Allylic Amination Reaction Research Articles

Synthesis of aryl allyl alkynes via reaction with allyl amine and aryl alkynoic acids through decarboxylation

Allyl alkynoic esters were synthesized by the reaction of allyl amines and alkynoic acids via deaminative esterification. The reaction of allyl alkynoic esters with Pd(dba)2 and Xantphos in digylme at 110 °C for 12 h afforded the desired decarboxylated allyl alkynes in good yields.

One-Pot Copper-Catalyzed Three-Component Reaction of Sulfonyl Azides, Alkynes, and Allylamines To Access 2,3-Dihydro-1H-imi­dazo[1,2-a]indoles

A copper-catalyzed multicomponent reaction of sulfonyl azides, alkynes, and allylamines affording 2,3-dihydro-1H-imidazo-[1,2-a]indoles in moderate yields is reported. Four C–N bonds are constructed­ by way of azide-alkyne cycloaddition (CuAAC) and double Ullmann-type coupling reactions in a one-pot process.

A palladium-catalyst stabilized in the chiral environment of a monoclonal antibody in water.

We report the first preparation of a monoclonal antibody (mAb) that can immobilize a palladium (Pd)-complex. The allylic amination reaction using a supramolecular catalyst consisting of the Pd-complex and mAb selectively gives the (R)-enantiomer product with an enantiomeric excess (ee) of 98 ± 2%. This is in sharp contrast to the reaction catalyzed by a conventional Pd-catalyst (ee < 2%).

Asymmetric Allylic Amination of Morita–Baylis–Hillman Adducts with Simple Aromatic Amines by Nucleophilic Amine Catalysis

Asymmetric allylic amination of Morita–Baylis–Hillman (MBH) adducts with simple aromatic amines is successfully realized by nucleophilic amine catalysis. A range of substituted α-methylene-β-arylamino esters is accessed in moderate to high yields (up to 88%) and with excellent enantioselectivities (up to 97% ee). Inorganic fluorides are found to be able to improve the enantioselectivity of the allylic amination reaction. A pyrrole-2-carboxylate and a cyclic imide are also compatible with this catalytic system. A chiral 2,3-dihydroquinolin-4-one derivative is easily obtained from the allylic amination product.

Cooperativity and serial ligand catalysis in an allylic amination reaction by Pd(ii)-bis-sulfoxide and Brønsted acids.

In recent years, transition metal catalysts have been increasingly employed in conjunction with Brønsted acids under one-pot reaction conditions, opening up newer avenues for dual catalytic protocols. Under such dual catalytic conditions, the general premise of holding the native ligands on the catalyst in the same manner throughout the catalytic cycle becomes immediately questionable. We have invoked the likelihood of Serial Ligand Catalysis in an important intramolecular allylic amination of N-Boc (N-tert-butoxycarbonyl) protected homoallylic amine leading to an anti-oxazolidinone product. The reported reaction conditions employed (bis-sulfoxide)Pd(OAc)2 and dibutyl phosphoric acid (DBPOH) as the catalysts and benzoquinone (BQ) as the oxidant. We used density functional theory computations at the B3LYP-D3 level of theory to examine a comprehensive set of ligand combinations around the Pd center so as to identify the energetically most preferred pathway. The key catalytic events consist of (i) a C-H activation at the allylic position in the catalyst-substrate complex [Pd(L)(L')2(substrate)], leading to a (L)(L')Pd-π-allyl intermediate, and (ii) an intramolecular C-O bond formation between the carbonyl oxygen of the N-Boc amine and the allyl carbon. Interesting cooperativity between the catalysts in both these steps has been found, wherein the Pd(DBPO-)2(BS) species is involved in the C-H activation transition state and Pd(DBPO-)(BQ) in the C-O bond formation step. The energetic advantage in swapping the bis-sulfoxide ligand on Pd with a benzoquinone upon moving from the first step to the second step confirms the significance of serial ligand catalysis in dual catalytic reactions.

Optimizing the Mizoroki–Heck reaction of cyclic allyl amines: Gram-scale synthesis of preclamol without protecting groups

Though a widely used metal-catalyzed cross-coupling process, the Mizoroki–Heck (MH) reaction can be a capricious transformation. This is particularly true for oxidation-prone alkene substrates containing ligating heteroatoms, as in the case of N-alkyl tetrahydropyridines, whose MH reactions have been underexplored due to the many side reactions that hamper the process. Since the products of tetrahydropyridine Heck reactions are direct precursors to potent pharmacophores, and therefore of commercial value, this is a significant drawback. We report here the results of our study designed to deliver an optimized, scalable MH procedure for N-alkyltetrahydropyridines and its exemplification in a gram-scale synthesis of the drug substance preclamol.

Synthesis, crystal structure, electrochemical properties and DFT calculations of three new Zn(II), Ni(II) and Co(III) complexes based on 5-bromo-2-((allylimino)methyl)phenol Schiff-based ligand

Abstract In this work, a new Schiff base ligand (HL: 5-bromo-2-((allylimino)methyl)phenol) was prepared from the reaction of 5-bromo salicylaldehyde and allylamine. Then, three new Schiff base complexes, ZnL2 (1), NiL2 (2) and CoL3 (3), were synthesized through the reaction of Zn(NO3)2·6H2O, Ni(OAC)2·4H2O, and CoCl2·6H2O with the new Schiff base ligand in methanol or chloroform. The ligand and its related complexes were characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, and 1H- NMR technique. The molecular structures of complexes (1–3) were determined by the single crystal X-ray diffraction technique. The crystallographic data revealed that complexes 1 and 2 are four-coordinated by two phenolate oxygen and two imine nitrogen atoms of two Schiff base ligands. On the other hand, the metal center is six-coordinated by three phenolate oxygen and three imine nitrogen atoms of three Schiff base ligands in 3. Eventually, DFT calculations and the study of electrochemical properties were performed on the new three complexes.

A Brønsted acid-promoted asymmetric intramolecular allylic amination of alcohols.

Reported herein is a chiral Brønsted acid-catalyzed asymmetric intramolecular allylic amination reaction, allowing facile access to a range of biologically interesting chiral 2-substituted hydroquinolines in up to 90% yield and with up to 93% ee. Furthermore, a significant effect of an N-protecting group was observed in this asymmetric process.

Pyridinium Salt Forming Rh(III)-Catalyzed Annulation Reaction of Secondary Allylamines with Internal Alkynes and Its Application to Surface Modification of a Mesoporous Material.

A Rh(III)-catalyzed C-H activation reaction has been developed for the preparation of pyridinium salts from secondary allylamines and internal alkynes. The pyridinium salts formed by this N-annulation reaction have interesting fluorescence properties. This protocol has been applied to the surface modification of mesoporous silica materials to generate functionalized silica that can be used for the detection of nitrobenzene.

Nucleobases as Nucleophiles in Asymmetric Allylic Amination Reactions

Nucleobases as Nucleophiles in Asymmetric Allylic Amination Reactions

Reactions of Secondary Allylamines with Bis(η5:η1-pentafulvene)titanium Complexes: Selective Formation of Monoazabutadiene Titanium Complexes by N–H and C–H Bond Activation

The N–H and C–H bond activation reactions at ambient conditions of seven different secondary allyl amines (Aa–g) with bis(η5:η1-pentafulvene)titanium complexes (1) have been investigated. Bis(η5:η1-adamantylidenepentafulvene)titanium (1a) reacts with N-allylaniline (Aa), N-allylbenzylamine (Ac), N-allyl-tert-butylamine (Ad), N-allylcyclohexylamine (Ae), and N-allyl-2-methylaniline (Af) to give the 1-azabutadiene complexes 2a,c–f with high yields. They are the first complexes of the CH2-terminated monoazadiene RN═CHCH═CH2. Using bis(η5:η1-di-p-tolylpentafulvene)titanium (1b), which exhibits a less Bronsted basic Cexo center, and Aa, the β-C–H bond activation can be slowed down so much that the agostic interaction between the titanium center and the C–H bond is detectable via NMR measurements at room temperature. In the reactions of the titanium azabutadiene complexes 2a,b and 3a with carbon monoxide a ligand exchange is observed, forming the titanocene dicarbonyls 4a,b.

ChemInform Abstract: An Iridium(I) N‐Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand.

The Aryne [2,3] Stevens Rearrangement.

Arynes are employed in the transition-metal-free and mild [2,3] Stevens rearrangement of tertiary allylic amines for the synthesis of functionalized homoallylic amines in moderate to good yield with a broad substrate scope. The key nitrogen ylide intermediate was generated by the N-arylation of allyl amines using arynes. Moreover, the reaction of chiral allyl amines with arynes resulted in the enantiospecific synthesis of homoallylic amines. In addition, preliminary studies on the [1,2] Stevens rearrangement is also presented.

Recent Developments in Asymmetric Allylic Amination Reactions

The asymmetric synthesis of allylic amines is an important research area in modern synthetic organic chemistry, primarily due to the inherent utility and ubiquity of this functional group in various synthetic intermediates and bioactive agents. For instance, a plethora of methods for the stereocontrolled construction of allylic amines now provides a vibrant array of strategies for the installation of this important functionality. This review highlights developments in the field since 1998 through the provision of the most important methods and their mechanistic aspects in order to provide insight into their current scope and limitations. Hence, we envisage it will be an essential guide to the current state-of-the-art for this important area, which highlights potential new opportunities for further developments. 1 Introduction 2 Allylic Substitution 2.1 Transition Metal Catalyzed via a π-Allyl Intermediate 2.2 Lewis Base Catalyzed 2.3 Azametallation/Elimination 2.4 Miscellaneous 3 Sigmatropic Rearrangements 3.1 [3,3]-Rearrangement 3.2 [2,3]-Rearrangement 3.3 Curtius Rearrangement 4 Amination of Alkenes 4.1 Hydroamination 4.2 Carboamination 4.3 Diamination 5 Wacker-Type Oxidative Amination 6 C–H Functionalization 7 Electrophilic Amination 8 Conclusions

ChemInform Abstract: Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium Complex‐Catalyzed C—N Bond Activation.

AbstractEnantiomerically pure allylic 1,3‐diamines are prepared with high regioselectivity involving a Pd‐catalyzed cascade C—N bond activation, aminomethylation, and asymmetric allylic amination reaction under mild reaction conditions.

Iridium-Catalyzed Asymmetric Allylic Amination Reactions with N-Aryl Phosphoramidite Ligands

A series of N-aryl phosphoramidite ligands were synthesized, and the iridium complexes derived from these novel ligands were proven to be efficient catalysts for asymmetric intermolecular allylic amination reactions. This C–N bond forming process readily accommodates a diverse range of amines and allylic carbonates, especially for the previously challenging ortho-substituted cinnamyl substrates. Moreover, isolation and characterization of the corresponding (π-allyl)–iridium complex K1 reveal that the active iridacycle is generated through a C(sp2)–H bond insertion of tetrahydroquinoline of the ligand.

Enantioselective Synthesis of Pyrrole-Fused Piperazine and Piperazinone Derivatives via Ir-Catalyzed Asymmetric Allylic Amination

Ir-catalyzed intramolecular asymmetric allylic amination reaction of pyrrole derivatives was achieved. The pyrrole-fused piperazine and piperazinone derivatives could be easily accessed from the pyrrole-tethered allylic carbonates in good yields and enantioselectivity (up to 98% ee).

ChemInform Abstract: Aerobic Linear Allylic C—H Amination: Overcoming Benzoquinone Inhibition.

AbstractAerobic linear allylic amination reactions of terminal olefins using an O2/Co/catalytic dihydroquinone redox relay in combination with a Pd/bis‐sulfoxide catalyst are investigated.

An Iridium(I) N‐Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions

AbstractA chiral iridium(I) N‐heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74–91 %) and excellent enantioselectivities (92–99 % ee). Preliminary mechanistic investigations reveal that the C−H activation occurs at the position ortho to the N‐aryl group of the ligand.

An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand.