Copper-Catalyzed Radical 1,4-Difunctionalization of 1,3-Enynes with Alkyl Diacyl Peroxides and N-Fluorobenzenesulfonimide

Abstract

Many reactions involving allenyl ion species have been studied, but reactions involving allenyl radicals are less well understood, perhaps because of the inconvenience associated with the generation of short-lived allenyl radicals. We describe here a versatile method for the generation of allenyl radicals and their previously unreported applications in the intermolecular 1,4-carbocyanation and 1,4-sulfimidocyanation of 1,3-enynes. With the assistance of the trifunctional reagents, alkyl diacyl peroxides or N-fluorobenzenesulfonimide, a range of synthetically challenging multisubstituted allenes can be prepared with high regioselectivity. These multisubstituted allenes can be easily transformed into synthetically useful structures such as fluorinated vinyl cyanides, lactones, functionalized allenyl amides, 1-aminonaphthalenes, and pyridin-2­(1H)-ones, and several novel transformations are reported. The results of radical scavenger and radical clock experiments are consistent with the proposed allenyl radical pathway. Density functional theory (DFT) and IR spectroscopy studies suggest the formation of an isocyanocopper­(II) species in the ligand exchange step. On the basis of the results of IR, DFT, and diastereoselectivity studies, an isocyanocopper­(II)/copper­(I) catalytic cycle is proposed, which differs from the previously considered Cu­(III) mechanism in cyanation reactions.

Copper‐Catalyzed Enantioselective Cyano(Fluoro)Alkylation of Alkenes

“…Based on these findings and the earlier literature, the mechanism in Scheme is proposed. First, the BOX‐ligated *LCu(I) catalyst ( I , *L=chiral ligand) undergoes a SET process with LPO to deliver a *LCu(II) complex (II), an undecyl radical, and a molecule of CO 2 .…”

“…The synthetic capability of the chiral cyano(fluoro)‐alkylation products was then examined (Table ). The product 5 a could be easily converted into a fluoroalkylated amide ( 7 ) and a fluoroalkylated carboxylic acid ( 8 ) in 81% and 79% yields respectively, without loss of enantiopurity. The cyanofluoroalkylation product 5 a can react with ethanolamine to afford product fluoroalkylated oxazole ( 9 ) in 82% yield but with no enantiomeric excess.…”

“…First, the BOX‐ligated *LCu(I) catalyst ( I , *L=chiral ligand) undergoes a SET process with LPO to deliver a *LCu(II) complex (II), an undecyl radical, and a molecule of CO 2 . Then, the *LCu(II) complex (II) undergoes a ligand exchange with TMSCN to form either a *LCu(II)CN species or the *LCu(II)NC species ( III ). Meanwhile, the undecyl radical reacts with an alkyl iodide in a radical relay process to provide an alkyl radical, which can attack an alkene to afford a stabilized benzyl radical.…”

Synthesis of difluoromethylated allenes through trifunctionalization of 1,3-enynes

“…1a) [37][38][39][40] and fluoroamination of styrenes ( Fig. 1b) [41][42][43][44][45] , also as one part of our continuous efforts on functionalization of unsaturated compounds [46][47][48][49] , herein, we report a metal-free consecutive trifunctionalization of 1,3-enynes for the assembly of various difluoromethylated allenyl amines ( Fig. 1c) using NFSI as the fluorination and amination source 41,44,[50][51][52][53][54][55][56][57][58][59] .…”

Enantioselective Synthesis of Multisubstituted Allenes by Cooperative Cu/Pd‐Catalyzed 1,4‐Arylboration of 1,3‐Enynes

“…[d] 51 5 L1 88 93.5:6.5 8 [d] 51 5 L2 90 90: 10 9 [d] 51 5 L3 89 93: 7 10 [d] 51 5 L4 76 92:8 11 [d] 51 5 L5 65 55:45 12 [d] 51 5 L6 72 52:48 13 [d] 51 5 L7 80 54:46 14 [d] 51 5 L8 81 54:46 15 [d,e] 51 5 L1 90 94.5:5.5 16 [d,e,f ] 51 5 L1 95 95.5:4.5 17 [d,e,f,g] 51 5 Elegant protocols of transition metal catalyzed 1,4difunctionalization of 2-substituted 1,3-enynes to afford racemic tetrasubstituted allenes were established recently. [15] To access nonracemic tetrasubstituted allenes with our catalysis,2 -arylsubstituted 1,3-enynes were employed as substrates (Table 4). Under the slightly modified reaction conditions,wewere pleased to find that the desired tetrasubstituted chiral allenes were successfully obtained with satisfactory yields and enantioselectivities.I na ddition, 1,1,3triaryl tetrasubstituted allene (4n)c an be prepared with modest yield (48 %) and good enantioselectivity (86.5:13.5 er), and the lower er value probably results from amore easily racemization of this conjugated a,g-diaryl-substituted allenylmetal intermediate.…”