High Regioselectivity Research Articles

Pd-catalyzed regioselective hydroesterification of 3-allyl-2-hydroxynaphthoquinones: Easy access to linear or branched naphthoquinone esters

The successful hydroesterification of 3-allyl-2-hydroxynapthoquinones is presented, providing excellent regioselectivity of the linear and branched esters. The Pd(OAc)2/dppf catalytic system was used to prepare a series of linear naphthoquinone esters with high regioselectivity. A slight modification of the initial conditions afforded branched esters with high regioselectivity using a PdCl2/dppe combination. Control experiments facilitated observation of a correlation between the hydroxy group present on the substrate and the selectivity of the reaction. In addition, a cytotoxic test was conducted on the synthesized esters against six tumor cell lines, which provided valuable information about their biological activity.

Metal-Free, Hindered, Regioselective Access to Multifunctional Groups Diarylamines via SN Ar Substitution of P-Nitroso Aromatic Methyl Ether by Arylamines.

Multifunctional groups diarylamines, an innovative product, efficiently produced from arylamines and p-nitrosoanisole derivatives by intermolecular SN Ar under weak acid conditions. This SN Ar proceeds under mild reaction conditions, and more significantly, the substrates involved do not necessarily require strong electron-withdrawing groups. Moreover, this SN Ar is characterized by resistance to space crowding, tolerance to halogen and nitroso functional groups, and high regioselectivity. Mechanistic observations suggest that the SN Ar is the result of the transfer of the positive charge center of the protonated nitroso group to the p-methoxy group.

Highly efficient biosynthesis of salidroside by a UDP-glucosyltransferase-catalyzed cascade reaction.

Salidroside is an important plant-derived aromatic compound with diverse biological properties. The main objective of this study was to synthesize salidroside from tyrosol using UDP-glucosyltransferase (UGT) with in situ regeneration of UDP-glucose (UDPG). The UDP-glucosyltransferase 85A1 (UGT85A1) from Arabidopsis thaliana, which showed high activity and regioselectivity towards tyrosol, was selected for the production of salidroside. Then, an in vitro cascade reaction for in situ regeneration of UDPG was constructed by coupling UGT85A1 to sucrose synthase from Glycine max (GmSuSy). The optimal UGT85A1-GmSuSy activity ratio of 1:2 was determined to balance the efficiency of salidroside production and UDP-glucose regeneration. Different cascade reaction conditions for salidroside production were also determined. Under the optimized condition, salidroside was produced at a titer of 6.0g/L with a corresponding molar conversion of 99.6% and a specific productivity of 199.1mg/L/h in a continuous feeding reactor. This is the highest salidroside titer ever reported so far using biocatalytic approach.

Visible-Light Photoredox-Catalyzed Intermolecular α-Aminomethyl/Carboxylative Dearomatization of Indoles with CO2 and α-Aminoalkyl Radical Precursors.

Disclosed here is a visible-light photoredox-catalyzed intermolecular sequential α-aminomethyl/carboxylative dearomatization of indoles with CO2 and α-aminoalkyl radical precursors, affording a series of functionalized indoline-3-carboxylic acids and lactams in good yields with high regioselectivity. This multicomponent reaction provides a green and facile method for the synthesis of diverse functionalized indolines by using CO2 as the carboxylic and carbonyl source.

Nickel‐Catalyzed Regio‐ and Stereoselective Defluorinative Arylation of gem‐Difluorinated Cyclopropanes

Comprehensive SummaryHerein, we report nickel‐catalyzed cross‐coupling of gem‐difluorinated cyclopropanes with boronic acids, providing the corresponding arylated 2‐fluoroallylic scaffolds. This approach used commercially available phosphine ligand Xantphos to obtain monofluorinated alkenes with high regioselectivity and Z‐stereoselectivity. Mechanistic studies proposed a Ni(II)‐fluoroallyl pathway and excluded the radical pathway. Meanwhile, DFT study of the reductive elimination clarified the origin of the high linear selectivity.

Oxone® Mediated Regioselective C(sp2)−H Selenylation and Thiocyanation of Pyrazolo[1,5‐a]pyrimidines at Room Temperature

AbstractA mild Oxone® mediated reaction for direct regioselective C−H selenylation and thiocyanation of pyrazolo[1,5‐a]pyrimidines is established at ambient temperature. This practical and efficient methodology employs Oxone® as a user friendly, green, non‐toxic and cheap reagent to facilitate selenylation and thiocyanation at room temperature. The present method offers high regioselectivity, broad substrate scope, mild conditions and excellent yields. Further, this eco‐friendly approach could easily be extended for mild C−H selenylation and thiocyanation of other heterocycles. Mechanistic studies indicate that the reaction occurs through electrophilic substitution mechanism via generation of an electrophilic chalcogen species.

Unlocking regioselective meta-alkylation with epoxides and oxetanes via dynamic kinetic catalyst control.

Regioselective arene C-H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Herein, we report the meta-C-H bond alkylation of aromatics bearing N-directing groups using (hetero)aromatic epoxides as alkylating agents. This method results in complete regioselectivity on both the arene as well as the epoxide coupling partners, cleaving exclusively the benzylic C-O bond. Oxetanes, which are normally unreactive, also participate as alkylating reagents under the reaction conditions. Our mechanistic studies reveal an unexpected reversible epoxide ring opening process undergoing catalyst-controlled regioselection, as key for the observed high regioselectivities.

Hydroboration and hydrosilylation of alkenes catalyzed by an unsymmetrical magnesium methyl complex.

The hydroboration and hydrosilylation of alkenes catalyzed by the unsymmetrical β-diketiminate magnesium methyl complex [(DippXylNacnac)MgMe (THF)] (1) have been reported. When complex 1 was employed as a highly efficient catalyst in the hydroboration of various alkenes with HBpin, only the anti-Markovnikov hydroboration products were obtained in high yields and with high regioselectivities under mild reaction conditions (60 °C). To our surprise, it showed different regioselectivities in the hydrosilylation of a range of alkenes with PhSiH3. Aromatic alkene substrates afforded the corresponding branched Markovnikov hydrosilylation products in high yields and with high regioselectivities; conversely, aliphatic alkenes produced the linear anti-Markovnikov products in moderate yields. This is completely consistent with the corresponding density functional theory (DFT) calculations. In addition, the practical utility was demonstrated via scale-up reactions of boronate esters and a preliminary plausible mechanism of hydroboration and hydrosilylation have been investigated as well.

Pd(II)-catalyzed hydroarylations/hydroalkenylations of terminal alkynes: regioselective synthesis of allylic, homoallylic, and 1,3-diene systems.

A Pd-catalyzed regioselective hydroarylation of terminal alkynes containing a heteroatom has been developed via carbopalladation for the synthesis of allylic ethers, amines, and homoallylic alcohols. Moreover, hydroalkenylation of alkynes produces a variety of stereodefined 1,4-dienes with high regioselectivity. The important features of the present protocol are that it is highly regioselective, operationally rapid, and scalable with a huge substrate scope using only 3 mol% of PdCl2(PPh3)2 catalyst in the presence of a mild base KOAc.

Electrochemically chalcogenative annulation enabled construction of functionalized saturated N-heterocycles.

An efficient chalcogenative annulation strategy for constructing functionalized saturated N-heterocycles from unactivated alkenes with dichalcogenides under electrochemical conditions has been presented. This protocol is applicable to mono-, di- or tri-substituted alkenes, providing a straightforward pathway to aziridines, azetidines, pyrrolidines, and piperidines with high regioselectivity. Moreover, the strategy is qualified to realize the oxychalcogenation of alkenes as well.

Palladium-catalyzed allylation and carbonylation: access to allylhydrazones and allyl acylhydrazones.

A palladium-catalyzed allylation of hydrazines with allyl alcohols and aldehydes was developed, enabling the syntheses of a series of allylhydrazones in good to excellent yields with high regioselectivity. Furthermore, the four-component tandem allylation carbonylation of hydrazines with allyl alcohols and aldehydes was established using the catalytic system, producing various allyl acylhydrazones. Additionally, the functionalized allyl acylhydrazones could be smoothly constructed with the catalytic system employing allylhydrazones as a partner. The catalytic system exhibited good functional tolerance with excellent regioselectivities and scaled-up capability, overcoming the limitations of chemoselectivity of the multicomponent transformation and poor conversion of the weak nucleophile.

Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6-endo-dig cyclization and trichloromethylation of N3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinone was prepared over five steps. The present method features broad substrate scope, good functional group tolerance, new dearomatization of pyridine rings, and chloroform as the trichloromethylation reagent.

Synthesis of acridones via Ir(III)-catalyzed amination annulation of oxazoles with anthranils.

An unprecedented Ir(III)-catalyzed C-H activation/amination/annulation of 2-phenyloxazoles with anthranils for the highly selective preparation of acridone derivatives in one-pot under controlled conditions is reported. This protocol is characterized by atom economy and high regioselectivity. A wide range of anthranils with 2-phenyloxazoles were well tolerated and afforded the desired products in moderate to good yields, in which the anthranil serves as a convenient amination reagent.

Au-allenylidene promoted decarboxylative annulation to access unsaturated γ-lactams/lactones.

A novel Au-allenylidene promoted decarboxylative annulation by intramolecular α-nucleophilic addition has been disclosed. The unsaturated cyclic ethynylethylene carbamates/carbonates can be converted to unique nucleophiles attached with alkylidene ketenes by sequential decarboxylation and oxidation processes. Such alkylidene ketenes can be rapidly trapped by intramolecular α-attacking annulation to generate potential biological active unsaturated γ-lactams/lactones with broad scope, facile post-modification, high regioselectivity and efficiency.

Copper-promoted ortho-directed C-H amination of 2-arylpyridines with NH-heterocycles.

Copper-mediated C-N coupling of azaheterocycles with aryl C-H bonds has been realized for the synthesis of N-(hetero)arylated heteroarenes. This method is characterized by high regioselectivity, atom economy and a wide substrate scope of 2-arylazines and azaheterocycles. The corresponding C-N coupling products were shown to undergo further transformation to synthesize more complex molecules.

SYNTHESIS, CRYSTAL STRUCTURE ANALYSIS AND DFT STUDIES OF TWO BENZOSPIROCYCLIC KETONES

The functionalized 3H-spiro[isobenzofuran-1,3'-isochromane] skeletons were synthesized in our laboratory with high regioselectivity by palladium-catalyzed intermolecular tandem cycloaddition reaction, two of these derivatives were selected for crystallographic analysis, and the structures of the title compounds were verified by FTIR, 1H NMR and 13C NMR, and MS. The compounds 3a:6'-methoxy-4'-methylene-3H-spiro[isobenzofuran-1,3'-isochromane], C18H16O3 and 3b: 6-fluoro-4-methylene-3'H-spiro[isochromane-3,1'-naphtho[2,3-c]furan ], C21H15O2F. The molecular structure was calculated by density functional theory (DFT) and compared with the x-ray diffraction data. The results of the conformational analysis also showed that the optimized molecular structure obtained by DFT calculations was the same as the optimized molecular structure obtained by X-ray diffraction analysis. In addition, the molecular electrostatic potentials and frontier molecular orbitals of the title compounds were further investigated by using DFT, which revealed the molecular structure features, conformations and some special physicochemical properties of the title compounds.

Transition-metal-catalyzed regiodivergent sulfonylation of aziridrines for the synthesis of β-amino sulfones

We developed the first transition-metal-catalyzed, regiodivergent sulfonylation of aziridines, enabling the efficient synthesis of diverse β-amino sulfones under mild conditions with broad substrate compatibility and high regioselectivity.

An aerobic copper-catalyzed multi-component reaction strategy for N′,N′-diaryl acylhydrazine synthesis: reactions and mechanism

A sequential multi-component reaction of aldehydes and aryl hydrazines for the synthesis of N',N'-diaryl acylhydrazines with high regioselectivity has been achieved via an aerobic copper-catalyzed process.

Rh(iii)-catalyzed sequential spiroannulation/lactonization of 3-aryl N-sulfonyl ketimines with 4-hydroxy-2-alkynoates by C–H bond activation

A rhodium(iii)-catalyzed C–H annulation strategy has been developed for the synthesis of a highly rigid spirobenzosultam lactones in good yields with high regioselectivity from 3-aryl N-sulfonyl ketimines and 4-hydroxy-2-alkynoates.

Regioselective synthesis of 2-aminophenols from N-arylhydroxylamines.

A novel strategy for the synthesis of 2-aminophenols in the absence of metals and oxidants was described. The 2-aminophenols were efficiently obtained through a cascade [3,3]-sigmatropic rearrangement and in situ hydrolysis process by using readily available N-arylhydroxylamines and the in situ-generated methyl chlorosulfonate from commercially available sulfuryl chloride and methanol under mild conditions. This method could be scaled up and has a wide substrate scope with great functional group tolerance and high regioselectivity. The 2-aminophenol products could be readily converted into structurally diverse functional molecules in good yields under various conditions.