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.

Iridium-Catalyzed Ortho-Selective C-H Borylation of Aryl Ketones with Transient Imine Ligands.

Ortho-selective C-H borylation of aromatic ketones has not been extensively explored. Herein, we report the iridium-catalyzed ortho-selective C-H borylation of aromatic ketones using in situ-formed imine as the ligand. Good compatibility is observed for various substituted acetophenones and other aromatic ketones, and corresponding products are obtained with medium to excellent yields.

Trialkoxysilane-Induced Iridium-Catalyzed para-Selective C-H Bond Borylation of Arenes.

An ideal approach for the construction of aryl boron compounds is to selectively replace a C-H bond in arenes with a C-B bond, and controlling regioselectivity is one of the most challenging aspects of these transformations. Herein, we report an iridium-catalyzed trialkoxysilane protecting group-assisted regioselective C-H borylation of arenes, including derivatives of benzaldehydes, acetophenones, benzoic acids, benzyl alcohols, phenols, aryl silanes, benzyl silanes, and multi-functionalized aromatic rings are all well tolerated and gave the para -selective C-H borylation products in a short time without the requirement of inert gases atmosphere. The site-selective C-H borylation can be adjustable by installing the developed trialkoxysilane protecting group on different functional groups on one aromatic ring. Importantly, the preparation process of the trialkoxychlorosilane is efficient and scalable. Mechanistic and computational studies reveal that the steric hindrance of the trialkoxysilane protecting group plays a key role in dictating the para-selectivity.

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.

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.

A Bipyridine-Promoted Csp3 -Csp3 Coupling of beta-Chlorophenones.

A novel, direct Csp3 -Csp3 coupling reaction of ß-chlorophenone with alkanes using 2-(tert-butylperoxy)-2-methylpropane (DTBP) as the oxidant and 2,2'-bipyridine (bpy) as the effective additive was developed. A variety of ß-chloropropiophenones were well tolerated, and afforded alkylated products in moderate to good yields. A mechanistic study indicated a free radical pathway was involved in this alkyl-alkyl cross-coupling reaction.

Ligand-Promoted Fluorinated Olefination of Isatins at the C5 Position via a Palladium Catalyst.

A palladium-catalyzed nondirected fluorinated olefination was developed. The oxalyl amide ligand greatly improved the yield of the reaction. A wide variety of isatin derivatives were well tolerated and yielded the corresponding products in moderate to good yields. Various fluorinated olefins were also compatible. The application and synthesis of bioactive compounds such as a Metisazone derivative highlight the synthetic value of this approach.

A Bi(OTf)3-Promoted Hydrosulfonylation of Alkenes with Sulfonyl Hydrazides: An Approach to Branched Sulfones.

The Bi(OTf)3-promoted hydrosulfonylation of alkenes with sulfonyl hydrazides to produce branched sulfones is reported, in which various branched sulfones (>40 examples) have been prepared in moderate to good yields. The gram-scale reaction and synthesis of the experimental inhibitor precursor showed the potential application. A preliminary mechanistic study revealed that double-bond migration to form the α,ß-conjugated alkene is crucial for this transformation.

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 Nickel-Catalyzed para-Selective Carboxylation of Anisoles.

It has always been a challenge in free radical chemistry to control site selectivity during the reaction of free radicals with aromatic rings. Herein, we report the site-selective carboxylation of anisoles through the direct reaction of the bromoform radical with a benzene ring at the para position under the assistance of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline with nickel(II) as the catalyst. A wide variety of anisoles were compatible, leading to para-carboxylated products in moderate to good yields. A preliminary mechanistic study suggested that the Ni(II) complex coordinates with the methoxyl group of the aromatic ring, which may have increased the steric hindrance at the ortho and meta positions, while this weak interaction reduces the aromaticity of the aromatic ring, affording an activated phenyl ring, thereby leading to highly para-selective carboxylation.

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.

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.

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.

Palladium-Catalyzed Isoquinoline Synthesis by Tandem C-H Allylation and Oxidative Cyclization of Benzylamines with Allyl Acetate.

A novel approach to synthesize 3-methylisoquinolines via a one-pot, two-step, palladium(II)-catalyzed tandem C-H allylation/intermolecular amination and aromatization is reported. A wide series of 3-methylisoquinoline derivatives were obtained directly using this method in moderate to good yields, and we highlight the synthetic importance of this new transformation.

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.

Palladium-Catalyzed Direct C-H Arylation of 3-Butenoic Acid Derivatives.

We report herein a direct method to synthesize 4-aryl-3-butenoic acid through a carboxylic-acid-directed oxidative Heck reaction. The various 4-aryl-3-butenoic acids are easily prepared in moderate to good yields. In view of the promising bioactivity of 4-phenyl-3-butenoic acid previously reported, its derivatives reported here may be bioactive.

Copper(i)-catalyzed radical carboamination reaction of 8-aminoquinoline-oriented buteneamides with chloroform: synthesis of-ß-lactams.

A novel Cu(CH3CN)4PF6-catalyzed carboamination reaction of 8-aminoquinoline-oriented buteneamides with chloroform to afford 4-(2,2,2-trichloroethyl)-ß-lactams is described. The reaction proceeded at 110 °C in air with di-t-butyl peroxide. Preliminary studies indicated that the reaction undergoes a free radical mechanism via a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle.

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.

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.