Palladium-catalyzed asymmetric allylic alkylation using (R)-2-(methoxymethyl)pyrrolidine-derived aminophosphine ligands

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 7a using a dimethyl malonate–BSA–LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands such as 4 in good yields with good enantioselectivities (up to 96% e.e.).     

Molecular design by cycloaddition reactions—36: Cycloaddition reactions of 7-azabenzonorbornadiene with troponoid compounds and photochemistry of the adducts

Reactions of 7-azabenzonorbornadiene 1 with tropone, tropolone and 2-aminotropone gave exclusively endo-exo adducts 3a–c in good yields. Similar reaction of other troponoid compounds like 2-acetylamino-, 2-acetoxy- and 2-methoxytropone afforded two isomeric cycloadducts in each case. Photolyses of tropone-adduct 3a in various solvents gave the corresponding cyclopropylcarboxylic acid derivatives 7–11 in high yields. Photochemical behaviors of these adducts 3c, e, f, 5e–f and 4d were also examined.     

Asymmetric Weitz–Scheffer epoxidation of conformationally flexible and fixed enones with sterically demanding hydroperoxides mediated by optically active phase-transfer catalysts

The asymmetric Weitz–Scheffer epoxidation of α,β-enones 1a–d with hydroperoxides 2 and mediated by cinchonine- and cinchonidine-derived phase-transfer catalysts (PTCs) 3 affords the optically active epoxides 4 with moderate to very good e.e.s and in near quantitative yields. For the conformationally flexible enone 1b, the enantioselectivity decreases with more sterically demanding tertiary hydroperoxides, while an opposite trend is observed for the rigid s-cis-enone 1. With the bulky cumyl hydroperoxide 2c and the PTC 3c, the enone 1 was converted to the epoxide 4c with the highest enantioselectivity (95% e.e.) so far observed for PTC-catalyzed epoxidations using hydroperoxides as oxygen sources.     

Synthesis of new chiral Schiff bases and their application in the asymmetric trimethylsilylcyanation of aromatic aldehydes

The new chiral Schiff base ligands 1a–1c were synthesized from (1R)-(+)-camphor and found to be efficient catalysts for the enantioselective silylcyanation of aromatic aldehydes. The corresponding aromatic cyanohydrins were obtained in good yields and with enantiomeric excesses (e.e.s) of up to 73%.     

Easy access to optically active Hagemann's esters

The synthesis of optically active Hagemann's esters was investigated. The starting materials in this approach were enamino esters (R,Z)-8, prepared through the condensation of keto ester 6 with (R)-1-phenylethylamine 7. Michael addition reaction of the enamino esters (R,Z)-8 with methyl vinyl ketone gave the expected adducts 10 with good e.e.s of 93–96%. Subsequent annulation of the adducts furnished optically active Hagemann's esters.     

New chiral 2,2′:6′,2″-terpyridine ligands from the chiral pool: synthesis,crystal structure of a rhodium complex and uses in copper- and rhodium-catalyzed enantioselective cyclopropanation of styrene

A number of chiral C₂-symmetric 2,2′:6′,2″ terpyridines L₁–L₄ were synthesized in moderate to good yields from commercially available chiral materials. Copper(II) and rhodium(III) chloride complexes of these ligands were prepared in good yields. The Rh(L₂)Cl₃ complex was isolated as a yellow crystalline solid and characterized by X-ray crystallography. Both Cu(L)(OTf)₂ and Rh(L)(OTf)₃ were found to be active catalysts in the cyclopropanation of styrene with ethyl diazoacetate. Enantioselectivity up to 82% e.e. was observed.     

Stereoselective formation and rearrangement of morpholinium ylides derived from copper carbenoids

Amino diazoacetoacetates 4a–e and 7a,b were prepared from readily available amino alcohols and subjected to copper-catalyzed carbene-transfer reaction. Substrates 4c–e furnished the morpholin-2-ones 5c–e in good yield via the corresponding cyclic ammonium ylides, albeit with poor diastereoselectivity. Substrates 4a,b failed to provide the corresponding morpholinones, perhaps as a result of steric congestion. Cyclic substrates 7a,b underwent conversion to bicyclic morpholinones 8 and 9 in good yield and with moderate to good diastereoselectivity. This result is rationalized via control of the transiently stereogenic ammonium center of the intermediate bicyclic ylides.     

Enantioselective Diels–Alder reactions of chiral racemic acyclic dienes with (SS)-2-(p-tolylsulfinyl)-1,4-naphthoquinone

Enantiopure sulfinylnaphthoquinone (+)-1 reacted with racemic acyclic dienes 2a–f bearing a stereogenic allylic center, through a tandem cycloaddition/pyrolytic sulfenic acid elimination, to afford enantio-enriched compounds 4a–f and 5a–f with good like:unlike selectivities (ca. 75:25) and good enantiomeric excesses (68–82%), arising from the partial kinetic resolution of the racemic dienes.     

Base-induced rearrangements of 3-(α-haloacyl)indoles : A convenient route to indole-3-acetic acids and tryptopholes

Base-induced reactions of 3-(α-haloacyl)indoles have been investigated. Rearrangement is a general reaction observed under the influence of various bases, e.g. hydroxide, hydride and Grignard reagent. Indole-3-acetic acids (20–32) are formed in fair yields when the reaction is performed with sodium hydroxide in 80% aqueous ethanol. The carbon monoxide evolved during the reaction appears to be eliminated from an intermediate cyclopropanone (33). Tryptopholes (53–55) are prepared in good yields by LiAlH₄-reduction of 3-(α-haloacyl)indoles.     

Enantioselective Michael addition of 2-nitropropane to chalcone analogues catalyzed by chiral azacrown ethers based on α-d-glucose and d-mannitol

The chiral monoaza-15-crown-5 type lariat ethers 1 and 2 derived from α-d-glucose and from d-mannitol, respectively, have been applied as phase transfer catalysts in the enantioselective Michael addition of 2-nitropropane to aromatic 3b–c and heteroaromatic 3d–h chalcone analogues. Among the catalysts, the glucose-based 1c with a phosphinoxidobutyl side arm proved to be the most effective, it inducing 34% e.e. for 4b, 59% e.e. for 4c, 80% e.e. for 4d, 64% e.e. for 4e, 17% e.e. for 4f. Catalyst 1a having 3-hydroxypropyl substituent resulted in 81% e.e. for compound 4g. The formation of the (+)-(S)-enantiomer of 4 was preferred using crown ethers 1a–c, while the (−)-(R)-enantiomer was in excess with catalyst 2. The absolute configuration of the Michael adduct 4d was determined by single-crystal X-ray analysis.     

Practical and efficient synthesis of chiral 2,4-disubstituted oxazolines from β-phosphonoamides

Herein we report a practical and efficient method for the synthesis of optically active 2,4-disubstituted oxazolines (S)-1a–h in good to excellent yields. The target compounds were prepared in good yield through the Horner–Wadsworth–Emmons reaction of β-phosphonoamide 3 bearing l-phenylalaninol with commercially available aryl aldehydes followed by the cyclodehydration of the corresponding N-(cinnamoyl)-(S)-phenylalaninol derivatives (S)-2a–h. Additionally, the cyclodehydration of β-phosphonoamide (S)-3 followed by the Horner–Wadsworth–Emmons reaction of β-phosphono-oxazoline (S)-4 with aryl aldehydes also gave the 2,4-disubstituted oxazolines (S)-1a–h.     

Tricyclic isoindolines by Heck cyclization

A series of 4-formyl esters 8a–d was prepared by Michael addition of an enamine with ethyl acrylate. A subsequent condensation with 2-bromobenzylamines 3 gave rise to cyclic enamides 9aa–dd. In a Heck cyclization reaction tricyclic isoindoles 10aa–dd were formed in good yields.     

Further enantioselective syntheses of α-arylalkanamines via intermediate addition of Grignard reagents to a chiral hydrazone derived from (R)-(−)-2-aminobutan-1-ol

Reaction of various aromatic aldehydes with the chiral hydrazine (R)-(−)-2, derived from 2-aminobutan-1-ol (R)-(−)-1, gave the corresponding hydrazones 5–12. Enantioselective addition of EtMgBr or n-BuMgBr to 5–8 gave the trisubstituted hydrazines 13a–f (d.e.s=100%). Catalytic hydrogenolysis (6 bar/Pd–C/110°C/5 h) of the N–N bond of the latter afforded the enantiomerically enriched α-arylalkanamines (R)-(+)-14a–f (e.e.s=90–93%).     

The role of the planar chirality of iron tricarbonyl substituted homochiral amino alcohols in the asymmetric alkylation of aldehydes with diethylzinc

Homochiral amino alcohols bearing an iron tricarbonyl moiety were prepared from 2-amino-1,1-diphenylethanol derivatives 4a–d and [(3S,4S)-η^4,7-octa-4,6-dien-3-ol]Fe(CO)₃ complex 2. The addition of diethylzinc to aldehydes bearing electron donating substituents in the presence of these chiral ligands gave the alkylated products in good enantiomeric excess (up to 93% e.e.), whereas the addition to aldehydes bearing electron withdrawing substituents resulted in low yields and poor enantiomeric excesses.     

A novel amphiphilic push-pull ferrocene derivative: Langmuir–Blodgett films and second-order optical nonlinearity

The Langmuir–Blodgett (LB) films built from the mixture of an amphiphilic push–pull ferrocene derivative (P) and behenic acid were investigated. Langmuir films of P diluted by behenic acid exhibit a very good cohesion and the mixed films can easily be transferred onto solid substrates. Linear dichroism UV-visible and IR spectroscopy measurements of the mixed LB multilayers confirm that the molecules (P) are oriented to the substrate. The nonlinear optical experiments on the mixed monolayer deposited on the CaF₂ slide showed that P displayed efficient optical second harmonic generation (SHG) with a molecular hyperpolarizability (β) as high as 6.0×10^-29 e.s.u.     

Thia-acyliminium cyclisations : Synthesis of five-membered rings and macrocycles

Cyclisations of carbinollactams 1b–3b afford macrocycles 4–6 in good yield by the intermediacy of N-acyliminium species. A similar process applied to lactams 21b–25b affords the pyrrolizidine type compounds 26–35 through consecutive azonium-Cope rearrangement and N-acyliminium ring closure. Additional results are concerned with the use of aromatic rings as π-nucleophiles.     

Synthesis and dyeing properties of some new monoazo disperse dyes derived from 2-amino-4-(2′,4′-dichlorophenyl)-1,3 thiazole

Ten new monoazo disperse dyes (4a–j) have been synthesized by coupling of diazotized 2-amino-4-(2′,4′-dichlorophenyl)-1,3 thiazole (2) with various N-alkyl derivatives of substituted aniline (3a–j) and their dyeing performance on polyester fiber has been assessed. These dyes are characterized by elemental analysis, UV–vis spectra, IR and NMR spectroscopy. The absorption maxima (λ_max) were recorded in DMF and were found to be in the range of 530–600 nm. The dyed polyester fabric showed fair to very good light fastness and very good to excellent washing and rubbing fastness properties with superior depth and levelness.     

Enantioselective syntheses of α-phenylalkanamines via intermediate addition of Grignard reagents to chiral hydrazones derived from (R)-(−)-2-aminobutan-1-ol

The hydrazine (R)-(−)-28 was obtained in four steps from 2-aminobutan-1-ol (R)-(−)-11, and reacted with benzaldehyde to give the hydrazone (R)-(−)-29. Nucleophilic addition of various alkyl Grignard reagents to the latter yielded the corresponding trisubstituted hydrazines (R,R)-30a–g in 70–89% yields and having d.e.s=100% (¹H and ¹³C NMR). Catalytic hydrogenolysis of these hydrazines afforded the corresponding (R)-(+)-α-phenylalkanamines (R)-(+)-31a–g having e.e.s=90–92% (chiral GPC).     

A convenient one-pot synthesis of 4-amino-3-arylpyrazoles from α-phthaloylaminoacetophenones

Condensation of α-phthaloylaminoacetophenones 1a-c with N,N-dimethylformamide dimethyl acetal afforded the novel enamines 3a-c. Cyclization of 3 with hydrazine, alkylhydrazine or phenylhydrazine salts (4a-d) gave 4-phthaloylamino-3-arylpyrazoles 7–9 in high yields. Deprotection of 7–9 was accomplished with hydrazine to provide 4-amino-3-arylpyrazoles 5 in good yields.     

A new and efficient chemoenzymatic route to both enantiomers of α′-acetoxy and α′-hydroxy-α-methoxy cyclic enones

A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting α′-acetoxy and α′-hydroxy-α-methoxy cyclic enones starting from α-hydroxy cyclic enones is described. Protection of 1,2-diketones, manganese(III) acetate-mediated acetoxylation followed by enzyme-mediated hydrolysis of α′-acetoxy enones gives acetoxy enones 3a–d and hydroxy enones 4a–d with high enantiomeric excesses (up to 99%) and good yields. The transesterification of rac-4b in the presence of DMAP afforded (+)-4b and (−)-3b in high enantiomeric excesses (91–94%) and good chemical yields.