6017-78-3

Usage

Physical properties

White to off-white powder, sparingly soluble in water

Main use

Precursor in the synthesis of other organic compounds and pharmaceuticals

Aromatic properties

Due to diphenyl structure

Applications

Building block for biologically active compounds, versatile intermediate in pharmaceutical industry

Upstream product

• 941-69-5 N-phenyl-maleimide 
• 98-80-6 phenylboronic acid 
• 92963-63-8 (+/-)-4-anilino-4-oxo-3-phenylbutanoic acid 
• 635-51-8 2-phenylsuccinic acid 
• 62-53-3 aniline 
• 411239-75-3 2-phenyl-2-phenylcarbamoyl-propane-1,1,3,3-tetracarboxylic acid tetraethyl ester 
• 36122-35-7 2-phenylmaleic anhydride 
• 75066-70-5 1,3-diphenyl-1H-pyrrole-2,5-dione 
• 92963-62-7 (+)-(2S)-4-anilino-4-oxo-2-phenylbutanoic acid 
• 123-30-8 4-amino-phenol 
• 536-74-3 phenylacetylene 
• 201230-82-2 carbon monoxide 
• 65-85-0 benzoic acid 
• 67-56-1 methanol 

Downstream Products

• 5685-21-2 1,3-diphenyl-3-methylsuccinimide 
• 1453206-80-8 (3R,4S)-tert-butyl 3-(2-((tert-butoxycarbonyl)amino)ethyl)-2,5-dioxo-1,4-diphenylpyrrolidine-3-carboxylate 
• 88461-02-3 5-Hydroxy-4-methyl-1,4-diphenyl-pyrrolidin-2-one 
• 635-51-8 2-phenylsuccinic acid 

Relevant academic research and scientific papers

Ligand- and Additive-Controlled Pd-Catalyzed Aminocarbonylation of Alkynes with Aminophenols: Highly Chemo- and Regioselective Synthesis of α,β-Unsaturated Amides

This work describes the chemo- and regioselective direct aminocarbonylation of alkynes and aminophenols to form hydroxy-substituted α,β-unsaturated amides in good to excellent yields. The latter are valuable compounds in pharmaceuticals and natural products. By a simple choice of different ligands and additives, branched or linear isomers could be selectively formed in excellent regioselectivity. Using a combination of boronic acid and 5-chlorosalicylic acid ( BCSA ) as the additives, linear amides were obtained in high yields and selectivities using 1,2-bis(di-tert-butylphosphinomethyl)benzene (DTBPMB) as the ligand. On the other hand, branched amides could be approached by introducing 1,3-bis(diphenylphosphino)propane as the ligand and p-TsOH·H2O as the additive. In addition to the hydroxyl group, other functional substituents, such as carboxyl and vinyl groups, could also be tolerated using this method. As an application of this strategy, the natural product avenanthramide A could be synthesized directly in 84% yield and in 99% regioselectivity via the carbonylation of 2-amino-5-hydroxybenzoic acid and 4-ethynylphenol. Further studies show that the ligands and the additives are keys to good yields and selectivities.

Ruthenium(II)-Catalyzed Hydroarylation of Maleimides Using Carboxylic Acids as a Traceless Directing Group

An efficient Ru(II)-catalyzed hydroarylation of maleimides with ready-stock aryl carboxylic acids has been developed based on weak carboxylate-directed ortho-C-H alkylation and concomitant decarboxylation processes, fabricating 3-aryl succinimides, a recurrent scaffold in drug molecules, in high yields (up to 97%). The protocol features operational simplicity, avoids the need for precious metal additives/oxidants, and offers broad substrate scope with formal meta- and para-selectivities. It represents the first example of Ru(II)-catalyzed direct arylation of maleimides with unbiased benzoic acids.

Mild Decarboxylative C?H Alkylation: Computational Insights for Solvent-Robust Ruthenium(II) Domino Manifold

Computational studies on decarboxylative C?H alkenylations provided key insights into the solvent-robust nature of C?H activation/decarboxylation domino reactions. These properties were exploited for ruthenium(II)-catalyzed C?H alkylations by a decarboxylative process with ample scope under copper-free and silver-free reaction conditions.

Pd(II)/bipyridine catalyzed conjugate addition of arylboronic acids to α,β-unsaturated amides

The Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acid to α,β-unsaturated amides was developed and optimized, and the reaction was proceeded smoothly in air. A series of arylboronic acid and α,β-unsaturated amide substrates were surveyed, and modest to excellent yields were given.

Highly Enantioselective Synthesis of Chiral Succinimides via Rh/Bisphosphine-Thiourea-Catalyzed Asymmetric Hydrogenation

We have successfully developed a highly enantioselective hydrogenation of various 3-aryl and 3-methyl maleinimides to access enantiomerically pure 3-substituted succinimides catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos). This efficient catalytic system furnished the desired 3-substituted succinimide products with high yields and enantioselectivities (up to 99% yield, full conversions, almost all 3-aryl succinimide products up to 99% ee, and 3-methyl succinimide with 83% ee). Our catalytic system has a strong substrate tolerance and generality. Whether the N-substituted group of maleinimides is H or other protecting groups, the maleinimides were hydrogenated well (up to >99% ee, 99% yield). Moreover, the hydrogenation succinimide products can be readily utilized for the construction of biologically active molecules, such as chiral amides and pyrrolidines.

Palladium-catalyzed aminocarbonylation of alkynes to succinimides

Succinimide derivatives are useful building blocks for the synthesis of natural products and drugs. We describe an efficient route to succinimide derivatives comprising Pd(xantphos)Cl2-catalyzed aminocarbonylation of alkynes with aromatic or aliphatic amines in the presence of p-TsOH. The utility of this route is demonstrated with the synthesis of a large number of succinimide compounds including an important photochromic molecule.

Direct Synthesis of Chiral 3-Arylsuccinimides by Rhodium-Catalyzed Enantioselective Conjugate Addition of Arylboronic Acids to Maleimides

Chiral rhodium catalysts comprising 2,5-diaryl- substituted bicyclo[2.2.1]diene ligands L1-L10 were utilized in the enantioselective 1,4-addition reaction of arylboronic acids to N-substituted maleimides. In the presence of 2.5mol % of RhI/L2, enantioenriched conjugate addition adducts were isolated in 72-99 % yields with 86-98 %ee. This protocol offers a convenient method to access a variety of 3-arylsuccinimides in a highly enantioselective manner. Maleimides with readily cleavable N-protecting groups were tolerated enabling the synthesis of useful synthetic intermediates. Pyrrolidine 4, a biologically active compound, and pyrrolidine 5, an ent-precursor to an HSD-1 inhibitor, were synthesized to demonstrate the utility of this method. The road to rhodium! Enantioselective conjugate addition of a range of arylboronic acids to variously N-substituted maleimides, catalyzed by RhI complexes prepared in situ using chiral bicyclo[2.2.1]diene ligands, afforded the corresponding 3-arylsuccinimides with up to 98 %ee at 50 C (see scheme).

Hydrogenations without hydrogen: Titania photocatalyzed reductions of maleimides and aldehydes

A mild procedure for the reduction of electron-deficient alkenes and carbonyl compounds is described. UVA irradiations of substituted maleimides with dispersions of titania (Aeroxide P25) in methanol/acetonitrile (1:9) solvent under dry anoxic conditions led to hydrogenation and production of the corresponding succinimides. Aromatic and heteroaromatic aldehydes were reduced to primary alcohols in similar titania photocatalyzed reactions. A mechanism is proposed which involves two proton-coupled electron transfers to the substrates at the titania surface.

Solvatochromic and quantum chemical investigations of newly synthesized succinimides: Substituent effect on intramolecular charge transfer

Two series of 1-aryl-3-phenyl- and 1-aryl-3,3-diphenylpyrrolidine-2,5- diones were synthesized and their solvatochromic properties were studied in a set of 15 solvents of different polarity. The effect of specific and non-specific solvent-solute interacti

Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated ketones with DIFLUORPHOS and SYNPHOS analogues

Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to α,β-unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with 99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to nonsubstituted maleimide substrates using the (R)-3,5-diCF3-SYNPHOS ligand is also reported. This protocol provides access to various enantioenriched 3-substituted succinimide units of biological interest, in high yields and good to excellent ee up to 93%, which could be upgraded up to 99% ee, after a single crystallization.