Stereoselective synthesis of spirooxindole derivatives using an organocatalyzed tandem Michael-Michael reaction.

A highly efficient stereoselective method for the synthesis of functionalized spirooxindole derivatives with three stereogenic centers was realized through an organocatalytic tandem Michael-Michael reaction. By employing (S)-α,α-diphenylprolinol trimethylsilyl ether as the catalyst and N,N'-bis[3,5-bis(trifluoromethyl)phenyl]thiourea as the cocatalyst, the reaction between N-tritylisatylidenemalononitriles and (E)-7-alkyl-7-oxohept-5-enals yields the desired spirooxindole products in good yields (76-95%) and with excellent diastereoselectivities (up to 97 : 3 dr) and enantioselectivities (up to 98% ee), which can be stereoselectively converted into the spiro[indoline-3,8'-isoquinoline] derivative through an intramolecular reductive amination reaction.

PPL catalyzed four-component PASE synthesis of 5-monosubstituted barbiturates: Structure and pharmacological properties.

Enzymatic four-component reactions are very rare although three-component enzymatic promiscuous reactions are widely reported. Herein, we report an efficient PASE protocol for the synthesis of potentially lipophilic zwitterionic 5-monosubstituted barbiturates by four component reaction of mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde and barbituric acid in ethanol at room temperature. Seven different lipases were screened for their promiscuous activity towards the synthesis of 5-monosubstituted barbiturates and the lipase from porcine pancreas (PPL) found to give optimum efficiency. The zwitterionic 5-monosubstituted barbiturates with pyrazolyl ring showed promising pharmacological activity upon screening for antibacterial and apoptotic properties.

A green four-component synthesis of zwitterionic alkyl/benzyl pyrazolyl barbiturates and their photophysical studies.

A novel series of unsymmetrically substituted alkyl/benzyl pyrazolyl barbiturates incorporating highly biologically active pyrazolone and barbiturate moieties was synthesized by four-component reactions of a mixture of ethyl acetoacetate, hydrazine hydrate, aldehydes and barbituric acid/thiobarbituric acid in ethanol without using a catalyst. The photophysical properties of the newly designed alkyl/benzyl pyrazolyl barbiturates were studied, and good quantum yield of some products indicated a definitive scope in the field of biochemical applications. Single-crystal X-ray crystallographic studies revealed that the newly synthesized compounds exist in zwitterionic form. The zwitterionic nature of the new chimera makes them interesting candidates for drug delivery as zwitterionic drugs are known to have highly water soluble properties, specific protein absorption, slow recognition by immune system, slow blood clearance from body and can constantly diffuse and deposit throughout the physiological pH.

Phosphine Ligand-Free Bimetallic Ni(0)Pd(0) Nanoparticles as a Catalyst for Facile, General, Sustainable, and Highly Selective 1,4-Reductions in Aqueous Micelles.

Phosphine ligand-free bimetallic nanoparticles (NPs) composed of Ni(0)Pd(0) catalyze highly selective 1,4-reductions of enones, enamides, enenitriles, and ketoamides under aqueous micellar conditions. A minimal amount of Pd (Ni/Pd = 25:1) is needed to prepare these NPs, which results in reductions without impacting N- and O-benzyl, aldehyde, nitrile, and nitro functional groups. A broad range of substrates has been studied, including a gram-scale reaction. The metal-micelle binding is supported by surface-enhanced Raman spectroscopy data on both the NPs and their individual components. Optical imaging, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy analyses reveal the formation of NP-containing micelles or vesicles, NP morphology, particle size distribution, and chemical composition. X-ray photoelectron spectroscopy measurements indicate the oxidation state of each metal within these bimetallic NPs.

Diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes by using the modularly designed organocatalysts upon switching on their iminium catalysis.

The cinchona thiourea moiety in the self-assembled modularly designed organocatalysts (MDOs) switches off the iminium catalysis of these catalysts. In this study, it was found that the inhibited iminium catalysis could be switched on by using an appropriate weak acid and that, once the iminium catalysis was switched on, these catalysts could be applied for the highly stereoselective and diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes via a domino reaction between ketones and α,ß-unsaturated aldehydes.

Shielding Effect of Micelle for Highly Effective and Selective Monofluorination of Indoles in Water.

Highly selective direct monofluorination of indoles and arenes was developed through an approach that allows site-specific solubility of substrate and fluorine source in the micelle. This approach was highly selective for a broad range of substrates with excellent functional group tolerance. Differences in binding constant and solubility of indoles and arenes in the micelle allowed the fine-tuning of selectivity. Control experiments suggested a radical pathway and provided insight into the role of micelles of the environmentally benign amphiphile PS-750-M. Dynamic light scattering experiments strongly indicated the site-specific solubility of the substrate and fluorine source. The methodology was successfully adapted to gram scale, and the E-factor established from a recycle study indicated that the process is environmentally responsible and sustainable.

Organocatalyzed Enantioselective Direct Mannich Reaction of α-Styrylacetates.

An organocatalyzed direct Mannich reaction of unactivated α-styrylacetates was realized for the first time. By using a quinidine-derived C6'-urea catalyst, the direct Mannich reaction of α-styrylacetates and N-tosylimines gave the desired ß-amino esters in high yields, diastereoselectivities, and ee values. The reaction provides a highly stereoselective (up to 96:4 dr and 97% ee) and the most straightforward synthesis of functionalized N-tosylated ß-amino esters. The products can be used as precursors for the highly selective synthesis of tetrahydrofuran derivatives.