Access to Benzylic Quaternary Carbons from Aromatic Ketones

Abstract

The construction of benzylic all-carbon quaternary stereocenters, which are ubiquitous in biomolecules and drugs, is a task of high practical significance. Herein, we disclose a highly efficient one-pot method of constructing all-carbon quaternary structural units from aryl ketones, revealing that the entire process involves three consecutive chemical events, namely nucleophilic addition, Meinwald 1,2-hydrogen migration, and alkylation. Interestingly, dimerization of acetophenones results in formation of 2,4-diarylfurans under the employed conditions rather than the quaternary carbon products.

Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C–C Bond Insertion

“…Tertiary bromide F was considered a potential side product accessible via competitive intermolecular displacement of nitrogen in diazonium C or nucleophilic opening of phenonium ion D at the more substituted position. The desired product E contains an acyclic, benzylic tertiary or quaternary centermotifs present in many pharmaceutical and agrochemical molecules (Figure D) , while retaining the alkyl bromide as a functional handle for further derivatization. , This method enables programmable introduction of trifluoromethyl, ester, amide, ketone, and sulfone functional groups via a unified approach. In particular, the incorporation of trifluoromethyl groups into molecules continues to be important in medicinal chemistry, and the use of substituted trifluoromethyl diazo derivatives is particularly underexplored in this regard …”

One‐Carbon Homologation of α,β‐Unsaturated Aldehydes: Access to α‐Tertiary β,γ‐Unsaturated Aldehydes

“…Full experimental procedures, characterization data, additional experimental observations, computational details, and Cartesian coordinates for all computed structures are available in the supplementary material of this article. The authors have cited additional references within the Supporting Information [22] …”

Synthetic Access to Aromatic α-Haloketones

“…The existence of two adjacent electrophilic centres, namely the α-halocarbon and the carbonyl group, transforms these reactive carbonyl compounds into highly valuable building blocks for the construction of more complex structures. In that context, a wide variety of N , S , and O -heterocycles have been accessed using protocols involving α-haloketones [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. These compounds have also proven to be important intermediates in the synthesis of various organometallic species.…”