Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(30), P. 13961 - 13972

Published: July 22, 2022

Regiodivergent alkyne hydroalkylation to generate different isomers of an alkene from the same starting material would be beneficial; however, it remains a challenge. Herein, we report ligand-controlled cobalt-catalyzed regiodivergent hydroalkylation. The sensible selection bisoxazoline (L1) and pyridine-oxazoline (L8) ligands led reliable predictable protocols that provided (E)-1,2-disubstituted 1,1-disubstituted alkenes with high E/Z stereoselectivity regioisomeric ratio identical terminal alkyl halide substrates produced trisubstituted in case internal alkynes. This method exhibits broad scope for alkynes wide range activated unactivated halides shows excellent functional group compatibility.

Language: Английский

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Recent Advances in the Functionalization of Terminal and Internal Alkynes

Asian Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 11(5)

Published: March 9, 2022

Abstract Alkynes are one of the most fundamental and diverse functional groups utilized in organic synthesis. Over past few years, development efficient synthetic methodologies for functionalization alkynes has been an active area research. A plethora alkyne reactions have reported literature to construct functionalized alkene scaffolds, which important building blocks many natural products, pharmaceuticals, key intermediates various transformations. In this review, we describe recent advances with emphasis on substrate scope, limitations, regioselectivity control applications these reactions. This review covers from 2016 2021.

Language: Английский

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Stereoselective Synthesis of Trisubstituted Alkenes via Copper Hydride-Catalyzed Alkyne Hydroalkylation

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17557 - 17563

Published: Aug. 4, 2023

Alkenes are ubiquitous in organic chemistry, yet many classes of alkenes remain challenging to access by current synthetic methodology. Herein, we report a copper hydride-catalyzed approach for the synthesis Z-configured trisubstituted with high stereo- and regioselectivity via alkyne hydroalkylation. A DTBM-dppf-supported Cu catalyst was found be optimal, providing substantial increase product yield compared reactions conducted dppf as ligand. DFT calculations show that DTBM substitution leads acceleration hydrocupration through combined ground transition state effects related preventing dimerization enhancing catalyst–substrate dispersion interactions, respectively. Alkyne hydroalkylation successfully demonstrated methyl larger alkyl tosylate electrophiles produce variety (hetero)aryl-substituted moderate yields complete selectivity Z stereochemically configured products. In formation key C–C bond, computational studies revealed direct SN2 pathway alkylation vinylcopper intermediate situ-formed iodides.

Language: Английский

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Data Science Guided Multiobjective Optimization of a Stereoconvergent Nickel-Catalyzed Reduction of Enol Tosylates to Access Trisubstituted Alkenes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 4699 - 4708

Published: March 13, 2024

Herein we report a method for stereoconvergent synthesis of trisubstituted alkenes in two steps from simple ketone starting materials. The key step is nickel-catalyzed reduction the corresponding enol tosylates that predominantly relies on monophosphine ligand to direct formation either E- or Z-trisubstituted alkene products. Reaction optimization was accomplished using data science workflow including training set design, statistical modeling, and multiobjective Bayesian optimization. campaign significantly improved access both products up ∼90:10 diastereoselectivity >90% yield. After identifying superior ligands only 25 reactions were required each objective (E- Z-isomer formation) converge reaction parameters search space ∼30,000 potential conditions EDBO+ platform. Additionally, hierarchical machine learning model developed predict stereoselectivity untested achieve validation mean absolute error (MAE) 7.1% selectivity (0.21 kcal/mol). Ultimately, present synergistic leveraging integration optimization, thereby expanding stereodefined alkenes.

Language: Английский

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Asymmetric anti-Selective Borylalkylation of Terminal Alkynes by Nickel Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(34), P. 18722 - 18730

Published: Aug. 15, 2023

Selective transformation of alkyne triple bonds to double serves as an efficient platform construct substituted alkenes. While significant advances have been made in its spatiotemporal regulation, achieving a multicomponent enantioselective reaction that requires multifaceted selectivity issues be overcome is still uncommon. Here, we report unprecedented asymmetric anti-stereoselective borylcarbofunctionalization terminal alkynes by nickel catalysis. The utilization inexpensive chiral diamine ligand enables the three-component cross-coupling alkynes, diboron reagent, and prochiral alkyl electrophiles with high levels regio-, stereo-, enantioselectivities. This provides protocol access enantioenriched alkenyl esters bearing α-stereogenic center, remarkably practical, has broad scope outstanding functional group compatibility. In addition, value this method highlighted diversity follow-up stereoretentive derivatizations stereoselective concise synthesis complex drug molecules.

Language: Английский

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A Bifunctional Copper Catalyst Enables Ester Reduction with H₂: Expanding the Reactivity Space of Nucleophilic Copper Hydrides

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(40), P. 16865 - 16873

Published: Oct. 4, 2021

Employing a bifunctional catalyst based on copper(I)/NHC complex and guanidine organocatalyst, catalytic ester reductions to alcohols with H2 as terminal reducing agent are facilitated. The approach taken here enables the simultaneous activation of esters through hydrogen bonding formation nucleophilic copper(I) hydrides from H2, resulting in hydride transfer esters. reduction step is further facilitated by proton shuttle mediated guanidinium subunit. This for first time shifts reactivity generally considered "soft" previously unreactive "hard" electrophiles paves way replacement stoichiometric agents H2.

Language: Английский

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Copper-Catalyzed Asymmetric Conjugate Addition of Alkene-Derived Nucleophiles to Alkenyl-Substituted Heteroarenes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 9611 - 9620

Published: July 22, 2022

We herein report the copper-catalyzed asymmetric conjugate addition of β-substituted alkenyl heteroarenes, one most challenging Michael acceptors, with alkenes as latent nucleophiles. Diverse chiral heteroarenes bearing two vicinal stereocenters were obtained in good to excellent yields, generally enantioselectivity, and a level diastereoselectivity. The products can be readily transformed into other valuable acyclic enantioenriched structures three contiguous via amine catalysis. Mechanistic studies, including an isotope labeling experiment, nonlinear effect study, kinetic experiments, initial-rate kinetics implemented, experimental results indicated that hydrocupration step might turnover-limiting step. Moreover, origin preferential alkene presence Ph-BPE-ligated CuH catalyst was also elucidated some control experiments.

Language: Английский

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α‐Halocarbonyls as a Valuable Functionalized Tertiary Alkyl Source

ChemistryOpen, Journal Year: 2024, Volume and Issue: unknown

Published: July 11, 2024

Abstract This review introduces the synthetic organic chemical value of α‐bromocarbonyl compounds with tertiary carbons. compound a carbon has been used primarily only as radical initiator in atom transfer polymerization (ATRP) reactions. However, recent development photo‐radical reactions (around 2010), research on use alkyl precursors became popular 2012). As more examples were reported, studied not radicals but also for their applications organometallic and ionic That is, act nucleophiles well electrophiles. The carbonyl group is attractive because it allows skeleton to be converted after reaction, being applied total synthesis. In our survey until 2022, can perform full range necessary synthesis, including multi‐component reactions, cross‐coupling, substitution, cyclization, rearrangement, stereospecific asymmetric α‐Bromocarbonyl have created new trend alkylation, which then had limited reaction patterns focuses how chemistry.

Language: Английский

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Enantioselective Multicomponent Electrochemical Difunctionalization of Terminal Alkynes

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The direct functionalization of alkyne triple bonds using a radical strategy provides an efficient platform for creating wide range substituted alkenes. However, developing multicomponent enantioselective reaction feedstock alkynes to forge all-carbon quaternary stereocenters─while addressing challenges related compatibility, selectivity, and efficiency─remains relatively rare. Here we report electrochemical nickel-catalyzed three-component cross-coupling readily available terminal alkynes, diverse racemic alkyl precursors, group transfer reagents (such as (TMS)3Si-H, RSe-SeR, RTe-TeR, CHI3), achieving excellent regio-, stereo-, enantioselectivities (more than 70 examples, up 95% ee). Electricity-mediated difunctionalizations significantly expand the scope both aliphatic aromatic demonstrating functional compatibility. key success lies in rational design anodically generated nickel-bound tertiary intermediates, which stereoselectively capture form vinyl radicals participate subsequently processes enable intermolecular anti-stereoselective difunctionalization alkynes. This approach allows transformation into structural entities with α-quaternary stereogenic centers.

Language: Английский

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Distinct Reactivity Modes of a Copper Hydride Enabled by an Intramolecular Lewis Acid

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(33), P. 15038 - 15046

Published: Aug. 12, 2022

We disclose a 1,4,7-triazacyclononane (TACN) ligand featuring an appended boron Lewis acid. Metalation with Cu(I) affords series of tetrahedral complexes including boron-capped cuprous hydride. demonstrate distinct reactivity modes as function chemical oxidation: hydride transfer to CO2 in the copper(I) state and oxidant-induced H2 evolution well alkyne reduction.

Language: Английский

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