Asymmetric Allylic Substitution Reactions Research Articles

Palladium allylic complexes with enantiopure bis(diamidophosphite) ligands bearing a cyclohexane-1,2-diamine skeleton as catalysts in the allylic substitution reaction

A series of cationic allyl palladium complexes [Pd(η3-CH3-C3H5)(P-P)]X (X = PF6, 2a-c, 2e; and X = BPh4, 3a, 3b, 3d, 3e) and [Pd(η3-1,3-Ph2-C3H3)(P-P)]X (X = PF6, 6b; and X = BPh4, 7a) have been prepared. The bis(diamidophosphite) ligands (P-P) contain a diazaphospholidine terminal fragment derived from (R,R)- and (S,S)-N,N’-dibenzyl- and (R,R)-N,N’-dimethyl-cyclohexane-1,2-diamines and dialcoxy bridging fragment derived from (R,R)- and (S,S)-butanediol, (R,R)-cyclohexanediol, (4R,5R)- and (4S,5S)-4,5-di(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane and (R)- and (S)-binaphthol. Complexes [Pd(η3-CH3-C3H5l)P2]X (X = PF6, 4f, 4g; and X = BPh4, 5f), where P are monodentate diamidophosphite ligands with diazaphospholidine heterocyclic backbone obtained from (R,R)- and (S,S)-N,N’-dibenzylcyclohexane-1,2-diamine and alcoxy groups coming from (R)-phenyl-ethanol and (S)-borneol have been also prepared. Neutral palladium complexes [PdCl2(P-P)] (1a, 1c) were synthesized to prove the C2 symmetry of the P-P ligand. The new compounds were fully characterized in solution by NMR spectroscopy. The X-ray crystal structure determination for 2e-(R,R,Ral,Ral;R,R) and 1a-(S,S;Sal,Sal;S,S) has been achieved.The new allyl-palladium complexes were applied in the asymmetric allylic substitution reaction of the benchmark substrate rac-3-acetoxy-1,3-diphenyl-1-propene with dimethyl malonate and benzylamine as nucleophiles in order to test their catalytic potential. The best results were obtained with the 3a-(R,R;Ral,Ral;R,R) precursor (up to 84% ee) while complexes with the e ligand derived from the (R,R)-N,N’-dimethylcyclohexane-1,2-diamine terminal fragment resulted inactive in the process. The influence of the nature and the absolute configuration of both the bridging and the terminal fragments of the bis(diamidophosphite) ligand on the asymmetric induction is discussed. A preliminary study of the anion effect (PF6− vs. BPh4-) on the activity and the enantioselectivity of the Pd-catalysed allylic substitution has also been performed.

ChemInform Abstract: Recent Progress in Copper‐Catalyzed Asymmetric Allylic Substitution Reactions Using Organoboron Nucleophiles

AbstractReview: [29 refs.

Recent Progress in Copper-Catalyzed Asymmetric Allylic Substitution Reactions Using Organoboron Nucleophiles

Recent progress in copper-catalyzed asymmetric allylic substitution reactions with organoboron nucleophiles is reviewed. Wide availability, high functional group compatibility, and mild reaction conditions are the main advantages over conventional highly reactive organometallic nucleophiles. The use of diboron and silylboron reagents for the synthesis of enantioenriched allylboronates and allylsilanes is also included. 1 Introduction 2 Chirality Transfer of Enantioenriched Allylic Substrates with Organoboron­ Nucleophiles 3 Enantioselective Allylic Substitution of Achiral Substrates with Organoboron Nucleophiles 4 Enantioselective Allylic Substitution of Achiral Substrates with Other Boron-Based Nucleophiles 5 Conclusions

Synthesis of novel chiral biquinolyl diphosphine ligand and its applications in palladium-catalyzed asymmetric allylic substitution reactions

A novel chiral diphosphine ligand, 6,6′-bis(diphenylphosphino)-5,5′-biquinoline (BIQAP) was synthesized via two step reactions using optical pure BIQOL as starting material and the molecular structure of (R)-BIQAP was determined by single-crystal X-ray diffraction. The ligand was used for Pd-catalyzed asymmetric allylic substitution reactions. High enantioselectiveties were obtained in the corresponding C–C and C–N bond formation of 1,3-diphenyl-2-propenyl acetate, with dimethyl malonate (up to 94% ee) and with potassium phthalimide (up to 96% ee).

ChemInform Abstract: Catalytic Enantioselective Synthesis of Planar‐Chiral Cyclic Amides Based on a Pd‐Catalyzed Asymmetric Allylic Substitution Reaction.

AbstractThe title reaction is investigated with some achiral linear precursors in the presence of (I) and (II) as the ligands of choice.

Stereoselective synthesis of amino ketones of the pinane series

At present, enantiomerically pure α-pinene and camphor derivatives are widely used in asymmetric syntheses as chiral auxiliaries [1], building blocks [2, 3], and chiral ligands [4]. For example, terpene amino alcohols derived from 2α-hydroxypinan-3-one, were studied as enantioselective ligands in the ruthenium-catalyzed reduction of acetophenone [5], while palladium chelates with bornane diimines and diamines efficiently catalyzed asymmetric allylic substitution reactions [6]. According to published data, search for new enantiomerically pure ligands on the basis of commercially available initial compounds is a topical problem. We previously reported the synthesis of chiral imines and amines from 2α-hydroxypinan-3-one [7]. The resulting nitrogen-containing derivatives were successfully used as ligands to obtain various palladium complexes [8, 9].

Catalytic enantioselective synthesis of planar-chiral cyclic amides based on a Pd-catalyzed asymmetric allylic substitution reaction.

The highly enantioselective synthesis of planar-chiral nine-membered cyclic amides was achieved by the Pd-catalyzed asymmetric allylic cyclization of achiral linear precursors in the presence of a catalytic amount of chiral ligand.

Mechanistic insights into the Pd-catalyzed intermolecular asymmetric allylic dearomatization of multisubstituted pyrroles: understanding the remarkable regio- and enantioselectivity.

In this article we report a comprehensive density functional theory study on the Pd-catalyzed intermolecular asymmetric allylic dearomatization reactions of multisubstituted pyrroles. The calculated results are in line with the previous experimental observations (J. Am. Chem. Soc. 2014, 136, 6590), and the remarkable regio- and enantioselectivity are well explained. Of all the potential nucleophilic sites around the multisubstituted pyrrole ring, the reaction always occurs at the position where the HOMO of the molecule distributes most significantly. In contrast to the common view on the enantioselectivity of the Pd-catalyzed asymmetric allylic substitution reactions, we find that the steric interaction between the nucleophile and the chiral ligand does not have the dominating effect on the enantioselectivity of the reaction. Instead, the interaction between the allyl moiety and the incoming nucleophile plays an important role in the enantioselectivity-determining process.

ChemInform Abstract: Transition‐Metal‐Catalyzed Asymmetric Allylic Dearomatization Reactions

AbstractReview: 72 refs.

Transition-metal-catalyzed asymmetric allylic dearomatization reactions.

Dearomatization reactions serve as powerful methods for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. Among processes of this type, catalytic asymmetric dearomatization (CADA) reactions are attractive owing to the large number of aromatic compounds that are readily available and the fact that they enable direct access to enantiopure polycycles and spirocycles, which frequently are key structural motifs in biologically active natural products and pharmaceuticals. However, as a consequence of their high stabilities, arenes only difficultly participate in dearomatization reactions that take place with high levels of enantioselectivity. Transition-metal-catalyzed asymmetric allylic substitution reactions have been demonstrated to be powerful methods for enantioselective formation of C-C and C-X (X = O, N, S, etc.) bonds. However, the scope of these processes has been explored mainly using soft carbon nucleophiles, some hard carbon nucleophiles such as enolates and preformed organometallic reagents, and heteroatom nucleophiles. Readily accessible aromatic compounds have been only rarely used directly as nucleophiles in these reactions. In this Account, we present the results of studies we have conducted aimed at the development of transition-metal-catalyzed asymmetric allylic dearomatization reactions. By utilizing this general process, we have devised methods for direct dearomatization of indoles, pyrroles, phenols, naphthols, pyridines, and pyrazines, which produce various highly functionalized structural motifs bearing all-carbon quaternary stereogenic centers in a straightforward manner. In mechanistic investigations of the dearomatization process, we found that the five-membered spiroindolenines serve as intermediates, which readily undergo stereospecific allylic migration to form corresponding tetrahydro-1H-carbazoles upon treatment with a catalytic amount of TsOH. It is worth noting that no notable loss of the enantiomeric excess of the spiroindolenine derivatives takes place during the rearrangement process as a consequence of the intervention of a "three-center-two-electron"-type transition state, a proposal that has gained support from the results of DFT calculations. Equally intriguing, upon tuning of the electronic nature of the tethers, pyrroles or indoles undergo unprecedented Ir or Ru catalyzed intramolecular allylic alkylation promoted dearomatization/migration reactions. The operation of this novel reaction pathway provides additional information leading to a greater mechanistic understanding of the transition-metal-catalyzed enantioselective intramolecular functionalizations of pyrroles and indoles. The combined results of this effort provide not only methods for the efficient synthesis of highly enantioenriched fused and spiro polycycles but also novel strategies in the field of asymmetric catalysis.

Synthesis of MeO-PEG-Supported Ferrocenyloxazoline Ligands and Their Application in Asymmetric Catalysis

A simple synthesis of ferrocenyloxazoline derived chiral N,P ligands and N,S ligands immobilized on a MeO- PEG-support is described. The metal complexes of chiral ligands have been successfully applied to 1,3-dipolar cycloaddition reaction of azomethine ylides and asymmetric allylic substitution reaction, providing the products with up to 97% ee and 90% ee, respectively. The MeO-PEG-supported metal complex catalysts can be recycled easily and reused. Keywords PEG; ferrocenyloxazoline ligands; asymmetric catalysis

ChemInform Abstract: Preparation of Chiral Multifunctional Thiourea—Phosphanes and Synthesis of Chiral Allylic Phosphites and Phosphane Oxides Through Asymmetric Allylic Substitution Reactions of Morita—Baylis—Hillman Carbonates.

AbstractThe reactions apply chiral multifunctional thiourea‐phosphane catalyst (TPB) to afford allylic phosphites and phosphane oxides in high yields and enantioselectivities.

Furanoside phosphite–phosphoroamidite and diphosphoroamidite ligands applied to asymmetric Cu-catalyzed allylic substitution reactions

A phosphite–phosphoroamidite and diphosphoroamidite ligand library was applied in the Cu-catalyzed allylic substitution of a range of cinnamyl-type substrates using several organometallic nucleophiles. Results indicated that selectivity depended strongly on the ligand parameters (position of the phosphoroamidite group at either C-5 or C-3 of the furanoside backbone, as well as the configuration of C-3, the introduction of a second phosphoroamidite moiety, the substituents and configurations in the biaryl phosphite/phosphoroamidite moieties), the nature of the leaving group of the substrate and the alkylating reagent. Good enantioselectivities (up to 76%) and activity combined with high regioselectivities were obtained.

Preparation of Chiral Multifunctional Thiourea–Phosphanes and Synthesis of Chiral Allylic Phosphites and Phosphane Oxides through Asymmetric Allylic Substitution Reactions of Morita–Baylis–Hillman Carbonates

AbstractWe developed a synthetic method to prepare chiral multifunctional thiourea–phosphane catalysts for the asymmetric allylic substitution reaction of Morita–Baylis–Hillman carbonates with diphenyl phosphite or diphenylphosphane oxide to give allylic phosphites and allylic phosphane oxides in high yields with excellent enantioselectivity.

Asymmetric Allylic Alkylation of Diverse Nitrogen-Containing Heterocycles

Asymmetric allylic substitution reactions work with a variety of carbon, oxygen, nitrogen, and sulfur nucleophiles (see Review below). However, the use of highly reactive organo-metallic reagents such as organolithiums or Grignard reagents still remains a challenge. The authors previously showed that, under certain conditions, lithiated 2-methylpyridine could participate in allylic alkylations with good yields and reactivity (B. M. Trost, D. A. Thaisrivongs J. Am. Chem. Soc. 2008, 130, 14092). In the present communication, a much wider range of nitrogen-containing heterocycles are shown to undergo similar reactivity.

Asymmetric Organocatalytic Allylic Substitution of Morita–Baylis–Hillman Carbonates with Allylamines for the Synthesis of 2,5-Dihydropyrroles

The asymmetric allylic substitution reaction of MBH carbonates with allylamines has been developed, which affords N-allyl-β-amino-α-methylene esters in high yields and enantioselectivities. After a subsequent ring-closure metathesis of the products, a series of optically active 2,5-dihydropyrroles could be obtained smoothly in high yields without any loss of enantioselectivity. Finally, a tentative mechanism for rationalization of the reaction has been proposed.

Ugi amine-derived P, N- and P, P-ligands with N-alkyltriethoxysilyl tethers: synthesis and evaluation of mesoporous silica-supported Pd complexes in asymmetric allylic substitution reactions

A facile approach to the synthesis of several types of chiral P, N- and P, P-ligands bearing triethoxysilyl groups starting from N, N-diemthyl-1-ferrocenylethylamine (Ugi amine) has been developed. Allyl palladium complexes of these ligands have been prepared, characterized, and grafted on mesoporous silica. The resulting silica-supported complexes have been shown to catalyze asymmetric allylic alkylation and aminations reactions with moderate enantioselectivities.

Chiral phosphinoferrocene carboxamides with amino acid substituents as ligands for Pd-catalysed asymmetric allylic substitutions. Synthesis and structural characterisation of catalytically relevant Pd complexes

An extensive series of chiral amino acid amides prepared from 1'-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) or its planar-chiral isomer, 2-(diphenylphosphino)ferrocene-1-carboxylic acid, have been tested as ligands for Pd-catalysed asymmetric allylic substitution reactions. In alkylation of 1,3-diphenylallyl acetate as a model substrate with dimethyl malonate the ligands performed well in terms of both reaction rate and enantioselectivity, achieving up to 98% ee. In contrast, the reactions of the same substrate with other nucleophiles proceeded either slowly and with poor ee's (amination with benzylamine) or not at all (etherification with benzyl alcohol). In order to rationalise the influence of the ligand structure on the reaction course, three model complexes, viz. [(η(3)-methallyl)PdCl(L-κP)], [(η(3)-methallyl)Pd(L-κ(2)O,P)]ClO(4) and [(η(3)-methallyl)Pd(L-κP)(2)]ClO(4) have been prepared from the achiral amide Ph(2)PfcCONHCH(2)CO(2)Me (L; fc = ferrocene-1,1'-diyl) and structurally characterised. The coordination study showed that the amido-phosphines readily form 1 : 1 complexes as O,P-chelates where the amino acid chirality is brought close to the Pd atom. At higher ligand-to-metal ratios, however, simple P-monodentate coordination prevails, minimising the influence of the chiral amino acid pendant.

ChemInform Abstract: Asymmetric Allylic Substitution Reaction with Nitrogen and Oxygen Nucleophiles Using Monodentate Chiral Phosphine, 9-PBN.

Abstract Asymmetric allylic substitution reactions between 1,3-diphenyl-2-propenyl acetate and various hetero nucleophiles were efficiently carried out using the catalysts derived from the monodentate phosphine ligands, (1R, 2S, 5R, 6S)-2,6-dimethyl-9-phenyl-9-phosphabicyclo[3.3.1] nonane and its enantiomer ((−)- and (+)-9-PBNs), and palladium (0).

ChemInform Abstract: The First Successful Use of Simple 1,2-Aminothioethers as Hybrid Ligands in the Palladium-Catalyzed Asymmetric Allylic Substitution Reaction.

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