Direct Function Method Research Articles

Copper-Nitroxyl-Catalyzed α-Oxygenation of Cyclic Secondary Amines Including Application to Late-Stage Functionalization.

Cyclic secondary amines are prominent subunits in pharmaceutical compounds. Methods for direct functionalization of N-unprotected/unsubstituted piperidines and related heterocycles have limited precedent despite their potential to impact medicinal chemistry and organic synthesis. Herein, we report a Cu/nitroxyl co-catalyzed method for direct conversion of cyclic secondary amines to the corresponding lactams via aerobic dehydrogenation and oxidative coupling with water. The mild reaction conditions tolerate diverse functional groups, enabling application to molecules that cover broad chemical space. The method is showcased in selective functionalization of building blocks and complex molecules, including late-stage functionalization of bromodomain inhibitors.

Carbene‐Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)−H Bonds

AbstractThe development of catalyst‐controlled methods for direct functionalization of two distinct C−H bonds represents an appealing approach for C−C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3)−H bonds employing readily available aldehyde as “acyl source” involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3)−H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho‐cyanoiodobenzene is essential in the oxidative radical N‐heterocyclic carbene catalysis to give a ketyl radical and C(sp3) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C−C formations in high efficiency under a metal‐ and light‐free catalytic conditions. Moreover, the prepared products show promising anti‐bacterial activities that shall encourage further investigations on novel agrochemical development.

Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)-H Bonds.

The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds represents an appealing approach for C-C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3)-H bonds employing readily available aldehyde as "acyl source" involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3)-H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp3) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C-C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.

Theoretical Investigation of Chemoselectivity between C-H Insertion and Amide Insertion in Intramolecular Rhodium-Carbene Reactions.

C-H insertion and amide insertion reactions using metal-carbene species provide a powerful synthetic method for direct functionalization of kinetically inert or thermodynamically stable chemical bonds. Our group previously developed an amide insertion reaction using a rhodium-dimer complex, constructing an array of nitrogen-bridged heterocycles. Another research group reported C-H insertion reactions using structurally related substrates and rhodium catalysts. Detailed mechanistic studies were not provided, however, and therefore, the origin of the chemoselectivity was ambiguous. Here we describe our theoretical investigation of the chemoselectivity between the amide insertion reaction and C-H functionalization. An energy gap of the identified transition states in the reaction coordinates could support the reported experimental results and the observed chemoselectivity. Moreover, frontier molecular orbital analysis revealed that functionalities adjacent to the metal-carbene species could affect orbital populations and their energy levels, resulting in the construction of a completely distinctive ring system.

Modular preparation of cationic bipyridines and azaarenes via C-H activation.

Bipyridines are ubiquitous in organic and inorganic chemistry because of their redox and photochemical properties and their utility as ligands to transition metals. Cationic substituents on bipyridines and azaarenes are valuable as powerful electron-withdrawing functionalities that also enhance solubility in polar solvents, but there are no general methods for direct functionalization. A versatile method for the preparation of trimethylammonium- and triarylphosphonium-substituted bipyridines and azaheterocycles is disclosed. This methodology showcases a C-H activation of pyridine N-oxides that enables a highly modular and scalable synthesis of a diverse array of cationically charged azaarenes. The addition of trimethylammonium functionalities on bipyridine derivatives resulted in more anodic reduction potentials (up to 700 mV) and increased electrochemical reversibility compared to the neutral unfunctionalized bipyridine. Additonally, metallation of 4-triphenylphosphinated biquinoline to make the corresponding Re(CO)3Cl complex resulted in reduction potentials 400 mV more anodic than the neutral derivative.

Various dynamic behaviors to the (2+1)-dimensional Nizhnik–Novikov–Veselov equations in incompressible fluids

In this paper, under investigation is the (2+1)-dimensional Nizhnik–Novikov–Veselov equations. The breather wave solutions are derived via the three-wave method. The double-periodic soliton solutions are studied based on a direct function method. Furthermore, the interaction solutions of the lump and periodic waves are investigated by a special function consist of the quadratic polynomial functions and periodic functions. At the same time, we also choose some specific examples to illustrate the dynamic behaviors of nonlinear waves.

Suzuki-Miyaura Coupling, Heck Alkenylation, and Amidation of DMTr-Protected 5-Iodo-2'-Deoxyuridine via Palladium-catalyzed Reactions.

Modification of nucleosides via cross-coupling processes has been carried out extensively on unprotected halonucleosides to produce functionalized nucleosides that are often developed for incorporation into oligonucleotides or used as fluorescent probes. This approach requires protection of the 5'-OH with the 4,4'-dimethoxytrityl (DMTr) group, which is complicated and a common cause of reaction failure. Here we report a method for direct functionalization of 5'-O-DMTr-5-iodo-2'-deoxyuridine via Suzuki-Miyaura cross-coupling, Heck alkenylation, and carboamidation. This approach facilitates rapid synthesis of a variety of C5-substituted 5'-O-DMTr-2'-deoxyuridine derivatives. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of the SerrKap palladacycle complex Basic Protocol 2: Suzuki-Miyaura coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 3: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 4: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine with Ruth linker using Pd(OAc)2 /PTABS Basic Protocol 5: Carbonylative amidation of 5'-O-DMTr-5-iodo-2'-deoxyuridine using Pd(OAc)2 /PTABS.

N-Hydroxybenzimidazole as a structurally modifiable platform for N-oxyl radicals for direct C-H functionalization reactions.

Methods for direct functionalization of C-H bonds mediated by N-oxyl radicals constitute a powerful tool in modern organic synthesis. While several N-oxyl radicals have been developed to date, the lack of structural diversity for these species has hampered further progress in this field. Here we designed a novel class of N-oxyl radicals based on N-hydroxybenzimidazole, and applied them to the direct C-H functionalization reactions. The flexibly modifiable features of these structures enabled facile tuning of their catalytic performance. Moreover, with these organoradicals, we have developed a metal-free approach for the synthesis of acyl fluorides via direct C-H fluorination of aldehydes under mild conditions.

Facile covalent functionalization of carbon nanotubes via Diels-Alder reaction in deep eutectic solvents

Deep eutectic solvents (DESs), a new type of cost-effective ionic liquid analogues, were employed to develop a novel and efficient method for direct functionalization of multiwalled carbon nanotubes (MWNTs) via Diels-Alder (DA) click reaction. Poly(ionic liquid)s featuring furfuryl moieties (P(F-ILs)) and butyl moieties (P(B-ILs)) were synthesized by the functionalization of poly(chloromethylstyrene-alt-maleic anhydride) with 1-methylimidazole and furfuryl amine or butylamine. Then, the polymer was directly grafted on the surface of untreated MWNTs in choline:ethylene glycol (ChCl:EG) based DES without any catalyst. The successful functionalization of the polymer on MWNTs was confirmed by Raman spectroscopy, TGA, and XPS analysis. It was shown that the reaction proceeded in a very rapid fashion (less than an hour) and the use of DESs significantly improved the grafting density (more than double) as compared with the reaction in water.

Fluoride-Catalyzed Esterification of Amides.

In recent years, it has been demonstrated that amide carbon-nitrogen bonds can be activated and selectively cleaved using transition metal catalysts. However, these methodologies have been restricted to specific amides; a one-to-one relationship exists between the catalytic system and the amides and also uses large amounts of transition-metal catalysts and ligands. Hence, we now report a general strategy for esterification of common amides using fluoride as a catalyst. This method shows high functional group tolerance, and notably it requires only a slight excess of the alcohol nucleophile, which is a rare case in transition-metal-free amide transformations. Moreover, this approach may provide a new understanding for further studies on esterification of amides and is expected to stimulate the development of alternative methods for direct functionalization of amides.

Advancement in Cascade [1,n]‐Hydrogen Transfer/Cyclization: A Method for Direct Functionalization of Inactive C(sp3)H Bonds

AbstractThe cascade [1,n]‐hydrogen transfer/cyclization, recognized one century ago, has received considerable interest in recent decades and great achievements have been made. This cascade process can functionalize C(sp3)H bonds directly into CC, CN, CO bonds under the catalysis by Lewis acids, Brønsted acids or organocatalysts, and even under thermal conditions. This methodology has shown preeminent power to construct 5‐ or 6‐membered heterocyclic as well as all‐carbon rings. In this review, various hydrogen donors and hydrogen acceptors are categorized and discussed.Abbreviations: Cbz: benzyloxycarbonyl; Cod: 1,5‐cyclooctadiene; CSA: camphorsulfonic acid; DCE: 1,1‐dichloroethane; DFT: density function theory; DMF: N,N‐dimethylformamide; DNBS: 2,4‐dinitrobenzenesulfonic acid; DPP: diphenyl phosphate; ERC: electrocyclic ring closure; Fmoc: 9‐fluorenylmethoxycarbonyl; HT: hydrogen transfer; IBX: ortho‐iodoxybenzoic acid; m‐CPBA: meta‐chloroperbenzoic acid; MW: microwave; MS: molecular sieves; Pg: protecting group; p‐TSA: para‐toluenesulfonic acid; r.t.: room temperature; TCE: 1,1,2‐trichloroethane; TFA: trifluoroacetic acid; TMS: trimethylsilyl.magnified image

ChemInform Abstract: Multifunctionalization of Alkenes via Aerobic Oxynitration and sp3 C—H Oxidation.

AbstractThe catalyst‐free aerobic oxynitration of different substrates is reported [13 examples].

Multifunctionalization of alkenes via aerobic oxynitration and sp3 C–H oxidation

A method for direct functionalization of three positions including an unactivated C-H bond of aliphatic alkenes using tert-butyl nitrite and molecular oxygen to give γ-lactols has been developed. The present reaction proceeds through a sequence of radical processes involving oxynitration followed by aerobic oxidation of an sp(3) C-H bond. This multifunctionalization reaction requires neither metallic reagents nor photolysis and proceeds under mild conditions.

A Study on Servo System of Radar Tracking Fast Targets

Reviewed the study of control method about radar servo in recent years, The most important thing is the non-linear improvement of the classical PID , including PID and fuzzy control combined; direct function method to construct NPID control; otherwise a weather radar servo system using the Bang-Bang control. On the basis of modern control theory, the new control strategy used in radar servo system is introduced to replay the new threat air defense in modern warfare; Establishing the state equations of the system and building state observer is to achieve the state feedback ; Utilizing the principle of optimality, fast and accurate indicators of the system converted to solve the optimized u in the state equation is to meet a new generation of high-quality performance of radar servo system.

Direct transition metal-catalyzed functionalization of heteroaromatic compounds.

During the last two decades there has been considerable growth in the development of catalytic reactions capable of activating unreactive C-H bonds. These methods allow for the synthesis of complex molecules from easily available and cheaper precursors in a fewer number of steps. Naturally, the development of C-H activation methods for direct functionalization of heterocyclic molecules, invaluable building blocks for pharmaceutical and synthetic chemistry and material science, has received substantial attention as well. This critical review summarizes the progress made in this field until November 2006 (117 references).