Studies On Electrochemical Cross Dehydrogenative C-N Condensation And Reductive Defunctionalization

In order to minimize the detrimental effects of chemical production on the natural environment human beings live by,the development of“green”and sustainable organic synthetic technology has become a major research focus of organic chemistry researchers.Employing electron as a“pure redox reagent”,organic electrosynthesis(or organic electrochemical synthesis)has been reviving for the aim of developing more sustainable chemical technologies.For the construction of the C-N double bonds of versatile N-sulfonyl amidines and the widely applied selective reduction of various functional groups,conventional organic transformations usually require harsh conditions,complex reaction system and experimental operation,reagents that unfriendly to users and the environment,and are often accompanied with drawbacks such as low atom-economy.By comparison,organic electrochemical reactions feature various merits,including the requirement for milder conditions,lower energy consumption,less addition and waste production.On the basis of these advantages,this dissertation aims to discover more cost-effective organic electrochemical protocols with simple system and convenient operation,with major emphasis on the cross dehydrogenative C-N condensation and selective reductive defunctionalization transformations.Employing 16 mA/cm~2 constant electric current as the driving force,2.0 equivalent of tetrabutylammonium iodide as the electrolyte,a highly N-methyl-selective C-N cross dehydrogenative condensation(CDC)reaction between diversely substituted primary sulfonyl amides(25 examples)and tertiary amines(10 examples)was developed at room temperature with two platinum plate electrodes(isolated yields of products up to 96%),providing an efficient and straightforward approach for the systhesis of versatile N-sulfonyl amidines.Three gram-scale reactions were successfully carried out,affording condensation products in 89%-93%yields.Cyclic voltammetry studies and control experiments revealed that the electrochemical CDC reaction was promoted by certain active iodine-containing species oxidized from the I~-of the electrolyte.Computational studies indicated an N-iodoaminium species as the key intermediate,and rationalized the exceptionally high N-methyl selectivity of the condensation processes.Under 10 mA/cm~2 constant current electrolysis with two platinum plate electrodes,34 types of?,?-unsaturated ketones bearing various substituents underwent 1,4-selective reduction in 4:1 volume ratio dimethyl sulfoxide/methanol system to provide saturated ketones in 52%-92%yields,with an inexpensive,easily available,and safe reagent ammonium chloride as the only additive.These additional reductant-free reactions were carried out in the open air at room temperature with easy operation and low energy consumption,showing significant superioriy over conventional reduction methods.By simultaneous augment of electrode surface area and the electric current applied,the gram-scale reaction of the model substrate(chalcone)was realized with a current density of11.1 mA/cm~2,after which the product was obtained in 79%yield.Deuterium labelling and control experiments confirmed that both ammonium chloride and methanol serve as the hydrogen sources,while dimethyl sulfoxide acts as the sacrificial reductant at the anode.An electro-reductive system for the hydrodehalogenation of 51 organic halides and defunctionalization of 29 substituted compounds was developed under 8-24 mA/cm~2constant current electrolysis with two platinum plate electrodes at ambient conditions,employing triethylamine as an inexpensive and easily available sacrificial reductant,with1:1 volume ratio dimethyl sulfoxide/ethanol(method A)or dimethyl sulfoxide(method B)as the reaction solvent,and the isolated yields of reduction products were up to 98%.Notably,simply by changing the solvent,both the reducing capability and selectivity of the system can be conveniently switched.This strategy has an exceptionally wide substrate scope,including(but not limited to)diversified halogenated compounds with various structures and electronic effects,sulfonyl-or acyl-protected secondary aromatic amines,phenols and alcohols,non-electron-rich aromatic cyanides,and N-benzyl substituted azole drug molecules,and is readily scalable.Deuterium labelling experiments confirmed that the added hydrogen atoms majorly come from the reaction solvent,and the major mechanistic pathway should be protic hydrogenation.