Palladium-catalyzed Allylic Amination Research Articles

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.

Optically Active 10,10′-Spirobi[10H-phenoxasilin]-1,1′-diol: Synthesis, Structure, and Application of its Phosphoramidite Derivative to Palladium-catalyzed Asymmetric Allylic Amination

Optically active (S)-(+)- and (R)-(−)-10,10′-spirobi[10H-phenoxasilin]-1,1′-diols were synthesized by the transesterification of their optically active di-p-toluoyl derivatives resolved by chiral H...

Asymmetric Synthesis of γ-Amino Esters by Palladium-Catalyzed Allylic Amination

Asymmetric Synthesis of γ-Amino Esters by Palladium-Catalyzed Allylic Amination

Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination.

Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields. Furthermore, this methodology can be easily applied to the one-step synthesis of two drugs, cinnarizine and naftifine, on a gram scale.

Palladium-catalyzed allylic amination: a powerful tool for the enantioselective synthesis of acyclic nucleoside phosphonates.

Acyclic nucleoside phosphonates have been prepared in a straightforward manner and in high yields by an enantioselective palladium-catalyzed allylic substitution involving nucleic bases as nucleophiles followed by cross-metathesis reaction with diethyl allylphosphonate.

Palladium-Catalyzed Regio- and Enantioselective Synthesis of Allylic Amines Featuring Tetrasubstituted Tertiary Carbons.

The first asymmetric synthesis of α,α-disubstituted allylic N-arylamines based on a palladium-catalyzed allylic amination has been developed. The protocol uses highly modular vinyl cyclic carbonates and unactivated aromatic amine nucleophiles as substrates. The catalytic process features minimal waste production, ample scope in reaction partners, high asymmetric induction up to 97% ee, and operational simplicity.

Reversible nucleophilic addition can lower the observed enantioselectivity in palladium-catalyzed allylic amination reactions with a variety of chiral ligands

Palladium-catalyzed allylic amination is an important synthetic reaction that is also frequently used as a benchmark for the design and evaluation of new chiral ligands. The effect of reversible nucleophilic addition on the reaction of benzylamine with (E)-1,3-diphenylallyl ethyl carbonate (1) in CH2Cl2 was examined with 12 different chiral ligands across a range of scaffolding types. In 8 out of 12 cases the observed ee was significantly higher when DBU or Cs2CO3 was added to suppress the proton-driven reversibility. For chiral ligand screening with this test reaction, adding DBU or Cs2CO3 provides a better measure of the ligand’s inherent enantioselectivity.

Palladium-Catalyzed Allylic Amination of Homoallylic Alcohols with Amines via Carbon–Carbon Bond Cleavage

An efficient approach for palladium(II) acetate catalyzed allylic amination of homoallylic alcohols with various amines via sequential retro-allylation and amination was developed, which afforded the corresponding allylic amines in up to 98% yield.

First evidence for the use of polyamines as nucleophiles in a regioselective palladium-catalyzed allylic amination reaction

Palladium-catalyzed reaction of unsymmetrical allylic electrophiles with polyamines gives rise to regioisomeric allylic polyamines. An original catalytic procedure providing an efficient method for the regioselective synthesis of new classes of polyamino derivatives of biological interest is reported. Based on experimental considerations, a mechanistic rationale involving a thermodynamically controlled isomerization of the initially formed branched product is proposed to account for the total regioselectivity observed.

ChemInform Abstract: The New World of Organic Reactions in Water

AbstractReview: 102 refs.

Synthesis of (±)-Amathaspiramide F and Discovery of an Unusual Stereocontrolling Element for the [2,3]-Stevens Rearrangement

A formal total synthesis of (±)-amathaspiramide F through a tandem palladium-catalyzed allylic amination/[2,3]-Stevens rearrangement is reported. The unexpected diastereoselectivity of the [2,3]-Stevens rearrangement was controlled by the substitution patterns of an aromatic ring. This discovery represents a new stereocontrolling element for [2,3]-sigmatropic rearrangements in complex molecular settings.

The new world of organic reactions in water

Different reactivities and selectivities are observed in water compared with those in organic solvents. In this article, such three examples are described. While ammonia was known not to react in metal-catalyzed allylic amination, palladium-catalyzed allylic amination using aqueous ammonia proceeded to afford primary amines in high yields. Second, allylboronates reacted with aldehydes in aqueous media to afford α-addition adducts exclusively in high yields with high diastereo- and enantioselectivities using Zn(OH)2 with ligands as catalysts. Finally, it was found that catalytic use of In(0) was effective for the reactions of allylboronates with ketones in water.

A chronicle review: Regioselective synthesis of trifluoromethyl group containing allylic amines using palladium-catalyzed allylic amination pathway

Palladium-catalyzed regioselective allylic amination of the α-trifluoromethyl group-substituted allyl acetate has been accomplished using Pd(OAc)2/DPPE and [Pd(π-allyl)(cod)]BF4/DPPF as catalysts. The selective formation of the γ-product was attained by the use of Pd(OAc)2/DPPE, while the α-product was obtained in the presence of [Pd(π-allyl)(cod)]BF4/DPPF. We also succeeded in synthesizing optically active allylic amines using Pd(OAc)2/DPPE and [Pd(π-allyl)(cod)]BF4/BINAP began from optically active trifluoromethyl-substituted allyl acetate. Furthermore, we established that kinetic resolution of two types of allylic amines was possible using enantioselective isomerization by the [Pd(π-allyl)(cod)]BF4/(S)-BINAP catalyst.

Achieving Control over the Branched/Linear Selectivity in Palladium-Catalyzed Allylic Amination

Palladium-catalyzed reaction of unsymmetrical allylic electrophiles with amines gives rise to regioisomeric allylic amines. We have found that linear products result from the thermodynamically controlled isomerization of the initially formed branched products. The isomerization is promoted by protic acid and active palladium catalyst. The use of base shuts down the isomerization pathway and allows for the preparation and isolation of branched allylic amines. Solvent plays a key role in achieving high kinetic regioselectivity and in controlling the rate of isomerization. The isomerization can be combined with ring-closing metathesis to afford the synthesis of exocyclic allylic amines from their endocyclic precursors.

Regioselective synthesis of trifluoromethyl group containing allylic amines by palladium-catalyzed allylic amination and sequential isomerization

The palladium-catalyzed regioselective allylic amination of the α-trifluoromethyl group-substituted allyl acetate has been accomplished using Pd(OAc) 2/DPPE and [Pd(π-allyl)(cod)]BF 4/DPPF as catalysts. The selective formation of the γ-product was attained in the presence of Pd(OAc) 2/DPPE, while the α-product was obtained using [Pd(π-allyl)(cod)]BF 4/DPPF. We also succeeded in the regioselective synthesis of the enantiomerically enriched aminated product from chiral allyl acetate using Pd(OAc) 2/DPPE and [Pd(π-allyl)(cod)]BF 4/( S)-BINAP. Furthermore, we found that kinetic resolution had occurred during the isomerization step from the γ-type product to the α-type product by the [Pd(π-allyl)(cod)]BF 4/( S)-BINAP catalyst.

P*,P*-Bidentate Diamidophosphite Ligands in Palladium-Catalyzed Reactions

Two diamidophospite ligands were used in palladium-catalyzed allylic sulfonylation, alkylation, amination, etherification, and desymmetrization reactions. The novel ligands take ­advantage of the chirogenic phosphorus donor atoms, which create a more efficient chiral environ­ment around the metal.

Palladium‐Catalyzed Ring‐Contraction and Ring‐Expansion Reactions of Cyclic Allyl Amines

Ring around the rosy: An amino group can act as the leaving group or the nucleophile in a palladium-catalyzed allylic amination. As a result, readily accessible cyclic amines can be either ring contracted or ring expanded (see scheme).

Regioselective Synthesis of Optically Active Trifluoromethyl Group Substituted Allylic Amines by Palladium-Catalyzed Allylic Amination

We succeeded in the regioselective synthesis of chiral trifluoromethyl group substituted allylic amines from chiral allyl acetate using two types of palladium catalysts. Furthermore, we found that the kinetic resolution had occurred during the isomerization step from the γ-type product to the α-type product by the [Pd(C3H5)(cod)]BF4/(S)-BINAP catalyst.

ChemInform Abstract: Palladium-Catalyzed Asymmetric Allylic Substitution Reactions Using New Chiral Phosphinite-Oxazoline Ligands Derived from D-Glucosamine.

Novel 2-alkyl- or 2-aryl-4,5-(4,6-O-benzylidene-3-O-(diphenylphosphino)-1,2-dideoxy-α-d-glucopyrano)-[2,1-d]-2-oxazolines (5a−f) have been prepared from d-glucosamine hydrochloride. They work effectively as chiral ligands and provide a high level of enantiomeric excess in palladium-catalyzed allylic alkylation and amination reactions. The allylic alkylation of 1,3-diphenyl-3-acetoxyprop-1-ene with dimethyl malonate proceeds smoothly in the presence of 0.25 mol % [Pd(η3-C3H5)Cl]2 and the chiral ligand 5a having the smallest substituent on oxazoline at 0 °C within 6 h to furnish the highest enantiomeric excess (96% ee). The ligand 5a is also effective for the Pd-catalyzed amination of ethyl 1,3-diphenylprop-2-enyl carbonate, leading to the corresponding allylic amine in 94% ee. The full scope and limitations using ligands 5a−f in the allylic substitution reactions are described.

Highly regio- and stereoselective palladium-catalyzed allylic carbonate amination. A practical route to dehydro-β-amino esters

A pratical, highly enantioselective method for the synthesis of dehydro-β-amino acids was developed starting from easily accessible enantiopure allylic carbonates. The substitution with amines for C–N bond formation on these substrates bearing substituents on the Cα, Cβ, and Cγ position of the allylic system has received, until now, little attention. The reactions, carried out under palladium-catalyzed conditions, resulted in good yields and complete regioselectivity. Moreover, starting from enantiopure carbonates, complete retention of the configuration could be observed, affording enantiopure allylic amines.