Pd-catalyzed Allylic Substitution Research Articles

Pd-Catalyzed Asymmetric Allylic Substitution Cascade via Desymmetrization for the Construction of Chiral Polyheterocycles

Chiral polyheterocycles represent an important class of compounds because of their prevalence in bioactive natural products and chiral drugs. Pd-catalyzed allylic substitution is a powerful synthetic tool for forming C–C and C–X bonds (X = N, O, S, etc.). Naturally, asymmetric cascade reactions that utilize allylic substitution are undoubtedly efficient pathways to construct heterocycles. In this article, we reviewed the Pd-catalyzed asymmetric allylic substitution cascade via the desymmetrization of meso-diol diesters of cycloolefins, for the construction of chiral polyheterocycles and their derivatives.

Application of mixed phosphorus/sulfur ligands based on terpenoids in Pd-catalyzed asymmetric allylic substitution and Rh-catalyzed hydrogenation.

A small library of easily prepared diamidophosphite-sulfides based on 1,3-thioether alcohols, primarily of terpenoid nature, was developed. Upon complexation with Pd(II) ions, these hemilabile ligands showed the ability to form both P,S-chelates and complexes with two ligands P-monodentately bonded to the metal. The structures of the ligands and their complexes were determined by 2D NMR spectroscopy and X-ray diffraction. The use of these stereoselectors provided up to 95% ee in the classic Pd-catalyzed asymmetric allylic substitution reactions of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 80% ee in the Pd-mediated allylic alkylation of cinnamyl acetate with β-ketoesters. In addition, ee values of up to 90% with quantitative conversion were achieved in the Rh-catalyzed asymmetric hydrogenation of methyl esters of unsaturated acids. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed.

Origin of Stereoselectivity in Pd-Catalyzed Asymmetric Allylic Substitutions with Trost-Type Mixed Bidentate Phosphorus Ligands

Origin of Stereoselectivity in Pd-Catalyzed Asymmetric Allylic Substitutions with Trost-Type Mixed Bidentate Phosphorus Ligands

Synthesis of C-N Axially Chiral N-Arylbenzo[g]indoles via a Central-to-Axial Chirality Conversion Strategy.

Gold-catalyzed cascade cyclization of diynes for the synthesis of previously unexplored C-N axially chiral N-arylbenzo[g]indoles was described. The transformation was achieved via a central-to-axial chirality conversion strategy. The chiral conversion exhibited high efficiency. Besides single C-N chiral axis, N-arylbenzo[g]indoles bearing both C-N and C-C chiral axes were also afforded. The title compound derived monophosphine ligand was prepared and was evaluated in Pd-catalyzed asymmetric allylic substitutions, showing excellent chiral induction ability.

Chiral P,N,N-Ligands for Pd-Catalyzed Asymmetric Allylic Substitutions

Chiral P,N,N-Ligands for Pd-Catalyzed Asymmetric Allylic Substitutions

TADDOL-based P,S-bidentate phosphoramidite ligands in palladium-catalyzed asymmetric allylic substitution.

A series of easy-to-prepare and modular chiral P,S-bidentate phosphoramidites were synthesized. With respect to Pd(II), these ligands showed the ability to form stable P,S-chelate allylic complexes. The structures of the ligands and their complexes were confirmed by 2D NMR spectroscopy and single-crystal X-ray diffraction. These chiral inducers provided up to 99% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 94% ee in the Pd-mediated allylic alkylation of cinnamyl esters with β-ketoesters and 2,5-dimethylpyrrole. Furthermore, up to 92% ee with quantitative conversion and chemo- and regioselectivity was achieved in the rare reaction between 2-(diethoxyphosphoryl)-1-phenylallyl acetate and aniline. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed. It was shown that the ligands surpass their analogues with different denticity.

Development of Catalytic Isocyanation via Precise Reactivity Control of Ambident Reagent

Isonitrile (R-NC) is a regioisomer of the corresponding nitrile (R-CN), whose C-terminus has carbene like property. Isonitriles have been deeply investigated from the viewpoint of their use. In contrast to the usability, the synthesis of isonitriles themselves are not sufficiently studied. In this manuscript, we describe our findings on catalytic nucleophilic isocyanation using cyanide with precise control of the ambident reactivity. We successfully demonstrated Pd-catalyzed allylic isocyanation. A wide variety of allylic isonitriles were obtained by this method, in high yield with good linear selectivity. Allylic nitriles were not observed at all, which were the possible side products in the reaction. Even though the reaction is the Pd-catalyzed allylic substitution, no π-allyl Pd(II) intermediate is involved in the catalytic cycle. Pd salt, such as Pd(OAc)2 and Pd(CN)2, was just the precursor of catalytic active species. It was reversibly converted into the ate complex, (Me3Si)[Pd-(CN)3], with excess amount of trimethylsilyl cyanide (Me3SiCN). The ate complex plays dual roles: 1) The Me3Si group activates phosphate leaving group on the allylation electrophile. 2) The [Pd(CN)3]- part reacts as the nucleophile with its N-terminus because the strong interaction between Pd center and C-terminus of cyanide suppresses the C-nucleophilicity. Benzylic isocyanation was successfully catalyzed by Ag2O. Both primary and secondary benzylic isonitriles were obtained in high yield. Pd-catalyzed synthesis of α-aryl-α-isocyanoacetamide derivative was also demonstrated. This catalytic procedure was appropriate to the sequential transformation into the trisubstituted oxazole without isolation of the isonitrile intermediate. Mechanistic investigations revealed that the nucleophilic isocyanation proceeded through a SN1-type substitution predominantly.

Synthesis of P-stereogenic 1-phosphanorbornane-derived phosphine-phosphite ligands and application in asymmetric catalysis.

A convenient synthesis of enantiopure mixed donor phosphine-phosphite ligands has been developed incorporating P-stereogenic phosphanorbornane and axially chiral bisnaphthols into one ligand structure. The ligands were applied in Pd-catalyzed asymmetric allylic substitution of diphenylallyl acetate, Rh-catalyzed asymmetric hydroformylation of styrene and Rh-catalyzed asymmetric hydrogenation of an acetylated dehydroamino ester. Excellent branched selectivity was observed in the hydroformylation although low ee was found. Moderate ee's of up to 60% in allylic substitution and 50% in hydrogenation were obtained using bisnaphthol-derived ligands.

Axially chiral N-alkyl-N-cinnamoyl amide type P,olefin ligands for Pd-catalyzed reactions.

We synthesized N-alkyl-N-cinnamoyl amide type phosphine-olefin compounds 1 and found axial chirality in a C(aryl)-N(amide) bond in compounds 1 by HPLC analysis using a chiral stationary phase column. We successfully obtained enantiomeric isomers of 1 and demonstrated the use of (-)-1 for chiral ligands in Pd-catalyzed asymmetric allylic substitution reactions of allylic esters with indoles (up to 97% ee).

Pd-Catalyzed Asymmetric Allylic Substitution Cascade of Substituted 4-Hydroxy-2H-pyrones with meso-Allyl Dicarbonates.

An efficient Pd-catalyzed asymmetric allylic substitution cascade of 4-hydroxy-2H-pyrones with meso-allyl dicarbonates has been developed for the synthesis of kinetic chiral tetrahydro-1H-pyrano[4,3-b]benzofuran-1-one products in ≤87% yield and ≤99% ee. The protocol was achieved via a temperature-controlled kinetic control process, which has been illustrated by means of the experimental results and control experiments. The reaction could be conducted on a gram scale, and the resulting product allows for several transformations.

Development of a novel phosphoramidite-selenide ligand for Pd-catalyzed asymmetric allylic substitution.

A novel chiral P,Se-heterodonor ligand has been designed and prepared through an efficient and simple operation. This ligand can be successfully applied to Pd-catalyzed asymmetric allylic substitution with C- and N-nucleophiles, producing a diverse range of chiral allylic products in high yields and enantioselectivities (up to 99% yield and 95% ee).

Diverse “roof shaped” chiral diamidophosphites: palladium coordination and catalytic applications

“Roof shaped” chiral diamidophosphites of various structures and denticities were obtained and tested in Pd-catalyzed asymmetric allylic substitution.

Betti base derived P-stereogenic phosphine-diamidophosphite ligands with a single atom spacer and their application in asymmetric catalysis

Small bite-angle P-chirogenic PNP ligands have been synthesized stereo-selectively and employed in Rh-catalyzed asymmetric hydrogenation and Pd-catalyzed asymmetric allylic substitution resulting in moderate to excellent enantioselectivities.

Recent Advances in Asymmetric Pd-Catalyzed Allylic Substitution of Vinylethylene Carbonates with Carbon and Hetero Nucleophiles in the Construction of Multifunctional Allylic Scaffolds

Recent Advances in Asymmetric Pd-Catalyzed Allylic Substitution of Vinylethylene Carbonates with Carbon and Hetero Nucleophiles in the Construction of Multifunctional Allylic Scaffolds

Pd-Catalyzed regio- and stereoselective allylic substitution of vinylethylene carbonates with 1,2,4-triazoles.

N 1-Substituted 1,2,4-triazoles are ubiquitous skeletons in medicinal agents, agrochemicals, and organic materials. Herein, an efficient and practical method for the synthesis of N1-allylated 1,2,4-triazoles via Pd-catalyzed allylic substitution of vinylethylene carbonates (VECs) with 1,2,4-triazoles has been developed. By using a catalyst generated in situ from Pd2(dba)3·CHCl3 and DPPE under mild conditions, the process allows rapid access to N1-allylated 1,2,4-triazoles bearing diverse functionalities in high yields with excellent N1-selectivities, linear-selectivities, and Z-stereoselectivities.

Chiral P*,S-bidentate diamidophosphites with 1,2-thioether alcohol–based exocyclic substituents in asymmetric Pd-catalyzed reactions

Chiral P*,S-diamidophosphites with a 1,3,2-diazaphospholidine core and exocyclic 1,2-hydroxyl-thioether fragments were prepared. These asymmetric inducers provided up to 86% ee in the Pd-catalyzed allylic substitution of (E)-1,3-diphenylallyl acetate with dimethyl malonate and pyrrolidine, and up to 76% in the Pd-mediated allylic alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate.

Celebrating Professor Barry M. Trost's 80th Birthday

Celebrating Professor Barry M. Trost's 80^th Birthday

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications.

This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.

Cinnamoyl amide type chiral P,olefin ligands for Pd-catalyzed reactions.

We synthesized cinnamoyl amide type chiral P,olefin ligand (S)-4. We successfully obtained separable diastereomers of 4d and demonstrated Pd-catalyzed asymmetric allylic substitution reactions of indoles using (S,aS)-4d as a chiral ligand with high enantioselectivities (up to 98% ee).

(2-Fluoroallyl)pyridinium tetrafluoroborates: novel fluorinated electrophiles for Pd-catalyzed allylic substitution.

An efficient two-step approach to 2-fluoroallyl amines was developed that involves the synthesis of (2-fluoroallyl)pyridinium tetrafluoroborates from readily available gem-bromofluorocyclopropanes and the application of the former as novel and stable 2-fluoroallyl electrophiles for Pd-catalyzed allylic substitution.