Copper catalyzed oxidative alkylation of sp3 C–H bond adjacent to a nitrogen atom using molecular oxygen in water

Beyond Traditional Cross Couplings: The Scope of the Cross Dehydrogenative Coupling Reaction

“…However, the reaction did not function under previously reported conditions for the CDC of two (sp 3 )C À H bonds using water as the solvent under an atmosphere of oxygen. [9] However, when the reaction was repeated using DME as the solvent under an oxygen atmosphere with aqueous TBHP (1.6 equiv) the coupling of N-phenyltetrahydroisoquinoline and phenylboronic acid gave 80 % of the coupled product. Both electron withdrawing and donating aryl boronic acids were successfully coupled to tetrahydro-A C H T U N G T R E N N U N G isoquinolines, even sterically hindered 2-naphthylboronic acid could be coupled.…”

“…Li and co-workers have reported several examples of (sp 3 )C À A C H T U N G T R E N N U N G (sp 3 )C CDCs using unfunctionalized starting materials. [9,19,20] The first report of a CDC between a (sp 3 )CÀA C H T U N G T R E N N U N G (sp 3 )C was achieved to yield Aza-Henry-type products, that is, b-nitroamine derivatives, Scheme 12. [20] Various copper(I) and (II) salts were investigated under the reaction conditions, however, copper(I) and (II) bromide were the most efficient.…”

“…[9] Initially, the reaction was examined with a ruthenium catalyst, which is known to oxidize tetrahydroisoquinolines under an atmosphere of oxygen. [21] Although these conditions provided the CDC products in a 45 and 67 % yield (when employing 5 and 10 mol % of RuCl 3 , respectively) it was found that the yields of the couplings could be substantially improved (up to 90 %) if copper(I) bromide was used as the catalyst, Scheme 13.…”

“…Several different malonates were investigated under the reaction conditions which gave the coupled products in moderate to excellent yields. [9] The authors state that although the exact mechanism of the coupling is not known, they hypothesize that the formation of a copper(II)-imine-type species, presumably by Hatom abstraction by the oxidant and a SET to the copper, participates as the electrophilic component to which the nucleophile, either the dialkylmalonate or the nitroalkane, can add to generate the coupled products.…”

“…Interestingly, there are some examples of CDCs that have been successfully applied in water, consequently, further enhancing their environmental friendliness. [6,9] A few enantioselective examples of CDCs have been reported, however, there is a significant amount of work to be realized in this area. CDCs constitute a very powerful tool for organic and organometallic chemists allowing the selective formation of new CÀC bonds without having to first functionalize the starting materials in terms of the synthesis of organohalides or organometallic species and without the stoichiometric formation of metal salts as byproducts.…”