Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.     

A third generation chiral phosphorus-containing dendrimer as ligand in Pd-catalyzed asymmetric allylic alkylation

The synthesis of a third generation phosphorus-containing dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2-amino-1-(diphenylphosphinyl)-3-methylbutane is described. In situ complexation of this dendrimer by [Pd(η³-C₃H₅)Cl]₂ affords a catalyst, which is used in asymmetric allylic alkylations of rac-(E)-diphenyl-2-propenyl acetate and pivalate. The percentage of conversion, the yield of isolated 2-(1,3-diphenylallyl)-malonic acid dimethyl ester, and its enantiomeric excess have been measured in each case, and were found to be good to very good (ee from 90% to 95%). Furthermore, the dendritic catalyst can be recovered and reused at least two times, with almost the same efficiency.     

Palladium-catalyzed asymmetric allylic alkylation using chiral hydrazone ligands with ferrocene skeleton

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral phosphine-hydrazone ligands such as 3a in good yields with good enantioselectivities (up to 84% ee).     

Asymmetric synthesis of all-carbon quaternary spirocycles via a catalytic enantioselective allylic alkylation strategy

Rapid access to enantioenriched spirocycles possessing a 1,4-dicarbonyl moiety spanning an all-carbon quaternary stereogenic spirocenter was achieved using a masked bromomethyl vinyl ketone reagent. The developed protocol entails an enantioselective palladium-catalyzed allylic alkylation reaction followed by a one-pot unmasking/RCM sequence that provides access to the spirocyclic compounds in good yields and selectivities.     

Synthesis of chiral 2-alkyl-8-quinolinyl-oxazoline ligands: reversal of enantioselectivity in the asymmetric palladium-catalyzed allylic alkylation

New chiral 2-alkyl-8-quinolinyl-oxazolines were synthesized from 2-alkyl-8-quinolinecarboxylic acids and enantiomerically pure amino alcohols using a convenient procedure. Enantioselective palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate in the presence of 2-alkyl-8-quinolinyl-oxazolines provided an alkylation product with an opposite configuration compared to those obtained from unsubstituted quinolinyl-oxazoline ligands.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

Application of chiral dipyridylmethane ligands in the enantioselective palladium-catalyzed allylic alkylation

New chiral C₁-symmetric dipyridylmethane ligands have been prepared from naturally occurring monoterpenes according to a method based on two consecutive constructions of the pyridine rings. These ligands have been assessed in the enantioselective palladium catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethylmalonate. Enantioselectivity up to 68% ee has been obtained.     

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.     

Palladium(0)-catalyzed amination of allylic natural terpenic functionalized olefins

The palladium(0) catalyzed amination of allylic acetates and carbonates derivatives from terpenic olefins was carried out under mild conditions. The reaction offers a very good method for the preparation of allylic amines and thus to provide a useful entry to new functionalized terpenic olefin products. The mechanism involving a formation of p-allyl-palladium intermediate complex is in good agreement with the results obtained with the optically active substrates, as well as via an analysis of the observed regio-and stereoselectivity.      

Screening of ligands in the asymmetric metallocenethiolatocopper(I)-catalyzed allylic substitution with Grignard reagents

Screening of metallocenethiolate ligands for copper(I)-catalyzed substitution of allylic acetates with Grignard reagents has been carried out. The previously used ligand, lithium (R,S_p)-2-(1-dimethylaminoethyl)ferrocenylthiolate (4a), possessing both central and planar chirality, was the starting point for the screening. It was found that the diastereomeric ligand lithium (R,R_p)-2-(1-dimethylaminoethyl)ferrocenylthiolate (4b) exhibiting reversed planar chirality gave increased enantioselectivity in the allylic substitution, at least when cinnamyl acetate was used as a substrate. The ruthenocene-based ligand lithium (R,S_p)-2-(1-dimethylaminoethyl)ruthenocenylthiolate (4c) gave an enhanced reaction rate, but lower chiral induction. The use of disulfide bis[(R,S_p)-2-(1-dimethylaminoethyl)ferrocenyl]disulfide (7a) as a ligand precursor worked well but resulted in lower enantioselectivity.     

钯催化烯基苯并噁嗪酮基于内球型机理的线性和不对称烯丙基烷基化反应

烯基苯并噁嗪酮作为底物参与反应受到有机合成工作者的广泛关注.在过渡金属催化作用下,烯基苯并噁嗪酮脱除一分子二氧化碳,生成的两性离子中间体既可以被亲核试剂进攻,得到结构丰富的芳香胺,也可以作为1,4-偶极子与硫叶立德,缺电子烯烃或α,β-不饱和醛参与成环,分别生成相应的五元、六元或七元含氮杂环.后者广泛存在于农药、医药和...     

Enantioselective synthesis of 10-allylanthrones via iridium-catalyzed allylic substitution reaction

A highly enantioselective allylic substitution reaction of anthrones with aromatic or aliphatic allyl carbonates was realized by using iridium catalyst prepared from [Ir(COD)Cl]₂ and BHPphos. Substituted 10-allylanthrones were obtained in excellent yields and with excellent enantioselectivity and regioselectivity (up to 98% yield, 99% ee) under mild conditions.     

Palladium(II)-catalyzed claisen rearrangement of allyl vinyl ethers

The Claisen rearrangement of allyl vinyl ethers is catalyzed by PdCl₂(CH₃CN)₂, provided that alkyl substituents protect the vinyl ether double bond from coordination by the metal catalyst.     

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.     

Highly enantioselective catalytic asymmetric Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers

Progress in the catalytic asymmetric Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ether is reported. Application of a more Lewis acidic catalyst, [Cu{(S,S)-t-Bu-box}](H₂O)₂(SbF₆)₂, afforded β-chiral α-keto ester with an enantiomeric excess up to 99%. We suggest a highly polarized transition state for the Lewis acid-catalyzed Claisen rearrangement in order to explain the experimental results.     

Synthesis of the new chiral tridentate ligand bis(pyrid-2-ylethyl) menthylphosphine and its use in the palladium-catalyzed allylic alkylations

We describe the synthesis of a new asymmetric P,N,N′-tridentate ligand (bis(pyrid-2-ylethyl) menthylphosphine, BPEMP), containing two pyridyl rings and (1S,2R,5S)-menthylphosphino group. The ligand is obtained in five steps from natural abundant l-menthol. The coordination behavior of the ligand toward cationic (allylic)Pd(II) moiety and its first application in palladium-catalyzed asymmetric allylic alkylation are presented. Crystallographic and spectroscopic analyses reveal that [(η³-allylic)Pd(BPEMP)]⁺ complex forms only one isomer in the solid state as well as in solution.     

Synthesis of diethyl 2-methyl-bicyclo[3.1.1]hept-2-ene-6,6-dicarboxylate by Pd-catalyzed intramolecular allylic alkylation. Stereoselective preparation of its optically homogeneous form from R-(−)-carvone

A new route to racemic diethyl 2-methyl-bicyclo[3.1.1]hept-2-ene-6,6-dicarboxylate (±)-1a by means of a palladium-catalyzed intramolecular allylic alkylation exercised on malonate-ester derivatives has been developed from R-(−)-carvone. The stereocontrolled synthesis of the enantiomerically pure (−)-1b by application of a six-step reactions sequence with a 28% overall yield from acetal 8, has been accomplished.     

Palladium(0)-catalyzed allylic alkylation of diketoester-dioxinones with allyl acetates under neutral conditions: synthesis of hexasubstituted benzene derivatives

Intermolecular palladium(0)-catalyzed allylic alkylation of diketoester-dioxinones was performed under neutral conditions with 2-alkenyl and 2-cycloalkenyl acetates. Subsequent aromatization using cesium carbonate gave rise to isopropylidene-protected hexasubstituted resorcylates.     

Highly regioselective Pd-catalyzed allylic alkylation of fluorobis(phenylsulfonyl)methane

A highly regioselective palladium-catalyzed allylic alkylation of fluorobis(phenylsulfonyl)methane has been studied. Using different allylic carbonates, a variety of terminal mono-fluoromethylated compounds were achieved in 85-99% yields with high regioselectivities.     

Effective synthesis of bicyclodienes via palladium-catalyzed asymmetric allylic alkylation and ruthenium-catalyzed cycloisomerization

[n.3.0]Bicycles (n = 3–6) can be synthesized using palladium-catalyzed asymmetric allylic alkylation followed by ruthenium-catalyzed cycloisomerization. New types of triarylphosphino-1,2-diaminooxazoline ligands show the same high levels of enantioselectivity observed with Trost ligand when employed in Pd-catalyzed allylic alkylation reactions. The enyne products of these allylic alkylation reactions were further elaborated using a Ru-catalyzed redox isomerization process, for which a mechanism is proposed.