Palladium-catalyzed Allylic Alkylation Research Articles

Steric and Electronic Effects of Benzoferrocenyl Phosphine Ligands on Palladium-Catalyzed Allylic Alkylation and Suzuki Coupling Reactions

Five benzoferrocenyl phosphine ligands with the phosphorus atom attached to the 5-position of the benzofer- rocene and some ligand-Mo(CO)5 complexes were prepared and fully characterized; the structure of one ligand was con- firmed by X-ray crystallography. These ligands were applied in palladium-catalyzed allylic alkylation and Suzuki cou- pling of chlorobenzene with phenylboronic acid. Results were compared with those reported previously using ligands hav- ing the phosphorus atom attached to the 4-position of benzoferrocene. This structural modification resulted in an increase of activity of the ligands in allylic alkylation reaction but a decrease of activity in Suzuki coupling reactions. The underly- ing reasons are analyzed with the help of X-ray single crystal determined structures and CO stretching frequencies in the IR spectra of complexes between the ligands and Mo(CO)5.

Synthesis of Chiral (Sulfinyl)furyloxazoline Ligands and Its Application to Enantioselective Palladium-Catalyzed Allylic Alkylation

Chiral ligands containing an oxazoline substituent and a sulfur functionality at the furan ring have been synthesized and examined for enantioselective palladium catalyzed allylic substitution reaction. The enantioselectivity observed was found to be dependent upon the nature of the sulfur center and oxazoline group, up to 91% ee was given with chiral (3-sulfinyl)furan-2-yl ligand.

Electronically varied quinazolinaps for asymmetric catalysis

The synthesis and resolution of electronically varied axially chiral Quinazolinaps is reported. These ligands bear different aryl groups on the donor phosphorus atom and were synthesised as part of our investigations into electronic effects within this ligand class. A diastereomerically pure palladacycle of one ligand was characterised by X-ray crystallography. The application of these Quinazolinaps to the rhodium-catalysed hydroboration of vinylarenes resulted in enantioselectivities of up to 92%. Their application to the palladium-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulted in conversions of up to 99% and enantioselectivities of up to 94%.

Pseudo-domino palladium-catalyzed allylic alkylation/Mizoroki–Heck coupling reaction: a key sequence toward (±)-podophyllotoxin

A formal synthesis of podophyllotoxin was carried out in nine steps. The key pseudo-domino step was accomplished through the succession of an intermolecular palladium-catalyzed allylic alkylation and an intramolecular Mizoroki–Heck coupling reaction.

Synthesis of 3‘,3‘-Difluoro-2‘- hydroxymethyl-4‘,5‘-Unsaturated Carbocyclic Nucleosides

3',3'-Difluoro-2'-hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides 1-3 have been stereoselectively synthesized from ester 10, which can be conveniently prepared from 2,3-isopropylidene-d-glyceraldehyde 7 in five steps. The whole synthesis highlighted the stereoselective Reformatskii-Claisen rearrangement, ring-closing metathesis (RCM), and palladium-catalyzed allylic alkylation, in which the regioselectivity was reversed from that of nonfluorinated substrates.

Stereoselective Palladium-Catalyzed Allylic Alkylation of Peptide Enolates

Stereoselective Palladium-Catalyzed Allylic Alkylation of Peptide Enolates

Synthesis of chiral iminoalkyl functionalised N-heterocyclic carbenes and their use in asymmetric catalysis

A library of new chiral iminoalkyl imidazolium salts has been synthesised from amino acids using a modular design approach. Deprotonation with silver oxide yields silver carbene transfer reagents, which can be used as ligand sources in asymmetric catalysis. Preliminary testing has shown that the ligands induce enantioselectivity in the palladium-catalysed allylic alkylation of 1,3-diphenylprop-3-enyl acetate with dimethyl malonate.

Synthesis of 1,5- P, N-phosphino-sulfoximines through phospha-Michael reaction of alkenyl sulfoximines and their evaluation as ligands in palladium-catalyzed allylic alkylation

We describe a modular synthesis of cyclic and acyclic 1,5- P, N-phosphino-sulfoximines by using a phospha-Michael reaction of the corresponding alkenyl sulfoximines with HPPh 2/KO tBu as key step, which proceeds with medium diastereoselectivity. The palladium-catalyzed allylic alkylation of racemic 1,3-diphenyl allyl acetate with malonate in the presence of a S S R C R C-configured N-benzyl-substituted cyclic phosphino-sulfoximine gave the corresponding alkene with 97% ee in 98% yield. A comparative study of N-substituted phosphino-sulfoximines showed the selectivity of the Pd(0)-catalyst to be dependent not only on the chiral backbone of the ligand but also on the N-substituent and configuration of the sulfoximine group.

Chiral Counteranions in Asymmetric Transition-Metal Catalysis: Highly Enantioselective Pd/Brønsted Acid-Catalyzed Direct α-Allylation of Aldehydes

We have developed a highly enantioselective Pd/chiral acid-catalyzed α-allylation of α-branched aldehydes with an allyl amine as the allylating species that creates all-carbon quaternary stereogenic centers in high yields and enantioselectivities. To our knowledge, this is the first time that a chiral anionic ligand is applied for achieving asymmetric induction in a palladium-catalyzed allylic alkylation reaction.

Highly Stereoselective Peptide Modifications through Pd‐Catalyzed Allylic Alkylations of Chelated Peptide Enolates

Deprotonation of peptides in the presence of zinc chloride gives rise to highly reactive nucleophiles that can be subjected to palladium-catalyzed allylic alkylation reactions. Excellent diastereoselectivities are obtained that are nearly independent of the allylic substrate used. By using this protocol, highly functionalized side chains can also be incorporated in excellent yields and selectivities. The stereochemical outcome of the reaction is exclusively controlled by the peptide chain as long as terminal pi-allyl-palladium complexes are involved. Probably, there is a threefold coordination, at least, of the deprotonated peptide chain to the chelating zinc ion. In such metal peptide complexes, one face of the generated enolate is shielded by the side chain of the adjacent amino acid, thus directing the electrophilic attack onto the opposite face. This behavior explains why an S amino acid always generates an R amino acid (and the other way round).

Quinolinophane-derived alkyldiphenylphosphines: two homologous P,N-planar chiral ligands for palladium-catalysed allylic alkylation

Two novel homologous [2]paracyclo[2](5,8)quinolinophane-derived P,N-bidentate planar chiral ligands have been synthesised and their effectiveness in asymmetric catalysis tested in palladium-catalysed allylic malonylation of 1,3-diphenylpropenyl acetate. The extent of asymmetric induction depends linearly on the ligand/metal molar ratio, indicating the involvement of P,P-type and chelate P,N-type π-allylpalladium complexes in equilibrium. The length of the chain that binds the diphenylphosphine group to the quinolinophane moiety, while appreciably affecting the P,N-complex stability, has little effect on the extent of asymmetric induction, which is due to the greater reactivity of the [PN]- exo–syn–syn– ([PN] xss) with respect to the [PN]- endo– syn– syn– ([PN] nss) π-allylpalladium complex.

Juvenile hormonal activity of mono‐ and polyenehomobenzenes in Drosophila virilis, Spodoptera frugiperda and Araschnia levana

A series of mono- and polyenehomobenzenes was synthesised by a highly regioselective palladium-catalysed allylic alkylation of substituted and unsubstituted benzylic Grignard reagents employing catalytic amounts of catalyst and tested for juvenile hormone activity on the fruit fly Drosophila virilis Sturtevant (Diptera: Drosophilidae), on an important agricultural pest species, the fall armyworm Spodoptera frugiperda JE Smith (Lepidoptera: Noctuidae), and on the map butterfly Araschnia levana L. (Lepidoptera: Nymphalidae). In D. virilis only polyenehomobenzenes with a geranyl chain and a methyl, methoxy or isopropyl group at the para position of the aromatic ring displayed significant juvenile hormonal activity at low doses. A monoenehomobenzene and polyenehomobenzenes with longer allylic chains or without a substituted aromatic ring were not active. In S. frugiperda and in A. levana, a mono-, a di- and a tetraene displayed juvenile hormonal activity. In the lepidopteran species, a trend for the necessity of a substitution at position 4 of the phenyl group for high juvenile hormonal activity was also found.

New Access to Kainic Acid via Intramolecular Palladium-Catalyzed Allylic Alkylation

The formal synthesis of kainic acid was carried out in eleven steps. The key cyclization step was accomplished through an intramolecular palladium-catalyzed allylic alkylation of an allylic sulfone. Further functionalization of the resulting pyrrolidone -featured, inter alia, a N-heterocyclic carbene-copper hydride (NHC-CuH)-mediated stereoconvergent conjugate reduction.

Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates

Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates

Synthesis of 2,6-dimethyl-9-aryl-9-phosphabicyclo[3.3.1]nonanes: their application to asymmetric synthesis of chiral tetrahydroquinolines and relatives

Synthesis of 2,6-dimethyl-9-aryl-9-phosphabicyclo[3.3.1]nonanes from 1,5-cyclooctadiene and their application to asymmetric cyclization leading to chiral tetrahydroquinolines and relatives through palladium-catalyzed allylic alkylation are described.

Palladium‐Catalyzed Regioselective Allylic Alkylation of 1‐Aryl‐2,3,3‐trifluoroallyl Acetates.

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Halide-free highly-pure imidazolium triflate ionic liquids: Preparation and use in palladium-catalysed allylic alkylation

The reaction of three oxygenated heterocycles (tetrahydrofuran, tetrahydropyran, 1,4-dioxane) with trifluoromethane sulfonic anhydride in the presence of the non-nucleophilic base poly(4-vinylpyridine) affords alkylditriflates quantitatively via ring opening. The alkylditriflates react with N-alkylimidazoles providing the bis-imidazolium bis-triflate salts in high yields. Hydroxymethyl substituted oxygenated heterocycles are converted into imidazolium triflate salts without opening of the heterocycle. Two imidazolium salts were characterized by X-ray crystallographic structure determination. The halide free ionic liquids were applied successfully as solvents in the palladium catalysed allylic alkylation. A co-crystal of 15 and tetrabutylammonium triflate has also been characterized by X-ray crystallographic structure analysis.

Aminophosphines with Axial Chirality for Asymmetric Catalysis

The utility of phosphine-containing chiral ligands has been well established and a new type of axially chiral C(aryl)-N(amine) ligand is described. The authors use a simple procedure to access a family of these axially chiral ligands in racemic form. Next, they expertly employ a palladium source with existing chirality to generate dia­stereomers which are separable on a simple silica gel column. The palladium is then titrated off with ethylene diamine to yield the ligands optically resolved, both with >99% ee. Application of the ligands in the palladium-catalyzed allylic alkylation was then employed and all ligands gave ee values ≥89%.

Palladium-Catalyzed Regioselective Allylic Alkylation of 1-Aryl-2,3,3-trifluoroallyl Acetates

The palladium-catalyzed allylic alkylation of 1-aryl-2,3,3-trifluoroallyl acetates, which possess fluorinated olefinic parts, has been demonstrated; the reaction was effectively conducted by using P(t-Bu) 3 or XANTPHOS as a ligand, and the reaction proceeded with a high regioselectivity.

Preparation of Allyl Sulfoxides by Palladium-Catalyzed Allylic Alkylation of Sulfenate Anions

Palladium-catalyzed allylic alkylation of sulfenate anions, generated from beta-sulfinylesters by retro-Michael reaction, can take place under biphasic conditions. This new reaction provides a simple, mild, and efficient route to allyl sulfoxides in good yields.