The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD₃Reagents

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(46), P. 11751 - 11772

Published: June 2, 2021

Abstract In the field of medicinal chemistry, precise installation a trideuteromethyl group is gaining ever‐increasing attention. Site‐selective incorporation deuterated “magic methyl” can provide profound pharmacological benefits and be considered an important tool for drug optimization development. This review provides structured overview, according to trideuteromethylation reagent, currently established methods site‐selective carbon atoms. addition CD 3 , selective introduction 2 H CDH groups also considered. For all methods, corresponding mechanism scope are discussed whenever reported. As such, this starting point synthetic chemists further advance methodologies. At same time, aims guide chemists, offering them available C−CD formation strategies preparation new or modified drugs.

Language: Английский

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Advancements in multifunctional manganese complexes for catalytic hydrogen transfer reactions

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(69), P. 8534 - 8549

Published: Jan. 1, 2021

Manganese catalyzed hydrogen transfer reactions enabled net reductions and cascade CC- CN-bond formation reactions. The success is aided by multifunctional ligand design namely metal–ligand bifunctionality, hemilability, redox non-innocence.

Language: Английский

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Nickel-Catalyzed Guerbet Type Reaction: C-Alkylation of Secondary Alcohols via Double (de)Hydrogenation

Organic Letters, Journal Year: 2021, Volume and Issue: 23(9), P. 3320 - 3325

Published: April 21, 2021

Acceptorless double dehydrogenative cross-coupling of secondary and primary alcohols under nickel catalysis is reported. This Guerbet type reaction provides an atom- a step-economical method for the C-alkylation mild, benign conditions. A broad range substrates including aromatic, cyclic, acyclic, aliphatic was well tolerated. Interestingly, cholesterol derivatives cyclopentanol with various were also demonstrated.

Language: Английский

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Research progress in electrochemical/photochemical utilization of methanol as a C1 source

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(21), P. 8313 - 8327

Published: Jan. 1, 2023

This review highlights the recent advances in various electrochemical and photochemical reactions using methanol as a sustainable C1 source.

Language: Английский

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Divergent Synthesis of Alcohols and Ketones via Cross‐Coupling of Secondary Alcohols under Manganese Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: April 21, 2023

A homogeneous manganese-catalyzed cross-coupling of two secondary alcohols for the divergent synthesis γ-disubstituted and β-disubstituted ketones is reported. Employing well-defined Mn-MACHOPh as catalyst, this novel protocol has a broad substrate scope with good functional group tolerance affords diverse library valuable disubstituted in moderate to yields. The strong influence reaction temperature on selective formation alcohol products was theorized preliminary DFT studies. Studies have shown that Gibbs free energy thermodynamically more favourable than corresponding at lower temperature.

Language: Английский

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Multi-Functionality of Methanol in Sustainable Catalysis: Beyond Methanol Economy

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(22), P. 15013 - 15053

Published: Nov. 6, 2023

Methanol is a fundamental feedstock and widely used in the chemical petroleum industries. It can serve as C1 source to make variety of C–C C–N bond formation dehydrogenative coupling products, which have important applications natural products drug discovery. A high hydrogen content (12.5 wt%) methanol makes it an effective H2 donor for transfer hydrogenation various reducible functional groups. plethora transition metal-based processes been developed using methanol. Notably, recent review articles focused on aspect However, more updated that examines challenges both C1-source H2-source organic transformations contributing concept economy has not presented yet. This Review summarizes (homogeneous, heterogeneous, photo-) catalyst system C-, N-, O-methylation ketones, alcohols, amides, nitriles, heterocyclic compounds, sulfones, amines, sulfonamides direct N-methylation nitro compounds under borrowing strategy N-formylation amines acceptorless dehydrogenation source. also covers insights into reaction mechanisms role carefully selected ligands metal catalysis activation incorporation -CD3, methylation molecules. Moreover, describes groups such aldehydes, alkynes, with detail.

Language: Английский

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Sustainable and Selective Alkylation of Deactivated Secondary Alcohols to Ketones by Non‐bifunctional Pincer N‐heterocyclic Carbene Manganese

ChemSusChem, Journal Year: 2020, Volume and Issue: 13(10), P. 2557 - 2563

Published: March 31, 2020

Abstract A sustainable and green route to access diverse functionalized ketones via dehydrogenative–dehydrative cross‐coupling of primary secondary alcohols is demonstrated. This borrowing hydrogen approach employing a pincer N‐heterocyclic carbene Mn complex displays high activity selectivity. variety are well tolerant result in satisfactory isolated yields. Mechanistic studies suggest that this reaction proceeds direct outer‐sphere mechanism the dehydrogenation alcohol substrates plays vital role rate‐limiting step.

Language: Английский

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Simple RuCl₃‐catalyzed N‐Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol

ChemCatChem, Journal Year: 2021, Volume and Issue: 13(7), P. 1722 - 1729

Published: Jan. 21, 2021

Abstract Methanol is a potential hydrogen source and C 1 synthon, which finds interesting applications in both chemical synthesis energy technologies. The effective utilization of this simple alcohol organic central importance attracts scientific interest. Herein, we report clean cost‐competitive method with the use methanol as synthon H 2 for selective N ‐methylation amines by employing relatively cheap RuCl 3 .xH O ligand‐free catalyst. This readily available catalyst tolerates various comprising electron‐deficient electron‐donating groups allows them to transform into corresponding ‐methylated products moderate excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine imipramine) were also successfully synthesized via late‐stage functionalization from feedstock chemicals, highlighting synthetic value advanced reaction. Using platform, attempted tandem reactions selected nitroarenes convert using MeOH under ‐free conditions including transfer hydrogenation nitroarenes‐to‐anilines prepared drug molecules benzocaine butamben) well key intermediates. We further enable one‐shot green syntheses 1‐methylbenzimidazole ortho ‐phenylenediamine (OPDA) coupling partners.

Language: Английский

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Ru-Catalyzed Selective Catalytic Methylation and Methylenation Reaction Employing Methanol as the C1 Source

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 86(15), P. 10544 - 10554

Published: July 15, 2021

Methanol can be employed as a green and sustainable methylating agent to form C–C C–N bonds via borrowing hydrogen (BH) methodology. Herein we explored the activity of acridine-derived SNS-Ru pincer for activation methanol apply it C1 building block in different reactions. Our catalytic system shows great success toward β-C(sp3)-methylation reaction 2-phenylethanols provide good excellent yields methylated products. We investigated mechanistic details, kinetic progress, temperature-dependent product distribution, which revealed slow steady generation situ formed aldehyde, is key factor get higher yield β-methylated product. To establish environmental benefit this reaction, chemistry metrics are calculated. Furthermore, dimerization 2-naphthol methylene linkage formation N-methylation amine also described study, offers wide range substrate scope with yield.

Language: Английский

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Recent advances in sustainable organic transformations using methanol: expanding the scope of hydrogen-borrowing catalysis

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(24), P. 7077 - 7096

Published: Jan. 1, 2021

Recent progress relating to sustainable approaches using methanol as a C1-alkylating agent for C–Me and N–Me bond formation is discussed.

Language: Английский

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