10175-00-5Relevant articles and documents
Photochemical C?H Hydroxyalkylation of Quinolines and Isoquinolines
Bieszczad, Bartosz,Perego, Luca Alessandro,Melchiorre, Paolo
, p. 16878 - 16883 (2019)
We report herein a visible light-mediated C?H hydroxyalkylation of quinolines and isoquinolines that proceeds via a radical path. The process exploits the excited-state reactivity of 4-acyl-1,4-dihydropyridines, which can readily generate acyl radicals upon blue light absorption. By avoiding the need for external oxidants, this radical-generating strategy enables a departure from the classical, oxidative Minisci-type pattern and unlocks a unique reactivity, leading to hydroxyalkylated heteroarenes. Mechanistic investigations provide evidence that a radical-mediated spin-center shift is the key step of the process. The method's mild reaction conditions and high functional group tolerance accounted for the late-stage functionalization of active pharmaceutical ingredients and natural products.
Photocatalytic redox-neutral hydroxyalkylation of: N -heteroaromatics with aldehydes
Fukatsu, Arisa,Fuse, Hiromu,Kanai, Motomu,Kondo, Mio,Masaoka, Shigeyuki,Mitsunuma, Harunobu,Nakao, Hiroyasu,Saga, Yutaka
, p. 12206 - 12211 (2020/11/26)
Hydroxyalkylation of N-heteroaromatics with aldehydes was achieved using a binary hybrid catalyst system comprising an acridinium photoredox catalyst and a thiophosphoric acid organocatalyst. The reaction proceeded through the following sequence: (1) photoredox-catalyzed single-electron oxidation of a thiophosphoric acid catalyst to generate a thiyl radical, (2) cleavage of the formyl C-H bond of the aldehyde substrates by a thiyl radical acting as a hydrogen atom transfer catalyst to generate acyl radicals, (3) Minisci-type addition of the resulting acyl radicals to N-heteroaromatics, and (4) a spin-center shift, photoredox-catalyzed single-electron reduction, and protonation to produce secondary alcohol products. This metal-free hybrid catalysis proceeded under mild conditions for a wide range of substrates, including isoquinolines, quinolines, and pyridines as N-heteroaromatics, as well as both aromatic and aliphatic aldehydes, and tolerated various functional groups. The reaction was applicable to late-stage derivatization of drugs and their leads. This journal is
Photo-induced reductive cross-coupling of aldehydes, ketones and imines with electron-deficient arenes to construct aryl substituted alcohols and amines
Liu, Zan,Nan, Xiaolei,Lei, Tao,Zhou, Chao,Wang, Yang,Liu, Wenqiang,Chen, Bin,Tung, Chenho,Wu, Lizhu
, p. 487 - 494 (2018/03/22)
Umpolung reactions of C=X bonds (X = O, N) are valuable ways of constructing new C–C bonds, which are sometimes difficult to be constructed using traditional synthetic pathways. Classical polarity inversion of C=X bonds (X = O, N) usually requires air or moisture-sensitive and strong reducing agents, which limit the feasibility of substrate scope. Herein we describe a photo-induced reductive cross-coupling reaction of aldehydes, ketones and imines with electron-deficient arenes (aromatic nitriles) using fac-Ir(ppy)3 as a photocatalyst and diisopropylethylamine (DIPEA) as a terminal reductant under visible light irradiation. Mild conditions and high yields mean that this new polarity inversion strategy can be used with aryl-substituted alcohols and amines. Spectroscopic studies and control experiments have demonstrated the oxidative quenching of Ir(ppy)3* by electron-deficient arenes involved in the key step for the C–C bond formation.
