Cathodic Carbonyl Alkylation of Aryl Ketones or Aldehydes with Unactivated Alkyl Halides

Abstract

An efficient cathodic carbonyl alkylation of aryl ketones or aldehydes with unactivated alkyl halides has been realized through the electrochemical activation of iron. The protocol is believed to include a radical–radical coupling or nucleophilic addition process, and the formation of ketyl radicals and alkyl radicals has been demonstrated. The protocol provides various tertiary or secondary alcohols by the formation of intermolecular C–C bonds under safe and mild conditions, is scalable, consumes little energy, and exhibits a broad substrate scope.

Electroreductive Cross‐Electrophile Coupling (eXEC) Reactions

“…This reaction can also be used for alkylation and benzylation of simple imines and is carried out at room temperature in a mixture of saturated aqueous NH 4 Br and tetrahydrofuran (Scheme 7). Recently, the Huang group [41] has developed an efficient method for the synthesis of tertiary and secondary alcohols, which involved cathodic carbonyl alkylation of aryl ketones or aldehydes with unactivated alkyl halides (Scheme 7). Iron ion was electrochemically activated to initiate the reaction, which was believed to proceed via a radical‐radical coupling or nucleophilic addition process.…”

Photoalkylation/-arylation of ortho-Diketones with Unactivated Organic Halides

“…However, this approach remained unexplored until recently, when Huang et al developed an electrochemical-promoted carbonyl addition reaction using organohalides as substrates. 3 Over the past few decades, there has been significant development in photoredox catalysis in organic synthesis, 4 with photocatalytic ketyl radical-involved carbonyl formal addition reactions being widely explored. 5 However, organohalides have not been used as reaction partners for carbonyl addition reactions.…”

“…First, we tested various alkyl halides. Surprisingly, a range of primary alkyl iodides CH 3 (CH 2 ) n I (n = 1, 2, 3,9,11) were well tolerated under these conditions, giving the corresponding products in good to excellent yields (4−8, 77−94%). Moreover, alkyl iodides with alcohol, ester, or heterocycles also reacted smoothly (9, 10, and 12).…”

“…Thus, directly using organohalides as reaction partners to achieve carbonyl addition reactions is highly desirable for economic and feasibility reasons. However, this approach remained unexplored until recently, when Huang et al developed an electrochemical-promoted carbonyl addition reaction using organohalides as substrates …”

Electroreductive Umpolung Enabling Reformatsky‐Type Reaction of Bromodifluoroamides with Aldehydes/Ketones

“…In recent years, electroreduction reactions [26,27] have become a powerful and promising tool for the generation of functional molecules because of their characteristics of availability, safety and sustainability. In this process, electricity acts as a traceless reductant to make umpolung transformations of reaction components by precisely controlling the electric current.…”