Palladium-catalyzed allylic substitution assisted by 1,3,2-diazaphospholidine derivatives of (<Emphasis Type="Italic">R,R</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-naphthyltartarimide

P,P-Bidentate diamidophosphite ligands containing the (3R,4R)-3,4-dioxy-1-(1-naphthyl)pyrrolidine-2,5-dione framework and 1,3,2-diazaphospholidine rings with the stereogenic P atoms were obtained. The use of these ligands provides up to 85% ee in Pd-catalyzed asymmetric amination of (E)-1,3-diphenylallyl acetate and up to 95% ee in its asymmetric alkylation with dimethyl malonate.     

Pd-Catalyzed asymmetric transformations involving P*-mono- and P*,N-bidentate diamidophosphites derived from (2S,3S)-N 2,3-dimethyl-N 1-phenylpentane-1,2-diamine

The synthesis of new P*-mono- and P*,N-bidentate diamidophosphites, containing 1,3,2-diazaphospholidine rings formed starting from (2S,3S)-N ²,3-dimethyl-N ¹-phenylpentane-1,2-diamine, is described. Comparison of their efficiency in the Pd-catalyzed enantioselective allylation with (E)-1,3-diphenylallyl acetate showed that up to 97% ee was reached in the reaction involving dimethyl malonate as a C-nucleophile. The Pd-catalyzed desymmetrization of N,N′-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate gave up to 61% ee.     

Diastereomeric P,N-bidentate amidophosphites based on (S,S)- and (R,R)-hydrobenzoin as ligands in the Pd-catalyzed asymmetric allylation

New P,N-bidentate diastereomeric amidophosphite ligands were obtained by phosphorylation of (S)-2-[(phenylamino)methyl]pyrrolidine involving (4S,5S)- and (4R,5R)-2-chloro-4,5-diphenyl-1,3,2-dioxaphospholanes. Their efficiency in the Pd-catalyzed enantioselective allylic substitution was compared, it was found that the reaction involving (E)-1,3-diphenylallyl acetate and pyrrolidine gives up to 75% ee.     

Diamidophosphites with remote P1-stereocentres and their performance in Pd-catalyzed enantioselective reactions

Diamidophosphite ligands based on 1,1′-bis(hydroxymethyl)ferrocene or N¹,N²-bis((S)-1-hydroxy-3,3-dimethylbutan-2-yl)oxalamide and bearing 1,3,2-diazaphospholidine rings with stereogenic phosphorus atoms were obtained. The use of these ligands provides up to 96% ee in Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl acetate, up to 70% ee in Pd-catalyzed desymmetrizations of N,N′-ditosyl-meso-cyclopent-4-ene-1,3-diol bis-carbamate and up to 80% ee in Pd-catalyzed allylic alkylations of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate. Results obtained with a diamidophosphite containing an oxalamide framework show the considerable potential of such ligands in enantioselective catalysis.     

Diastereomeric bisamidophosphites based on oxalamide 1,3-diol in asymmetric metal complex catalysis

Diastereomeric P*,P*-bisdiamidophosphite ligands of the 1,3,2-diazaphospholidine series bearing an oxalamide moiety have been synthesized. A possibility of their application in palladium- and rhodium-catalyzed asymmetric transformations was demonstrated. In Pd-catalyzed sulfonylation of (E)-1,3-diphenylallyl acetate with sodium p-toluenesulfinate enantioselectivity of up to 57% ee, in alkylation with dimethyl malonate of up to 77% ee, in amination with pyrrolidine of up to 78% ee, and in alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate of up to 52% ee, in Rh-catalyzed hydrogenation of (Z-methyl 2-acetamido-3-phenylacrylate of up to 88% ee was achieved. An effi ciency of diastereomeric chirality inducers was compared.     

A first <Emphasis Type="Italic">P,N</Emphasis>-bidentate phosphite with a chiral ketimine fragment. Catalytic properties of its Rh<Superscript>I</Superscript> and Pd<Superscript>II</Superscript> complexes in comparison with those of phosphine analogs

A chiral P,N-bidentate aryl phosphite ligand containing peripheral (R)-(+)-camphor-derived ketimine and its rhodium(I) and palladium(II) chelate complexes were synthesized for the first time. These compounds were found to be suitable for asymmetric allylic substitution. The Pd-catalyzed sulfonylation of 1,3-diphenylallyl acetate with sodium p-toluenesulfinate gave the product in 73% ee; in the alkylation of the same substrate with dimethyl malonate, the ee was 94%. These ee values are higher than the enantioselectivity achieved with the known phosphine analogs.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1942–1945, September, 2004.     

Diamidophosphite based on (1<Emphasis Type="Italic">R</Emphasis>,2<Emphasis Type="Italic">R</Emphasis>)-1,2-bis(3-hydroxybenzamido)cyclohexane in Pd-catalyzed enantioselective allylation

Diamidophosphite ligand bearing (1R,2R)-1,2-bis(3-hydroxybenzamido)cyclohexane fragment and stereogenic phosphorus atoms in the 1,3,2-diazaphopholidine cycles was synthesized. Catalytic performance of this ligand was evaluated in asymmetric allylic substitution. In the reactions involving (E)-1,3-diphenyl allyl acetate as a substrate, up to 94% ee in alkylation with dimethyl malonate and up to 68% ee in amination with pyrrolidine was achieved in the presence of this ligand.     

Novel BIPHEN H2 based P,S-bidentate phosphoramidite ligand in palladium-catalyzed asymmetric allylation

The reaction of P,S-phosphoramidite bearing (R_a)-BIPHEN H2 core and exocyclic amino sulfide as the new ligand with [Pd(ppp-allyl)Cl]₂ in the presence of AgBF₄ yielded a cationic metallochelate [Pd(ppp-allyl)(L)]BF₄. This new chiral inducer provided up to 90% ee in the Pd-mediated allylic substitution reaction of (E)-1,3-diphenylallyl acetate with various C- and N-nucleophiles. In the Pd-catalyzed amination of 2-diethoxyphosphoryl-1-phenylallyl acetate with aniline, ee values up to 57% were achieved.     

Chiral 1,3,2-dioxaphospholane amidophosphite in the palladium-catalyzed enantioselective allylation

Phosphorylation of (S)-1,1,2-triphenylethane-1,2-diol furnishes cyclic P*-chiral amidophosphite, whose application as a ligand in the Pd-catalyzed allyl substitution in 1,3-diphenylallyl acetate provides the products ee up to 70%.     

BINOL-derived diphosphoramidites bearing unsymmetrical 1,2-diamine link and their application in asymmetric catalysis

New P,P-bidentate diastereomeric diphosphoramidite chiral ligands with mixed stereogenic elements and a C₁ backbone symmetry have been prepared from (S_a)- and (R_a)-1,1′-binaphthyl-2,2′-diol (BINOL) and (S)-N-benzyl-1-(pyrrolidin-2-yl)methanamine and are fully characterized. The use of these ligands provides up to 84% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate and up to 95% ee in the Rh-catalyzed asymmetric hydrogenation of α-dehydrocarboxylic acid esters. The results indicate that the catalytic performance is highly affected by the axial chirality of the binaphthyl moieties of the ligand and the nature of the solvent.     

Chiral amido- and diamidophosphites with a peripheral pyridine ring in Pd-catalyzed asymmetric allylation

New chiral amidophosphite and diamidophosphite ligands with exocyclic pyridyl-containing substituents were obtained. Their efficiency in the Pd-catalyzed enantioselective allylic substitution was compared: in the sulfonylation of (E)-1,3-diphenylallyl acetate with sodium p-toluenesulfinate, the ee can reach 77%; its alkylation with dimethyl malonate and amination with pyrrolidine gave up to 80% and 74% ee, respectively. The asymmetric alkylation of cinnamyl acetate with ethyl 2-oxocyclohexanecarboxylate can provide to 68% ee. The complexation of zinc(ii) 5,10,15,20-tetraphenylporphyrinate with diamidophosphite ligand and its influence on conversion and enantioselectivity of the process were studied.     

Asymmetric synthesis of tert-butyl ((1R,4aR,8R,8aR)-1-hydroxyoctahydro-1H-isochromen-8-yl)carbamate

The asymmetric synthesis of methyl (E)-4-((1R,2S,3R)-3-amino-2-((E)-2-methoxycarbonyl-eten-1-yl)cyclohexyl)but-2-enoate 14 has been achieved from dimethyl (2E,7E)-nona-2,7-dienedioate 2. A key step is the asymmetric synthesis of 1-hydroxyoctahydro-1H-isochromene derivative 5 whose X-ray analysis corroborated the stereochemistry of the new stereocenters. The asymmetric synthesis of the isochromenyl acetate derivative 11 shows the potential of this methodology for fused cyclohexanic system heterocyclic synthesis.     

Chiral thiophosphoramide catalyzed asymmetric aryl transfer reactions for the synthesis of functional diarylmethanols

In this investigation, chiral thiophosphoramide 3d was easily prepared from chiral (1R,2R)-1,2-diphenylethylenediamine and then applied as an efficient chiral ligand in the catalytic asymmetric arylation reactions of various aromatic aldehydes. The corresponding diarylmethanol products were produced with good to excellent yields (up to 98%) and enantioselectivities (up to 94%). The recovery of chiral ligand 3d could be as high as 96%.     

[(1S)-endo]-(−)-borneol-tethered oxazoline phosphite as a P,N-bidentate ligand in palladium-catalyzed enantioselective allylic amination

P,N-Bidentate oxazoline phosphite containing an acyclic phosphorus center with [(1S)-endo]-(−)-borneol fragments and its palladium chelate complex [Pd(η-C₃H₅)(η²-P,N)]BF₄ were synthesized for the first time. The use of this new ligand in Pd-catalyzed asymmetric amination of 1,3-diphenylpropenyl acetate with pyrrolidine afforded the product with 86% ee. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2106–2108, December, 2006.     

Development of P1-monodentate diamidophosphites with a C1-symmetric 1,2-diamine backbone: the effects of substituents in the 1,3,2-diazaphospholidine cycle on Pd-catalyzed asymmetric allylations

We have designed and synthesized a small library of modular monodentate diamidophosphite ligands with stereogenic phosphorus atoms. The library was prepared efficiently from the commercially available and inexpensive (S)-N-Boc-amino acids. These novel ligands were screened in the Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl acetate with dimethyl malonate as the C-nucleophile with up to 93% ee being obtained. The results showed that the different substituents in the 1,3,2-diazaphospholidine cycle had remarkable effects on the enantioselectivity.     

Preparation of quarternary ammonium salt-tagged ferrocenylphosphine-imine ligands and their application to palladium-catalyzed asymmetric allylic substitution

A series of novel quarternary ammonium salt-modified chiral ferrocenylphosphine-imine ligands have been synthesized and the molecular structure of BIT5 has been determined by single-crystal X-ray diffraction. The applicability of these ligands in asymmetric C1–C and C1–N bond formation was demonstrated. High enantioselectivity was obtained in the Pd-catalyzed asymmetric substitution of 1,3-diphenyl-2-propenyl acetate, with dimethyl malonate (up to 94.6% ee) and benzylamine (up to 92.6% ee).     

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral P_xN_y-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)₅] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP₂N₄ (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.     

Phosphites and diamidophosphites based on mono-ethers of BINOL: a comparison of enantioselectivity in asymmetric catalytic reactions

Novel P-monodentate phosphite-type ligands have been synthesized in one step from BINOL mono-tosylate and BINOL mono-(?)-menthylcarbonate. The use of these ligands provides up to 96% ee in Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate and up to 99% ee in Rh-catalyzed asymmetric addition of phenylboronic acid to cyclohex-2-enone. The influence of the structural modules such as the nature of phosphorus-containing ring or exocyclic substituent on the enantioselectivity is discussed.     

Acylative kinetic resolution of racemic aromatic β-hydroxy esters catalyzed by chiral nucleophilic N-(1-arylethyl)benzoguanidines

An efficient acylative kinetic resolution of racemic aromatic β-hydroxy esters with cyclohexanecarboxylic anhydride was achieved using newly designed (R)-N-methylbenzoguanidine ((R)-NMBG) derivatives. A series of (R)-NMBG derivatives was synthesized by modifying the original (R)-NMBG catalyst with the introduction of branched N-substituents containing a stereogenic center, and their catalytic performance was evaluated. (R,R)-N-(1-(β-1-Naphthyl)ethyl)benzoguanidine [(R,R)-NβNpEtBG] was found to function as an efficient acyl transfer catalyst for the reaction of a broad variety of substrates, regardless of the substituent type and substitution pattern.     

Facile one-pot synthesis of BINOL- and H8-BINOL-based aryl phosphites and their use in palladium catalysed asymmetric allylation

Novel P-monodentate aryl phosphite ligands have been synthesised in one step from (R)-BINOL, (R)-H₈-BINOL and (R)-H₈-3,3′-dibromo-BINOL. With the new aryl phosphites, up to 86% ee was observed in the asymmetric Pd-catalysed amination of 1,3-diphenyl-2-propenyl acetate with sodium diformylamide. In the enantioselective alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate, up to 97% enantioselectivity was achieved.