Enantioselective Three-Component Fluoroalkylarylation of Unactivated Olefins through Nickel-Catalyzed Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(21), P. 9604 - 9611

Published: May 11, 2020

A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization alkenes, providing direct access valuable β-fluoroalkyl arylalkanes high efficiency excellent enantioselectivity. The mild conditions allow for broad substrate scope good functional toleration.

Language: Английский

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Asymmetric Ni-Catalyzed Radical Relayed Reductive Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(31), P. 13515 - 13522

Published: June 29, 2020

Alkene dicarbofunctionalizations enable the streamlined construction of aliphatic structures and have thus been subject intense research efforts. Despite significant progress, catalytic asymmetric variants remain scarce. Inspired by advantages reductive cross-coupling approaches, we present here a highly efficient intermolecular Ni-catalyzed dicarbofunctionalization alkenes. Two distinct readily available electrophiles, namely, Csp2- Csp3-halides, are added simultaneously across variety olefins (vinyl amides, vinyl boranes, phosphonates) at room temperature in regio- enantioselective manner. The reaction, devoid sensitive organometallic reagents, takes advantage an situ generated chiral alkyl Ni(III)-intermediate to ensure stereodefined outcome Csp3–Csp2 bond-forming reaction. An (l)-(+)-isoleucine bisoxazoline ligand presence coordinating sites on alkene key for successful these "asymmetric radical relayed couplings" (ARRRCs). Further, multiple transformations amides obtained this process showcase potential new methodology straightforward assembly building blocks such as primary secondary amines oxazolines, highlighting its synthetic utility.

Language: Английский

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Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(5), P. 2180 - 2186

Published: Jan. 23, 2020

An unprecedented asymmetric acyl-carbamoylation of pendant alkenes tethered on aryl carbamic chlorides with both aliphatic and aromatic aldehydes has been developed via the cooperative catalysis a chiral nickel-PHOX complex tetrabutylammonium decatungstate. This reaction represents first example merging hydrogen-atom-transfer photochemistry transition metal in difunctionalization alkenes. Using this protocol, variety oxindoles bearing challenging quaternary stereogenic center are furnished under mild conditions highly enantioselective manner.

Language: Английский

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Nickel‐Catalyzed Asymmetric Reductive Arylalkylation of Unactivated Alkenes

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(20), P. 6722 - 6726

Published: March 20, 2019

Abstract Reported is an asymmetric reductive dicarbofunctionalization of unactivated alkenes. Under the catalysis a Ni/BOX system, various aryl bromides, incorporating pendant olefinic unit, were successfully reacted with array primary alkyl bromides in presence Zn as reductant, furnishing series benzene‐fused cyclic compounds bearing quaternary stereocenter high enantioselectivities. Notably, this reaction avoids use pregenerated organometallics and demonstrates tolerance sensitive functionalities. The preliminary mechanistic investigations reveal that Ni‐catalyzed proceeds cascade consisting migratory insertion cross‐coupling nickel(I)‐mediated intramolecular 5‐ exo cyclization enantiodetermining step.

Language: Английский

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Nickel-Catalyzed Ligand-Controlled Selective Reductive Cyclization/Cross-Couplings

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(5), P. 515 - 535

Published: Jan. 23, 2023

ConspectusThe use of quaternary stereocenters during lead candidate optimization continues to grow because improved physiochemical and pharmacokinetic profiles compounds with higher sp3 fraction. Pd-catalyzed redox-neutral alkene difunctionalization involving carbopalladation alkenes followed by nucleophilic-trapping σ-alkyl-palladium intermediates has been developed as an efficient method construct stereocenters. However, the low chemoselectivity air sensitivity organometallic nucleophiles, well their availability accessibility, limit scope application this elegant strategy. Recently, Ni-catalyzed reductive cross-coupling evolved into a privileged strategy easily valuable C(sp3)-C bonds. Despite great progress, enantioselective coupling C(sp3) electrophiles still relies on activated or functionalized alkyl precursors, which are often unstable require multiple steps prepare. Therefore, via selective cyclization/cross-coupling was developed. This not only offers robust practical alternative for traditional but also provides strategic complementarity electrophiles. In Account, we summarize latest results from our laboratory topic. These findings mainly include explorations in modulating enantioselectivity cyclization mode cyclization/cross-couplings.We will first discuss chiral heterocycles focus effects ligands, reductants, additives roles cross-coupling. A wide range have explored, including aryl halides, vinyl alkynyl gem-difluoroalkenes, CO2, trifluoromethyl alkenes, cyano The synthetic potential approach demonstrated synthesis biologically active natural products drug molecules. Second, detail how tune steric nickel catalysts modifying bipyridine ligands regiodivergent cyclization/cross-couplings. Specifically, bidentate favors exo-selective cyclization/cross-coupling, while carboxylic acid-modified ligand permits endo-selective cyclization/cross-coupling. We show activate amide substrate altering electronic properties substituents nitrogen, thereby enabling nucleophilic addition halides carbonyls. Further investigation led tunable cyclization/cross-couplings (addition carbonyl vs 7-endo-cyclization) divergent pharmacologically important 2-benzazepine frameworks. Finally, serendipitously discover that changing oxidation state can control migratory aptitude different groups, thus providing switchable skeletal rearrangement transformation is high value it represents conceptually unprecedented new C-C bond activation. Thus, Account summarizes methods allow formation using variety insight relationship between structure, substrate, selectivity.

Language: Английский

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Gold‐Catalyzed 1,2‐Diarylation of Alkenes

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(29), P. 11808 - 11813

Published: March 23, 2020

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through interplay ligand-enabled AuI /AuIII catalysis with idiosyncratic π-activation mode gold complexes. Unlike classical migratory-insertion-based approach to 1,2-diarylation, present not only circumvents formation direct Ar-Ar' coupling and Heck-type side products but more intriguingly demonstrates reactivity selectivity complementary those previously known metal (Pd, Ni, or Cu). Detailed investigations underpin mechanistic scenario revealed oxidative addition aryl iodides an complex be rate-limiting step owing non-innocent nature alkene.

Language: Английский

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Enantioselective Difunctionalization of Alkenes by a Palladium‐Catalyzed Heck/Sonogashira Sequence

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(7), P. 2769 - 2775

Published: Nov. 22, 2019

Abstract Sonogashira‐type cross‐couplings are one of the most significant alkynylations in organic chemistry. One first palladium‐catalyzed intramolecular Heck/Sonogashira reactions alkenes with terminal alkynes is now reported. With this method, a variety uniquely substituted chiral benzene‐fused heterocycles bearing propargyl‐substituted all‐carbon quaternary stereocenter were obtained straightforward, high‐yielding, and highly stereoselective manner under mild conditions. Salient features process include use readily available substrates, high selectivities, broad substrate scope as well versatile product functionalizations.

Language: Английский

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Palladium‐Catalyzed Enantioselective Heck Carbonylation with a Monodentate Phosphoramidite Ligand: Asymmetric Synthesis of (+)‐Physostigmine, (+)‐Physovenine, and (+)‐Folicanthine

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(29), P. 12199 - 12205

Published: April 2, 2020

Abstract Reported herein is the development of first enantioselective monodentate ligand assisted Pd‐catalyzed domino Heck carbonylation reaction with CO. The highly N ‐aryl acrylamides and various nucleophiles, including arylboronic acids, anilines, alcohols, in presence CO was achieved. A novel phosphoramidite ligand, Xida‐Phos, has been developed for this it displays excellent reactivity enantioselectivity. employs readily available starting materials, tolerates a wide range functional groups, provides straightforward access to diverse array enantioenriched oxindoles having β‐carbonyl‐substituted all‐carbon quaternary stereocenters, thus providing facile complementary method asymmetric synthesis bioactive hexahydropyrroloindole its dimeric alkaloids.

Language: Английский

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Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(9), P. 3475 - 3479

Published: Dec. 23, 2019

Abstract A ruthenium(II)‐catalyzed asymmetric intramolecular hydroarylation assisted by a chiral transient directing group has been developed. series of 2,3‐dihydrobenzofurans bearing all‐carbon quaternary stereocenters have prepared in remarkably high yields (up to 98 %) and enantioselectivities >99 % ee ). By this methodology, novel total synthesis CB2 receptor agonist MDA7 successfully

Language: Английский

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Synthesis of All‐Carbon Quaternary Centers by Palladium‐Catalyzed Olefin Dicarbofunctionalization

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(6), P. 2375 - 2379

Published: Oct. 31, 2019

The redox-neutral dicarbofunctionalization of tri- and tetrasubstituted olefins to form a variety (hetero)cyclic compounds under photoinduced palladium catalysis is described. This cascade reaction process was used couple styrenes or acryl amides with broad range highly decorated tethered aryl alkyl bromides (>50 examples). procedure enables one two contiguous all-carbon quaternary centers be formed in single step. products could readily diversified applied the synthesis bioactive oxindole analogue.

Language: Английский

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