5966-41-6

Usage

Uses

Spasmolitic; choleretic.

InChI:InChI=1/C21H29N/c1-17(2)22(18(3)4)16-15-21(19-11-7-5-8-12-19)20-13-9-6-10-14-20/h5-14,17-18,21H,15-16H2,1-4H3

Upstream product

• 1016-09-7 benzhydryl methyl ether 
• 96-79-7 (2-chloroethyl)-diisopropylamine 
• 530-48-3 1,1-Diphenylethylene 
• 201230-82-2 carbon monoxide 
• 108-18-9 diisopropylamine 
• 10342-97-9 N,N-diisopropylmethylamine 
• 20017-67-8 3,3-diphenylpropan-1-ol 
• 4801-14-3 3,3-diphenylprop-2-en-1-ol 
• 41140-53-8 1-Methanesulfonyloxy-3,3-diphenylpropane 
• 23795-34-8 3-phenylpropenoic acid N,N-diisopropylamide 
• 102-92-1 cinnamoyl chloride 
• 621-82-9 Cinnamic acid 
• 4279-81-6 3,3-diphenylpropanal 

Relevant academic research and scientific papers

Site-Selective α-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis

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.

Migratory Arylboration of Unactivated Alkenes Enabled by Nickel Catalysis

An unprecedented arylboration of unactivated terminal alkenes, featuring 1,n-regioselectivity, has been achieved by nickel catalysis. The nitrogen-based ligand plays an essential role in the success of this three-component reaction. This transformation displays good regioselectivity and excellent functional-group tolerance. In addition, the incorporation of a boron group into the products provides substantial opportunities for further transformations. Also demonstrated is that the products can be readily transformed into pharmaceutically relevant molecules. Unexpectedly, preliminary mechanistic studies indicate that although the metal migration favors the α-position of boron, selective and decisive bond formation is favored at the benzylic position.

Selective Pd-catalyzed hydrogenation of 3,3-diphenylallyl alcohol: Efficient synthesis of 3,3-diarylpropylamine drugs diisopromine and feniprane

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.

Tandem superelectrophilic hydroarylation of CC bond and carbonyl reduction in cinnamides: Synthetic rout to 3,3-diarylpropylamines, valuable pharmaceuticals

Cinnamides ArCHCHCONRR′ in reactions with arenes Ar′H under the action of Bronsted (TfOH, FSO3H) or Lewis (AlBr3) superacids at rt for 1-2 h give CC bond hydroarylation products ArAr′CHCH2CONRR′ in yields of 63-98%. Reduction (LiAlH4/Et2O) of carbonyl group in the latter results in the formation of 3,3-diarylpropylamines ArAr′CHCH2CH2NRR′, valuable drugs. The reaction intermediates, superelectrophilic dications ArC+H-CH2C(OH+)NRR′, have been characterized by DFT calculations in terms of global electrophilicity index, natural charges, and atomic orbitals contributions.

Cascade synthesis of fenpiprane and related pharmaceuticals via rhodium-catalyzed hydroaminomethylation

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.

Hydroaminomethylation with novel Rhodium-Carbene complexes: An efficient catalytic approach to pharmaceuticals

Starting from [{Rh(cod)Cl}2] and 1,3-dimesitylimidazole-2- ylidenes the novel [RhCl(cod)(carbene)] complexes 1-5 have been synthesized, characterized, and tested in the hydroaminomethylation of aromatic olefins. The influence of different ligands and reaction parameters on the catalytic activity was investigated in detail applying 1,1-diphenylethylene and piperidine as a model system. The scope and limitations of the novel catalysts is shown in the preparation of 16 biologically active 1-amino-3,3-diarylpropenes. In general, high chemo- and regioselectivity as well as good yields of the desired products were achieved.

One-pot synthesis of pharmacologically active secondary and tertiary 1- (3,3-diarylpropyl)amines via rhodium-catalysed hydroaminomethylation of 1,1- diarylethenes

Pharmacologically active secondary and tertiary 1-(3,3- diarylpropyl)amines 1 are prepared in high yields and chemoselectivity by the reaction of 1,1-diarylethenes 4, primary or secondary amines 5, carbon monoxide and hydrogen in presence of [Rh(cod)Cl]2/PBu3 as catalyst via a one-pot hydroformylation - amine condensation - reduction sequence.

Reductive electrophilic substitution of diarylmethyl methyl ethers: Synthetic applications

The reductive cleavage of diarylmethyl methyl ethers with Li metal in THF led to quantitative formation of the corresponding diarylmethyl anions. Quenching with electrophiles afforded substituted diarylmethanes in good to excellent yields.