Nickel‐Catalyzed Asymmetric Reductive Carbo‐Carboxylation of Alkenes with CO₂

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(25), P. 14068 - 14075

Published: April 1, 2021

Abstract Reductive carboxylation of organo (pseudo)halides with CO 2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo‐carboxylation unsaturated hydrocarbons via fixation highly challenging but desirable approach for structurally diverse acids. There are only few reports and no examples alkenes transition metal catalysis. We report first asymmetric nickel A variety aryl (pseudo)halides, such as bromides, triflates inert chlorides particular note, undergo reaction smoothly give important oxindole‐3‐acetic acid derivatives bearing C3‐quaternary stereocenter. This transformation features mild conditions, wide substrate scope, facile scalability, good excellent chemo‐, regio‐ enantioselectivities. The highlights formal synthesis (−)‐Esermethole, (−)‐Physostigmine (−)‐Physovenine, total (−)‐Debromoflustramide B, (−)‐Debromoflustramine B (+)‐Coixspirolactam A; thereby, opening an avenue chiral natural products .

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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Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

Chemical Science, Journal Year: 2020, Volume and Issue: 11(35), P. 9341 - 9365

Published: Jan. 1, 2020

This review summarizes the advances in catalytic enantioselective construction of vicinal quaternary carbon stereocenters, introduces major synthetic strategies and discusses their advantages limitations, outlines opportunities.

Language: Английский

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Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO₂

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(47), P. 18825 - 18835

Published: Nov. 8, 2019

The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction tertiary chiral centers. generation acyclic products containing all-carbon quaternary stereocenters from substituted represents a more challenging, desirable, synthetic process for which there very few examples. Herein, we report selective copper-catalyzed via with CO2. A variety 1,1-disubstituted 1,3-dienes, as well 1,3,5-triene, undergo reductive hydroxymethylation high chemo-, regio-, E/Z-, and enantioselectivities. reported method features good functional group tolerance, scaled up at least 5 mmol starting diene, generates that useful building blocks further derivatization. Systemic mechanistic investigations using density theory calculations were performed provided first theoretical investigation an transformation involving These computational results indicate 1,2-hydrocupration 1,3-diene proceeds π-facial selectivity generate (S)-allylcopper intermediate, induces chirality carbon center in final product. 1,4-addition internal allylcopper complex, differs previous reports terminal allylmetallic intermediates, CO2 kinetically determines E/Z- regioselectivity. rapid reduction copper carboxylate intermediate corresponding silyl-ether presence Me(MeO)2SiH provides exergonic impetus leads chemoselective rather than carboxylation. provide new insights guiding development C-C bond formations

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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1,4‐Migration of Transition Metals in Organic Synthesis

Chinese Journal of Chemistry, Journal Year: 2019, Volume and Issue: 37(9), P. 929 - 945

Published: June 11, 2019

Generation of carbon‐metal species is extremely important in transition metal‐catalyzed organic synthesis. Among the various methods, 1,4‐metal migration a very useful way to create new species, which are not readily accessible via classic methods. This review summarized recent advances reactions, involved one or more steps migration. It focused mostly on achievements Pd and Rh‐catalyzed along with some remarkable results Pt, Ir, Co, Fe‐involved transformations.

Language: Английский

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Construction of All-Carbon Quaternary Stereocenters by Scandium-Catalyzed Intramolecular C–H Alkylation of Imidazoles with 1,1-Disubstituted Alkenes

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(3), P. 1200 - 1205

Published: Jan. 6, 2020

The exo-selective C–H cycloaddition of imidazoles to 1,1-disubstituted alkenes has been achieved for the first time by using half-sandwich scandium catalysts. A wide range imidazole compounds bearing various aliphatic alkenes, styrenes, dienes, and enynes have selectively converted in high yields corresponding bicyclic derivatives β-all-carbon-substituted quaternary stereocenters. By a chiral catalyst, asymmetric cyclization also with level enantioselectivity.

Language: Английский

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Pd/Cu‐Catalyzed Enantioselective Sequential Heck/Sonogashira Coupling: Asymmetric Synthesis of Oxindoles Containing Trifluoromethylated Quaternary Stereogenic Centers

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(7), P. 2764 - 2768

Published: Oct. 30, 2019

Abstract An asymmetric palladium and copper co‐catalyzed Heck/Sonogashira reaction between o ‐iodoacrylanilides terminal alkynes to synthesize chiral oxindoles was developed. In particular, a wide range of CF 3 ‐substituted reacted with alkynes, affording the corresponding containing trifluoromethylated quaternary stereogenic centers in high yields excellent enantioselectivities (94–98 % ee ). This provides general approach access oxindole derivatives including ones.

Language: Английский

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