Electroorganic chemistry. 120. New patterns of anodic oxidation of amides. Synthesis of .alpha.-amino aldehyde acetals and pyrrolidines from amines

Merging Photochemistry with Electrochemistry: Functional‐Group Tolerant Electrochemical Amination of C(sp3)−H Bonds

“…[5] The Hofmann-Lçffler-Freytag (HLF) reaction is ap ioneering example of such reactivity, [6,7] and numerous variations of the HLF reaction have emerged for C À Hh alogenation and nitrogen-heterocycle synthesis. [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B). [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B).…”

“…[14] However, the N-iodo intermediates tend to undergo b-elimination of HI to afford imine-derived products under thermal conditions.T his insight, together with the use of visible-light promoted homolysis of the N À Ib ond in PhI-(OAc) 2 /I 2 -promoted HLF-type reactions,p rompted us to consider iodide-mediated electrochemical conditions illuminated by ac ompact fluorescent light (CFL) bulb. Good reactivity and product yields were observed with 1a under each of the three reported reaction conditions.I nc ontrast, negligible CÀNb ond formation was observed for 1b,a nd nearly complete consumption of the starting material led to acomplex mixture of products in each case.W ith these benchmarks established, we turned our attention to electrochemical conditions with iodide as amediator.S honoso riginal report on bromide-mediated CÀH amination included one example of iodide-mediated reactivity.…”

“…[8][9][10][11] Electrochemical methods, summarized in Figure 1, have been explored as am eans to bypass the use of undesirable stoichiometric oxidants or pregeneration of N À Xc ompounds,b oth of which compromise the atom-economy and other appealing features of these methods.S everal distinct mechanistic approaches have been investigated in these electrochemical HLF-type reactions ( Figure 1A): i) stepwise ET-PT-ET to generate ab enzyl cation, which reacts with an appended nitrogen nucleophile, [12] ii)proton-coupled electron transfer (PCET) to generate an itrogen-centered radical that promotes 1,5-HAT, similar to the key C À Hactivation step in the HLF reaction, [13] and iii)bromide-mediated formation of an N-bromo intermediate that undergoes thermal NÀBr homolysis to achieve the key 1,5-HATs tep. [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B). These issues could be addressed by using am ediator that undergoes regeneration at lower potentials.Anumber of modified HLF reactions have been reported with stoichiometric chemical oxidants,c atalytic I 2 ,a nd visible-light illumination, [11] raising the possibility that iodide could be used as an electrochemical mediator ( Figure 1A iv ).…”

Electrochemical and Scalable Dehydrogenative C(sp3)−H Amination via Remote Hydrogen Atom Transfer in Batch and Continuous Flow

“…[12] From ap ractical perspective, organic electrosynthesis can minimize total energyl osses and reduce waste formation,a nd as ar esult,t hese techniques will decreaset he overall costs of industrial synthesis. [13] Because Nradicals can be produced electrochemically,a sh as been demonstrated by Shono and others [14] we aimed to combines uch a strategyw ith as ubsequent1 ,5-HAT( 1,5-hydrogen atom transfer) to circumvent knowno bstacles related to C(sp 3 )ÀHa mination (HLF reaction) and make the developed protocol applicable to large-scale syntheticapplications(Scheme 1).…”

Alkylation of α-tert-butoxycarbonylamino ketone enolate anions. A useful synthesis of α-alkyl-α-amino ketones, 2-acylpyrrolidines, and 2-acylpiperidines

“…Numerous syntheses of these important starting materials have been devised (1) and new developments in this field continue apace (2)(3)(4)(5)(6)(7)(8). We recently demonstrated (9) that the monoanions of N-formylated a-amino ketones, like those of benzamidoacetone (lo), are regioselectively alkylated on the a-carbon atom and that acidic hydrolysis of these products provided access to a-alkyl-aamino ketones with satisfactory efficiency.…”