ABSTRACT
A Pd-catalyzed asymmetric isomerization-hydroamidocarbonylation of amide-containing alkenes was developed, affording a variety of chiral a-alkyl succinimides in moderate to good yields with high enantioselectivities. The key to success was introducing bulky 1-adamentyl P-substitution and 2,3,5,6-tetramethoxyphenyl group into the rigid P-chirogenic bisphosphine ligand to create stronger steric hinderance and deeper catalytic pocket. By this approach, regio- or stereo-convergent synthesis of enantiomeric succinimides from the mixture of olefin isomers was achieved.
ABSTRACT
The nucleophilic ring-opening of aziridine derivatives provides an important synthetic tool for the preparation of various ß-functionalized amines. Amines as nucleophiles are employed to prepare synthetically useful 1,2-diamines in the presence of various catalysts or activators. Herein, the B2(OH)4-mediated reductive ring-opening transformation of N-tosyl aziridines by nitroarenes was developed. This aqueous protocol employed nitroarenes as cheap and readily available amino sources and proceeds under external catalyst-free conditions. Control experiments and DFT calculations pointed to the in situ reduction of nitroarenes to aryl amines via N-aryl boramidic acid (E) and an SN1-type ring-opening of N-tosylaziridines by the resultant aryl amines with high regioselectivity.
ABSTRACT
The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation of asymmetric organocatalyzed reactions via an enantioselective hydrogen atom transfer (HAT) process. Herein, an unprecedented type of chiral C2-symmetric arylthiol catalysts derived from readily available enantiomeric lactate ester was developed. With these catalysts, an asymmetric anti-Markovnikov alkene hydroamination-cyclization reaction was established, affording a variety of pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity. Results of the designed control experiments and theoretical computation rationalized the origin of stereocontrol and disclosed the spatial effect of the moiety of chiral thiols on the enantioselectivity. We believed the facile synthesis, flexible tunability, and effective enantioselectivity-controlling capability of these catalysts would shed light on the development of versatile chiral HAT catalysts and related asymmetric reactions.
ABSTRACT
We here reported a highly stereoselective method for the synthesis of polysubstituted conjugated dienes from α-aryl α-diazo alkynyl ketones and pyrazole-substituted unsymmetric aminals under mild conditions, which was promoted by photo-irridation and involved with 1,6-dipolar intermediate and quadruple sigmatropic rearrangements, was successfully developed. In this transformation, the cleavage of four bonds and the recombination of five bonds were implemented in one operational step. This protocol provided a modular tool for constructing dienes from amines, pyrazoles and α-alkynyl-α-diazoketones in one-pot manner. The results of mechanistic investigation indicated that the plausible reaction path underwent the 1,6-sigmatropic rearrangement instead of the 1,5-sigmatropic rearrangement.
ABSTRACT
Controlling the regioselectivity for the alkoxycarbonylation of unsymmetric internal alkynes is challenging. Herein, a palladium-catalyzed ligand-controlled regiodivergent alkoxycarbonylation of internal trifluoromethylthiolated alkynes was achieved. A series of α- or ß-SCF3 acrylates from the same trifluoromethylthiolated alkyne were obtained with moderate to high yield and regioselectivity.
ABSTRACT
Photoredox/nickel-catalyzed enantioconvergent acyl cross-coupling of carboxylic derivatives with racemic secondary organotrifluoroborate was developed for the synthesis of an enolizable chiral α-aryl ketone under mild neutral conditions. Moderate to high yields and good enantioselectivities were achieved.
ABSTRACT
A paired electrochemical method for paralleling benzylic bromination of alkylarenes under irradiation with reductive pinacol coupling in a divided cell has been developed. A variety of benzyl bromides at the anode and pinacols at the cathode were obtained simultaneously in moderate-to-high faradaic efficiency. This parallel paired electrochemical protocol showed a broad substrate scope and high chemoselectivity as well as high synthetic and faradaic efficiencies.
ABSTRACT
Using full configuration interaction (FCI) and multi-reference configuration interaction methods (MRCI), reliable geometrical and energetic references for Bn (n = 1-4) clusters were established. The accuracy of the computed results was confirmed by comparison with available experimental data. Benchmark calculations indicated that B97D3, B97D, VSXC, HCTH407, BP86 and CCSD(T) methods provided reasonable results for structural parameters, with mean absolute error (MAEs) within 0.020 Å. Among the tested density functional theory (DFT) methods, the VSXC functional showed the best performance in predicting the relative energies of B1 B4 with a MAE of 12.8 kJ mol-1 . Besides, B1B95, B971, TPSS, B3LYP, and BLYP functionals exhibited reasonable performance with MAE values of less than 15.0 kJ mol-1 . T1 diagnostic values between 0.035 and 0.109 at the CCSD(T) level revealed strong correlations in B2 B4 clusters, highlighting the need for caution in using CCSD(T) as an energy reference for small boron clusters. The methods of CCSDT, CCSDT(Q) and CCSDT[Q], which incorporate three-electron and four-electron excitations, effectively improved the accuracy of the energy calculations.
ABSTRACT
An unprecedented Pd-catalyzed fluorinative bifunctionalization of aziridines and azetidines was successfully developed via regioselective C-C and C-F bond cleavage of gem-difluorocyclopropanes, leading to various ß,ß'-bisfluorinated amines and ß,γ-bisfluorinated amines. This reaction was achieved by incorporating a 2-fluorinated allyl group and a fluorine atom scissored from gem-difluorocyclopropane in 100 % atom economy for the first time. The mechanistic investigations indicated that the reaction underwent amine attacking 2-fluorinated allyl palladium complex to generate η2 -coordinated N-allyl aziridine followed by fluoride ligand transfer affording the final ß- and γ-fluorinated amines.
ABSTRACT
A parallel paired electrosynthetic method, coupling electrocarboxylation incorporating CO2 into ketone, imine, and alkene with alcohol oxidation or oxidative cyanation of amine, was developed for the first time. Various carboxylic acids as well as aldehyde/ketone or α-nitrile amine were prepared at the cathode and anode respectively in a divided cell. Its utility and merits on simultaneously achieving high atom-economic CO2 utilization, elevated faradaic efficiency (FE, total FE of up to 166 %), and broad substrate scope were demonstrated. The preparation of pharmaceutical intermediates for Naproxen and Ibuprofen via this approach proved its potential application in green organic electrosynthesis.
ABSTRACT
A metal-free protocol for visible-light-driven intramolecular hydrodifluoroacetylative cyclization of N-propargyl or N-homopropargyl-2-bromo-2,2-difluoroacetamide to α,α-difluorinated ß-substituted γ- or δ-lactam without an additional photosensitizer has been developed. By using thiol and Hantzsch ester as the catalyst and hydrogen donor, respectively, to implement a hydrogen atom transfer process, moderate to high (Z) selectivity was achieved. The results of a mechanistic investigation revealed the critical contribution of the thiol catalyst in attaining the stereoselectivity.
ABSTRACT
With the aid of an innate amide group, an intramolecular Pd-catalyzed enantioselective hydroamidocarbonylation reaction of α-substituted acrylamides was developed, and a series of chiral 2-substituted succinimides were obtained in moderate to high yields and enantioselectivities. The generality of this approach was demonstrated by the carbonylation of both aryl- and alkyl-substituted acrylamides containing numerous functional groups.
ABSTRACT
A Pd-catalyzed asymmetric double hydroxycarbonylation of terminal alkynes was developed by using relay catalysis, providing a highly efficient route to chiral succinic acids (41 examples, 76-94 %, 94-99 % ee). Key to success was the combinatorial use of a Pd precursor with two distinct phosphine ligands in one pot. The synthetic utilities of this protocol were showcased in the facile synthesis of key intermediates for chiral pharmaceuticals.
Subject(s)
Alkynes , Palladium , Catalysis , Molecular Structure , Stereoisomerism , SuccinatesABSTRACT
A Ni/(S,S)-BDPP-catalyzed intramolecular Heck cyclization of N-(2-iodo-aryl) acrylamide with 2-methyl-2-phenylmalononitrile was developed to give oxindoles with good enantioselectivities. We found that utilizing such an electrophilic cyanation reagent could tackle the deleterious effect of the coordinative cyanide ion in the asymmetric alkene arylcyanation.
ABSTRACT
Palladium-catalysed diastereoselective hydroesterification of alkenes assisted by the coordinative hydroxyl group in the substrate afforded a variety of chiral γ-butyrolactones bearing two stereocenters. Employing the carbonylation-lactonization products as the key intermediates, the route from the alkenes with single chiral center to chiral THF-fused bicyclic γ-lactones containing three stereocenters was developed.
Subject(s)
Alkenes , Lactones , Molecular Structure , Palladium , StereoisomerismABSTRACT
A palladium-catalyzed asymmetric hydroesterification of α-aryl acrylic acids with CO and alcohol was developed, preparing a variety of chiral α-substituted succinates in moderate yields with high ee values. The kinetic profile of the reaction progress revealed that the alkene substrate first underwent the hydroesterification followed by esterification with alcohol. The origin of the enantioselectivity was elucidated by density functional theory computation.
ABSTRACT
As a fundamental type of carbonylation reaction, the alkoxy- and hydroxy-carbonylation of unsaturated hydrocarbons constitutes one of the most important industrial applications of homogeneous catalysis. However, owing to the difficulties in controlling multi-selectivities for asymmetric hydrocarbonylation of alkenes, this reaction is typically limited to vinylarenes and analogues. In this work, a highly efficient asymmetric alkoxy- and hydroxy-carbonylation of ß-carbonyl functionalized alkenes was developed, providing practical and easy access to various densely functionalized chiral molecules with high optical purity from broadly available alkenes, CO, and nucleophiles (>90 examples, 84-99 % ee). This protocol features mild reaction conditions and a broad substrate scope, and the products can be readily transformed into a diverse array of chiral heterocycles. Control experiments revealed the key role of the ß-carbonyl group in determining the enantioselectivity and promoting the activity, which facilitates chiral induction by coordination to the transition metal as rationalized by DFT calculations. The strategy of utilizing an innate functional group as the directing group on the alkene substrate might find further applications in catalytic asymmetric hydrocarbonylation reactions.
ABSTRACT
A palladium-catalyzed asymmetric hydroesterification-cyclization of 1,6-enynes with CO and alcohol was developed to efficiently prepare a variety of enantioenriched γ-lactams bearing a chiral quaternary carbon center and a carboxylic ester group. The approach featured good to high chemo-, region-, and enantioselectivities, high atom economy, and mild reaction conditions as well as broad substrate scope. The correlation between the multiple selectivities of such process and the N-substitutes of the amide linker in the 1,6-enyne substrate has been depicted by the crystallographic evidence and control experiments.
ABSTRACT
Reductive cyanation of tertiary alkyl bromides using electrophilic cyanating reagent and zinc reductant was developed, providing various α-cyano ketones, esters, and carboxamides containing a nitrile-bearing all-carbon quaternary center in good to excellent yields under mild reaction conditions. The corresponding reaction mechanism involving in situ generated organozinc reagent and reactivity distinction was elucidated by density functional theory computation.
ABSTRACT
Synthesis of optically active gem-difluorinated organic molecules attracts a great deal of interest due to their unique properties in pharmaceutical and agrochemical areas. Herein, a series of enantioenriched α,α-difluoro-ß-arylbutanoic esters were prepared in high yields (83-99%) with moderate to excellent enantioselectivities (≤97:3 er) by palladium-catalyzed asymmetric hydrogenation.