Cross-dehydrogenative coupling of secondary benzylic ethers with indoles and pyrroles

Current studies on cross-dehydrogenative coupling of benzylic ethers for new C–C bond construction predominantly focus on primary ether moieties. Oxidative cross-coupling of secondary benzylic ethers remains elusive. Herein, we describe the first cross-dehydrogenative coupling of secondary benzylic ethers with indoles and pyrroles for tertiary ether construction. A broad range of α-aryl substituted isochromans react with a variety of electronically varied indoles and pyrroles smoothly under mild metal-free conditions in high efficiency. In addition, the catalytic asymmetric variant was preliminarily explored, and corresponding tertiary ether was obtained in 69% ee.     

Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy

The first redox deracemization of a series of cyclic benzylic ethers, including 6H ‐benzo[c ]chromenes, isochromans, and 1H ‐isochromenes, is described. An “acetal pool” strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.     

Oxidative C -H alkynylation of 3,6-dihydro-2H-pyrans

Current synthesis of α-substituted 3,6-dihydro-2H-pyrans dominantly relies on functional group transformation. Herein, a direct and practical oxidative C-H alkynylation and alkenylation of 3,6-dihydro-2H-pyran skeletons with a range of potassium trifluoroborates is developed. The metal-free process is well tolerated with a wide variety of 3,6-dihydro-2H-pyrans, rapidly providing a library of 2,4-disubstituted 3,6-dihydro-2H-pyrans with diverse patterns of α-functionalities for further diversification and bioactive small molecule identification.     

Oxidative Kinetic Resolution of Cyclic Benzylic Ethers

A manganese‐catalyzed oxidative kinetic resolution of cyclic benzylic ethers through asymmetric C(sp³)?H oxidation is reported. The practical approach is applicable to a wide range of 1,3‐dihydroisobenzofurans bearing diverse functional groups and substituent patterns at the α position with extremely efficient enantiodiscrimination. The generality of the strategy was further demonstrated by efficient oxidative kinetic resolution of another type of five‐membered cyclic benzylic ether, 2,3‐dihydrobenzofurans, and six‐membered 6H‐benzo[c]chromenes. Direct late‐stage oxidative kinetic resolution of bioactive molecules that are otherwise difficult to access was further explored.     

The synthesis of unique structures of tetra-crown ethers through Michael addition

Unique structures of tetra-crown ethers were successfully synthesized by the reaction of tetramethylolmethane tetraacrylate (TMMT) reacted with crown ethers containing primary amine functional group such as 2-aminomethyl crown ethers and 4-aminobenzo crown ethers; containing secondary amine group like 1-aza crown ethers through Michael reaction. The newly synthesized tetra-crown ethers were characterized by ¹H NMR, ¹³C NMR, FAB mass spectrum, elemental analyses, IR, respectively.     

Mechanism of cooperative catalysis in a lewis Acid promoted nickel-catalyzed dual C-h activation reaction

The mechanism of cooperativity offered by AlMe(3) in a Ni-catalyzed dehydrogenative cycloaddition between substituted formamides and an alkyne is investigated by using DFT(SMD(toluene)/M06/6-31G**) methods. The preferred pathway is identified to involve dual C-H activation, with first a higher barrier formyl C(sp(2))-H oxidative insertion followed by benzylic methyl C(sp(3))-H activation. The cooperativity is traced to be of kinetic origin as evidenced by stabilized transition states when AlMe(3) is bound to the formyl group, particularly in the oxidative insertion step.     

Synthesis and Complexation Behavior Studies of Novel Bis-crown Ethers

The novel unique structures of bis-crown ethers were successfully synthesized from tri (propylene glycol) di-acrylate with amino- and aza-crown ethers through Michael addition. The crown ethers contained the primary and the secondary amine group such as 2-aminomethyl crown ethers, 4-aminobenzo crown ethers and 1-aza crown ethers. The newly synthesized bis-crown ethers were characterized by elemental analyses, IR, ¹H NMR, ¹³C NMR, mass spectrum, respectively. The newly synthesized host compounds of bis-crown ethers showed complex ability with various sizes of alkali metal cations such as Na⁺, K⁺, Rb⁺ and Cs⁺. The complexation behavior was examined by ¹H NMR spectroscopy and UV spectrometry.     

Ferric nitrate-catalyzed aerobic oxidation of benzylic sp3 CH bonds of ethers and alkylarenes

A simple catalytic oxidation system was developed for the selective aerobic oxidation of structurally diverse benzylic sp³ CH bonds of ethers and alkylarenes. The reactions were performed with Fe(NO₃)₃·9H₂O as the catalyst, KPF₆ as the additive and molecular oxygen as the terminal oxidant without any ligands. Under the optimal reaction conditions, a number of isochromans, xanthenes and thioxanthenes can be converted to their corresponding esters or ketones in good to excellent yields.     

Silver‐Promoted Oxidative Benzylic C−H Trifluoromethoxylation

A silver‐promoted oxidative benzylic C?H trifluoromethoxylation has been reported for the first time. With trifluoromethyl arylsulfonate as the trifluoromethoxylation reagent, various arenes, having diverse functional groups, undergo trifluoromethoxylation of their benzylic C?H bonds to form trifluoromethyl ethers under mild reaction conditions. In addition, the trifluoromethoxylation and the fluorination of methyl groups of electron‐rich arenes have been achieved to prepare α‐fluorobenzyl trifluoromethyl ethers in one step.     

Traceless directing group for stereospecific nickel-catalyzed alkyl-alkyl cross-coupling reactions

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic 2-methoxyethyl ethers are reported for the preparation of enantioenriched 1,1-diarylethanes. The 2-methoxyethyl ether serves as a traceless directing group that accelerates cross-coupling. Chelation of magnesium ions is proposed to activate the benzylic C-O bond for oxidative addition.     

Catalytic Enantioselective Oxidative Cross‐Coupling of Benzylic Ethers with Aldehydes

The first one‐pot enantioselective oxidative coupling of cyclic benzylic ethers with aldehydes has been developed. A variety of benzylic ethers were transformed into the corresponding oxygen heterocycles with high enantioselectivity. Mechanistic experiments were conducted to determine the nature of the reaction intermediates. The application of this strategy to coupling reactions with other nucleophiles besides aldehydes was also explored.     

羰基化合物在Si(100)表面[2+2]环加成和α-H裂解反应的选择性

最近研究表明: 丙酮能与半导体Si(100)表面发生[2+2]环加成和α-H 裂解反应形成相应的Si―C键或Si―O键, 在半导体材料的合成方面具有重要意义. 为进一步弄清不同羰基化合物在Si(100)表面的反应机理,本文应用密度泛函理论方法在B3LYP/6-311++G(d,p)//6-31G(d)水平上较为系统地研究了一系列羰基化合物CH₃COR (R=CH₃, H, C₂H₅, C₆H₅)与Si(100)表面的反应. 研究结果表明: 不论是[2+2]环加成反应还是α-H 裂解反应都对应较低的反应势垒(小于25 kJ·mol^-1); 环加成反应的势垒比α-H 裂解反应的势垒略高; 羰基上的取代基对反应势垒的影响较少; α-H裂解反应产物为动力学和热力学控制产物; 对丁酮来说, 1-位和3-位H原子的裂解反应都比较容易, 势垒相差很小. 这些结果表明羰基化合物与Si(100)表面的反应将得到多种产物.     

Copper-catalyzed selective benzylic C-O cyclization of N-o-tolylbenzamides: synthesis of 4H-3,1-benzoxazines

A novel Selectfluor-mediated copper-catalyzed highly selective benzylic C-O cyclization for the synthesis 4H-3,1-benzoxazines is reported. The predominant selectivity for a benzylic C(sp(3))-H over an aromatic C(sp(2))-H bond in N-o-tolylbenzamides is achieved.     

TBHP-Mediated Oxidative Cross-Coupling of Disulfides with Ethers through a C(sp3)-H Thiolation Process

A new tert-butyl hydroperoxide (TBHP)–mediated oxidative cross-coupling of disulfides with ethers is presented for the synthesis of etherified sulfides. This method is achieved by a C(sp³)-H thiolation strategy under metal-free conditions and provides a simple route to constructing the C-S bonds.     

Practical and Highly Selective C?H Functionalization of Structurally Diverse Ethers

A trityl ion mediated C H functionalization of ethers with a wide range of nucleophiles at ambient temperature has been developed. The reaction displays high chemoselectivity and good functional group tolerance. The protocol also exhibits excellent regio‐ and diastereoselectivities for the unsymmetric ethers, thus stereoselectively generating highly functionalized disubstituted 2,5‐trans tetrahydrofurans (THF), 2,6‐trans tetrahydropyrans (THP), 2,6‐trans dihydropyrans (DHP), and 1,3‐trans isochromans, and highlighting the capacity of the protocol in complex molecule synthesis.     

Chemoselective and Direct Functionalization of Methyl Benzyl Ethers and Unsymmetrical Dibenzyl Ethers by Using Iron Trichloride

Methyl and benzyl ethers are widely utilized as protected alcohols due to their chemical stability, such as the low reactivity of the methoxy and benzyloxy groups as leaving groups under nucleophilic conditions. We have established the direct azidation of chemically stable methyl and benzyl ethers derived from secondary and tertiary benzyl alcohols. The present azidation chemoselectively proceeds at the secondary or tertiary benzylic positions of methyl benzyl ethers or unsymmetrical dibenzyl ethers and is also applicable to direct allylation, alkynylation, and cyanation reactions, as well as the azidation. The present methodologies provide not only a novel chemoselectivity but also the advantage of shortened synthetic steps, due to the direct process without the deprotection of the methyl and benzyl ethers.     

Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected C(sp3)-H activation

A new strategy for generating benzylpalladium reactive species from toluenes via nondirected C(sp(3))-H activation has been developed. This led to construction of an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives from inexpensive, commercially available starting materials.     

Practical and Highly Selective CH Functionalization of Structurally Diverse Ethers

A trityl ion mediated C? H functionalization of ethers with a wide range of nucleophiles at ambient temperature has been developed. The reaction displays high chemoselectivity and good functional group tolerance. The protocol also exhibits excellent regio‐ and diastereoselectivities for the unsymmetric ethers, thus stereoselectively generating highly functionalized disubstituted 2,5‐trans tetrahydrofurans (THF), 2,6‐trans tetrahydropyrans (THP), 2,6‐trans dihydropyrans (DHP), and 1,3‐trans isochromans, and highlighting the capacity of the protocol in complex molecule synthesis.     

Palladium-Catalyzed Cascade Process Consisting of Isocyanide Insertion and Benzylic C(sp(3))-H Activation: Concise Synthesis of Indole Derivatives

Synthesis of the indole skeleton was achieved using a Pd-catalyzed cascade process consisting of isocyanide insertion and benzylic C(sp(3))-H activation. It was found that slow addition of isocyanide is effective for reducing the amount of catalyst needed and Ad(2)P(n)Bu is a good ligand for C(sp(3))-H activation. The construction of the tetracyclic carbazole skeleton was also achieved by a Pd-catalyzed domino reaction incorporating alkyne insertion.     

Lewis Acid Promoted Reactions. (IV.)1a,b Oxidation Deprotection of Trimethylsilyl Ethers with Silver and Sodium Bromates; AgBrO3, NaBrO3

Primary and secondary benzylic and saturated trimethylsilyl ethers are converted to their carbonyl compounds with AgBrO₃/AlCl₃ efficiently. p-Hydroquinonetrimethylsilyl ether is also converted with both AgBrO₃/AlCl₃ and NaBrO₃/AlCl₃ to p-benzoquinone. AgBrO₃/AlCl₃ is also able to oxidize primary trimethylsilyl ethers to their carboxylic acids. Primary and secondary benzylic trimethylsilyl ethers are also converted to their carbonyl compounds with NaBrO₃/AlCl₃; AgBrO₃ is more efficient and selective oxidant than NaBrO₃.