Pd-catalyzed Allylic Amination Research Articles

Acyclic nucleosides via allylic amination of 2-methylidenetrimethylene carbonate with N-heteroaromatics

A highly efficient Pd-catalyzed allylic amination reaction using N-heteroaromatics to react with 2-methylidenetrimethylene carbonate was achieved (24 examples, up to 95 % yield, up to >20:1 N9/N7 selectivities). The presented strategy offers an efficient and convenient approach to construct acyclic nucleosides with a double bond in side chain.

Axially Chiral N,N-Ligand-Promoted Pd-Catalyzed Enantioselective Allylic Amination and Alkylation.

An axially chiral N,N-ligand developed from a [1,1'-binaphthalene]-2,2'-diol (BINOL)-based skeleton and phenanthroline is found to be capable of promoting Pd-catalyzed asymmetric allylic amination and alkylation of allyl acetates. The reaction is compatible with cyclic and acyclic secondary amines, primary aliphatic amines, malononitrile, and dialkyl malonates, affording the corresponding chiral products in up to 99% yield and with up to >99% enantiomeric excess.

Inherently Chiral 6,7-Diphenyldibenzo[ e,g ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Selective approach to N-substituted tertiary 2-pyridones

Commercially available 2-hydroxypyridines are converted into enantiomerically enriched allylic 2-pyridones with elusive N-substituted tertiary carbon by means of Pd-catalyzed allylic amination of vinyl cyclic carbonates.

Counteranion-controlled regioselectivity in palladium-catalyzed allylic amination of dienyl allylic carbonates

a bstract A regioselective Pd-catalyzed allylic amination reaction of dienyl allylic carbonates and aromatic amines has been developed by means of phosphoramidite-palladium catalysis. The regioselectivity could be altered by the counterion of the π-allylpalladium intermediate. As a result, either branched Z-dienyl allylic amines or linear conjugated allylic amines were generated in high levels of regioselectivity from the same substrates by tuning the reaction conditions.

Regio- and Enantioselective Pd-Catalyzed Allylic Amination of Monosubsti­tuted Allylic Substrates with BocNHOMe

A new type of N-nucleophile has been developed in Pd-catalyzed asymmetric allylic amination with monosubstituted allyl substrates, affording corresponding branched allyl amines in high regio- and enantioselectivities. Either OMe or Boc group in products can be removed easily to provide primary amine derivatives with the optical purity unchanged.

Synthesis of chiral unsaturated aminolactones using Pd-catalyzed allylic amination

Stereoselective synthesis of (5 R,6 R)- and (5 S,6 S)-5-benzylamino-6-( tert-butyldimethylsilanyloxymethyl)-5,6-dihydropyran-2-ones starting from d-glucal and furanaldehyde, respectively, is described. The synthesis relies on a Sharpless asymmetric dihydroxylation, an Achmatowicz reaction, and a stereoselective Pd-catalyzed allylic amination as the key steps.

Pd-catalyzed allylic amination in supercritical carbon dioxide: Synthesis of carborane-containing terpenoids

Pd-catalyzed amination of allylic carbonates with N-( ortho-carboran-3-yl)- N-methylamine was carried out in supercritical CO 2. It has been demonstrated that complete conversion of allylic carbonates to the corresponding carborane amines with excellent regioselectivity may be achieved in scCO 2 (170 atm, 60 °C) using NaHCO 3 as the acceptor base. The reaction offers a selective method for the preparation of allylic amines and provides a useful approach to new terpenoids.

Carborane-derived diphosphites: New ligands for Pd-catalyzed allylic amination

A series of chiral diphosphite ligands bearing sterically congested carborane fragments have been prepared and applied in the Pd-catalyzed allylic amination of 1,3-diphenylallyl acetate with pyrrolidine and di- n-propylamine (up to 83% ee).

Preparation of 2,4‐Disubstituted Cyclopentenones by Enantioselective Iridium‐Catalyzed Allylic Alkylation: Synthesis of 2′‐Methylcarbovir and TEI‐9826

A broadly applicable synthesis of chiral 2- or 2,4-substituted cyclopent-2-enones has been developed by combining asymmetric iridium-catalyzed allylic alkylation reactions and ruthenium-catalyzed ring-closing metathesis. Enantiomeric excesses (ee values) in the range of 95-99 % ee have been achieved. This method offers a straightforward access to biologically active prostaglandins of the PGA type. As an example, an enantioselective synthesis of the prostaglandin-analogue 13,14-dihydro-15-deoxy-Delta(7)-prostaglandin-A1-methyl ester (TEI-9826) has been carried out. Furthermore, the carbonucleoside 2'-methylcarbovir has been prepared from O-protected 4-hydroxymethyl-2-methyl-cyclopent-2-enone by Pd-catalyzed allylic amination.

Allylic alkylation and amination using mixed (NHC)(phosphine) palladium complexes under biphasic conditions

A dramatic improvement of the catalytic activity was observed when a phosphine was added in allylic alkylation reactions catalyzed by (NHC)Pd(η 3-C 3H 5)Cl complexes. Consequently, several palladium complexes, generated in situ from different NHC–silver complexes, [Pd(η 3-C 3H 5)Cl] 2 and PPh 3, were tested in this reaction to evaluate their potential. High reaction rates and conversions could be obtained with this catalytic system in the alkylation of allylic acetates with dimethylmalonate, particularly under biphasic conditions using water/dichloromethane and KOH 1 M as the base. These conditions are experimentally more convenient and gave higher reaction rates than the classical anhydrous conditions (NaH/THF). In this system, the phosphine is essential since no conversion was obtained when it is not present. The steric hindrance of the carbene ligand has a great influence on the activity and the stability of the catalytic system. The best NHC ligands for this reaction are either 1-mesityl-3-methyl-imidazol-2-ylidene or 1-(2,6-diisopropylphenyl)-3-methyl-imidazol-2-ylidene which are less bulky among the NHC tested. These two ligands led in 5 min to a complete conversion at 20 °C. The Pd-catalyzed allylic amination reaction using ( E)-1,3-diphenylprop-3-en-yl acetate and benzylamine was also tested with (NHC)(PPh 3)Pd complexes and under the biphasic conditions. This reaction was found to be slower than the alkylation with dimethylmalonate but a complete conversion could be reached in 6 h at 20 °C using K 2CO 3 1 M as the base. NMR experiments indicated that mixed (NHC)(PPh 3)Pd complexes are formed in situ but their structure could not be established exactly.

Enantioselective Pd-catalyzed allylic amination with self-assembling and non-assembling monodentate phosphine ligands

New chiral phospholanes were prepared by coupling of bromo-substituted heterocycles with the enantiopure, building block (2 R,5 R)-2,5-dimethyl-1-chlorophospholane. Some of the new phosphine ligands have the potential for self-assembling via hydrogen bondings in a metal complex. By application of these and related ligands in the palladium catalyzed allylic amination reaction, high enantioselectivities (up to 99%) were achieved. The influence of the construction of the cyclic phosphine ligands on the enantioselectivity is analyzed.

Asymmetric synthesis of 1-vinyltetrahydroisoquinoline through Pd-catalyzed intramolecular allylic amination

Asymmetric synthesis of 6,7-dimethoxy-1-vinyltetrahydroisoquinolines through Pd-catalyzed intramolecular allylic amination of 3-(amidoethylphenyl)prop-2-enyl carbonates was studied, using a library of fine-tunable monodentate phosphoramidite ligands. Under optimized conditions, excellent enantiopurity (up to 96% ee) and 100% product selectivity were achieved. 1-Vinyltetrahydroquinoline thus obtained is a highly versatile intermediate for the synthesis of various biologically active alkaloids of medicinal interest.

Palladium(0)-Catalyzed Allylic Aminations: Kinetics and Mechanism of the Reaction of Secondary Amines with Cationic [(η3-allyl)PdL2]+ Complexes

The mechanism of the reaction of secondary amines (piperidine, morpholine) with the cationic complexes [(η3-PhCHCHCHR)PdL2]+BF4- (R = Ph, L = PPh3 or L2 = dppb; R = H, L2 = dppb) has been investigated in DMF. The reaction, which affords the tertiary allylic amine, is irreversible when L is a monodentate ligand such as PPh3, whereas the reaction is reversible when L2 is a bidentate ligand such as dppb. In all cases, piperidine is more reactive than morpholine. The rate and equilibrium constants have been determined in DMF. These results can be combined with our previous results on the mechanism of the reversible formation of cationic [(η3-PhCHCHCHPh)PdL2]+AcO- by reacting Pd0L2 complexes with (E)-PhCHCHCH(Ph)OAc. Fully established catalytic cycles are now proposed for the Pd-catalyzed allylic amination of (E)-PhCHCHCH(Ph)OAc by piperidine and morpholine. The amine and AcO- are in competition in their reaction with the cationic complexes [(η3-PhCHCHCHPh)PdL2]+. The nucleophilic attack of the amine may be fa...

Efficient Synthesis of 3‐Substituted 2,3‐Dihydroquinolin‐4‐ones Using a One‐Pot Sequential Multi‐Catalytic Process: Pd‐Catalyzed Allylic Amination—Thiazolium Salt‐Catalyzed Stetter Reaction Cascade.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Ferrocenyl‐QUINAP: A Planar Chiral P,N‐Ligand for Palladium‐Catalyzed Allylic Substitution Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Efficient synthesis of 3-substituted 2,3-dihydroquinolin-4-ones using a one-pot sequential multi-catalytic process: Pd-catalyzed allylic amination–thiazolium salt-catalyzed Stetter reaction cascade

We developed an efficient method for the synthesis of 3-substituted 2,3-dihydroquinolin-4-ones using a one-pot sequential multi-catalytic process: Pd-catalyzed allylic amination–thiazolium salt-catalyzed Stetter reaction cascade. Measurement of the initial rate of the developed sequential process revealed a significant increase in the reaction rate of the Stetter reaction in the presence of Pd(OAc) 2 and AcOH· i-Pr 2NEt, the constituents of the first Pd catalysis.

Ferrocenyl-QUINAP: a planar chiral P,N-ligand for palladium-catalyzed allylic substitution reactions

The new planar chiral P,N-ligands 1a and 1b were prepared via a straightforward enantioselective synthesis using a Negishi cross-coupling and a sulfoxide/lithium exchange. Ligand 1a was successfully applied to Pd-catalyzed allylic alkylation (86% ee) and amination (83% ee) reactions.

Novel Strategies for the Preparation of Aminocarbasugar Analogues: Syntheses of N‐Substituted Aminocyclitols from D‐Mannose.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Pd-catalyzed allylic amination of 1,3-diphenylallyl acetate with dipropylamine in ionic and molecular solvents

Asymmetric catalytic allylic amination of 1,3-diphenylallyl acetate with dipropylamine in an ionic liquid, 1-butyl-2,3-dimethylimidazolium tetrafluoroborate, and in THF and CH2Cl2 in the presence of palladium complexes of P-monodentate phosphite and phosphoramidite derivatives of S-1,1′-bis-2-naphthol was carried out. This gave a product with ee of up to 65%. The level of asymmetric induction is retained after three catalyst cycles.