Hindered dialkyl ether synthesis with electrogenerated carbocations

Abstract

Hindered ethers represent an underexplored area of chemical space due to the difficulty and inoperability associated with conventional reactions, despite the high-value of such structural motifs in a variety of societal applications 1-2. For example, such motifs are highly coveted in medicinal chemistry, as extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid in vivo degradation. Demonstrated herein is an exceptionally simple solution to this problem that leverages the power of electrochemical oxidation to liberate *

Nickela‐electrocatalyzed C−H Alkoxylation with Secondary Alcohols: Oxidation‐Induced Reductive Elimination at Nickel(III)

“…[8] Despite major advances in CÀH activation, C À Halkoxylations are less developed than typical hydroxylations, [9] acetoxylations, [10] and phenoxylations [11] because competing b-hydride elimination or overoxidation represent undesired side reactions.S pecifically,C ÀHa lkoxylations with sterically encumbered secondary alcohols continue to be difficult, which contrasts the wealth of viable methods for the use of primary alcohols. [12] In recent years,e lectrosynthesis [13] has gained significant attention through the use of waste-free and inexpensive electric current as redox equivalent, thereby avoiding stoichiometric amounts of toxic and costly chemical redox reagents.E lectrochemical CÀHa ctivations [14] have until recently largely required expensive 5d and 4d metals,s uch as palladium, [15] ruthenium, [16] rhodium, [17] and iridium. [18] In sharp contrast, major recent momentum was gained by the use of earth-abundant, less toxic 3d metals, [19] such as cobalt [20] and copper, [21] as reported by the groups of Ackermann, Lei, and Mei, among others.Inspite of the indisputable progress, such cost-effective nickel electrocatalysis has proven elusive until very recently,w hen we established nickela-electrocatalyzed CÀHa minations,w hich were however restricted to morpholine-type amines.…”

Cubane Electrochemistry: Direct Conversion of Cubane Carboxylic Acids to Alkoxy Cubanes Using the Hofer–Moest Reaction under Flow Conditions

“…This non‐Kolbe carbocation pathway, known as the Hofer–Moest reaction, has very recently been optimised by Baran, Blackmond and co‐workers for the synthesis of hindered ethers through carbocation formation under batch electrolysis conditions. Despite reporting an impressive array of ether products (>80), cubane carboxylic acid was reported to be a challenging substrate, which did not give the Hofer–Moest product under their conditions . Herein, we report direct anodic functionalisation from the commercially available carboxylic acid 1 under flow conditions as a convenient method for cubane to give a variety of ethers.…”

“…Despite reporting an impressive array of ether products (> 80), cubane carboxylic acid was reported to be a challenging substrate, which did not give the Hofer-Moest product under their conditions. [28] Herein, we report direct anodic functionalisation from the commercially available carboxylic acid 1 under flow conditions as a convenient method for cubane to give a variety of ethers. Furthermore, the scalability of the process was demonstrated.…”

Graphene‐Oxide‐Catalyzed Cross‐Dehydrogenative Coupling of Oxindoles with Arenes and Thiophenols

“…The radical intermediate could be further oxidized to the cation species which was trapped by alcohol, which indicated the existence of cation species under the reaction condition. (eq 2) . In addition, when using bis(4‐chlorophenyl) disulfide 6 instead of thiophenol, no desired product 5 b could be observed, indicating that 6 is not the intermediate (eq 3)…”