P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(14), P. 8657 - 8739

Published: July 2, 2024

Chiral phosphorus ligands play a crucial role in asymmetric catalysis for the efficient synthesis of useful optically active compounds. They are largely categorized into two classes: backbone chirality and P-stereogenic ligands. Most reported belong to former class. Privileged ones such as BINAP DuPhos frequently employed wide range catalytic transformations. In contrast, latter class has remained small family many years mainly because their synthetic difficulty. The late 1990s saw emergence novel with superior enantioinduction ability Rh-catalyzed hydrogenation reactions. Since then, numerous have been synthesized used This Review summarizes thus far, including stereochemical electronic properties that afford high excellent enantioselectivities. Examples reactions use this described together applications construction key intermediates natural products therapeutic agents. literature covered dates back 1968 up until December 2023, centering on studies published later years.

Language: Английский

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Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9241 - 9251

Published: March 19, 2024

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, construction nonadjacent stereocenters is significant importance but challenging because lack remote induction models. Herein, based a C═C bond relay strategy, we report synergistic Pd/Cu-catalyzed 1,5-double model. All four stereoisomers target products bearing 1,5-nonadjacent involving both allenyl axial and central chirality could be obtained divergently by simply changing combination catalysts with different configurations. Control experiments DFT calculations reveal novel mechanism 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, conjugate nucleophilic substitution, which play crucial roles in control reactivity, regio-, enantio-, diastereoselectivity. It expected that this strategy may provide general protocol for synthesis structural motifs distant

Language: Английский

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Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15453 - 15463

Published: May 25, 2024

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, simultaneous construction acyclic 1,3-nonadjacent stereocenters via catalyst in an enantioselective and diastereoselective manner remains formidable challenge. Here, we demonstrate diastereodivergent through Ni-catalyzed reductive cyclization/cross-coupling alkene-tethered aryl bromides α-bromoamides, which represents major remaining stereochemical challenge cyclization/difunctionalization alkenes. Using Ming-Phos as ligand, diverse set oxindoles containing were obtained high levels enantio- diastereoselectivity. Mechanistic experiments density functional theory calculations indicate that magnesium salt plays key role controlling Furthermore, another complementary stereoisomeric products constructed from same starting materials using Ph-Phox ligand.

Language: Английский

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Stereodivergent Construction of 1,5/1,7‐Nonadjacent Tetrasubstituted Stereocenters Enabled by Pd/Cu‐Cocatalyzed Asymmetric Heck Cascade Reaction

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(35)

Published: May 16, 2024

Abstract The construction of chiral motifs containing nonadjacent stereocenters in an enantio‐ and diastereoselective manner has long been a challenging task synthetic chemistry, especially with respect to their stereodivergent synthesis. Herein, we describe protocol that enables the 1,5/1,7‐nonadjacent tetrasubstituted through Pd/Cu‐cocatalyzed Heck cascade reaction. Notably, C=C bond relay strategy involving shift π‐allyl palladium intermediate was successfully applied asymmetric 1,7‐nonadjacent stereocenters. current method allows for efficient preparation molecules bearing two privileged scaffolds, oxindoles non‐natural α‐amino acids, good functional group tolerance. full complement four stereoisomers products could be readily accessed by simple combination metal catalysts different enantiomers.

Language: Английский

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Palladium-Catalyzed Allylic Alkylation Reactions of Nucleophilic Allenones: Asymmetric Allylic Alkylation, Z/E Divergent Allylic Alkylation, and [5 + 2] Annulation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9940 - 9954

Published: June 19, 2024

Metal-catalyzed allenylic substitution reactions where allenes serve as electrophilic precursors have been recognized a rapid way for novel allene construction. On the contrary, chemistry in which act nucleophiles has far less investigated, especially powerful platform such metal-catalyzed allylic alkylation reactions. We herein describe two unprecedented palladium-catalyzed of an nucleophile. In first reaction, using vinyloxazolidinones allyl precursor, asymmetric allylation trisubstituted allenones worked well to prepare array axially chiral tetrasubstituted allenes. Mechanistic studies and density functional theory (DFT) calculations indicated that weak hydrogen-bonding interaction between acidic C(sp2)–H allenone nitrogen anion π-azaallyl-Pd species is key success stereocontrol. This reaction revealed intriguing reactivity nucleophilic time. second with use allenylethylene carbonates π-oxyallyl-Pd precursors, presented unique under different conditions provide divergent synthetic access (E)- (Z)-allenyl diene products. Interestingly, subsequent sequential intramolecular cyclization/isomerization (Z)-product delivered dihydrooxepine derivatives [5 + 2] annulation

Language: Английский

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Enantioselective Synthesis of Axially Chiral Alkylidenecycloalkanes via Copper-Catalyzed Functionalization of Acyl Allenols

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2351 - 2358

Published: Jan. 24, 2025

Language: Английский

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Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 15, 2023

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring nonadjacent 1,3-stereocenters. Notably, reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct byproducts. This approach introduces new activation mode for selective transformations gem-diborylmethane asymmetric catalysis. Additionally, found that other gem-diborylalkanes, previously challenging steric hindrance, also participated reaction. incorporation 1,2-bis(boryl)alkenes facilitated diversification alkenyl two boron moieties our target compounds, thereby enabling access broad array versatile molecules. DFT calculations were performed elucidate mechanism shed light on factors responsible observed excellent enantioselectivity diastereoselectivity. These determined arise ligand-substrate repulsions syn-addition transition state.

Language: Английский

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Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(4), P. 949 - 977

Published: April 8, 2024

P-Chiral phosphorus ligands received little attention in organic chemistry until Knowles made his landmark contribution asymmetric hydrogenation by developing the P-chiral CAMP and DIPAMP. The development of accelerated end last century with advent some highly efficient renowned for hydrogenation, including BisP*, TangPhos, QuinoxP*, DuanPhos, et al. However, most reported were air-sensitive, difficult to make, or lacked structural modularity, hampering their availability applicability. sterically electronically tunable is particularly desirable. Over past decade, a family hindered, electron-rich, structurally tunable, air-stable dihydrobenzooxaphosphole emerged that proved be versatile various transformations. 5 years witnessed an increasing number studies related these discovery unprecedented catalytic properties This review highlights unique catalysis applications synthesis natural products therapeutic agents.

Language: Английский

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Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence

Chemical Science, Journal Year: 2024, Volume and Issue: 15(26), P. 10135 - 10145

Published: Jan. 1, 2024

A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol.

Language: Английский

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Pd-Catalyzed Enantioselective Creation of All-Carbon Quaternary Center with 2,3-Allenylic Carbonates

Organic Letters, Journal Year: 2024, Volume and Issue: 26(12), P. 2349 - 2353

Published: March 15, 2024

Enantioselective construction of all-carbon quaternary centers has been achieved via the palladium-catalyzed highly enantioselective allenylation oxindoles with 2,3-allenylic carbonates to afford a variety optically active allene products, which contain oxindole units different functional groups, in high ee. The corresponding synthetic applications have also demonstrated.

Language: Английский

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