Dicationic (BINAP)palladium-catalyzed enantioselective aldol reaction of aldehydes with a silyl enol ether: a simplified practical procedure

The dicationic ((R)-BINAP)palladium-catalyzed enantioselective aldol reaction of benzaldehyde with 1-phenyl-1-trimethylsilylethene has been reinvestigated regarding the reaction conditions in the presence of ((R)-BINAP)palladium chloride and AgSbF₆ with 3 Å molecular sieves. The simplified practical procedure with 1 mol % catalyst loading realized the high performance of 98% yield and 76% ee with reliable reproducibility.     

Catalytic enantioselective Mukaiyama aldol reaction via a chiral indium(III)-pybox complex

A chiral indium(III) complex prepared from indium triflate and a pybox ligand has been developed to give good yields and enantioselectivities (up to 92% ee) in the addition of (1-methoxy-2-methyl-propenyloxy)-trimethylsilane to various aromatic and aliphatic aldehydes via the Mukaiyama aldol reaction.     

Proline-mediated enantioselective construction of tetrahydropyrans via a domino aldol/acetalization reaction

Highly enantioselective synthesis of tetrahydropyrans was accomplished via a domino proline-mediated aldol reaction/intramolecular acetal formation from an aldehyde and inexpensive aqueous tetrahydro-2H-pyran-2,6-diol as a five-carbon unit.     

Total synthesis of (−)-diospongin A and (+)-cryptofolione via asymmetric aldol reaction

Stereoselective synthesis of two distinctive pyranone skeletons diospongin A and cryptofolione has been described based on an asymmetric aldol reaction starting from Chan’s diene. The synthetic strategy involves the enantioselective Mukaiyama aldol, diastereoselective reduction of δ-hydroxy-β-keto ester, a tandem sequence of deprotection, and intramolecular oxa-Michael reaction to obtain diospongin A and an asymmetric allylation and lactone formation using ring-closing metathesis reaction to obtain cryptofolione.     

High stereocontrol in aldol reaction with ketones: enantioselective synthesis of beta-hydroxy gamma-ketoesters by ester enolate aldol reactions with 2-acyl-2-alkyl-1,3-dithiane 1-oxides

The asymmetric aldol reaction of 1,2-diketones, masked as nonracemic 2-acyl dithiane oxides, with lithium enolates derived from several esters and lactones, proceeds with a high degree of stereocontrol at both carbonyl and enolate prochiral centers, the stereocontrol mainly determined by the configuration of the sulfoxide sulfur atom. The sense of induced stereochemistry observed for ester enolates is different from that seen for lactone enolates. Hydrolysis of the dithiane oxide units of the major diastereoisomerically pure aldol products affords enantiomerically pure tertiary alpha-substituted beta-hydroxy-gamma-ketoesters.     

Scope of enantioselective palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine

Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k(rel) values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.     

A new type of amino amide organocatalyzed enantioselective crossed aldol reaction of ketones with aromatic aldehydes

A new type of amino amide organocatalysts was designed and synthesized from commercially available amino acids in easy steps. Their catalytic activities were examined in enantioselective crossed aldol reaction of various acyclic and cyclic ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn:anti?=?1:99, up to 97% ee).     

Direct generation of nucleophilic chiral palladium enolate from 1,3-dicarbonyl compounds: catalytic enantioselective Michael reaction with enones

Generation of chiral palladium enolates from 1,3-dicarbonyl compounds with the palladium aqua complex and its application to the highly efficient catalytic enantioselective Michael reaction with enones are described. The palladium aqua complexes are likely to supply Br?nsted base and Br?nsted acid successively during the reaction. The former activates the carbonyl compounds to give chiral palladium enolates, and the latter cooperatively activates enones. Using a catalytic amount (2-10 mol %) of the palladium complexes, the various 1,3-dicarbonyl compounds including diketones and beta-ketoesters were converted to the desired Michael adducts in good yields (69-92%) with excellent enantiomeric excesses (89-99% ee).     

One-pot synthesis of diaryl ketones from aldehydes via palladium-catalyzed reaction with aryl boronic acids

A Pd-catalyzed coupling-type reaction of aldehydes and organoboronic acids was achieved in the presence of P(1-nap)₃, using Cs₂CO₃ in toluene, providing diaryl ketones with yields ranged from moderate to excellent. The efficiency of this reaction was demonstrated by the compatibility with nitro, cyano, trifluoromethyl, fluoro and chloro groups. Moreover, the rigorous exclusion of air/moisture is not required in these transformations.     

Dienyl homoallyl alcohols via palladium catalyzed ene-type reaction of aldehydes with 1,3-dienes

The combination of Pd catalyst and Xantphos ligand in the presence of Et(3)B nicely promotes the allylation of aldehydes with conjugated dienes to provide dienyl homoallyl alcohols in excellent yields. The reaction occurs selectively at the C-C double bond bearing higher electron density.     

Aluminum enolates via retroaldol reaction: catalytic tandem aldol-transfer—Tischtschenko reaction of aldehydes with aldol adducts of ketones to ketones

Bidentate aluminum chelates derived from biphenol, binaphthol and catechol were found to be efficient catalysts for aldol-transfer reactions of ketone to ketone aldol adducts with aliphatic or aromatic aldehydes giving rise to the formation of aldol adducts of ketones to the aldehydes. In the presence of an excess of an aliphatic aldehyde, a catalytic tandem aldol-transfer—Tischtschenko reaction is observed. The tandem reaction produces monoesters of 1,3-diols with high anti selectivity and with modest to good chemical yield. 1,2-Unsaturated aldehydes are less reactive in the aldol-transfer reaction and require 2-4 times higher load of the catalyst to be used than aliphatic and aromatic aldehydes. Poor diastereoselectivity was observed in the formation of α-substituted aldols and 2-substituted monoesters of anti-1,3-diols indicating that the aldol-transfer reaction is not diastereoselective with the catalysts studied. The utility of the highly 1,3-anti selective formation of diolmonoesters was found to be limited by acyl migration.     

Development of a general, enantioselective organocatalytic Mukaiyama-Michael reaction with α,β-unsaturated aldehydes

LUMO-lowering organocatalysis has been extended to promote the conjugate addition of S-alkyl and 1-pyrrolyl silylketene acetals to α,β-unsaturated aldehydes, yielding both, syn and anti Mukaiyama-Michael products with high levels of enantioselectivity. This strategy allows for the generation of chemically useful 1,5-dicarbonyl systems and again highlights the utility of organocatalysis.     

Diastereoselective aldol reaction of N,N-dibenzyl-alpha-amino aldehydes with ketones catalyzed by proline

[reaction: see text] L-proline-catalyzed direct aldol reaction of L-amino acid-derived N,N-dibenzyl amino aldehydes with acetone, cyclopentanone, or hydroxyacetone provides gamma-amino-beta-hydroxy- or gamma-amino-alpha,beta-dihydroxy-ketones with moderate to excellent yields and diastereoselectivities.     

Bis(μ-iodo)bis((−)-sparteine)dicopper(I): versatile catalyst for direct N-arylation of diverse nitrogen heterocycles with haloarenes

The easy-to-prepare dimeric bis(μ-iodo)bis((−)-sparteine)dicopper(I) complex is shown to be a versatile catalyst for N-arylation of number of NH-heterocycles with structurally divergent aryl halides including activated aryl chloride substrates under mild conditions. The DFT studies not only provide structural insights into square-pyramidal Cu(III) intermediate complexes derived from (−)-sparteine, but also highlight the important role of sterically demanding (−)-sparteine ligand framework in promoting activation of aryl-chlorine bonds for N-arylation of imidazoles.     

The first enantiospecific synthesis of (−)-koumidine via the intramolecular palladium-catalyzed enolate driven cross coupling reaction. The stereospecific introduction of the 19-(Z) ethylidene side chain

The stereospecific synthesis of (−)-koumidine was realized by replacement of triphenylphosphine with tricyclohexylphosphine in the enolate driven palladium-catalyzed cross coupling process.     

Development of highly diastereo- and enantioselective direct asymmetric aldol reaction of a glycinate Schiff base with aldehydes catalyzed by chiral quaternary ammonium salts

A highly efficient direct asymmetric aldol reaction of a glycinate Schiff base with aldehydes has been achieved under mild organic/aqueous biphasic conditions with excellent stereochemical control, using chiral quaternary ammonium salt 1b as a phase-transfer catalyst. The initially developed reaction conditions, using 2 equiv of aqueous base (1% NaOH (aq)), exhibited inexplicably limited general applicability in terms of aldehyde acceptors. The mechanistic investigation revealed the intervention of an unfavorable yet inevitable retro aldol process involving the chiral catalyst. On the basis of this information, a reliable procedure has been established by use of a catalytic amount of 1% NaOH (aq) and ammonium chloride, which tolerates a wide range of aldehydes to afford the corresponding anti-beta-hydroxy-alpha-amino esters almost exclusively in an essentially optically pure form.     

Synthesis of 1,3-diynes via palladium-catalyzed reaction of 1, 1-dibromo-1-alkenes

[reaction: see text] Both symmetric and unsymmetric 1,3-diynes were prepared from the palladium-catalyzed reaction of 1,1-dibromo-1-alkenes. The formation of symmetric 1,3-diynes 2 (homocoupling) was catalyzed by a weak ligand, tris(2-furyl)phosphine (TFP), and the addition of catalytic amount of CuI accelerated the reaction. The synthesis of unsymmetric 1,3-diynes 4 (the Sonogashira reaction) required a highly electron rich tris(4-methoxyphenyl)phosphine as the ligand, and CuI promotes the formation of byproduct 1,1-diynyl-1-alkenes 5.     

Synthesis of (−)-hygrine, (−)-norhygrine, (−)-pseudohygroline and (−)-hygroline via Nef reaction

Synthesis of tropane alkaloids (−)-hygrine, (−)-norhygrine and sedum alkaloids (−)-pseudohygroline and (−)-hygroline is described from l-proline via Henry and Nef reactions.     

Highly diastereo- and enantioselective direct aldol reactions of cycloketones with aldehydes catalyzed by a trans-4-tert-butyldimethylsiloxy-l-proline amide

An organocatalyst derived from trans-4-hydroxy-l-proline and (1S,2S)-1,2-diphenyl-2-aminoethanol catalyzes the direct aldol reactions of cycloketones with a wide scope of aldehydes in high yields and with excellent diastereoselectivities of up to >99:1 and enantioselectivities of up to >99% ee.