10175-00-5Relevant academic research and scientific papers
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.
Reductive arylation of aliphatic and aromatic aldehydes with cyanoarenes by electrolysis for the synthesis of alcohols
Zhang, Xiao,Yang, Chao,Gao, Han,Wang, Lei,Guo, Lin,Xia, Wujiong
supporting information, p. 3472 - 3476 (2021/05/10)
An electroreductive arylation reaction of aliphatic and aromatic aldehydes as well as ketones with electro-deficient (hetero)arenes is described. A variety of cyano(hetero)arenes and carbonyl compounds, especially aliphatic aldehydes, have been examined, providing secondary and tertiary alcohols in moderate to good yields. Mechanistic studies, including cyclic voltammetry (CV), electron paramagnetic resonance (EPR), and divided-cell experiments, support the generation of aliphatic ketyl radicals and persistent heteroaryl radical anions via cathodic reduction followed by radical-radical cross-coupling.
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
Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent
Liu, Qixing,Wang, Chunqin,Zhou, Haifeng,Wang, Baigui,Lv, Jinliang,Cao, Lu,Fu, Yigang
, p. 971 - 974 (2018/02/23)
A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.
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.
Diastereomeric reissert compounds of isoquinoline and 6,7-dimethoxy-3,4- dihydroisoquinoline in stereoselective synthesis
Gibson, Harry W.,Berg, Michael A. G.,Dickson, Jennifer Clifton,Lecavalier, Pierre R.,Wang, Hong,Merola, Joseph S.
, p. 5759 - 5770 (2008/02/11)
(Chemical Equation Presented) Chiral acid chlorides were reacted with isoquinoline and 6,7-dimethoxy-3,4-dihydroisoquinoline to form diastereomeric Reissert compounds 8-11 and 18-21, respectively. The best diastereoselectivity (80:20) was achieved in formation of the 9-phenylmenthyl derivative 20. The diastereomers of 2-l-menthoxy-carbonyl-1,2-dihydroisoquinaldonitriles (S)-8/(R)-8), formed in equal amounts, were inseparable. However, the individual diastereomers of 2-cholesteryloxycarbonyl-1,2-dihydroisoquinaldonitriles ((R)-11 and (5)-11) and the 2-l-menthoxycarbonyl-6,7-dimethoxy-1,2,3,4- tetrahydroisoquinaldonitriles ((S)-19/(R)-19)) were each readily purified. (S)-8/(R)-8 (1:1) via the corresponding anions (NaH, -40°C, DMF) with pivaldehyde yielded in 82:18 predominance the S-diastereomer of 1-isoquinolyl tert-butyl carbinyl l-menthyl carbonate ((S)-12), which was obtained in pure form by a single recrystallization; hydrolysis produced 99% pure S-(-)-1-isoquinolyl tert-butyl carbinol [(S)-16]. Reactions of the anions of diastereomeric Reissert compounds, either as mixtures or pure single species, with aromatic aldehydes and alkyl halides proceeded with at best modest selectivity (diastereomeric ratios up to 66:34 and 72:28, respectively). Therefore, it is concluded that the Reissert anions are either planar or rapidly inverting tetrahedral structures.
Indium metal as a reducing agent in organic synthesis
Pitts,Harrison,Moody
, p. 955 - 977 (2007/10/03)
The low first ionisation potential (5.8 eV) of indium coupled with its stability towards air and water, suggest that this metallic element should be a useful reducing agent for organic substrates. The use of indium metal for the reduction of C=N bonds in imines, the heterocyclic ring in benzo-fused nitrogen heterocycles, of oximes, nitro compounds and conjugated alkenes and the removal of 4-nitrobenzyl protecting groups is described. Thus the heterocyclic ring in quinolines, isoquinolines and quinoxalines is selectively reduced using indium metal in aqueous ethanolic ammonium chloride. Treatment of a range of aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can be selectively reduced to the corresponding N-protected amine with indium powder, acetic acid in THF in the presence of acetic anhydride or di-tert-butyl dicarbonate. Conjugated alkenes are also reduced by indium in THF-acetic acid.
Reissert Compound Studies. LXV. Praparation of Reissert Compounds Derived from α,β-Unsaturated Acid Chlorides
Hahn, Jung-Tai,Kant, Joydeep,Popp, Frank D.,Chhabra, Siri Ram,Uff, Barrie C.
, p. 1165 - 1176 (2007/10/02)
Reissert compounds derived from α,β-unsaturated acid chlorides were prepared.The conjugate base obtained from these Reissert compounds exhibited the following carbanion reactions: 1) Alkylation, 2) Condensation with benzaldehyde, 3) Rearrangement to give dimeric compounds rather than simple rearranged compounds.In the case of alkylated isoquinoline Reissert compounds, the attempted rearrangement led to ring annellated amines.
Nature of Reissert Analogs Derived from N,N-Dialkyl and N,N-Diaryl Carbamoyl Chlorides
Kant, Joydeep,Popp, Frank D.,Uff, Barrie C.
, p. 1065 - 1070 (2007/10/02)
Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method.Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.
