P. 2870 - 2883

Published: Jan. 1, 2024

DFT calculations were performed to investigate palladium-catalyzed decarboxylative allylic alkylation of allyl difluoro-β-ketoesters. The synergistic effects ligand and fluorine substituents on regioselectivity uncovered.

Language: Английский

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Development of Chemo‐ and Enantioselective Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α‐Nitroesters

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(34), P. 11820 - 11825

Published: June 24, 2019

Abstract We describe the development of a Pd‐catalyzed decarboxylative asymmetric allylic alkylation α‐nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo‐ enantioselective C ‐alkylation electronically challenging benzylic nitronates sterically encumbered 2‐allyl esters. Substrates were efficiently accessed in combinatorial fashion by cross‐Claisen/ α‐arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies α‐tertiary amine synthesis.

Language: Английский

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Machine Learning Enables a Top-Down Approach to Mechanistic Elucidation in Asymmetric Catalysis

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8799 - 8810

Published: May 9, 2025

Language: Английский

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