The use of a new carboranylamidophosphite ligand in the asymmetric Pd-catalysed allylic alkylation in organic solvents and supercritical carbon dioxide

A novel P-monodentate ligand based on carboranyl alcohol and (S)-2-(anilinomethyl)pyrrolidine provides high enantioselectivities (ee’s up to 95%) in the Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate. The first example of the Pd-catalysed allylic alkylation in supercritical carbon dioxide is also described.     

Allylic geminal diacetates as a a1,a3 synthon. A convenient synthesis of bicyclo[3.3.1]nonan-9-one derivatives

2-Acetoxy bicyclo[3.3.1]nonan-9-one derivatives could be systhesized from the reaction of allylic 1,1-diol diacetates(1) with pyrrolidine enamine of cyclohexanone under the catalysis of palladium complex in one step.     

Stereodivergent synthesis via iridium-catalyzed asymmetric double allylic alkylation of cyanoacetate

Methods that enable the rapid construction of multiple C–C bonds using a single catalyst with high diastereo- and enantio-control are particularly valuable in organic synthesis. Here, we report an Ir-catalyzed double allylic alkylation reaction in which bisnucleophilic cyanoacetate reacted successionally with electrophilic π-allyl-Ir species, producing various pseudo-C₂-symmetrical cyanoacetate derivatives in high yield with excellent stereocontrol. More challenging sequential allylic alkylation/allylic alkylation with two distinct allylic carbonates that can deliver the corresponding products bearing three contiguous tertiary–quaternary–tertiary stereocenters was also developed by using a modified catalytic system, which is revealed to be associated with the quasi-dynamic kinetic resolution of the initially formed diastereomeric monoallylation intermediates. Notably, stereodivergence for this sequential process depending on a single iridium catalyst was successfully realized, and up to six stereoisomers could be predictably prepared by combining the appropriate enantiomer of the chiral ligand for the iridium catalyst and adjusting the adding sequence of two distinct allylic precursors.

Ir-catalyzed asymmetric double AAA reaction of cyanoacetate was developed, affording cyanoacetate derivatives in high yield with excellent stereocontrol. Notably, quasi-DKR is involved in the sequential protocol with two distinct allylic carbonates.     

Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxides: DIAPHOXs. Formal enantioselective synthesis of (−)-paroxetine

An Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxide is described. Asymmetric allylic alkylation of terminal allylic carbonates proceeded using 5 mol % of Ir catalyst, 5 mol % of DIAPHOX 1i, 10 mol % of NaPF₆, 10 mol % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), affording the corresponding branched products in excellent yield and in up to 95% ee. The developed catalytic asymmetric reaction was successfully applied to a formal enantioselective synthesis of (−)-paroxetine.     

Highly enantioselective allylic alkylation of 5H-oxazol-4-ones with Morita-Baylis-Hillman carbonates

An organocatalytic enantioselective allylic alkylation of 5H-oxazol-4-ones with Morita-Baylis-Hillman carbonates has been developed. With 10?mol% of commercially available cinchonidine, a wide range of substituted 5H-oxazol-4-one derivatives were constructed in good-to-excellent yields with high diastereo- and enantioselectivities. The allylic alkylation adducts obtained are valuable precursors for the synthesis of chiral α-alkyl α-hydroxycarboxylic acid derivatives, which represent a series of versatile building blocks in many biologically active compounds.     

Simple d-glucosamine-based phosphine-imine and phosphine-amine ligands in Pd-catalyzed asymmetric allylic alkylations

A new family of phosphine-imine and phosphine-amine ligands based on d-glucosamine were synthesized in order to probe previous asymmetric allylic alkylation results with those of disaccharide ligands of the same class. In most cases, good-to-excellent activities and enantioselectivies were observed with these ligands with ee’s reaching up to 87% in the Pd-catalyzed allylic alkylation reaction of racemic (E)-1,3-diphenyl-2-propenyl acetate with dimethyl malonate as the nucleophile.     

Palladium-catalyzed asymmetric allylic nucleophilic substitution reactions using chiral tert-butanesulfinylphosphine ligands

The asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propenyl acetate 3 with dimethyl malonate proceeded smoothly in the presence of lithium acetate, BSA (N,O-bis(trimethylsilyl)acetamide), [Pd(η³-C₃H₅)Cl]₂, and chiral tert-butanesulfinylphosphine ligand 2c to give the allylic alkylation product in good yield and high enantiomeric excess (up to 93% ee), while the enantioselectivities of allylic amination of 3 with various amines were moderate (up to 76% ee).     

Synthesis of (-)-11 Hydroxy-delta8-6a, 10a-trans-tetrahydrocannabinol

When (?)-Δ⁸-6a, 10a-trans-THC (THC = Tetrahydrocannabinol), in the form of its diacetate, was irradiated in the presence of oxygen and a sensitizer, followed by reduction with NaBH₄, three allylic alcohols were formed: (?)-8α-and (?)-8β-hydroxy-Δ^9,11-THC (proportion 3:1) and (?)-9α-hydroxy-Δ^7,8-THC. Acetylation of the epimeric 8-hydroxy-compounds with Ac₂O/pyridine gave the corresponding diacetates. When (?)-Δ⁸-6a, 10a-trans-THC, in the form of its tetrahydropyranyl derivative, was heated with m-chloroperbenzoic acid, the two epimeric 8,9-epoxides were formed in equal amounts. These compounds, on treatment with butyllithium, afforded (?)-8α- and (?)-8β-hydroxy-Δ^9,11- 6a, 10a-trans-THC-tetrahydropyranylether. After removing the protecting group and treatment with Ac₂O/pyridine the same diacetates, as formed by photooxygenation of (?)-Δ⁸-THC-acetate, were obtained as a 1:1-mixture. On heating these epimeric diacetates to 290° they underwent allylic rearrangement to (?)-11-acetoxy-Δ⁸-THC-acetate. From this (?)-11-hydroxy-Δ⁸-6a, 10a-trans-THC was obtained by treatment with LiAlH₄.     

First P,P*-bidentate phosphine-phosphite-type ligand with a P*-stereocenter in the phosphite moiety: synthesis and application in the Pd-catalyzed asymmetric allylic alkylation

A new P,P*-bidentate phosphine-diamidophosphite bearing an asymmetric phosphorus atom in the 1,3,2-diazaphospholidine ring was obtained. A possibility of its application in the palladium-catalyzed enantioselective allylic substitution was demonstrated. A 70% ee was reached in the alkylation of (E)-1,3-diphenylallyl acetate with dimethyl malonate.     

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.     

Syntheses of (5E)-PGE2 and New 6-Functionalized Derivatives by the Use of Palladium-Catalyzed Decarboxylative Allylic Alkylation

(5 )-Prostaglandin E₂ (7) was synthesized fron ( )-4- -butyldimethylsilyloxy-2-cyclopentenone (1) by 2-alkenyloxycarbonylatlon of the organocopper conjugate-addition adduct (3) followed by intramolecular palladium-catalyzed decarboxylative allylic alkylation. The (5 )-prostaglandin E₂ skeleton was also obtained from the β-keto allylic ester (11) by a similar decarboxylative allylic alkylation. The decarboxylative allylic alkylation of another type of the three-component coupling product (12) gave new 6-methyleneprostaglandin E1 skeleton (15a), which was converted into new 6-methylprosta-glandin I methyl ester (20) 6-methyleneprostaglandin F₁ derivative (16) by two different ways. The stereochemistry of this intramolecular decarboxylative allylic alkylation was discussed in the reaction of 2-[( )- or ( )-2-butenyloxy-carbonyl] cyclopentanone systems.     

Discovery of Novel Catalysts for Allylic Alkylation with a Visual Colorimetric Assay

The first non-phosphane iridium catalyst, made from [{IrCl(cod)}(2)] and iPr-pybox (shown schematically; cod=1,5-cyclooctadiene), for allylic alkylation in neutral medium was discovered by a simple, rapid, and inexpensive screening assay. The red coloration upon treatment of the reaction mixtures with Fast Red (see the 96-well plate) indicates the presence of 1-naphthol and thus the occurrence of allylic alkylation.     

Chiral phenylselenyl derivatives of pyrrolidine and Cinchona alkaloids: nitrogen–selenium donating ligands in palladium-catalyzed asymmetric allylic alkylation

Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu₃P in toluene at 0–25 °C to give the corresponding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethers obtained were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. When chiral selenium pyrrolidine derivatives were applied, the enantioselectivity observed was improved versus the respective sulfur pyrrolidine derivatives up to over 98% ee. The results suggest that the pyrrolidine selenoethers served as the effective N(sp³), Se-donating chiral ligands. The selenoethers obtained from Cinchona alkaloids also gave the allylic alkylation product with a higher ee over those for the corresponding thioethers. The results are in agreement with nucleophilic attack directed at the allylic carbon located trans to the chalcogen atom in the intermediate η³-allylpalladium complex.     

Expanding the scope of atropisomeric monodentate P-donor ligands in asymmetric catalysis. Asymmetric allylic alkylation of 1,3-diphenylpropenyl-1-esters by Pd/BINEPINE catalysts

Monodentate binaphthophosphepines (BINEPINES) have been tested in the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenylallyl esters. Stereoselectivities of up to 92% ee have been achieved in the alkylation of the acetate ester with the C-nucleophile, generated in situ by the action of BSA (N,O-bis(trimethylsilyl)acetamide) on dimethylmalonate in the presence of a catalytic amount of sodium acetate.     

Pd-catalyzed asymmetric allylic alkylation with nitromethane using a chiral diaminophosphine oxide: (S,RP)-Ph-DIAPHOX. Enantioselective synthesis of (R)-preclamol and (R)-baclofen

A Pd-catalyzed asymmetric allylic alkylation with nitromethane using an aspartic acid-derived P-chirogenic diaminophosphine oxide [(S,R_P)-Ph-DIAPHOX] is described. This method was successfully applied to enantioselective synthesis of (R)-preclamol and (R)-baclofen.     

Total synthesis of rac-longamide B

rac-Longamide B has been synthesized in six-steps from known starting materials. The synthesis is highlighted by a novel palladium-catalyzed double allylic alkylation of amidopyrroles with 2-butene-1,4-di-tert-butyl dicarbonate.     

Chiral,non-racemic diols,and α-amino acid-derived β-amino alcohols as templates for chiral catalysts in the Tsuji–Trost reaction

A commercially available collection of β-amino alcohols have been converted to their corresponding β-(o-diphenylphosphino) benzoyloxy(o-diphenylphosphino) benzamides and have been employed in the Tsuji–Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. The best ligand was derived from l-tert-leucinol and when applied to the asymmetric allylic alkylation reaction, yielded the product in an enantiomeric ratio of 99.5:0.5 favoring the (S)-enantiomer.     

Synthesis of P-chirogenic diarylphosphinoacetic acids and their proline derivatives for palladium-catalysed allylic alkylation reactions

The synthesis of P-chirogenic diarylphosphinocarboxylic acids was achieved, from which a new class of amido- and amino-diphosphine ligands (PNP*) were derived, containing an l-proline backbone. The catalytic activities of the novel ligands were evaluated in the palladium-catalysed allylic alkylation reaction of 1,3-diphenylpropenyl acetate.     

CuPd Nanoparticles as a Robust Catalyst for Electrochemical Allylic Alkylation

An efficient CuPd nanoparticle (NP) catalyst (3 nm CuPd NPs deposited on carbon support) is designed for catalyzing electrochemical allylic alkylation in water/isopropanol (1:1 v/v) and 0.2 m KHCO₃ solution at room temperature. The Pd catalysis was Pd/Cu composition‐dependent, and CuPd NPs with a Pd/Cu ratio close to one are the most efficient catalyst for the selective cross‐coupling of alkyl halides and allylic halides to form C?C hydrocarbons with product yields reaching up to 99 %. This NP‐catalyzed electrochemical allylic alkylation expands the synthetic scope of cross‐coupling reactions and can be further extended to other organic reaction systems for developing green chemistry electrosynthesis methods.     

Features and applications of [Rh(CO)(2)Cl](2)-catalyzed alkylations of unsymmetrical allylic substrates

A novel regio- and stereoselective [Rh(CO)2Cl]2-catalyzed allylic alkylation of unsymmetrical allylic carbonates was discovered. The regioselectivity of the reaction favors product ratios in which substitution occurs at the carbon bearing the leaving group. When an enantiomerically enriched carbonate (> or = 99% ee) was examined, the Rh(I)-catalyzed allylic alkylation proceeded stereoselectively to provide the alkylation product with retention of absolute stereochemistry (98% ee). To establish the scope of the [Rh(CO)2Cl]2-catalyzed allylic alkylation, a variety of carbon and heteroatom nucleophiles were examined and the results described. As an application of the Rh(I)-catalyzed allylic alkylation, a series of novel domino reactions have been developed that couple the unique regio- and stereoselective [Rh(CO)2Cl]2-catalyzed alkylation of allylic trifluoroacetates with an intramolecular Pauson-Khand annulation, a cycloisomerization, or a [5+2] cycloaddition. A unique aspect of the method described is the use of a single catalyst to effect sequential transformations in which the catalytic activity is moderated simply by controlling the reaction temperature. Implementation of such processes provides a rapid and efficient entry to a variety of bicyclic carbon skeletons from simple precursors.