Palladium-catalyzed oxidative alkynylation of arene C–H bond using the chelation-assisted strategy

Palladium-catalyzed alkynylation of arene C–H bonds with (triisopropylsilyl)acetylene was developed for the first time under oxidative conditions in the present study. Among various type of directing groups examined, the N-phenyl-2-aminopyridine skeleton was shown to be most effective and selective for the Pd-catalyzed direct alkynylation reaction, and the desired alkynylated products were obtained in moderate to good yields.     

Palladium-catalyzed ortho-selective C–H bond chlorination of aromatic ketones

A palladium-catalyzed ortho-selective C–H bond chlorination reaction for the preparation of 2-chloro aromatic ketones was described. Both electron-withdrawing and electron-donating groups on the aromatic rings are well tolerated under the optimized conditions. The 2-chloro aromatic ketones obtained by our method could be applied to synthesize the derivatives of 1H-indazole or benzo[d]isoxazole.     

A new approach to the synthesis of α-chlorocycloalkanones

α-Chlorocycloalkanones(Ⅳ) were synthesized from cycloalkanones via potassiumα-oxocycloalkylsulfonates(Ⅱ).A two-step mechanism was proposed to explain the formation ofⅣfromⅡ.     

Dienyl esters synthesis: Palladium-catalyzed C–H olefination of electron-deficient alkenes with allenoates

The palladium(II)-catalyzed direct oxidative C–H olefination of readily available N-tosylacrylamides and allenoates for the synthesis of dienyl esters is described. The amide and ester moieties both act as the directing groups for the regio- and the stereo-controlled C–H functionalization/cyclization, which was proved by DFT calculations. Molecular oxygen was used as the terminal oxidant in the approach, rendering the reaction more sustainable.     

Palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes initiated by C–H activation

A novel palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes has been developed. The reaction proceeded through palladium-catalyzed vinyl C–H bond activation of enamides followed by two migratory insertions, β-(N)H elimination and hydrolyzation cascade steps. The reaction tolerates a range of functional groups and provides an effective method for the synthesis of cyclopropane-fused norbornanes in good yields under mild conditions.     

A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15–C16 bond formation

The esterification of fragment C1–C8 (2) with fragment C16–C23 (3) to give iodo derivative 4, followed by a Pd-catalysed coupling with a C9–C15 fragment (7 or 8), may provide a common precursor of most palmerolides. Ligands and reaction conditions were exhaustively examined to perform the C15–C16 bond formation via Negishi reaction. With simple models, pre-activated Pd–Xantphos and Pd–DPEphos complexes were the most efficient catalysts at RT. Zincation of the C9–C15 fragment (8) and cross coupling with 4 required 3 equiv of t-BuLi, 10 mol % of Pd–Xantphos and 60 °C.     

Studies towards the total synthesis of altohyrtin A: a convergent approach to the C38–C51 carbon framework

The first pyranose-based approach to the F ring (C38–C43) of altohyrtin A 1 together with a synthetic approach to the C44–C51 chloro diene unit of 1 is described.     

DDQ-mediated oxidation of sp C–H bond for the direct synthesis of vicinal tricarbonyl compounds

A facile and direct synthetic method was developed for the construction of vicinal tricarbonyl compounds (VTCs) in moderate to excellent yields (46–92%), by treating the readily available 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reaction pathway involves the DDQ-mediated oxidative activation of sp³ C–H bond and subsequent coupling to TEMPO to form the key intermediate TEMPO-substrate adduct, which can be further converted to VTC products promoted by DDQ.     

Copper-catalyzed C–N coupling/C–H functionalization: A tandem approach to azole-fused quinazoline derivatives

A Cu-catalyzed tandem synthesis of azole-fused pyrimido[1,2-c]quinazolines and imidazo[1,2-c]quinazolines has been developed. The reaction is based on a C–N cross-coupling/C–H functionalization reaction of 2-(2-bromophenyl)-1,4,5,6-tetrahydropyrimidines with azoles. A variety of the desired polycyclic products were obtained in moderate to excellent yields.     

Palladium-catalyzed oxidative C-H bond and C═C double bond cleavage: C-3 acylation of indolizines with α,β-unsaturated carboxylic acids

A novel palladium-catalyzed C-3 acylation of indolizines with α,β-unsaturated carboxylic acids via C-H bond and C═C double bond cleavage under oxidative conditions is described. The regioselectivity is assisted by the carboxylic group, and the selection of the oxidant is crucial to the reaction.     

C(sp<Superscript>3</Superscript>)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed. This method provides a new approach for C(sp³)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.     

C(sp~3)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed.This method provides a new approach for C(sp~3)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.     

Friedlander synthesis of highly functionalized isoxazolyl quinoline libraries via addition of C(sp3)–H bond to aldehydes

A novel protocol for ionic liquid (IL)-mediated C(sp³)–H bond functionalization of 3,5-dimethyl-4-nitroisoxazoles 4 to substituted o-amino benzaldehydes 5 was developed in excellent yields. Isoxazolyl aryl ethanones 7 have been synthesized from isoxazolyl aryl ethanol synthon 6. Furthermore, utilizing the later as synthons for IL promoted Friedlander synthesis of highly functionalized isoxazole substituted quinoline libraries 9. The merit of this synthesis is easily available and economical starting materials, effective utilization of all the reactants, and simple workup procedure. It is noteworthy that ionic liquid used in C(sp³)–H bond functionalization and Friedlander synthesis reactions can be recycled and reused five times without significant decrease in activity.     

A new application of Baylis–Hillman alcohols to a diastereoselective synthesis of 3-nitrothietanes

Three key reactions, the generation of a nucleophile, an thia-Michael addition and an intramolecular cyclisation, were used to achieve an efficient one-pot diastereoseletive synthesis of 3-nitrothietanes. Thus, Baylis–Hillman alcohols and their aldehydes were reacted with either O,O-diethyl hydrogen phosphorodithioate or O,O-diethyl hydrogen phosphorodithioate in combination with a task-specific ionic liquid [bmim]X–Y to afford the corresponding 2,3-di- or 2,3,4-trisubstituted thietanes, respectively. The reaction is high yielding and proceeds with complete diastereoselectivity in favour of the trans isomers.     

Stereoselective reduction of endocyclic carbon–nitrogen double bond: application to the synthesis of biomolecules

Recent advances in the stereoselective synthesis of nitrogen containing heterocyclic compounds using the reduction of endocyclic double carbon–nitrogen bond are surveyed.     

The development of a catalytic synthesis of münchnones: a simple four-component coupling approach to alpha-amino acid derivatives

A new palladium-catalyzed route to prepare 1,3-oxazolium-5-oxides (i.e., Münchnones) directly from imine, carbon monoxide, and acid chloride building blocks has been developed. This provides a straightforward catalytic synthesis of Münchnones and is amenable to generating a diverse range of products by simple modification of the imine or acid chloride starting materials. Münchnones are vital synthetic intermediates to a variety of heterocyclic and peptide-based molecules. As such, this methodology has been utilized to design a new catalytic synthesis of alpha-amino acid derivatives via a one-pot coupling of imines, carbon monoxide, and acid chloride followed by alcohol. The latter represents the first reported catalytic synthesis of alpha-amino acids directly from imine and carbon monoxide building blocks.     

Visible light promoted synthesis of N-aroylsulfoximines by oxidative C–H acylation of NH-sulfoximines

The visible light-promoted synthesis of N-aroylsulfoximines has been accomplished via an oxidative dehydrogenative coupling at room temperature under air without the addition of a photosensitizer, metal catalyst, or base. This process exhibits good functional group tolerance, allows facile isolation and purification, and affords N-aroylsulfoximines with high efficiency. The efficiency of the newly developed protocol is described in detail with 27 examples with yields ranging from 80% to 96%.Furthermore, the chirality of the NH-sulfoximine is completely maintained in the desired N-aroylsulfoximine product(99% ee).     

Palladium-catalyzed one-pot Suzuki–Miyaura cross coupling followed by oxidative lactonization: a novel and efficient route for the one-pot synthesis of benzo[c]chromene-6-ones

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Copper-catalyzed intermolecular C(sp3)–H bond functionalization towards the synthesis of tertiary carbamates

We describe the development of an intermolecular unactivated C(sp³)–H bond functionalization towards the direct synthesis of tertiary carbamates. The transformation proceeded using a readily available, abundant first-row transition metal catalyst (copper), and isocyanates as the source of the amide moiety. This is a novel strategy for direct transformation of a variety of unactivated hydrocarbon feedstocks to N-alkyl-N-aryl and N,N-dialkyl carbamates without pre-functionalization or installation of a directing group. The reaction had a broad substrate scope with 3° > 2° > 1° site selectivity. The reaction proceeded even on a gram scale, and a corresponding free amine was directly obtained when the reaction was performed at high temperature. Kinetic studies suggested that radical-mediated C(sp³)–H bond cleavage was the rate-determining step.