A New Approach to Ethyl 1-Aroyl/Aroylmethyl-5-methyl-3- methylthiopyrazole-4-carboxylates: High Regioselectivity in Alkylation and Acylation Reactions between N-1 and N-2 of a Pyrazole Derivative

Two series, totalizing twelve, of new compounds, ethyl 1-aroyl/aroylmethyl-5-methyl-3- methylthiopyrazole-4-carboxylates 5/6, have been synthesized via highly regioselective acylation and alkylation of ethyl 3-methyl-5-methylthio-1H- pyrazole-4-carboxylate 2a with aroyl chloride 3 and alpha-tosyloxysubstitutedacetophenones 4. Unexpected structures of the product have been unambiguously determined by both X-ray crystallographic analysis and 2D NMR.

A Study on the Regioselectivity of the Cyclization Reaction of 5－Amino－1， 2， 4－triazole with Asym－l， 3－dicarbonyl Compound

This paper reports the primary results of the study. on the regioselectivity of the cyclization reaction of 5-amino-1, 2, 4-triazole and its analogues until asym-1, 3-dicarbonyl compounds. The mechanistic explanation for the regioselectivity is presented.

Regioselectivity Study on Propylene Polymerization Catalyzed by Neutral Salicyladiminato Pd(II) Model Complex with DFT Method

Many attempts have been made to control the regioselectivity for olefin poly- merization by varying the structures of ligands in catalysts. The regioselectivity of propylene polymerization was investigated by replacing a nitrogen atom in the Pd(II) diimine catalyst with an oxygen atom from density functional theory method at the B3LYP/LANL2DZ level. The results show that the 1,2-insertion becomes a rival mechanism to the 2,1-insertion when the nitrogen atom is replaced by the oxygen atom leading to an asymmetric environment in the catalyst, and that the steric effect in the asymmetrical catalyst plays an important part in the polymerization. The insertion barrier from 2-O is much higher than that from 2-N. A pyramid transition state was characterized for the catalyst to convert 2-O back to 2-N through internal rotation. The propylene prefers to coordinate at the opposite side of O in the catalyst. This is the driving force for the internal rotation. The results are significant for isotactic and syndiotactic polymerization.

Theoretical Study of Mechanism and Regioselectivity of 1,3-dipolar Cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] Nitrilimine with Dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate

The mechanism and regioselectivity of 1,3-dipolar cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] nitrilimine with dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate were investigated using activation energy calculations and density functional theory-based reactivity indexes. The reaction proceeds by an asynchronous concerted mechanism. The calculations are performed at the B3LYP/6-31G（d） level of theory and the obtained results are in agreement with experimental outcome.

Polymerization of 1,3-Butadiene with Catalysts Based on Cobalt Dichloride Complexes with Aminophosphines: Switching the Regioselectivity by Varying the MAO/Co Molar Ratio

Several novel cobalt dichloride complexes with amino-phosphine bidentate ligands were synthesized and characterized.For some of them single crystals were obtained and their molecular structure was determined by X-ray diffraction method.All the complexes were then used in combination with MAO for the polymerization of 1,3-butadiene,obtaining polymers with different structures(i.e.,predominantly 1,2 or cis-1,4)mainly depending on the type of ligand and on the MAO/Co molar ratio.The behavior of these novel catalysts was compared with that exhibited,in the polymerization of the same monomer,by the systems CoCl_(2)(PR3)2-MAO and CoCl_(2)(PRPh2)2-MAO(R=alkyl or cycloalkyl group),and by the systems based on cobalt dichloride complexes with various bi-and tridentate ligands(e.g.,diphosphines,bis-imines,pyridyl-imines,bis-iminopyridines).The comparison between the different systems allowed us to make some clarity about the actual and effective role played by the various types of ligands in the polymerization of conjugated dienes with catalytic systems CoCl_(2)(L)-MAO,in which L=mono-,bi-,or tri-dentate ligand.

From Reactivity and Regioselectivity to Stereoselectivity: An Odyssey of Designing PIP Amine and Related Directing Groups for C-H Activation

What is the most favorite and original chemistry developed in your research group? Developing PIP amine for regio-and enantioselective methylene C-H activation. How do you get into this specific field? Could you please share some experiences with our readers?

Switchable regioselectivity in amine-catalysed asymmetric cycloadditions

Subject Code:B02 With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Chen Yingchun(陈应春)from Sichuan University and Dr.Ouyang Qin(欧阳勤)from the Third Military Medical University demonstrates switchable regioselective[6+2]。

Structure-guided manipulation of the regioselectivity of the cyclosporine A hydroxylase CYP-sb21 from Sebekia benihana

The cytochrome P450 enzyme CYP-sb21 from the rare actinomycete Sebekia benihana is capable of hydroxylating the immunosuppressive drug molecule cyclosporine A(CsA)primarily at the 4th N-methyl leucine(MeLeu4),giving rise toγ-hydroxy-N-methyl-L-Leu4-CsA(CsA-4-OH).This oxidative modification of CsA leads to dramatically reduced immunosuppressive activity while retaining the hair growth-promoting side-effect,thus demonstrating great application potential in both pharmaceutical and cosmetic industries.However,this P450 enzyme also hydroxylates CsA at the unwanted position of the 9th N-methyl leucine(MeLeu9),indicating that the regioselectivity needs to be improved for the development of CsA-4-OH into a commercial hair growth stimulator.Herein,we report the crystal structure of CYP-sb21 in its substrate-free form at 1.85Å.Together with sequence and 3D structure comparisons,Autodock-based substrate docking,molecular dynamics(MD)simulation,and site-directed mutagenesis,we identified a number of key residues including R294,E264,and M179 that can improve catalytic efficiency or change the regioselectivity of CYP-sb21 towards CsA,setting the stage for better enzymatic preparation of CsA-4-OH.This study also provides new insights into the substrate recognition and binding mechanism of P450 enzymes that accommodate bulky substrates.

Acidic rearrangement of benzyl group in flavone benzyl ethers and its regioselectivity

The benzyl-substituted flavone compounds are rare in nature, while some of which have interesting biological activities. The total synthesis of benzyl-substituted flavone derivatives via the acidic rearrangement of benzyl groups in flavone benzyl ethers, and the complicated regioselectivity of the rearrangement were reported. The regioselectivity was proposed to be determined by the steric hindrance as well as the ease of electrophilic substitution reaction for benzyl cations at different positions of corresponding debenzylated fiavone compounds.

Trifluoromethyl Radical Addition versus Radical Trifluoromethylation:Reversed Regioselectivity in Carbotrifluoromethylation of Alkenes

Professor Chaozhong Li's research group has long been interested in radicals in organic synthesis. They have developed a series of silver-catalyzed radical fluorination reactions since the year 2012.[1] In 2015, the research group joined the Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. I joined the Li group in the same year.

Mechanistic study on the regioselectivity of Co-catalyzed hydroacylation of 1,3-dienes

Density functional theory（DFT） method was used to explore the origin of the regioselectivity of Cocatalyzed hydroacylation of 1,3-dienes.The reaction of 2-methyl-1,3-butadiene and benzaldehyde with1,3-bis（diphenylphosphino）propane ligand was chosen as the model reaction.The energies of the intermediates and transition states in the stages of oxidative cyclization,β-H elimination and C-H reductive elimination were investigated.Computational results show that β-H elimination is the ratedetermining step for the whole catalytic cycle.C1-Selective oxidative cyclization is favored over C4-selective oxidative cyclization.Besides.C4-selective oxidative cyclization is kinetically disfavored than all the steps in C1-hydroacylation mechanisms,consistent with the experimentally obtained C1-selective hydroacylation products.Analyzing the reason for such observation,we suggest that both electronic and steric effects contribute to the C1-selectivity.On the electronic aspect,C1 is more electron rich than C4 due to the methyl group on C2,which makes the electrophilic attack of aldehyde carbon on C1 more favorable.On the steric aspect,the methyl group locates farther from the ligands in the transition state of C1-selective oxidative cyclization than in that of C4-selective oxidative cyclization.

Post-spin crossing dynamics determine the regioselectivity in open-shell singlet biradical recombination

Radical recombination is among the fastest reactions in organic chemistry.Achieving high levels of selectivity in this type of reaction is rather challenging.In a recent report on visible-light-induced dearo-mative cycloaddition of pyrrole-tethered vinylcyclopropanes,extraordinary regioselectivity was observed during the intramolecular open-shell singlet biradical recombination step.

Rationalization of regioselectivity of electrophilic substitution reaction for cyclic compounds in terms of D_(pb) values

Accepted theories predict that substitution reactions are controlled by the electronic nature of the attacked site for electrophilic aromatic substitution. Here it is shown that in addition the bond strength of the broken bond may also influence the regioselectivity of the substitution reaction, and that the Dpb is a good indicator of the strength of a chemical bond. The Dpb denotes the depth of the potential acting on one electron in a molecule at the bond center （bc）. In this letter, the values of Dpb along the C-H and N-H bonds have been investigated, and it is demonstrated that for aromatic compounds, the regioselectivity of the electrophilic substitution can well be rationalized in terms of Dpb values.

ACYL RADICAL CYCLISATIONS

Several phenylselenyl esters were selected as precursors of acyl radicals and synthesised by our established method. Treatment of these phenylselenyl esters with tributyltinhydride and AIBN generated the corresponding acyl radicals, which were found to proceed in 5 exo trig or 6 endo trig cyclisations to afford high yields of cyclopentanones and cyclohexanones, The substitution groups on the substrates have played an important role on the regioselectivity of cyclisations.

Synthesis of kanamycin A derivatives by regioselective masking drug resistant enzymes targeting hydroxyl groups

The 3＇-OH, 4＇-OH and 2＂-OH of kanamycin A were modified in search of new aminoglycosides to overcome resistant enzymes, ANTs and APHs. The key intermediate was a dibenzylidene-protected derivative of kanamycin A. The aimed sites were masked by benzyl, methyl and allyl groups. Multi-step reactions gave the desired aminoglycoside derivatives but showed less antibiotic activity than kanamycin A.

Synthesis of Phenylpropanoid Glycoside Analogs

The regioselective acylation of unprotected phenylethyl glucoside withcinnamoyl chloride leads to 6-OH cin-namoylated glucoside. In this manner, thirteen phenylpropanoidglycoside analogs were designed and prepared. Their structure was confirmed by ~1H NMR and ^(13)CNMR spectra.

Enhancing the activity,selectivity,and recyclability of Rh/PPh_(3) system‐catalyzed hydroformylation reactions through the development of a PPh_(3)‐derived quasi‐porous organic cage as a ligand

In contrast to heterogeneous network frameworks(e.g.,covalent organic frameworks and metal‐organic frameworks)and porous organic polymers,porous organic cages(POCs)are soluble molecules in common organic solvents that provide significant potential for homogeneous catalysis.Herein,we report a triphenylphosphine‐derived quasi‐porous organic cage(denoted as POC‐DICP)as an efficient organic molecular cage ligand for Rh/PPh_(3) system‐catalyzed homogeneous hydroformylation reactions.POC‐DICP not only displays enhanced hydroformylation selectivity(aldehyde selectivity as high as 97%and a linear‐to‐branch ratio as high as 1.89)but can also be recovered and reused via a simple precipitation method in homogeneous reaction systems.We speculate that the reason for the high activity and good selectivity is the favorable geometry(cone angle=123.88°)and electronic effect(P site is relatively electron‐deficient)of POC‐DICP,which were also demonstrated by density functional theory calculations and X‐ray absorption fine‐structure characterization.

Regioselective enzymatic acylation of troxerutin in nonaqueous medium

A series of monosubstituted troxerutin esters have been synthesized by enzyme-catalyzed regioselective acylation of troxerutin in nonaqueous medium.Using divinyl dicarboxylates(CH_2=CH-OOC-(CH_2)_n-COO-CH=CH_2,n = 2,3,4,7,8,11) featuring different chain length as acyl donors and alkaline protease from Bacillus subtilis as catalyst,troxerutin was regioselective acylated at B ethoxyl group.The results indicated that the regioselectivity of the enzyme-catalyzed acylation was not affected by the chain length o...

Synthesis and Crystal Structure of Ethyl 1-(2-bromoethyl)-3-(4-meth-oxyphenyl)-1H-pyrazole-5-carboxylate

The title compound ethyl 1-（2-bromoethyl）-3-（4-methoxyphenyl）-1H-pyrazole-5-carboxylate 1 has been synthesized and structurally characterized by single-crystal X-ray diffraction.The crystal is of monoclinic（C15H17BrN2O3,Mr = 353.22）,space group C21 with a = 24.691（7）,b = 6.7678（17）,c = 17.884（5） ,β = 97.184（5）o,V = 2965.1（13） 3,Z = 8,Dc = 1.583 g.cm-3,F（000） = 1440,μ = 2.784 mm-1,the final R = 0.0260 and wR = 0.0596 for 2684 observed reflections with I 2σ（I）.All the carbon atoms in the molecule are nearly coplanar except C（15）,with a large conjugated system among the carbonyl group,pyrazole ring and the benzene ring.Three non-classical intermolecular hydrogen bonds help to stabilize the crystal lattice.The regioselectivity was rationalized based on the coordination of potassium ion with the N-anion and the carbonyl oxygen atom.

Intermediate formation enabled regioselective access to amide in the Pd-catalyzed reductive aminocarbonylation of olefin with nitroarene

An efficient route for the palladium-catalyzed reductive aminocarbonylation of olefins with nitroarenes was developed using carbon monoxide(CO)as both reductant and carbonyl source,which enables facile access to amides with excellent regioselectivity and broad substrate scope.It is found that the counter anions of the Pd catalyst precursors significantly affect the reaction chemoselectivity and amide regioselectivity.Branched amides were mainly obtained with K2PdCl4 as the metal catalyst,and phosphine ligands had no influence on the regioselectivity but affected the catalytic reactivity.However,phosphine ligands had significant effects on aminocarbonylation regioselectivity when Pd(CH3CN)4(OTf)2 was used;monodentate phosphines tended to form branched amides,and bidentate phosphines mainly formed linear amides.Trapping experiments,primary kinetic studies,and control reactions with all possible N-species reduced from nitroarene indicated that the catalytic synthesis of branched and linear amides produced nitrene(further converted to enamide)and aniline,respectively,different from the previous ligand-controlled regioselective synthesis of amides via the aminocarbonylation of olefins with amines.Furthermore,the proposed synthesis route could be applied in the synthesis of gram-scale propanil under mild conditions.