Photoinduced Remote Functionalisations by Iminyl Radical Promoted C−C and C−H Bond Cleavage Cascades

Abstract

Aphotoinduced cascade strategy leading to avariety of differentially functionalised nitriles and ketones has been developed. These reactions rely on the oxidative generation of iminyl radicals from simple oximes.R adical transposition by C(sp 3 ) À (sp 3 )and C(sp 3 ) À Hbond cleavage gives access to distal carbon radicals that undergo S H 2f unctionalisations.T hese mild, visible-light-mediated procedures can be used for remote fluorination, chlorination, and azidation, and were applied to the modification of bioactive and structurally complex molecules.

Functionalization of remote C(sp3)-H bonds enabled by copper-catalyzed coupling of O-acyloximes with terminal alkynes

“…In this context, redox-active acyclic 15 and cyclic 16 oxime derivatives, pioneered by Forrester and Zard, respectively, have been demonstrated to be versatile precursors of iminyl radicals under either oxidative or reductive conditions. Depending on the structure of oximes, the iminyl radicals can evolve to a carbon radical through either β-scission [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] or 1,5hydrogen atom transfer (1,5-HAT) process [33][34][35][36][37][38][39] . The resulting carbon radicals can then be trapped by radical acceptors, affording remote C(sp 3 ) functionalized alkylnitriles and ketones.…”

Iron‐Catalysed Remote C(sp3)−H Azidation of O‐Acyl Oximes and N‐Acyloxy Imidates Enabled by 1,5‐Hydrogen Atom Transfer of Iminyl and Imidate Radicals: Synthesis of γ‐Azido Ketones and β‐Azido Alcohols

“…Nickel, [27] copper [8,9] and iron salts [28] are known to reduce the O-acyl oximes to the iminyl radicals. Our major concern at the outset of this research was that the translocation of the iminyl to the carbon radicals is, in general,e ndergonic and reversible, [16] and that the iminyl radicals can undergo as econd SET with these metals or metal salts to afford the iminato-metal species, diverting therefore the reactions equence. Notably, this second SET process was not an issue with cyclobutanone derived iminyl radicals because of the very rapid strain-releasing CÀCb ond-cleavage process.…”

“…The reactionw as therefore further optimised by varying the catalysts,t he solvents, the azide sources and the temperature (see the Supporting Information). The optimisedc onditions consisted of performing the azidation of 4a in EtOAc in the presence of Fe(acac) 3 (0.05 equiv) and TMSN 3 (1.5 equiv) at 70 8Ct oa fford am ixture of 5a, 15,16,17 and a small amounto f18.S tirring as olution of the above crude reaction mixture in MeOH and aq NaOH solution (2.0 N) at room temperature then afforded 5a in 77 %i solated yield. It is interesting to note that the yield of 5a decreased when the reaction was performed with higherl oading of Fe(acac) 3 under otherwise identical conditions.…”

“…However, recent advances in the field of photoredox catalysis have provided the impetus for the exploitation of this cascader eactioni nt he remote functionalisation of unactivated C(sp 3 )ÀHb onds. [13] Indeed, mild photocatalytic conditions have been developed by Nevado, [14] Wu, [15] Leonori, [16] Studer, [17] Yu, [18] Duan, [19] and Guo, [20] for the conversion of oxime derivatives into g-functionalisedk etones (Scheme 1b). Synthetic transformations involving translocated carbonr adicals were nevertheless limited to the radical addition (CÀCb ond forma-tion), homolytics ubstitution (S H 2) and Minisci-type reactions.…”

Synthesis of β‐Substituted γ‐Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

“…Compound 3e contains af luorinated quaternary stereocenter, which is aformidable challenge in the field of asymmetric photocatalysis (entry 6). [28] Control experiments verified that visible light (entry 7) was essential and air strongly diminished the yield (entry 8).…”