Palladium‐Catalyzed Synthesis of α‐Methyl Ketones from Allylic Alcohols and Methanol

Abstract

One‐pot synthesis of α‐methyl ketones starting from 1,3‐diaryl propenols or 1‐aryl propenols and methanol as a C1 source is demonstrated. This one‐pot isomerization‐methylation is catalyzed by commercially available Pd(OAc)2 with H2O as the only by‐product. Mechanistic studies and deuterium labelling experiments indicate the involvement of isomerization of allyl alcohol followed by methylation through a hydrogen‐borrowing pathway in these isomerization‐methylation reactions.

One-pot three-component synthesis of α-methylated ketones from secondary and primary aryl alcohols

“…15 b Among the three catalysts screened, cross-linked polymer-supported catalyst Pd@IP1 showed better catalytic activity. 15 In continuation of our effort to activate methanol 16 and other alcohols under borrowing hydrogen methodology using our reported catalyst Pd@IP1, 15 b we reacted secondary alcohols with primary alcohols and methanol to obtain the α-branched methyl ketones. Alkylation–methylation of 1-( p -tolyl)ethanol by benzyl alcohol and methanol was chosen as the model reaction for optimisation of the reaction parameters.…”

Base-Catalyzed Traceless Silylation and Deoxygenative Cyclization of Chalcones to Cyclopropanes

“…Product 57 was isolated in 57% (81 mg) yield, and product 55 was isolated in 15% (25 mg) isolated yield. Product 57 was isolated as a colorless liquid . IR (DCM): 3332, 3023, 2920, 2848, 1490, 1455, 977, 736, 700 cm –1 .…”

“…Product 57 was isolated as a colorless liquid. 25 Reaction of Allyl Alcohol 57 in Base-Catalyzed Cyclopropanation. An oven-dried sealed tube (25 mL) equipped with a magnetic stir bar was charged with allylic alcohol 57 obtained from reduction of the corresponding chalcone-((E)-2-benzylidene-1,2,3,4tetrahydronaphthalen-1-ol, 0.5 mmol, 118 mg), phenylsilane (2.5 mmol, 308 μL), KOH (20 mol %, 5.6 mg), and toluene (2.0 mL) under a nitrogen atmosphere.…”

Theoretical Study for Evaluating and Discovering Organic Hydride Compounds as Potential Novel Methylation Reagents

“…The introduction of the methyl group to drug molecules is helpful to improve their binding affinity, biological availability, and metabolic stability (called “magic methyl effect”), which greatly changes the pharmacological properties of bioactive molecules. − Methylation plays an important role in the modification of drug molecules, DNA, as well as proteins. − According to different reaction mechanisms, the methylation agents are divided into three classes, i.e., electrophilic methylation reagents, nucleophilic methylation reagents, and free radical methylation reagents . At present, great progress has been made in the methylation reaction. − Many chemists have made outstanding contributions in this field, and a large number of new methyl reagents − and new methylation reactions have been developed, − especially electrocatalytic, , visible-light-induced, or transition-metal-catalyzed − methylation, in recent years. In 2021, Dixon and co-workers published an important review about C–H methylation in chemical synthesis, which covered the various methylation reagents and diverse strategies employed to realize the selective installation of the C–Me bond in extensive chemical structures .…”