Copper-Catalyzed Intramolecular Olefinic C(sp2)-H Amidation for the Synthesis of γ-Alkylidene-γ-lactams.

Herein, we report the copper-catalyzed dehydrogenative C(sp2)-N bond formation of 4-pentenamides via nitrogen-centered radicals. This reaction provides a straightforward and efficient preparation method for γ-alkylidene-γ-lactams. Notably, we could controllably synthesize α,ß-unsaturated- or α,ß-saturated-γ-alkylidene-γ-lactams depending on the reaction conditions.

Transition-Metal-Free Intermolecular Hydrocarbonation of Styrenes Mediated by NaH/1,10-Phenanthroline.

A transition-metal-free intermolecular coupling reaction of halocompounds with styrenes in the presence of NaH and 1,10-phenanthroline was developed. This reaction afforded hydrocarbonated products with complete anti-Markovnikov selectivity. The method allows the use of a wide range of halocompounds, including aryl and alkyl halides, and good functional group tolerance. Detailed mechanistic studies indicated that an anilide anion generated in situ by the NaH-mediated reduction of 1,10-phenanthroline works as an electron donor and a hydrogen source.

Defluorinative Transformation of (2,2,2-Trifluoroethyl)arenes Catalyzed by the Phosphazene Base t-Bu-P2.

In this study, we demonstrated that 1-tert-butyl-2,2,4,4,4-pentakis(dimethylamino)-2λ5,4λ5-catenadi(phosphazene) (t-Bu-P2) catalyzes the defluorinative functionalization reactions of (2,2,2-trifluoroethyl)arenes with alkanenitriles to produce monofluoroalkene products. The reaction proceeds through HF elimination from a (2,2,2-trifluoroethyl)arene to form a gem-difluorostyrene intermediate, which is followed by nucleophilic addition of an alkanenitrile and elimination of a fluoride anion. The catalysis is compatible with a variety of functional groups.

LiHMDS-Mediated Deprotonative Coupling of Toluenes with Ketones.

We demonstrate that lithium hexamethyldisilazide (LiHMDS) acts as an effective base for deprotonative coupling reactions of toluenes with ketones to afford stilbenes. Various functionalities (halogen, OCF3 , amide, Me, aryl, alkenyl, alkynyl, SMe, and SPh) are allowed on the toluenes. Notably, this system proved successful with low-reactive toluenes bearing a large pKa value compared to that of the conjugate acid of LiHMDS (hexamethyldisilazane, 25.8, THF), as demonstrated by 4-phenyltoluene (38.57, THF) and toluene itself (∼43, DMSO).

Palladium-Catalyzed Borylative Cyclizations of α-(2-Bromoaryl) Ketones to Form 1,2-Benzoxaborinines.

Herein, we report that palladium catalyzes the borylative cyclization of α-(2-bromoaryl) ketones to afford 1,2-benzoxaborinines. The developed system is compatible with a variety of functionalities (Me, t-Bu, OMe, NMe2, F, Cl, CN, CF3, CO2Me, and heteroaryl groups) and is applicable to the synthesis of B-O-containing tri- and tetracyclic fused-ring compounds.

Combined Brønsted Base-Promoted CO2 Fixation into Benzylic C-H Bonds of Alkylarenes.

Interest in developing methods for direct CO2 fixation into readily available unfunctionalized C-H bonds in organic substances has recently surged. In contrast to the well-studied carboxylations of alkynyl C(sp)-H and aromatic C(sp2)-H bonds, carboxylation of benzylic C(sp3)-H bonds to produce 2-arylacetic acids is limited to photoirradiation reactions and continues to be a challenging issue because of the low chemical reactivity. We herein describe that a combined Brønsted base (i.e., LiO-t-Bu/CsF and LiOCEt3/CsF) achieves benzylic carboxylation of electron-deficient, -neutral, and -rich alkylarenes and enables various functionalities, including fragile ones such as bromide, alkene, alkyne, and carbonyl moieties. Dicarboxylation at the benzylic position is also established. Cs-alkoxide generated in situ acts as a reactive base, as demonstrated in experiments with independently prepared CsO-t-Bu and by 133Cs nuclear magnetic resonance studies.

Copper-catalyzed aerobic benzylic C(sp3)-H lactonization of 2-alkylbenzamides via N-centered radicals.

Herein, we describe the copper-catalyzed aerobic C(sp3)-H functionalization of 2-alkylbenzamides for the synthesis of benzolactones. This reaction proceeds via 1,5-hydrogen atom transfer of N-centered radicals directly generated by N-H bond cleavage and does not require the synthesis of pre-functionalized N-centered radical precursors or the use of strong stoichiometric oxidants.

Direct C-H Carboxylation Forming Polyfunctionalized Aromatic Carboxylic Acids by Combined Brønsted Bases.

CO2 fixation into electron-deficient aromatic C-H bonds proceeds with the combined Brønsted bases LiO-t-Bu and LiO-t-Am/CsF/18-crown-6 (t-Am = CEtMe2) under a CO2 atmosphere to afford a variety of polyfunctionalized aromatic carboxylic acids.

Construction of 1,2,3-Benzodiazaborole by Electrophilic Borylation of Azobenzene and Nucleophilic Dialkylative Cyclization.

1,2,3-Benzodiazaboroles can be conveniently prepared from azobenzenes by a two-step protocol involving electrophilic ortho-borylation with BBr3 and dialkylative cyclization with the Grignard reagent. The methodology provides a diverse range of products equipped with functionalities from azobenzenes containing substituents (Me, t-Bu, F, Cl, Br, I, and OCF3) and a series of Grignard reagents (alkyl- and arylmagnesium reagents). Moreover, this study displays the moderate aromaticity of the B-N-N-containing five-membered ring and mechanistic investigations of the cyclization reaction.

Regio- and Stereoselective Hydroiodination of Internal Alkynes with Ex Situ-Generated HI.

Herein, we report an efficient and practical hydroiodination of internal alkynes using HI generated ex situ from the readily available triethylsilane and I2. This system offers high regio- and stereoselectivity to afford (E)-vinyl iodides in good yields under mild conditions. Furthermore, the hydroiodination reaction shows high functional group tolerance toward alkyl, methoxy, halogen, trifluoromethyl, cyano, ester, halomethyl, acid-sensitive silyl ether, and acetal moieties.

Copper-catalyzed aerobic double functionalization of benzylic C(sp3)-H bonds for the synthesis of 3-hydroxyisoindolinones.

A copper-catalyzed aerobic 3-hydroxyisoindolinone synthesis was developed via the benzylic double C(sp3)-H functionalization of 2-alkylbenzamides. In this reaction, molecular oxygen was used as both an oxidant for C(sp3)-H functionalization and an oxygen source. Our method can be extended to diverse benzylic C(sp3)-H bonds and shows excellent functional group tolerance.

Catalytic amide base system generated in situ for 1,3-diene formation from allylbenzenes and carbonyls.

The amide base generated in situ from tetramethylammonium fluoride and N(TMS)3 catalyzes the synthesis of 1,3-diene from an allylbenzene and carbonyl compound. The system is applicable to the transformations of a variety of allylbenzenes with functional groups (halogen, methyl, phenyl, methoxy, dimethylamino, ester, and amide moieties). Acyclic and cyclic diaryl ketones, pivalophenone, pivalaldehyde, and isobutyrophenone are used as coupling partners. The role of transß-methyl stilbenes in product formation is also elucidated.

Di-tert-butyl Peroxide (DTBP)-Mediated Oxysilylation of Unsaturated Carboxylic Acids for the Synthesis of Silyl Lactones.

Herein, we describe the first oxysilylation of unsaturated carboxylic acids mediated by di-tert-butyl peroxide (DTBP), which enables the rapid and efficient preparation of silyl lactone compounds. This process tolerates functional groups, such as methyl, methoxy, halogen (fluoride and chloride), and cyano moieties. Furthermore, the strategy allows the application of a wide range of primary, secondary, and tertiary hydrosilanes for functionalization.

Catalytic C(sp2)-C(sp3) Bond Formation of Methoxyarenes by the Organic Superbase t-Bu-P4.

The organic superbase catalyst t-Bu-P4 achieves nucleophilic aromatic substitution of methoxyarenes with alkanenitrile pronucleophiles. A variety of functional groups [cyano, nitro, (non)enolizable ketone, chloride, and amide moieties] are allowed on methoxyarenes. Moreover, an array of alkanenitriles with/without an aryl moiety at the nitrile α-position can be employed. The system also features no requirement of a stoichiometric base, MeOH (not salt waste) formation as a byproduct, and the production of congested quaternary carbon centers.

NaH-mediated direct C-H arylation in the presence of 1,10-phenanthroline.

Transition-metal-free coupling of haloarenes with unactivated arenes has been developed in the presence of NaH and 1,10-phenanthroline. Various haloarenes bearing methyl, methoxy, halogen (fluoride, chloride, and bromide), cyano, trifluoromethyl, ester, and amide groups can be cross-coupled with unactivated arenes, or heteroarenes in this reaction.

Copper-Catalyzed Oxidative Benzylic C(sp3 )-H Cyclization for the Synthesis of ß-Lactams.

ß-Lactams are important structural motifs because of their ubiquity in natural products and pharmaceuticals. We report herein a Cu-catalyzed intramolecular oxidative C(sp3 )-H amidation for the synthesis of ß-lactams using tBuOOtBu. This method is based on Kharasch-Sosnovsky amidation and does not require prefunctionalization of C(sp3 )-H bonds or the installation of a directing group, thereby allowing for the straightforward synthesis of ß-lactams. Our intramolecular functionalization protocol can be extended to diverse benzylic C(sp3 )-H bonds and shows excellent functional-group tolerance.

Deprotonative Coupling of Pyridines with Aldehydes Catalyzed by an HMDS-Amide Base Generated in Situ.

Herein, the deprotonative functionalization of pyridine derivatives with aldehydes under ambient conditions has been demonstrated using an amide base generated in situ from a catalytic amount of CsF and a stoichiometric amount of tris(trimethylsilyl)amine (N(TMS)3). Pyridine substrates bearing two electron-withdrawing substituents (i.e., fluoro, chloro, bromo, and trifluoromethyl moieties) at the 3- and 5-positions efficiently react at the 4-position with various aldehydes including arylaldehydes, pivalaldehyde, and cyclohexanecarboxaldehyde.

Tetramethylammonium Fluoride Tetrahydrate-Mediated Transition Metal-Free Coupling of Aryl Iodides with Unactivated Arenes in Air.

Biaryls are important compounds with widespread applications in many fields. Tetramethylammonium fluoride tetrahydrate was found to promote the biaryl coupling of aryl iodides bearing electron-withdrawing substituents with unactivated arenes. The reaction takes place at temperatures between 100 and 150°C and can be applied to a wide range of aromatic and heteroaromatic rings, affording the products in moderate to high yields. The reaction does not require strong bases or expensive additives that are employed in the existing methods and can be conducted in air and moisture without any precautions.

Super electron donor-mediated reductive desulfurization reactions.

The desulfurization of thioacetals and thioethers by a pyridine-derived electron donor is described. This methodology provides efficient access to the reduced products in high yields and does not require the use of transition-metals, elemental alkali-metals, or hydrogen atom donors.

Catalytic Amination of ß-(Hetero)arylethyl Ethers by Phosphazene Base t-Bu-P4.

We describe the catalytic amination of ß-(hetero)arylethyl ethers with amines using the organic superbase t-Bu-P4 to obtain ß-(hetero)arylethylamines. The reaction has a broad substrate scope and allows the transformations of electron-deficient and electron-neutral ß-(hetero)arylethyl ethers with various amines including pyrrole, N-alkylaniline, diphenylamine, aniline, indole, and indoline derivatives. Mechanistic studies indicate a two-reaction pathway of MeOH elimination from the substrate to form a (hetero)arylalkene followed by the hydroamination of the alkene.