Diamination Of Alkenes Research Articles

A general, electrocatalytic approach to the synthesis of vicinal diamines.

This protocol describes an electrochemical synthesis of 1,2-diazides from alkenes. Organic azides are highly versatile intermediates for synthetic chemistry, materials, and biological applications. 1,2-Diazides are commonly reduced to form 1,2-diamines, which are prevalent structural motifs in bioactive natural products, therapeutic agents, and molecular catalysts. The electrochemical formation of 1,2-diazides involves the anodic generation of an azidyl radical from sodium azide, followed by two successive additions of this N-centered radical to the alkene, and is assisted by a Mn catalyst. The electrosynthesis of 1,2-diazides can be carried out using various experimental setups comprising custom-made or commercially available reaction vessels and a direct-current power supply. Readily accessible electrode materials can be used, including carbon (made from reticulated vitreous carbon and pencil lead), nickel foam, and platinum foil. This protocol is also demonstrated using ElectraSyn, a standardized electrochemistry kit. Compared with conventional synthetic approaches, electrochemistry allows for the precise control of the anodic potential input, eliminates the need for stoichiometric and often indiscriminate oxidants, and minimizes the generation of wasteful byproducts. As such, our electrocatalytic synthesis exhibits various advantages over existing methods for alkene diamination, including sustainability, operational simplicity, substrate generality, and exceptional functional-group compatibility. The resultant 1,2-diazides can be smoothly reduced to 1,2-diamines in a single step with high chemoselectivity. To exemplify this, we include a procedure for catalytic hydrogenation using palladium on carbon. This protocol, therefore, constitutes a general approach to accessing 1,2-diazides and 1,2-diamines from alkenes.

Enantioselective Synthesis of 2-Aminomethyl and 3-Amino Pyrrolidines and Piperidines through 1,2-Diamination of Aldehydes.

An efficient method for the synthesis of 1,2-diamines from aldehydes through proline-catalyzed asymmetric α-amination followed by reductive amination is reported. The products resemble those obtained through direct asymmetric diamination of terminal alkenes. The methodology is used to synthesize 2-aminomethyl and 3-amino pyrrolidines and piperidines in high yields and with a good enantioselectivity. The usefulness of the method is demonstrated through the synthesis of a 2-aminomethyl iminocyclitol.

Pd-Catalyzed Alkene Diamination Reactions of Nitrogen Electrophiles: Synthesis of Cyclic Guanidines and Ureas Bearing Dialkylaminomethyl Groups.

The Pd-catalyzed coupling of N-allylguanidines or N-allylureas with O-benzoylhydroxylamine derivatives affords cyclic guanidines or cyclic ureas bearing dialkylaminomethyl groups. The desired products are obtained in good yield, and substrates bearing substituents at the allylic position are transformed with moderate diastereoselectivity. The mechanism of these reactions appears to involve anti-aminopalladation of the alkene, followed by a rare sp3C-sp3N bond-forming reductive elimination from an alkylpalladium complex that contains β-hydrogen atoms.

Promoting Intermolecular C-N Bond Formation under the Auspices of Iodine(III).

The quest for the development of new protocols that provide general conditions for oxidative carbon-nitrogen bond formation has grown over recent years. Within this context, due to feasibility and benignity considerations in biochemical sciences, reactions that rely on main group oxidants as the only promoters have received particular interest. We have recently found that simple protonolysis events enable the incorporation of nitrogenated groups of the bissulfonimide family into the coordination sphere of common iodine(III) complexes such as diacetoxy iodobenzene. The products of the type ArI(OAc)(NTs2) represent rare examples of iodine(III) compounds displaying reactive iodine-nitrogen single bonds. Further protonolysis furnishes the corresponding iodine(III) compounds ArI(NTs2)2 containing two defined iodine-nitrogen single bonds for unprecedented dual transfer of both nitrogenated groups. It is of great synthetic importance that these new compounds contain iodine-nitrogen entities, which upon dissociation in solution lead to electrophilic iodine centers and nucleophilic nitrogen groups. This has enabled the development of a body of conceptually new amination reactions, which do not rely on conventional electrophilic nitrogen reagents but rather employ iodine(III) as an electrophilic activator and bissulfonimides as the source of subsequent nucleophilic amination. Additional diversification arises from the ambident nature of bissulfonimines enabling oxygenation pathways. The exciting chemistry covered in this Account comprises structural features of the reagents (including X-ray analysis), scope and limitation in synthetic amination of different hydrocarbons (including sp-, sp2-, and sp3-hybridized centers as in acetylenes, alkenes, enols, butadienes, allenes, arenes, and alkylketones), and physical-organic and theoretical analysis of the underlying reaction mechanisms. The oxidative transformations with all their rich diversifications originate from the versatile redox chemistry of the iodine(III) and iodine(I) pair, which shares several aspects of transition metal high oxidation state chemistry. For the present aryliodine(III) reagents, steric and electronic fine-tuning is possible through accurate engineering of the arene substituent. In addition to the general reactivity of the I-N bond, chiral aryliodine(III) reagents with defined stereochemical information in the aryl backbone are conceptually compatible with this approach. Thus, the development of enantioselective amination reactions with up to 99% ee was also successful. Several of the active enantioselective reagents have been isolated and structurally characterized. Following this approach for the important class of chiral vicinal diamines, an unprecedented direct diamination of alkenes could be conducted in an enantioselective catalytic manner under full intermolecular reaction control. This latter reaction is based on the precise engineering of a chiral aryliodine(III) catalyst in combination with bismesylimide as nitrogen source. It is the consequence of the precise understanding of the reaction behavior of structurally defined bisimidoiodine(III) reagents.

Iron-Catalyzed Direct Olefin Diazidation via Peroxyester Activation Promoted by Nitrogen-Based Ligands.

We herein report an iron-catalyzed direct diazidation method via activation of bench-stable peroxyesters promoted by nitrogen-based ligands. This method is effective for a broad range of olefins and N-heterocycles, including those that are difficult substrates for the existing olefin diamination and diazidation methods. Notably, nearly a stoichiometric amount of oxidant and TMSN3 are sufficient for high-yielding diazidation for most substrates. Preliminary mechanistic studies elucidated the similarities and differences between this method and the benziodoxole-based olefin diazidation method previously developed by us. This method effectively addresses the limitations of the existing olefin diazidation methods. Most notably, previously problematic nonproductive oxidant decomposition can be minimized. Furthermore, X-ray crystallographic studies suggest that an iron-azide-ligand complex can be generated in situ from an iron acetate precatalyst and that it may facilitate peroxyester activation and the rate-determining C-N3 bond formation during diazidation of unstrained olefins.

Copper-Catalyzed Diamination of Alkenes of Unsaturated Ketohydrazones with Amines.

A convenient copper-catalyzed intra-/intermolecular diamination of β,γ-unsaturated hydrazones has been developed with simple amines as external amine sources. The protocol enables efficient access to various nitrogen-containing pyrazolines under mild reaction conditions.

Electrocatalytic Difunctionalization of Olefins as a General Approach to the Synthesis of Vicinal Diamines

Vicinal diamines are highly prevalent structural motifs in therapeutic agents, bioactive natural products, and molecular catalysts. However, there are currently few unified methodological approaches for making these pertinent synthetic building blocks. This Synpacts article provides an overview of selected landmark developments in the area of olefin diamination. In particular, we highlight our recent contribution on the electrocatalytic diazidation of olefins as a general, selective, and sustainable method for the synthesis of vicinal diamines.1 Introduction2 Background: Intermolecular Diamination of Olefins3 Background: Intermolecular Diazidation of Olefins4 Electrocatalytic Diazidation of Olefins

Removing the Mask in Catalytic Asymmetric Diamination of Alkenes

In this issue of Chem , Liu and co-workers report an extremely general and mild radical diamination protocol that permits the asymmetric synthesis of vicinal diamines in a highly enantioselective manner under a copper(I)/chiral phosphate dual-catalytic system. Notably, this work represents the first asymmetric radical alkene diamination that allows for direct alkylamine incorporation.

Catalytic Asymmetric Radical Diamination of Alkenes

Summary Catalytic asymmetric diamination of alkenes is a highly attractive method for creating chiral vicinal diamines, which are ubiquitous in biologically active molecules and versatile ligands as well as organocatalysts. We report the use of O -acylhydroxylamines as dialkylaminyl radical precursors to trigger asymmetric diamination of alkene under Cu(I)/chiral phosphoric acid dual catalysis. This reaction allows for direct alkylamine incorporation and features high enantioselectivity, a broad substrate scope, wide functional-group tolerance, and mild reaction conditions, providing convenient and practical access to a wide range of highly enantio-enriched β-alkylamine-containing pyrrolidines. We have also achieved asymmetric azidoamination of alkenes by using azidoiodinane as an azidyl radical precursor, offering a complementary method for preparing diverse chiral β-amino pyrrolidines. The application of the resultant α-tertiary pyrrolidine-derived diamine was showcased to significantly promote the enantioselectivity of an asymmetric Michael reaction.

Stereoselective Synthesis of Isoxazolidines via Copper-Catalyzed Alkene Diamination.

A convenient copper-catalyzed intramolecular/intermolecular alkene diamination reaction to synthesize 3-aminomethyl-functionalized isoxazolidines under mild reaction conditions and with generally high levels of diastereoselectivity was achieved. This reaction demonstrates that previously underutilized unsaturated carbamates are good [Cu]-catalyzed diamination substrates. Sulfonamides, anilines, benzamide, morpholine, and piperidine can serve as the external amine source. This relatively broad amine range is attributed to the mild reaction conditions. Reduction of the N-O bond could also be achieved, revealing the corresponding 3,4-diamino-1-alcohols efficiently.

Preparation of isoindolinones via a palladium-catalyzed diamination

A Pd(II)-catalyzed cyclization using oxidative olefin diamination was developed for the preparation of isoindolinones from ortho-olefinic N-methoxybenzamides. Using the optimized reaction conditions, the desired products were obtained in up to 90% yield using NFSI as the oxidant. This reaction provides an efficient and direct access to isoindolinones with amine functionality, an important drug skeleton.

Stereoselective Synthesis of Cyclic Guanidines by Directed Diamination of Unactivated Alkenes.

A method for a directed stereoselective guanidinylation of alkenes is described. The guanidine unit can be delivered as an intact fragment by a hydroxy or carboxy group, usually with a high level of stereocontrol. After the guanidine delivery, the directing group can be cleaved under exceptionally mild conditions, typically by alcoholysis in the presence of acetic acid. Broad functional group tolerance and mild reaction conditions for the cycloguanidilation suggest applications in medicinal chemistry and natural products synthesis.

Copper-Catalyzed Oxidative Oxyamination/Diamination of Internal Alkenes of Unsaturated Oximes with Simple Amines

A convenient and versatile oxidative intra/intermolecular oxyamination and diamination of unactivated alkenes has been developed through copper-catalyzed radical reactions of β,γ- and γ,δ-unsaturated ketoximes with electron-rich aryl and aliphatic amines. These reactions were carried out by employing di-tert-butyl peroxide (DTBP) or air as the terminal oxidant, and a series of useful nitrogen-containing 4,5-dihydroisoxazoles and cyclic nitrones were formed.

Regioselective Intermolecular Diamination and Aminooxygenation of Alkenes with Saccharin.

Palladium catalysis enables the regioselective difunctionalization of alkenes using saccharin as the nitrogen source in the initial step of aminopalladation. Depending on the reaction conditions, diamination or aminooxygenation pathways can be accessed using hypervalent iodine reagents as the terminal oxidants. The aminooxygenation of allylic ethers originates from an unprecedented ambident behavior of saccharin. The participating palladium catalysts contain a palladium-saccharide unit. Two representative complexes of this type could be isolated and characterized.

Rhodium-Catalyzed Alkene Difunctionalization with Nitrenes.

The Rh(II) -catalyzed oxyamination and diamination of alkenes generate 1,2-amino alcohols and 1,2-diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh-bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]2 =NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N⋅⋅⋅N=[Rh]2 bond formation, in addition to the N⋅⋅⋅[Rh]2 =NR coordination mode.

ChemInform Abstract: Copper‐Catalyzed Diamination of Unactivated Alkenes with Hydroxylamines.

AbstractA wide range of 1,2‐diamines are regio‐ and stereoselectively synthesized by the first example of metal‐catalyzed alkene diamination for directly installing an electron‐rich amino group.

ChemInform Abstract: Copper‐Promoted Synthesis of 1,4‐Benzodiazepinones via Alkene Diamination.

A new method for the synthesis of 2-aminomethyl functionalized 1,4-benzodiazepin-5-ones is presented. The benzodiazepine core is well-known to interact with biological receptors and many pharmaceutical drugs are derived from this structure. The alkene diamination strategy is employed for the first time for the synthesis of 1,4-benzodiazepinones. In this reaction, copper(2-ethylhexanoate)2 serves as promoter and a range of external amines can be coupled with 2-sulfonamido-N-allyl benzamides to generate the 1,4-benzodiazepinones in good yields.

ChemInform Abstract: Synthesis of Saturated Heterocycles via Metal‐Catalyzed Alkene Diamination, Aminoalkoxylation, or Dialkoxylation Reactions

ChemInform Abstract: Synthesis of Saturated Heterocycles via Metal‐Catalyzed Alkene Diamination, Aminoalkoxylation, or Dialkoxylation Reactions

ChemInform Abstract: Intramolecular Aminochalcogenation and Diamination of Alkenes Employing N‐Iodosuccinimide.

AbstractA new NIS‐mediated intramolecular diamination and aminosulfuration of alkenes with N‐alkyl or N‐aryl thioureas is presented.

Oxidative inter-/intermolecular alkene diamination of hydroxy styrenes with electron-rich amines.

Doubly intermolecular alkene diamination is achieved with electron-rich, terminal alkenes through the use of a hypervalent iodine (PhI(OAc)2) reagent, iodide, and electron-rich amines. Mono- and disubstituted amines combine with electron-rich alkenes, particularly o-hydroxystyrenes, to achieve the greatest level of generality. This operationally straightforward protocol, unreliant on conventional metal-based activation, is compatible with a broad range of functional groups.