Showing papers on "Tsuji–Trost reaction published in 2008"

Metal-catalyzed enantioselective allylation in asymmetric synthesis.

Abstract: Metal-catalyzed enantioselective allylation, which involves the substitution of allylic metal intermediates with a diverse range of different nucleophiles or S(N)2'-type allylic substitution, leads to the formation of C-H, -C, -O, -N, -S, and other bonds with very high levels of asymmetric induction. The reaction may tolerate a broad range of functional groups and has been applied successfully to the synthesis of many natural products and new chiral compounds.

Catalytic asymmetric conjugate addition and allylic alkylation with Grignard reagents.

Abstract: Catalytic asymmetric C-C bond-forming reactions using organometallic reagents are among the most important of organic transformations. Frequently, these transformations are key steps in the synthesis of complex biologically active molecules. The conjugate addition (CA) and allylic alkylation (AA) with organometallic compounds are especially versatile in asymmetric C-C bond-forming reactions. These transformations are complementary to the catalytic asymmetric allylic alkylation and the Michael addition, both based on soft carbon nucleophiles (Scheme 1A). For both CA and AA, the organic moiety of the organometallic reagent reacts with the sp carbon of an electron-deficient substrate, converting it to an sp carbon (Scheme 1B). In the case of CA, subsequent quenching of the enolate leads to the final product, whereas for the related AA an appropriate leaving group is expelled to form the chiral product. The organometallic compounds used most frequently for these transformations are organozinc, Grignard, organoaluminium, organolithium and cuprate reagents. Over the last three decades considerable effort has been directed toward the development of efficient catalytic systems for the asymmetric CA and AA reactions using organometallic reagents. Complexes derived from Cu salts and chiral ligands have provided the broadest scope in the catalyzed enantioselective CA and AA of organometallic reagents. Organozinc reagents have been the most successful of the organometallic reagents in this respect. Major contributions and progress in the field of asymmetric CA and AA based on organozinc reagents have been summarized in several reviews. Organomagnesium compounds were among the first organometallic compounds to be applied to synthetic organic chemistry and the use of Grignard reagents in Cu-catalyzed CA was first reported in 1941 by Kharash and Tawney. Achieving chemo-, regioand stereocontrol in both asymmetric conjugate addition (ACA) and asymmetric allylic alkylation (AAA), however, has proven to be challenging and has restricted the application of these transformations, in particular, to total synthesis. Typical selectivity issues pertain to 1,2versus 1,4-addition (Scheme 2A) and SN2versus SN2′-substitution (Scheme 2B). The challenge faced in the development of stereoselective C-C bond-forming reactions is apparent when one considers that, despite three decades of intensive research in this area, only recently has efficient Cu-catalyzed enantioselective CA of Grignard reagents been achieved. The earlier discovery of the highly enantioselective Cu-catalyzed CA of dialkylzinc reagents allowed for replacement of Grignard reagents in this asymmetric C-C bond-forming reaction. Dialkylzinc reagents offer distinct advantages over Grignard reagents in their low reactivity in noncatalyzed reactions and their high tolerance to functional groups both on the substrate and on the organozinc reagent itself. Nevertheless, there are several advantages to the use of common mono-alkylMg halide reagents, most importantly their widespread availability and the ability to transfer all of the alkyl groups of the organometallic compound. The synthetic potential of these asymmetric transformations has driven intensive research in this area, and over the past few years major breakthroughs have been realized in the enantioselective CA and AA of Grignard reagents. * Author for correspondence. E-mail: B.L.Feringa@rug.nl Chem. Rev. 2008, 108, 2824–2852 2824

Intra/intermolecular direct allylic alkylation via Pd(II)-catalyzed allylic C-H activation.

Abstract: The first catalytic direct alkylation of allylic C−H bonds via Pd(II)-catalysis is described in the absence of base. Polysubstituted cyclic compounds can also be constructed by the intramolecular direct allylic alkylation.

Highly site- and enantioselective Cu-catalyzed allylic alkylation reactions with easily accessible vinylaluminum reagents.

Abstract: An efficient method for catalytic asymmetric allylic alkylation (AAA) of allylic phosphates with vinylaluminum reagents is reported. The vinylmetal reagents are prepared by reaction of commercially available DIBAL-H and a terminal alkyne. The resulting vinylaluminum reagent can be used directly, without isolation or purification. AAA reactions are promoted in the presence of 0.5−2.5 mol % of a readily available chiral N-heterocyclic carbene (NHC) complex and 1−5 mol % commercially available and air stable Cu salt (CuCl2·2H2O). The desired products are typically obtained within 2−12 h in 74% to 95% isolated yield, 77% to >98% ee, and in >98% E selectivity; >98% SN2‘ selectivity is obtained in all but one instance (90%). The hydroalumination/catalytic AAA sequence can be performed in a single vessel, on gram scale.

Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of monodentate BINOL-derived phosphoramidites

Abstract: The monodentate BINOL-derived phosphoramidite PipPhos is used as ligand for the iridium-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines If tri-ortho-tolylphosphine and/or chloride salts are used as additives enantioselectivities are strongly enhanced up to 89% NMR indicates that no mixed complexes are formed upon addition of tri-ortho-tolylphosphine

Artificial Metalloenzymes for Asymmetric Allylic Alkylation on the Basis of the Biotin–Avidin Technology†

Abstract: Palladium in the active site: The incorporation of a biotinylated palladium diphosphine within streptavidin yielded an artificial metalloenzyme for the title reaction (see scheme). Chemogenetic optimization of the catalyst by the introduction of a spacer (red star) between biotin (green triangle) and palladium and saturation mutagenesis at position S112X afforded both R- and S-selective artificial asymmetric allylic alkylases.

Counterintuitive Kinetics in Tsuji-Trost Allylation: Ion-pair Partitioning and Implications for Asymmetric Catalysis

Abstract: The kinetics of Pd-catalyzed Tsuji-Trost allylation employing simple phosphine ligands (L = Ar3P, etc.) are consistent with turnover-limiting nucleophilic attack of an electrophilic [L2Pd(allyl)]+ catalytic intermediate. Counter-intuitively, when L is made more electron donating, which renders [L2Pd(allyl)]+ less electrophilic (by up to an order of magnitude), higher rates of turnover are observed. In the presence of catalytic NaBAr′F, large rate differentials arise by attenuation of ion-pair return (via generation of [L2Pd(allyl)]+ ∥ [BAr′F]−) a process that also increases the asymmetric induction from 28 to 78% ee in an archetypal asymmetric allylation employing BINAP (L*) as ligand. There is substantial potential for analogous application of [M]n+([BAr′F]−)n cocatalysis in other transition metal catalyzed processes involving an ionic reactant or reagent and an ionogenic catalytic cycle.

Gold-catalysed allylic alkylation of aromatic and heteroaromatic compounds with allylic alcohols.

Abstract: Friedel–Crafts allylic alkylation of a wide variety of aromatic and heteroaromatic compounds with allylic alcohols catalysed by AuCl3 (5 mol%) under mild conditions at room temperature was accomplished in good to excellent yields (up to 99%) and regioselectivity.

Ligand Controlled Highly Regio- and Enantioselective Synthesis of α-Acyloxyketones by Palladium-Catalyzed Allylic Alkylation of 1,2-Enediol Carbonates

Abstract: The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl 1,2-enediol carbonates 1 can decompose to either α-hydroxyketones 3 or α-hydroxyaldehydes 4. The product distribution is largely controlled by the ligand. Using Lnaph in DME we exclusively obtained the ketone product in good to excellent yields and high enantiomeric excesses. The reaction proceeds under extremely mild conditions, so we can have a broad range of choices of OR. Besides the commonly used protection groups such as OAc and OPiv, a more functionalized group such as methyl but-2-enoyl group can also be used, downstream process of which can afford other synthetically interesting structures.

Development of Biisoquinoline-Based Chiral Diaminocarbene Ligands : Enantioselective SN2' Allylic Alkylation Catalyzed by Copper-Carbene Complexes

Abstract: Chiral biisoquinoline-based diaminocarbene ligands (BIQ) were designed to create a chiral environment extended toward the metal center, which was confirmed by an X-ray structure. The concise ligand synthesis is highlighted by a modified Bischler−Napieralski cyclization of bisamides prepared from readily available chiral phenethylamines, and allows easy variation of the stereodifferentiating groups. The cyclohexyl-BIQ−copper complex is an efficient catalyst for enantioselective SN2‘ allylic alkylation with Grignard reagents showing SN2‘ regioselectivity higher than 5:1 and enantioselectivity in the range of 68−77% ee.

Palladium Nanoparticles in Allylic Alkylations and Heck Reactions: The Molecular Nature of the Catalyst Studied in a Membrane Reactor

Abstract: A series of palladium nanoparticles stabilized by five chiral sugar-based oxazolinyl-phosphite ligands, containing various substituents at the oxazoline and phosphite moieties has been synthesized. They were characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), infrared spectroscopy (IR) and elemental analysis. These nanoparticles were applied in Pd-catalyzed asymmetric allylic alkylation and Heck coupling reactions. A detailed study to elucidate the nature of the active species using a continuous-flow membrane reactor (CFMR), accompanied by TEM observations, classical poisoning experiments, and kinetic measurements have been carried out. Conclusive evidence of the nature of the species involved in the use of PdNPs in asymmetric catalytic reactions has been obtained. The CFMR experiments proved the molecular nature of the true catalysts and all conversions can be justified by the amount of molecular palladium that leached as measured by ICP-AES.

Catalytic Enantioselective Synthesis of Vicinal Dialkyl Arrays

Abstract: With a consecutive "asymmetric allylic alkylation (AAA)/cross-metathesis (CM)/conjugate addition (CA)" protocol it is possible to synthesize either stereoisomer of compounds containing a vicinal dialkyl array with excellent stereoselectivity. The versatility of this protocol in natural product synthesis is demonstrated in the preparation of the ant pheromones faranal and lasiol.

Palladium-Catalyzed Diastereoselective and Enantioselective Allylic Alkylations of Ketone Enolates

Abstract: Lithium and magnesium enolates of cyclohexanone undergo palladium-catalyzed allylic alkylations under mild conditions. Diastereoselectivity and enantioselectivity are observed when the diphenyl- and dimethyl-substituted allylic substrates 1a and 1b are reacted with cyclohexanone or ethyl mesityl ketone. The lithium enolates of cyclohexanone, cyclopentanone and α-tetralone lead to the alkylations products 12–14 in an enantioselective manner. Axially chiral biphenyl- and binaphthyl-bisphosphanes provide high enantioselectivity and/or diastereoselectivity. In the case of the lithium enolates, the presence of lithium chloride is also crucial to reactivity and stereoselectivity. The stereochemical outcome of the allylic alkylation of cyclohexanone and acetophenone has been investigated by the palladium-catalyzed reaction of their lithium enolates with the cis/trans isomeric alkenes (Z)-18 and (E)-19. It turns out that the preformed, non-stabilized enolates attack π-allyl-palladium complexes generated in situ from the face opposite to the noble metal thus following the stereochemical pathway of soft, stabilized carbanions.

Iridium-Catalyzed Enantioselective Allylic Alkylation using Chiral Phosphoramidite Ligand Bearing an Amide Moiety

Abstract: New chiral phosphoramidites with an amide moiety were used for iridium-catalyzed asymmetric allylic alkylation reactions. The best results were obtained with a ligand bearing an oxazolidinone moiety. The reaction of cinnamyl acetate with diethyl sodiomalonate without the use of lithium chloride gave the branched product with 94% ee.

[2.2]Paracyclophane-derived chiral P,N-ligands: design, synthesis, and application in palladium-catalyzed asymmetric allylic alkylation.

Abstract: With the idea of tuning structural flexibility and rigidity, several [2.2]paracyclophane-derived P,N-ligands were designed and synthesized. A full investigation of the relationship between the ligands' structures and their abilities to induce asymmetry in palladium-catalyzed asymmetric allylic alkylations of malonates with 1,3-diphenyl 2-propenyl acetate was carried out, and high yields and enantioselectivities (i.e., 99% yield, 97% ee) were observed while using ligands bearing matched planar and central chirality.

On the Nature of the Intermediates and the Role of Chloride Ions in Pd-Catalyzed Allylic Alkylations: Added Insight from Density Functional Theory

Abstract: The reactivity of intermediates in palladium-catalyzed allylic alkylation was investigated using DFT (B3LYP) calculations including a PB-SCRF solvation model. In the presence of both phosphine and chloride ligands, the allyl intermediate is in equilibrium between a cationic η3-allylPd complex with two phosphine ligands, the corresponding neutral complex with one phosphine and one chloride ligand, and a neutral η1-allylPd complex with one chloride and two phosphine ligands. The η1-complex is unreactive toward nucleophiles. The cationic η3-complex is the intermediate most frequently invoked in the title reaction, but in the presence of halides, the neutral, unsymmetrically substituted η3-complex will be formed rapidly from anionic Pd(0) complexes in solution. Since the latter will prefer both leaving group ionization and reaction with nucleophiles in the position trans to phosphorus, it can rationalize the observed “memory effect” (a regioretention) in the title reaction, even in the absence of chiral ligands.

Preparation of 2,4-disubstituted cyclopentenones by enantioselective iridium-catalyzed allylic alkylation: synthesis of 2'-methylcarbovir and TEI-9826.

Abstract: A broadly applicable synthesis of chiral 2- or 2,4-substituted cyclopent-2-enones has been developed by combining asymmetric iridium-catalyzed allylic alkylation reactions and ruthenium-catalyzed ring-closing metathesis. Enantiomeric excesses (ee values) in the range of 95-99 % ee have been achieved. This method offers a straightforward access to biologically active prostaglandins of the PGA type. As an example, an enantioselective synthesis of the prostaglandin-analogue 13,14-dihydro-15-deoxy-Delta(7)-prostaglandin-A1-methyl ester (TEI-9826) has been carried out. Furthermore, the carbonucleoside 2'-methylcarbovir has been prepared from O-protected 4-hydroxymethyl-2-methyl-cyclopent-2-enone by Pd-catalyzed allylic amination.

High Diversity on Simple Substrates: 1,4-Dihalo-2-butenes and Other Difunctionalized Allylic Halides for Copper-Catalyzed SN2′ Reactions

Abstract: Enantioselective allylic alkylation with an organomagnesium reagent catalyzed by copper thiophene carboxylate (CuTC) was carried out on difunctionalized substrates, such as commercially available 1,4-dichloro-2-butene and 1,4-dibromo-2-butene, and on similar compounds of higher substitution pattern of the olefin for the formation of all-carbon chiral quaternary centers. The high regioselectivity obtained throughout the reactions favored good regiocontrol for the addition of phenyl Grignard reagents. Other difunctionalized substrates (allylic ethers and allylic alcohols) also underwent asymmetric SN2′ substitution.

Transition metal-catalyzed asymmetric reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs.

Abstract: This review describes the development of a new class of chiral phosphorus ligands: amino acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation with cyclic beta-keto esters as prochiral nucleophiles was initially examined using P-chirogenic diaminophosphine oxide 1a, resulting in highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 13, which functions as the actual ligand. Pd-catalyzed asymmetric allylic substitutions of both acyclic and cyclic substrates were also examined using various nucleophiles such as malonate derivatives, nitromethane, aliphatic amines, and aromatic amines, providing a variety of chiral compounds with good to excellent enantioselectivity. In addition, Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were examined using structurally optimized P-chirogenic diaminophosphine oxides, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed catalytic asymmetric process was successfully applied to the catalytic enantioselective synthesis of biologically active compounds, (R)-preclamol, (R)-baclofen hydrochloride, and (-)-paroxetine.

Kinetic resolution of allylic esters in palladium-catalyzed asymmetric allylic alkylations using C–N bond axially chiral aminophosphine ligands

Abstract: Chiral allylic esters, such as ( R )-1,3-diphenyl-2-propenyl acetate ( R )- 2a , were synthesized by kinetic resolution in a palladium-catalyzed asymmetric allylic alkylation using N -aryl indoline type C–N bond axially chiral aminophosphines ( S )- 1 as ligands.

New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences.

Abstract: Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.