One-Pot Conversion of Allylic Alcohols to α-Methyl Ketones via Iron-Catalyzed Isomerization–Methylation

Latham, Daniel E.; Polidano, Kurt; Williams, Jonathan M. J.; Morrill, Louis C.

doi:10.1021/acs.orglett.9b02900

Cited by 33 publications

(24 citation statements)

References 83 publications

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“…To further demonstrate the usefulness of the Fe‐catalyzed procedure, the Morrill group showed that the process may be extended to allyl alcohols, resulting in products with moderate to excellent yields (Scheme 7 d, below). [30] During methylation with CD 3 OD there was near complete incorporation of deuterium at the α‐ and for 54 % at β‐position. This percentage of 54 % can be understood when an iron hydride, formed by dehydrogenation of allyl alcohol or methanol, is involved in the mechanism.…”

Section: [D 4 ]Methanolmentioning

confidence: 99%

“…The complex showed good reactivity towards the selective β‐methylation of substituted 2‐arylethanol derivatives. To further demonstrate the usefulness of the Fe‐catalyzed procedure, the Morrill group showed that the process may be extended to allyl alcohols, resulting in products with moderate to excellent yields (Scheme 7d, below) [30] . During methylation with CD 3 OD there was near complete incorporation of deuterium at the α‐ and for 54 % at β‐position.…”

Section: [D4]methanolmentioning

confidence: 99%

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

Steverlynck

Sitdikov

Rueping

2021

Chemistry A European J

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In the field of medicinal chemistry, the precise installation of a trideuteromethyl group is gaining ever‐increasing attention. Site‐selective incorporation of the deuterated “magic methyl” group can provide profound pharmacological benefits and can be considered an important tool for drug optimization and development. This review provides a structured overview, according to trideuteromethylation reagent, of currently established methods for site‐selective trideuteromethylation of carbon atoms. In addition to CD3, the selective introduction of CD2H and CDH2 groups is also considered. For all methods, the corresponding mechanism and scope are discussed whenever reported. As such, this review can be a starting point for synthetic chemists to further advance trideuteromethylation methodologies. At the same time, this review aims to be a guide for medicinal chemists, offering them the available C−CD3 formation strategies for the preparation of new or modified drugs.

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Section: [D 4 ]Methanolmentioning

confidence: 99%

Section: [D4]methanolmentioning

confidence: 99%

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

Steverlynck

Sitdikov

Rueping

2021

Chemistry A European J

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“…Next, Morrill and co‐workers [17] reported a one‐pot transformation of allylic alcohols to α ‐C‐methyl ketones. This reaction proceeded through isomerization‐methylation using Fe‐catalyst (1) (2 mol%) in the presence of Me 3 NO (4 mol%) and K 2 CO 3 (2 equiv.)…”

Section: Fe‐catalyzed C‐methylation Reactions Using Methanolmentioning

confidence: 99%

Base Metal‐Catalyzed C‐Methylation Reactions Using Methanol

et al. 2021

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C‐methylation is a vitally important reaction applicable in chemical synthesis and structure‐based drug design. Notably, the “magic methyl” effect has become decisive in medicinal chemistry and drug discovery for the modulation of bio‐active properties in life science molecules. In this regard, C‐methylation reaction is widely applied chemical modification in various biomolecules, pharmaceuticals, and natural products. In general, this reaction often relies on activated, hazardous and uneconomical methyl sources such as diazomethane, dimethyl sulfate, and methyl halides. To achieve methylation reactions in a sustainable and cost‐effective manner, the use of ‘ideal’ C1 source is crucial. In this regard, methanol constitutes an expedient −CH3 source because this simple alcohol is less‐hazardous, inexpensive, and abundantly available platform chemical as well as it produces only water as the by‐product in methylation processes. Regarding potential catalysts to perform C‐methylation using methanol by hydrogen borrowing methodology, non‐noble metal‐based catalysts are highly preferable due to their unique advantages such as more abundance, inexpensive and low‐toxicity. In recent years, chemists made significant contributions towards catalytic valorization of methanol as C1 source to insert methyl groups via C−H activation in a variety of compounds and life science molecules. Consequently, in this minireview we summarize the C‐methylation process using methanol by applying Fe‐, Mn‐, Co‐ and Ni‐based catalysts as well as metal free catalysts.

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“…Subsequently, they developed a one‐pot synthesis of α ‐methyl ketones from the corresponding allylic alcohol applying an isomerization‐methylation strategy (Scheme 31A) [131] . Later, Renaud and co‐workers developed an α ‐alkylation to access β ‐disubstituted carbonyl compounds directly in presence of 11 a [132] .…”

Section: Alkylation Reactionsmentioning

confidence: 99%

(Cyclopentadienone)iron Complexes: Synthesis, Mechanism and Applications in Organic Synthesis

Akter

Anbarasan

2021

Chemistry An Asian Journal

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(Cyclopentadienone)iron tricarbonyl complexes are catalytically active, inexpensive, easily accessible and air‐stable that are extensively studied as an active pre‐catalyst in homogeneous catalysis. Its versatile catalytic activity arises exclusively due to the presence of a non‐innocent ligand, which can trigger its unique redox properties effectively. These complexes have been employed widely in (transfer)hydrogenation (e. g., reduction of polar multiple bonds, Oppenauer‐type oxidation of alcohols), C−C and C−N bond formation (e. g., reductive aminations, α‐alkylation of ketones) and other synthetic transformations. In this review, we discuss the remarkable advancement of its various synthetic applications along with synthesis and mechanistic studies, until February 2021.

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One-Pot Conversion of Allylic Alcohols to α-Methyl Ketones via Iron-Catalyzed Isomerization–Methylation

Cited by 33 publications

References 83 publications

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

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

Base Metal‐Catalyzed C‐Methylation Reactions Using Methanol

(Cyclopentadienone)iron Complexes: Synthesis, Mechanism and Applications in Organic Synthesis

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One-Pot Conversion of Allylic Alcohols to α-Methyl Ketones via Iron-Catalyzed Isomerization–Methylation

Cited by 33 publications

References 83 publications

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

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

Base Metal‐Catalyzed C‐Methylation Reactions Using Methanol

(Cyclopentadienone)iron Complexes: Synthesis, Mechanism and Applications in Organic Synthesis

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Product

Resources

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

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