Synergistic Pd/Amine-Catalyzed Stereodivergent Hydroalkylation of 1,3-Dienes with Aldehydes: Reaction Development, Mechanism, and Stereochemical Origins

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(29), P. 10948 - 10962

Published: July 15, 2021

Metal-hydride-catalyzed hydroalkylation of 1,3-dienes with enolizable carbonyl compounds is an atom- and step-economical method for preparing chiral molecules allylic stereocenters. Although high diastereo- enantioselectivities have been achieved many coupling partners, aldehydes not yet used this purpose because they are less stable than other under basic conditions the potential to rapidly epimerize at α-position. Moreover, stereodivergent reactions access complementary diastereomers vicinal stereocenters challenging. Herein, we describe a synergistic palladium/amine catalyst system that allowed us achieve first aldehydes. By choosing appropriate combination palladium amine catalysts, could obtain either syn or anti products, therefore provides highly enantioselective α,β-vicinal Density functional theory calculations revealed mechanism involving PdH formation migratory insertion into alkene, followed by C–C bond formation. The origin stereoselectivities was investigated means distortion/interaction analysis.

Language: Английский

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Synergizing palladium with Lewis base catalysis for stereodivergent coupling of 1,3-dienes with pentafluorophenyl acetates

Chem, Journal Year: 2022, Volume and Issue: 8(10), P. 2784 - 2796

Published: Aug. 17, 2022

Language: Английский

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Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3915 - 3925

Published: Feb. 10, 2023

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit synthetic chemistry. Abundant applications free enantioenriched allyl alcohol and hydroxylamine motifs have made the asymmetric hydration hydroaminoxylation conjugated dienes from water hydroxylamine, respectively, intriguing efficient routes that have, however, unachievable thus far. A fundamental challenge is failure to realize transition-metal-catalyzed enantioselective C–O bond constructions via hydrofunctionalization dienes. Here, we perform comprehensive study toward stereoselective formal by synthesizing set new P,N-ligands identifying an aryl-derived oxime surrogate for both hydroxylamine. Asymmetric hydroalkoxylation with also elucidated. Furthermore, versatile derivatizations following provide indirect but concise hydrophenoxylation, hydrofluoroalkoxylation, hydrocarboxylation unreported Finally, ligand-to-ligand hydrogen transfer process proposed based on results preliminary mechanistic experiments.

Language: Английский

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Palladium-Catalyzed Regio- and Enantioselective Hydrosulfonylation of 1,3-Dienes with Sulfinic Acids: Scope, Mechanism, and Origin of Selectivity

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(37), P. 15860 - 15869

Published: Aug. 19, 2020

Chiral sulfones are important structural motifs in organic synthesis because of their widespread use pharmaceutical chemistry. In particular, chiral allylic have drawn particular interest synthetic utility. However, enantioselective 1,3-disubstituted unsymmetrical remains a challenge. this article, we report protocol for (R)-DTBM-Segphos/Pd-catalyzed regio- and hydrosulfonylation 1,3-dienes with sulfinic acids, which provides atom- step-economical access to sulfones. The reaction occurs under mild conditions has broad substrate scope. Combined experimental computational studies suggest that the is initiated by ligand-to-ligand hydrogen transfer followed C–S bond reductive elimination via six-membered transition state. Steric repulsion between olefinic C–H tert-butyl group (R)-DTBM-Segphos was found be key factor enantiocontrol.

Language: Английский

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Ni-Catalyzed Regiodivergent and Stereoselective Hydroalkylation of Acyclic Branched Dienes with Unstabilized C(sp³) Nucleophiles

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(38), P. 16486 - 16492

Published: Sept. 1, 2020

Two complementary regiodivergent [(P,N)Ni]-catalyzed hydroalkylations of branched dienes are reported. When amides employed as unstabilized C(sp3) nucleophiles, a highly regioselective 1,4-addition process is favored. The addition products obtained in high yield and with excellent stereocontrol the internal olefin. With use chiral ligand imides carbon 3,4-addition protocol was developed, enabling construction two contiguous tertiary stereocenters single step moderate to levels diastereocontrol enantiocontrol. Both methods operate under mild reaction conditions, display broad scope, show functional group tolerance. synthetic potential 3,4-hydroalkylation established via series postcatalytic modifications.

Language: Английский

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Mechanistic Study of Ni and Cu Dual Catalyst for Asymmetric C–C Bond Formation; Asymmetric Coupling of 1,3-Dienes with C-nucleophiles to Construct Vicinal Stereocenters

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(11), P. 6643 - 6655

Published: May 21, 2021

We report details of the reaction mechanism for a coupling 1,3-dienes with C-nucleophiles that was catalyzed by Ni/Cu cooperative catalyst system using Ni(cod)2 and [Cu(CH3CN)4]PF6 in presence chiral JOSIPHOS-type bisphosphine ligand iPr2NEt, providing direct access to highly valuable vicinal quaternary tertiary stereocenters high enantio- diastereoselectivity. The bimetallic exhibited broad substrate scope, including both cyclic/acyclic stabilized nucleophiles aryl-/alkyl-substituted 1,3-dienes. elucidated depth isolating characterizing four key complexes nickel copper conducting deuterium labeling experiments, kinetic studies, density functional theory calculations. turnover-limiting step this is proton-transfer diene-coordinated Ni complex 6 from cationic Cu 8 yield π-allyl 7 enolate 9, respectively. stereoselectivity also clarified according single-point calculations intermediates 9.

Language: Английский

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Enantioselective C3‐Allylation of Pyridines via Tandem Borane and Palladium Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: July 3, 2023

Abstract Herein, we report a one‐pot method for enantioselective C−H allylation of pyridines at C3 via tandem borane and palladium catalysis. This involves borane‐catalyzed pyridine hydroboration to generate dihydropyridines, then palladium‐catalyzed the dihydropyridines with allylic esters, finally air oxidation allylated afford products. enables introduction an group excellent regio‐ enantioselectivities.

Language: Английский

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Enantioselective Synthesis of Functionalized Arenes by Nickel‐Catalyzed Site‐Selective Hydroarylation of 1,3‐Dienes with Aryl Boronates

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(33), P. 14070 - 14075

Published: May 6, 2020

A catalytic method for the site-selective and enantioselective synthesis of functionalized arenes by intermolecular hydroarylation terminal internal 1,3-dienes with aryl pinacolato boronates is reported. The reactions are promoted 5.0 mol % a readily available monodentate phosphoramidite-Ni complex in ethanol, affording variety enantioenriched products up to 96 yield 99:1 er. Mechanistic studies indicate that Ni-allyl formation irreversible related nature arylboronate.

Language: Английский

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Palladium-Catalyzed Asymmetric Hydrofunctionalizations of Conjugated Dienes

Chinese Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 43(8), P. 2614 - 2614

Published: Jan. 1, 2023

Because of the broad substrate availability, high atom economy and efficient stereocontrol, palladium-catalzyed asymmetric hydrofunctionalizations conjugated dienes have emerged as an route to construct enantioenriched allylic motifs, including C-C, C-N, C-S, C-P, C-Si C-O bonds.The development, advance mechanistic features this area in past decades are summarized.Based on types stereogenic centers constructed via strategy, review is divided into six parts, hydroalkylation, hydroamination, hydrophosphinylation, hydrosulfonylation, hydrosilylation hydroalkoxylation.

Language: Английский

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Ligand‐Dictated Regiodivergent Allylic Functionalizations via Palladium‐Catalyzed Remote Substitution

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

Published: March 15, 2023

Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing remote group is scarcely viewed as potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent C-H functionalizations via palladium-catalyzed substitution, which provides novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by suitable ligand, process involved 4,3-hydrofunctionalization of generated conjugated diene intermediate metal walking observed in generally >20 : 1 regioselectivity. Unexpectedly, related 1,4-hydrofunctionalization pathway found be major route with newly synthesized electron-rich bisphosphine challenges conventional viewpoint on regioselectivity hydrofunctionalizations linear internal dienes η3 -substitution. A series deuterium experiments and kinetic studies provide preliminary insight into catalytic cycle.

Language: Английский

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