5966-41-6Relevant articles and documents
Site-Selective α-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis
Shen, Yangyang,Funez-Ardoiz, Ignacio,Schoenebeck, Franziska,Rovis, Tomislav
supporting information, p. 18952 - 18959 (2021/11/22)
Trialkylamines are widely found in naturally occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and preclinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective α-C(sp3)-H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery, and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between α-amino C(sp3)-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3)-C(sp3) bond with the more-crowded α-amino radical, with the overall selectivity guided by the Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C-C bonds from a diverse set of trialkylamines with high levels of site selectivity and preparative utility. Simple correlation of site selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, hold potential to streamline complex trialkylamine synthesis and accelerate small-molecule drug discovery.
Selective Pd-catalyzed hydrogenation of 3,3-diphenylallyl alcohol: Efficient synthesis of 3,3-diarylpropylamine drugs diisopromine and feniprane
Claudino, Thiago S.,Scholten, Jackson D.,Monteiro, Adriano L.
, p. 53 - 56 (2017/09/01)
The Pd-catalyzed selective hydrogenation of C[dbnd]C double bond in (3,3-diphenylallyl)diisopropylamine or 3,3-diphenylallyl alcohol was evaluated using different catalytic systems [Pd/C, Pd(OAc)2/ionic liquid, isolated Pd(0) nanoparticles]. For the (3,3-diphenylallyl)diisopropylamine, hydrogenolysis is preferred over hydrogenation, and only moderate selectivities were obtained for the desired product. However, complete conversion and 100% selectivity were obtained for the hydrogenation of 3,3-diphenylallyl alcohol using isolated Pd(0) nanoparticles under mild condition. This successful strategy enabled the effective synthesis of diisopromine and feniprane drugs and opens new possibilities for the preparation of other biologically active compounds.
Cascade synthesis of fenpiprane and related pharmaceuticals via rhodium-catalyzed hydroaminomethylation
Li, Shengkun,Huang, Kexuan,Zhang, Jiwen,Wu, Wenjun,Zhang, Xumu
supporting information, p. 1036 - 1039 (2013/04/23)
A novel rhodium catalytic system with Naphos as ligand was developed for an efficient hydroaminomethylation of 1,1-diphenylethene under relatively mild conditions. This will allow for an atom-economic and environmentally benign synthesis of fenpiprane and related pharmaceuticals.
