Metal Reagents Research Articles

Transition-Metal-Free TBAI-Facilitated Addition-Cyclization of N-Methyl-N-arylacrylamides with Arylaldehydes or Benzenesulfonohydrazides: Access to Carbonyl- and Sulfone-Containing N-Methyloxindoles.

A highly efficient addition-cyclization of N-methyl-N-arylacrylamides with arylaldehydes or benzenesulfonohydrazides was developed using a catalytic amount of the quaternary ammonium salt (TBAI) under metal-free conditions, leading to the carbonyl- and sulfone-containing oxindoles. Compared to previous methods, which require excessive amounts of explosive organic peroxides and precious or toxic metal reagents, the present protocol, which gave access to 3,3-disubstituted oxindoles, is a safe and green approach, resulting in the formation of various useful carbonyl- and sulfone-containing oxindoles in yields of 40-94%.

ChemInform Abstract: Selective and Tunable Synthesis of 3‐Arylsuccinimides and 3‐Arylmaleimides from Arenediazonium Tetrafluoroborates and Maleimides.

AbstractApart from broad substrate scope and good functional‐group compatibility, the method provides the selective synthesis of two classes of products by simple switching different metal reagents.

Classical-Reaction-Driven Stereo- and Regioselective C(sp(3) )-H Functionalization of Aliphatic Amines.

A large variety of synthetic methods have been developed for the synthesis of functionalized aliphatic amines because of their broad spectrum of application. Metallic reagents/catalysts and/or toxic oxidants are involved in most of the cases. Direct CH functionalization of aliphatic amines via their classical condensation reactions with suitable carbonyl compounds is advantageous because this method avoids hazardous metallic reagents, toxic oxidants and pre-activation/pre-functionalization step(s). In this account, the concept of direct CH functionalization of aliphatic amines based on the classical condensation-isomerization-addition (CIA) strategy followed by recent contributions from our ongoing research in the field along with relevant examples from other groups are described. Successes in stereo- and regioselective CC and CO bond formation via direct α- as well as β-C(sp(3) )-H functionalization are discussed.

Structural Studies of Cesium, Lithium/Cesium, and Sodium/Cesium Bis(trimethylsilyl)amide (HMDS) Complexes.

Reacting cesium fluoride with an equimolar n-hexane solution of lithium bis(trimethylsilyl)amide (LiHMDS) allows the isolation of CsHMDS (1) in 80% yield (after sublimation). This preparative route to 1 negates the need for pyrophoric Cs metal or organocesium reagents in its synthesis. If a 2:1 LiHMDS:CsF ratio is employed, the heterobimetallic polymer [LiCs(HMDS)2]∞ 2 was isolated (57% yield). By combining equimolar quantities of NaHMDS and CsHMDS in hexane/toluene [toluene·NaCs(HMDS)]∞ 3 was isolated (62% yield). Attempts to prepare the corresponding potassium-cesium amide failed and instead yielded the known monometallic polymer [toluene·Cs(HMDS)]∞ 4. With the aim of expanding the structural diversity of Cs(HMDS) species, 1 was reacted with several different Lewis basic donor molecules of varying denticity, namely, (R,R)-N,N,N',N'-tetramethylcyclohexane-1,2-diamine [(R,R)-TMCDA] and N,N,N',N'-tetramethylethylenediamine (TMEDA), N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDETA), tris[2-(dimethylamino)ethyl]amine (Me6-TREN) and tris[2-(2-methoxyethoxy)ethyl]amine (TMEEA). These reactions yielded dimeric [donor·NaCs(HMDS)2]2 5-7 [where donor is (R,R)-TMCDA, TMEDA and PMDETA respectively], the tetranuclear "open"-dimer [{Me6-TREN·Cs(HMDS)}2{Cs(HMDS)}2] 8 and the monomeric [TMEEA·Cs(HMDS)] 9. Complexes 2, 3, and 5-9 were characterized by X-ray crystallography and in solution by multinuclear NMR spectroscopy.

Synthesis, Structure and Chemical Vapour Deposition Studies on the Group 13 Complexes [Me2M­{tfacnac}] [M = Al, Ga, In; Htfacnac = F3CC(OH)CHC(CH3)NCH2CH2OCH3

AbstractA family of group 13 metal dimethyl complexes of the general formula [Me2M{MeC(O)CHC(NCH2CH2OMe)CF3}] [M = Al (2), Ga (3) or In (4)] was synthesised by reaction of the isolated free ligand 1 with the corresponding trimethyl metal reagents. The isolated complexes 2–4 were characterised by elemental analysis and NMR spectroscopy, and the molecular structures of the complexes were determined by single‐crystal X‐ray diffraction, which revealed them to be monomeric five‐coordinate complexes with coordination of the pendent ether‐bearing lariat in the solid state. Thermogravimetric analysis showed complexes 2–4 all to have residual masses at 200 °C of 2.4 % or less, well below the value for the respective metal oxides, and vapour pressure measurements showed the indium complex 4 to be an order of magnitude less volatile (0.09 Torr at 80 °C) than the Al (2) and Ga (3) analogues, despite their being isoleptic systems. Complexes 2–4 were investigated for their utility in the low‐pressure metal organic chemical vapour deposition of the respective metal oxides in the absence of additional oxidant at 400 °C on silicon substrates.

ChemInform Abstract: Catalytic, Stereoselective Dihalogenation of Alkenes: Challenges and Opportunities

AbstractReview: [235 refs.

ChemInform Abstract: Synthesis of Cyclic Alkenyl Triflates by a Cationic Cyclization Reaction and Its Application in Biomimetic Polycyclizations and Synthesis of Terpenes.

AbstractA novel and very simple method for the acid‐mediated cationic cyclization reaction of a range of enyne derivatives or alkynols is developed providing access to a variety of the title triflates without the need of any metallic reagent or catalyst.

ChemInform Abstract: Unified Protocol for Cobalt‐Catalyzed Oxidative Assembly of Two Aryl Metal Reagents Using Oxygen as an Oxidant.

The first cobalt-catalyzed oxidative cross-coupling reaction of two aryl metal reagents is described. An equivalent amount of two aryl Grignard or lithium reagents, after mediation by an equivalent amount of simple ClTi(OEt)3, was facilely assembled under the catalysis of 1 mol % of CoCl2/10 mol % of DMPU using oxygen. The cross-couplings between various aryl metal reagents, especially between two structurally similar aryl Grignard reagents, proceeded smoothly and selectively and, thus, provided a highly general and efficient method for the construction of biaryl compounds.

Variable mechanism of nucleophilic substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents.

The variable mechanism for substitution of P-stereogenic phosphoryl chloride with alkynyl metallic reagents, which depends on temperature, stoichiometry of starting materials, and the structure of the nucleophilic reagent, is assumed as either SN2-like or Berry pseudorotation of pentacoordinated phosphorus intermediates, affording inversion and retention products, respectively. The formation of the inversion product can be controlled to occur predominantly to afford (RP)-alkynylphosphinates.

Direct synthesis of dicarbonyl PCP-iron hydride complexes and catalytic dehydrogenative borylation of styrene.

A new and efficient method based on the simple metalating reagent Fe(CO)5 has been developed for the straightforward synthesis of well defined cyclometalled PCP iron carbonyl pincer complexes. The reaction proceeds cleanly under mild conditions at 30 °C and UV irradiation. Four hydride pincer complexes are synthesized and fully characterized as well as an intermediate dinuclear species. The new iron complexes are active and selective catalytic precursors for the dehydrogenative borylation of styrene with HBpin.

Selective Double Carbomagnesiation of Internal Alkynes Catalyzed by Iron-N-Heterocyclic Carbene Complexes: A Convenient Method to Highly Substituted 1,3-Dienyl Magnesium Reagents

Controlled multicarbometalation of alkynes has been envisaged as an efficient synthetic method for dienyl and polyenyl metal reagents, but an effective catalyst enabling the transformation has remained elusive. Herein, we report that an iron(II)-N-heterocyclic carbene (NHC) complex (IEt2Me2)2FeCl2 (IEt2Me2 = 1,3-diethyl-4,5-dimethylimidazol-2-ylidene) can serve as a precatalyst for the double carbometalation of internal unsymmetrical alkynes with alkyl Grignard reagents, producing highly substituted 1,3-dienyl magnesium reagents with high regio- and stereoselectivity. Mechanistic studies suggest the involvement of low-coordinate organoiron(II)-NHC species as the in-cycle intermediates. The strong σ-donating nature of IEt2Me2 and its appropriate steric property are thought the key factors endowing the iron-NHC catalyst fine performance.

Catalytic, Stereoselective Dihalogenation of Alkenes: Challenges and Opportunities.

Although recent years have witnessed significant advances in the development of catalytic, enantioselective halofunctionalizations of alkenes, the related dihalogenation of olefins to afford enantioenriched vicinal dihalide products remains comparatively underdeveloped. However, the growing number of complex natural products bearing halogen atoms at stereogenic centers has underscored this critical gap in the synthetic chemist's arsenal. This Review highlights the selectivity challenges inherent in the design of enantioselective dihalogenation processes, and formulates a mechanism-based classification of alkene dihalogenations, including those that may circumvent the "classical" haliranium (or alkene-dihalogen π-complex) intermediates. A variety of metal and main group halide reagents that have been used for the dichlorination or dibromination of alkenes are discussed, and the proposed mechanisms of these transformations are critically evaluated.

ChemInform Abstract: Direct β‐C(sp3)—H Functionalization of Aliphatic Amines to α,β‐Unsaturated Imines, Aldehydes, and Chromenes.

A metal-free method for direct β-C(sp3)–H functionalization of aliphatic amine was developed. The method is based on a reaction that yields enamine directly from the corresponding aliphatic amine, which otherwise requires the aid of metallic reagent and/or external oxidant. The reaction is operationally simple, general, and highly efficient in functionalizing both cyclic and acyclic amines. Structurally diverse unsaturated imines were obtained from N-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde and benzopyran derivatives with excellent E/Z-selectivity.

Synthesis of Cyclic Alkenyl Triflates by a Cationic Cyclization Reaction and its Application in Biomimetic Polycyclizations and Synthesis of Terpenes

AbstractCyclic alkenyl triflates are useful intermediates in organic synthesis usually synthesized from ketones through a reaction involving enolization and trapping with a triflating agent. This sequence suffers from some stereochemical drawbacks owing to the basic conditions required. Herein, we describe a new acid‐mediated cationic cyclization reaction of enyne derivatives (or alkynols) to access cyclic alkenyl triflates. This new atom‐economical process is high yielding, scalable, technically very simple, proceeds without the need of any metallic reagent or catalyst, and more importantly, it complements and challenges conventional methodologies. We have also developed new biomimetic cationic cyclization reactions to yield interesting polycyclic compounds. As a demonstration of the potential of this method in the context of total synthesis, we have synthesized two terpenes: austrodoral and pallescensin A. Using the cationic cyclization in the key step of the synthetic routes allowed the synthesis of these natural products in a very simple, concise, scalable, and efficient way.

Synthesis of Cyclic Alkenyl Triflates by a Cationic Cyclization Reaction and its Application in Biomimetic Polycyclizations and Synthesis of Terpenes.

Cyclic alkenyl triflates are useful intermediates in organic synthesis usually synthesized from ketones through a reaction involving enolization and trapping with a triflating agent. This sequence suffers from some stereochemical drawbacks owing to the basic conditions required. Herein, we describe a new acid-mediated cationic cyclization reaction of enyne derivatives (or alkynols) to access cyclic alkenyl triflates. This new atom-economical process is high yielding, scalable, technically very simple, proceeds without the need of any metallic reagent or catalyst, and more importantly, it complements and challenges conventional methodologies. We have also developed new biomimetic cationic cyclization reactions to yield interesting polycyclic compounds. As a demonstration of the potential of this method in the context of total synthesis, we have synthesized two terpenes: austrodoral and pallescensin A. Using the cationic cyclization in the key step of the synthetic routes allowed the synthesis of these natural products in a very simple, concise, scalable, and efficient way.

Environmentally benign treatments for inhibiting the release of aqueous extracts from merbau heartwood

Merbau (Intsia spp.) is one of the most valued commercial trees due to its high strength, dimensional stability, and durability. However, one major disadvantage in some applications is that its red aqueous extracts (RAEs) can be easily leached out to stain adjacent materials and discolor the wood itself. Since some plant extracts are known to act as chelators of metal ions, seven metal compounds (FeCl3, FeCl2, FeSO4, CuCl2, CuSO4, AlCl3, and Zn(NO3)2) and two boron compounds (H3BO3 and Na2BO7) were used to evaluate their abilities for minimizing extract-staining. The results reveal that FeCl3, FeCl2, FeSO4, CuCl2, and AlCl3 at the concentration of 1.0 % are effective reagents for chelating the RAEs of merbau. FeCl2 and CuCl2 perform better than the other three metal reagents, and in particular, FeCl2 has excellent reactivity with RAEs. In addition, drying at 100 °C could enhance the bleed resistance of treated wood, and an even more significant effectiveness was observed with CuCl2 treatment. Treatment with 0.1 % FeCl2 and CuCl2 followed by drying at 100 °C are the optimum treatments for inhibiting RAEs in merbau, with weight losses of only 1.6 and 1.7 %, respectively, compared with 13.2 % for untreated wood after a 16-day leaching test. These two treatments were also proven to have good metal fixation ability. Moreover, CuCl2 treatment can enhance the decay resistance of merbau. The treatments explored in this study are environmentally benign and efficient approaches to solving problems caused by the RAEs of merbau heartwood.

Unified Protocol for Cobalt-Catalyzed Oxidative Assembly of Two Aryl Metal Reagents Using Oxygen as an Oxidant.

The first cobalt-catalyzed oxidative cross-coupling reaction of two aryl metal reagents is described. An equivalent amount of two aryl Grignard or lithium reagents, after mediation by an equivalent amount of simple ClTi(OEt)3, was facilely assembled under the catalysis of 1 mol % of CoCl2/10 mol % of DMPU using oxygen. The cross-couplings between various aryl metal reagents, especially between two structurally similar aryl Grignard reagents, proceeded smoothly and selectively and, thus, provided a highly general and efficient method for the construction of biaryl compounds.

Synthetic Strategies for the Preparation of Butenolides and Their Transformation into Other Derivatives

Butenolides, five membered α,&946;-unsaturated γ-lactones, are ubiquitous moieties present in the structures of many natural products and synthetic compounds endowed with a large array of biological activities. Butenolides with an γ-alkylidene moiety are termed as γ-alkylidenebutenolides. Because of their chemical structures as well as their biological activities, butenolides have attracted the attention of synthetic organic chemistry community. As a consequence, several methodologies have been developed to synthesize these classes of compounds. The potential use of such substances is expanded due to their easy conversion into lactams and pyridazine derivatives which are also of potential biological interest. Moreover, the chemistry of such compounds is very rich in large extension associated also with the nature of their substituents. Herein, we present some classical and recent methodologies for the synthesis of butenolides and γ-alkylidene butenolides. These methods involve the use of several transition metal reagents, condensation and conjugated addition reactions. Some methods used to convert butenolides and γ-alkylidene congeners into lactams and pyridazines are described. Methodologies for the preparation of oxazolones namely azlactones, compounds which are structurally similar to butenolides and have attracted the attention of synthetic organic chemists due to their versatility as building blocks, are also highlighted. Examples of applications of the methodologies in the synthesis of natural products as well as in the preparation of analogues endowed with biological activities, including some contributions from the author’s groups, are discussed. Keywords: Aldol reaction, Alkylidenebutenolide, Butenolide, Pyridazinone, Butyrolactone, Azlactones.

A Mild and General One-Pot Synthesis of Densely Functionalized Diaryliodonium Salts.

Diaryliodonium salts are powerful and widely used arylating agents in organic chemistry. Here we report a scalable, synthesis of densely functionalized diaryliodonium salts from aryl iodides under mild conditions. This two-step, one-pot process has remarkable functional group tolerance, is compatible with commonly employed acid-labile protective group strategies, avoids heavy metal and transition metal reagents, and provides a direct route to stable precursors to PET imaging agents.

Direct β-C(sp(3))-H Functionalization of Aliphatic Amines to α,β-Unsaturated Imines, Aldehydes, and Chromenes.

A metal-free method for direct β-C(sp(3))-H functionalization of aliphatic amine was developed. The method is based on a reaction that yields enamine directly from the corresponding aliphatic amine, which otherwise requires the aid of metallic reagent and/or external oxidant. The reaction is operationally simple, general, and highly efficient in functionalizing both cyclic and acyclic amines. Structurally diverse unsaturated imines were obtained from N-heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde and benzopyran derivatives with excellent E/Z-selectivity.