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

---

Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(23), P. 12532 - 12540

Published: May 30, 2023

An asymmetric three-component carbosulfonylation of alkenes is presented here. The reaction, involving the simultaneous formation a C-C and C-S bond across π-system, uses dual nickel/photoredox catalytic system to produce both β-aryl β-alkenyl sulfones in high yields with excellent levels stereocontrol (up 99:1 er). This protocol exhibits broad substrate scope functional group tolerance its synthetic potential has been demonstrated by successful applications toward pharmacologically relevant molecules. A array control experiments supports involvement secondary alkyl radical intermediate generated through addition sulfonyl double bond. Moreover, stoichiometric cross-over further suggest an underlying Ni(0)/Ni(I)/Ni(III) pathway operative these transformations.

Language: Английский

---

Metallaphotoredox-enabled aminocarboxylation of alkenes with CO2

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(10), P. 959 - 968

Published: Sept. 21, 2023

Language: Английский

---

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO₂

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2919 - 2927

Published: Jan. 26, 2024

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward sustainable route to dicarboxylic acids, it is still highly challenging limited generation of achiral or racemic acids. To date, asymmetric give chiral has not been reported. Herein, we report first 1,3-dienes via Cu catalysis. This strategy provides an efficient environmentally benign high regio-, chemo-, enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation carboxylated allyl boronic ester intermediates subsequent carboxylation C–B bonds dicarboxylates, key success this dicarboxylation. Moreover, protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, facile synthesis liquid crystalline polyester drug-like scaffolds.

Language: Английский

---

Catalytic Regio- and Enantioselective Boracarboxylation of Arylalkenes with CO₂ and Diboron

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2888 - 2894

Published: Jan. 26, 2024

Catalytic asymmetric carboxylation of readily available alkenes with CO2, an abundant and sustainable one-carbon building block, that gives access to value-added α-stereogenic carboxylic acids in atom- step-economic manner is highly attractive. However, it has remained a formidable challenge for the synthetic community. Here, first example Cu-catalyzed regio- enantioselective boracarboxylation reaction on various arylalkenes diboron under atmospheric pressure CO2 described, which afforded variety chiral β-boron-functionalized α-aryl up 87% yield 97% ee mild conditions. Importantly, α-substituted could also be subject this protocol excellent enantiopurities, thereby rendering efficient approach generation enantioenriched α-chiral all-carbon quaternary center. Moreover, high functional group tolerance, scalable synthesis, facile bioactive compounds, like (−)-scopolamine, (−)-anisodamine, (−)-tropicamide, further demonstrated utility strategy.

Language: Английский

---

Recent progress and challenges in carboxylation with CO2

Current Opinion in Green and Sustainable Chemistry, Journal Year: 2021, Volume and Issue: 32, P. 100525 - 100525

Published: June 8, 2021

Language: Английский

---

Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(33), P. 12961 - 12967

Published: Aug. 12, 2021

Catalytic asymmetric dicarbofunctionalization of tethered alkenes has emerged as a promising tool for producing chiral cyclic molecules; however, it typically relies on aryl-tethered to form benzene-fused compounds. Herein, we report an enantioselective cross-electrophile divinylation reaction nonaromatic substrates, 2-bromo-1,6-dienes. The approach thus offers route new architectures, which are key structural motifs found in various biologically active proceeds under mild conditions, and the use t-Bu-pmrox 3,5-difluoro-pyrox ligands resulted formation divinylated products with high chemo-, regio-, enantioselectivity. method is applicable incorporation hetero- carbocycles into complex molecules.

Language: Английский

---

The road to industrialization of fine chemical carboxylation reactions

Chem, Journal Year: 2021, Volume and Issue: 7(11), P. 2927 - 2942

Published: Nov. 1, 2021

Language: Английский

---

Selectively Regulating Lewis Acid–Base Sites in Metal–Organic Frameworks for Achieving Turn‐On/Off of the Catalytic Activity in Different CO₂Reactions

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(18)

Published: Feb. 24, 2022

Regulating Lewis acid-base sites in catalysts to investigate their influence the chemical fixation of CO2 is significant but challenging. A metal-organic framework (MOF) with open metal Co sites, {(NH2 Me2 )[Co3 (μ3 -OH)(BTB)2 (H2 O)]⋅9 H2 O⋅5 DMF}n (1), was obtained and results catalytic investigation show that 1 can catalyze cycloaddition aziridines give 99 % yield. The efficiency cyclization propargyl amines only 32 %. To improve ability 1, ligand XN base introduced into coordinated resulting a decrease acid an increase related MOF 2 ({(NH2 -OH)(NHMe2 )(BTB)2 (XN)]⋅8 O⋅4 ). Selective regulation type active centers causes yield oxazolidinones be enhanced by about 2.4 times, suggesting this strategy turn on/off activity for different reactions. from treated solution support conclusion. This work illuminates MOF-construction produces efficient conversion.

Language: Английский

---

Switchable 1,2-Rearrangement Enables Expedient Synthesis of Structurally Diverse Fluorine-Containing Scaffolds

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(26), P. 11626 - 11637

Published: May 23, 2022

Skeletal rearrangement that changes the connectivity of molecule via cleavage and reorganization carbon–carbon bonds is a fundamental powerful strategy in complex molecular assembly. Because lack effective methods to control migratory tendency different groups, achieving switchable selectivity skeletal has been long-standing quest. Metal-based dyotropic provides unique opportunity address this challenge. However, remains unexplored. Herein, we show such problem could be solved by modifying ligands on metal catalyst changing oxidation states aptitude thereby providing ligand-controlled, strategy. Experimental density functional theory calculation studies prove rational design. The occurs only when nickel(II) intermediate reduced more nucleophilic nickel(I) species, sterically hindered iPrPDI ligand facilitates 1,2-aryl/Ni rearrangement, while terpyridine promotes 1,2-acyl/Ni rearrangement. This method allows site-selective activation C–C applied for divergent synthesis four medicinally relevant fluorine-containing scaffolds from same starting material.

Language: Английский

---