Year: 2023
Type: editorial
Abstract: Fier et al. from Merck & Co. reported the traceless conversion of aromatic esters to ketones using alkyl sulfinates (Org.Lett., DOI: 10.1021/acs.orglett.3c00992).The authors took inspiration from the multistep Weinreb and Claisen methodologies for ketone formation from esters to explore alternative reagents that could favor ketone formation.This is realized by either stabilizing the tetrahedral adduct or by promoting the enolization of an intermediate that would ultimately release the ketone upon quenching the reaction.Alkyl sulfinate anions were explored, as it was envisaged that following addition to the ester starting material the resulting stabilized αketosulfinate would undergo elimination of sulfur dioxide upon quenching with water to leave the ketone product.The reaction conditions were surveyed using methyl benzoate as model substrate, with LiHMDS in toluene proving to give the best yields of methyl ketone using sodium methanesulfinate as methylating agent.Alternative counterions for the base (sodium, potassium) or solvents known to complex with lithium (e.g., THF) resulted in low yields.Release of sulfur dioxide gas was not observed, as in the presence of the water quench it reacts rapidly to form aqueous bisulfite.A range of aromatic esters were converted to methyl ketones in moderate to high yields dependent on the presence of other functional groups in the substrates.The methodology was extended to four examples of ethyl ketones starting from commercially available sodium ethanesulfinate.The speculation is that the methodology could be expanded to incorporate more complex alkyl substituents if the corresponding sulfinates can be readily accessed. ■ MODULAR FORMATION OF META-SUBSTITUTED BENZENESZhuo and co-workers from Xiamen University reported the synthesis of meta-substituted benzenes through the fusion of ynones and allylic amines using a molybdenum catalyst (J.Am.Chem.Soc., DOI: 10.1021/jacs.3c01330).Meta-substituted benzenes are important in the field of functional molecules and have some limited applications in bioactive molecules.Methodology that allows ready access to this framework without issues of regioselectivity are valuable in both the discovery of new molecules and their efficient synthesis.The authors discovered a molybdenum-catalyzed intermolecular deoxygenative coupling between ynones and allylic amines that delivers 1,3-di-and 1,3,5-trisubstituted benzenes depending on the substitution of the starting materials.Catalytic amounts of Mo(CO) 6 and 3,5-di-tert-butyl-o-benzoquinone (10 mol % each) in combination with a stoichiometric amount of reductant were key to successful reaction.Screening of the reductant highlighted that 1,8-bis(diphenylphosphino)octane (DPPO) was optimal, with 0.5 equiv (1 equiv of free phosphine) returning excellent yield for the model system.For 1,3-disubstituted benzenes, both aromatic and aliphatic substituents could be incorporated at both positions of products, demonstrating a wide range of possible products in moderate to excellent yields.Substitution of the allylic amine at
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4379801081