A Type of Chiral C2-Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination.

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.

Benchmarking boron cluster calculations: Establishing reliable geometrical and energetic references for Bn (n = 1-4).

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.

Parallel Paired Photoelectrochemical Bromination of Alkylarenes with Electrochemical Pinacol Coupling.

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.

B2(OH)4-Mediated Reductive Ring-Opening of N-Tosyl Aziridines by Nitroarenes: A Green and Regioselective Access to Vicinal Diamines.

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.

Palladium-Catalyzed Enantioselective Migratory Hydroamidocarbonylation of Amide-Linked Alkenes to Access Chiral α-Alkyl Succinimides.

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.

Stereoselective Synthesis of Polysubstituted Conjugated Dienes Enabled by Photo-Driven Sequential Sigmatropic Rearrangement.

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.

Pd-Catalyzed Enantioselective Hydroamidocarbonylation of α-Substituted Acrylamides to Chiral Succinimides.

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.

Palladium-Catalyzed Fluorinative Bifunctionalization of Aziridines and Azetidines with gem-Difluorocyclopropanes.

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.

Asymmetric Double Hydroxycarbonylation of Alkynes to Chiral Succinic Acids Enabled by Palladium Relay Catalysis.

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.

Diastereoselective Alkene Hydroesterification Enabling the Synthesis of Chiral Fused Bicyclic Lactones.

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.

Asymmetric Alkoxy- and Hydroxy-Carbonylations of Functionalized Alkenes Assisted by ß-Carbonyl Groups.

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.

Amine-Responsive Disassembly of AuI -CuI Double Salts for Oxidative Carbonylation.

A sensitive amine-responsive disassembly of self-assembled AuI -CuI double salts was observed and its utilization for the synergistic catalysis was enlightened. Investigation of the disassembly of [Au(NHC)2 ][CuI2 ] revealed the contribution of Cu-assisted ligand exchange of N-heterocyclic carbene (NHC) by amine in [Au(NHC)2 ]+ and the capacity of [CuI2 ]- on the oxidative step. By integrating the implicative information coded in the responsive behavior and inherent catalytic functions of d10 metal complexes, a catalyst for the oxidative carbonylation of amines was developed. The advantages of this method were clearly reflected on mild reaction conditions and the significantly expanded scope (51 examples); both primary and steric secondary amines can be employed as substrates. The cooperative reactivity from Au and Cu centers, as an indispensable prerequisite for the excellent catalytic performance, was validated in the synthesis of (un)symmetric ureas and carbamates.

Polyoxometalate-Based Catalysts for CO2 Conversion.

Polyoxometalates (POMs) are a diverse class of anionic metal-oxo clusters with intriguing chemical and physical properties. Owing to unrivaled versatility and structural variation, POMs have been extensively utilized for catalysis for a plethora of reactions. In this focused review, the applications of POMs as promising catalysts or co-catalysts for CO2 conversion, including CO2 photo/electro reduction and CO2 as a carbonyl source for the carbonylation process are summarized. A brief perspective on the potentiality in this field is proposed.

Palladium-Catalyzed Carbonylative Multicomponent Reactions.

The achievements on palladium-catalyzed carbonylative multicomponent reactions (CMCR) have been summarized and discussed according to the type of carbonylation reaction involved.

Ligand- and Solvent-Tuned Chemoselective Carbonylation of Bromoaryl Triflates.

The palladium-catalyzed chemoselective carbonylation of bromoaryl triflates is reported. The selective C-Br bond versus C-OTf (OTf=triflate) bond functionalization can be remarkably tuned by the combination of the ligand [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) vs. 1,1'-bis(diphenylphosphino)ferrocene (DPPF)] and the solvent (toluene vs. DMSO). The respective ligand and solvent effects are rationalized by DFT calculations. In contrast, the monodentate ligands BuPAd2 and tBu3 P prefer the selective C-Br bond activation and are solvent insensitive.

Palladium-Catalyzed Carbonylative Four-Component Synthesis of Thiochromenones: The Advantages of a Reagent Capsule.

Multicomponent reactions, especially those involving four or even more reagents, have been a long-standing challenge because of the issues associated with balancing reactivity, selectivity, and compatibility. Herein, we demonstrate how the use of a reagent capsule provides straightforward access to synthetically valuable thiochromenone derivatives by a palladium-catalyzed carbonylative four-component reaction. To the best of our knowledge, this is the first example of applying a capsule to prevent catalyst poisoning and undesired side reactions of the multicomponent reaction.

Palladium-catalyzed dicarbonylative synthesis of tetracycle quinazolinones.

An interesting procedure for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-ones has been developed. Starting from commercially available 2-bromoanilines and 2-bromobenzyl amines, with the assistance of a palladium catalyst, the desired products were isolated in good yields. Notably, this procedure proceeded in a highly selective manner; two molecules of CO were incorporated into the substrates selectively.

Ligand-Controlled Regiodivergent Alkoxycarbonylation of Trifluoromethylthiolated Internal Alkynes.

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.

Synthesis of Chiral α-Aryl Ketones by Photoredox/Nickel-Catalyzed Enantioconvergent Acyl Cross-Coupling with Organotrifluoroborate.

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.

Thiol-Catalyzed Photodriven Stereoselective Hydrodifluoroacetylative Cyclization of Alkyne.

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.