Ruthenium-Catalyzed Meta-Selective Trifluoroisopropylation of Arenes.

This work reports the mild and efficient Ru-catalyzed trifluoroisopropylation of arenes using 2-bromo-1,1,1-trifluoropropane. Various bioactive molecules, such as purine and nucleoside derivatives, were well-suited for this transformation, affording the corresponding products in moderate-to-good yields. This method provides an efficient strategy for synthesizing trifluoroisopropyl molecules for drug discovery.

A Novel Approach to α-Arylacetonitrile Skeletons via para-Selective Alkylation of Protected Anilines.

A ruthenium-catalyzed para-selective alkylation of protected anilines to construct α-arylacetonitrile skeletons has been reported. We firstly disclosed the ethyl 2-bromo-2-cyanopropanoate was an effective alkylating reagent in ruthenmuim-catalyzed remote-selective C-H functionalization. A wide variety of α-arylacetonitrile skeletons can be directly obtained with moderate to good yields. Importantly, the products contain both nitrile and ester groups guaranteeing its direct transformation into other useful synthetic units, indicating the synthetic importance of this method.

Palladium-Catalyzed E-Selective Oxidative Amination of Aromatic Amine with 3-Butenoic Acid.

A palladium-catalyzed oxidative amination of inactive olefins with an aromatic amine was developed using a copper acetate oxidant to yield corresponding secondary and tertiary enamines in moderate to good yields. This new procedure outlines an efficient approach for the construction of enamine skeletons.

Organic photoredox-catalyzed oxidative azolation of unactivated fluoroarenes.

Inexpensive and commercially available 2,4,6-triphenylpyrrolium tetrafluoroborate (TPT) is used as an organic photocatalyst for the nucleophilic aromatic substitution of unactivated fluoroarenes with pyrazole derivatives (SNAr) to form azole arenes. The use of organic photoredox catalysis enables the easy operation of this method under mild conditions. Various fluorinated aromatic compounds are suitable electrophiles for this transformation.

Visible-Light-Induced para-Difluoroalkylation of Aniline Derivatives.

Visible-light-induced, iridium catalyzed, para-selective C-H difluoroalkylation of aniline derivatives under mild reaction conditions is reported. Various substrates and bioactive compounds, such as precursors of vorinostat and chlorpropham, were all well tolerated. This protocol features a wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.

A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light.

This work presents a palladium-catalyzed oxime ether-directed ortho-selective benzoylation using benzoylformic acid as the acyl source with a palladium catalyst and 4CzIPN as the co-catalyst under light. Various non-symmetric benzophenone derivatives were obtained in moderate to good yields. A preliminary mechanism study revealed that the reaction proceeds through a free radical pathway.

Ligand Promoted Olefination of Anilides for Indirectly Introducing Fluorinated Functional Groups via Palladium Catalyst.

We report a palladium-catalyzed, ligand promoted, C-H fluorine-containing olefination of anilides with 4-bromo-3,3,4,4-tetrafluorobutene as the fluorinated reagent, which has a potential transformation into other compounds due to its -CF2CF2Br functional group. -CF2CF2H was obtained by using the mild reducing agent sodium borohydride. Bioactive compounds such as aminoglutethimide derivative and propham were well-tolerated in this reaction, both of which highlight the synthetic importance of this method.

Direct para-Selective C-H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines.

Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C-H amination reaction.

Photoredox-Catalyst-Enabled para-Selective Trifluoromethylation of tert-Butyl Arylcarbamates.

The direct incorporation of a trifluoromethyl group on an aromatic ring using a radical pathway has been extensively investigated. However, the direct highly para-selective C-H trifluoromethylation of a class of arenes has not been achieved. In this study, we report a light-promoted 4,5-dichlorofluorescein (DCFS)-enabled para-selective C-H trifluoromethylation of arylcarbamates using Langlois reagent. The preliminary mechanistic study revealed that the activated organic photocatalyst coordinated with the arylcarbamate led to para-selective C-H trifluoromethylation. Ten-gram scale reaction performs well highlighting the synthetic importance of this new protocol.

Iron-Catalyzed Highly para-Selective Difluoromethylation of Arenes.

Direct functionalization of a C-H bond at either the meta or para position by only changing the catalyst system poses a significant challenge. We herein report the [Fe(TPP)Cl]-enabled, selective, C-H difluoromethylation of arenes using BrCF2CO2Et as the difluoromethylation source, which successfully altered the selectivity from the meta to the para position. A preliminary mechanistic study revealed the iron porphyrin complex not only activated the aromatic ring but also induced para selectivity due to the influence of ligand sterics.

Palladium-Catalyzed Para-Selective Difluoromethylation of Arene Esters.

Highly efficient, palladium-catalyzed, para-selective difluoromethylation of arene esters has been developed using [1,1'-biphenyl]-2-dicyclohexylphosphine as the effective ligand. A wide variety of arene esters bearing various functional groups were all compatible with the reaction conditions, leading to para-difluoromethylated products in moderate to good yields. Moreover, benzoylamide and benzenesulfonamide were also well-tolerated, suggesting that this novel catalyst system has broad applications to a variety of substrates.

Ruthenium-Catalyzed Meta-Selective C-H Difluoromethylation of Phenol Derivatives.

With pyrimidine as the directing group, we achieved the meta-selective difluoromethylation of phenol derivatives using ruthenium as a catalyst. This synthetic scheme provided an efficient method for the syntheses of fluorine-containing phenol derivatives. A wide variety of phenol derivatives were well-suited, affording the corresponding products in moderate-to-good yields.

Mn-Enabled Radical-Based Alkyl-Alkyl Cross-Coupling Reaction from 4-Alkyl-1,4-dihydropyridines.

Highly efficient alkylation of ß-chloro ketones and their derivatives was achieved by means of domino dehydrochlorination/Mn-enabled radical-based alkyl-alkyl cross-coupling reaction. In situ-generated α,ß-unsaturated ketones and their analogues were identified as the reaction intermediates. Known bioactive compounds, such as melperone and azaperone, could be easily prepared from ß-chloropropiophenone in two steps.

A Ligand-Enabled Palladium-Catalyzed Highly para-Selective Difluoromethylation of Aromatic Ketones.

A practical and highly para-selective C-H difluoromethylation of aromatic ketones has been developed by employing tetrakis(triphenylphosphine)palladium(0) as the catalyst and triphenylphosphine as the ligand. In addition to general aromatic ketones, this transformation was compatible with bioactive compounds and well-known drugs, such as oxybenzone, ketoprofen, zaltoprofen, and propafenone. Moreover, a mechanistic study revealed that a palladium intermediate coordinated by a carbonyl group promotes highly para-selective difluoromethylation.

Ruthenium(II)-Catalyzed C-H Difluoromethylation of Ketoximes: Tuning the Regioselectivity from the meta to the para Position.

A highly para-selective CAr -H difluoromethylation of ketoxime ethers under ruthenium catalysis has been developed. A wide variety of ketoxime ethers are compatible with the reaction, which leads to the corresponding para-difluoromethylated products in moderate to good yield. A mechanistic study clearly showed that chelation-assisted cycloruthenation is the key factor in the para selectivity of the difluoromethylation of ketoxime ethers. Density functional theory was used to gain a theoretical understanding of the para selectivity.

Ruthenium-Catalyzed Carbonylation of Oxalyl Amide-Protected Benzylamines with Isocyanate as the Carbonyl Source.

An efficient synthesis of isoindolin-1-ones from oxalyl amide-protected benzylamines, through ruthenium-catalyzed intramolecular C(sp2)-H carbonylation, has been developed. Variously substituted benzylamines could be well tolerated in this new protocol, affording the corresponding products in moderate to excellent yields. This approach constitutes the first example of Ru(II)-catalyzed C(sp2)-H carbonylation with isocyanate as a novel commercially available carbonyl source.

Pd-Catalyzed regioselective sequential meta-, ortho-C-H functionalization of arenes: a predictable approach to the synthesis of polysubstituted ß-arylethylamines.

With the assistance of the same bidentate directing group, the first example of sequential, controllable C-H functionalization of ß-arylethylamines at different positions for the construction of polysubstituted arenes is reported. Pd-Catalyzed highly regioselective ortho-C-H functionalization reactions of meta-aryl substituted arylethylamines are performed, including alkynylation, iodination, acetoxylation and amination, which led to a concise approach to the synthesis of polysubstituted ß-arylethylamine derivatives.

Palladium-Catalyzed Carbonylation of ß-Arylethylamide Directed by Oxalyl Amide in the Presence of Carbon Monoxide.

Pd-catalyzed regioselective coupling of ß-C(sp(2))-H bonds in aromatic amines protected by oxalyl amide with carbon monoxide is reported. The reaction could tolerate various functional groups and could afford good to excellent yields of the corresponding 3,4-dihydroisoquinolinone derivatives. Remarkably, it could also tolerate ß-arylethylamino acid and thiopheneethylamine derivatives, thus showing their potential for producing several important units for bioactive compound synthesis.

Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.

Palladium(II)-Catalyzed Acetoxime Directed ortho-Arylation of Aromatic Alcohols.

Biaryls, which contained a benzyloxy motif, were directly constructed through a ligand-promoted Pd(II) -catalyzed ortho-arylation of masked aromatic alcohols. A variety of acetoxime ethers could be coupled with a diverse range of arylboronic acid pinocol esters, giving direct access to bioactive biaryls in modest to good yield. Not only could acetoxime be subsequently removed without a separation, functionalized hydroxylamine derivatives could also be obtained.