Asymmetric hydrogenation of di and trisubstituted enol phosphinates with N,P-ligated iridium complexes

The iridium-catalyzed asymmetric hydrogenation of various di- and trisubstituted enol phosphinates has been studied. Excellent enantioselectivities (up to >99% ee) and full conversion were observed for a range of substrates with both aromatic and aliphatic side chains. Enol phosphinates are structural analogues of enol acetates, and the hydrogenated alkyl phosphinate products can easily be transformed into the corresponding alcohols with conservation of stereochemistry. We have also hydrogenated, in excellent ee, several purely alkyl-substituted enol phosphinates, producing chiral alcohols that are difficult to obtain highly enantioselectively from ketone hydrogenations.     

Enantioselective hydrogenation of diaryl-substituted α,β-unsaturated nitriles

α,β-Unsaturated nitriles can be hydrogenated with enantioselectivities up to 88% ee using chiral ruthenium-diphenylphosphino bisaryl and bisheteroaryl complexes such as ruthenium(II)-BINAP and ruthenium(II)-BINP. Mechanistic investigations indicate that conversion is accelerated by electron-rich ligands and that an additional coordinative group needs be present in order to promote conversion. The chiral products are useful building blocks for the synthesis of histamine H₂ agonists of the arpromidine type.     

Rh(I)-catalyzed enantioselective hydrogenation of (E)- and (Z)-beta-(acylamino)acrylates using 1,4-bisphosphine ligands under mild conditions

[reaction: see text] Rh-Me-BDPMI (1a) complex can be an effective catalyst for the hydrogenations of (E)- and (Z)-beta-(acylamino)acrylates, in which the Z-isomers hydrogenated with the same or even higher ee values than the corresponding E-isomers. The conversion yield and enantioselectivity of E- and Z-isomers were largely dependent on the solvent, and thus, the E-isomers were hydrogenated more effectively in CH(2)Cl(2), whereas the Z-isomers were hydrogenated more effectively in polar MeOH solvent.     

Highly enantioselective reduction of the C–C double bond of N-phenyl-2-methyl- and N-phenyl-2,3-dimethyl- maleimides by fungal strains

The CC double bond of non-substituted and substituted maleimides were hydrogenated to the corresponding succinimides by fungal strains. 2- and 2,3-methylated-phenyl-maleimides were enantioselectively reduced to (R)-N-phenyl-3-methylsuccinimide and to trans-(R,R)-N-phenyl-2,3-dimethylsuccinimide respectively by Aspergillus niger, A. flavus and A. fumigatus (conversion 96 to 99%), Fusarium graminearum and Penicillium sp (conversion: 37 and 39%), with 99% ee.     

Asymmetric reduction and hydrogenation over heterogenous catalysts prepared by reacting nickel-boride with norephedrine

The reduction of acetophenone with borane–THF over heterogeneous catalysts prepared by reacting nickel-boride with (1R,2S)-(−)-norephedrine, afforded (R)-(+)-1-phenylethanol with high enantioselectivity (ee=90%). The catalysts can be recycled two times with little or no loss of performance. The excellent enantioselective properties resulted from the formation of 1,3,2-oxazaborolidine which is strongly anchored at the surface of the nickel-boride. Used for the hydrogenation of acetophenone, 4-methylpentan-2-one and isophorone, the catalyst hydrogenated with a slight predominance of the S configuration. The ee was poor but it remained constant when the catalyst was reused.     

Development of catalysts for the stereoselective hydrogenation of α,β-unsaturated ketones

Iridium phosphinitoxazoline complexes were found to be new efficient catalysts for the asymmetric hydrogenation of arylated α,β-unsaturated ketones. Linear as well as cyclic substrates are hydrogenated with similar success, giving selectivities of up to 99.7% ee.     

神府煤与胜利减压渣油共处理反应特性的研究

用共振搅拌反应器研究了神府煤与胜利减压渣油共处理液化的过程,在430 ℃、460 ℃、490 ℃;3 min～18 min,考察了煤的转化率。结果表明,煤油共处理的最佳反应温度为460 ℃,最佳反应时间为15 min,最高转化率为48.56％,反应过程可分为三个阶段：快速裂解加氢阶段、慢速裂解加氢阶段和缩聚反应阶段。采取了胜利减压渣油加氢处理、添加蒽油、煤油共处理三种措施所得苯可溶物作溶剂,结果表明,胜利减压渣油∶蒽＝1∶1作供氢溶剂时煤转化率有较大提高,达到54.11％;加氢处理后的胜利减压渣油供氢效果也不佳;用煤油共处理所得苯可溶物作供氢溶剂在460 ℃、 6 min时达最高转化率 65.33％。     

Asymmetric hydrogenation of alpha-hydroxy ketones catalyzed by MsDPEN-Cp*Ir(III) complex

Asymmetric hydrogenation of a series of alpha-hydroxy aromatic ketones in methanol catalyzed by Cp*Ir(OTf)(MsDPEN) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the 1-aryl-1,2-ethanediols in up to 99% ee. The reaction can be conducted with a substrate-to-catalyst molar ratio as high as 6000 under 10 atm of H2. 1-hydroxy-2-propanone is also hydrogenated with high enantioselectivity.     

Iridium-catalyzed asymmetric hydrogenation of β-keto esters with f-amphox ligands

The iridium-catalyzed asymmetric hydrogenation of β-keto esters with chiral tridentate P,N,N-ligands (f-amphox) has been developed. Under the optimized conditions, a wide range of β-keto esters can be hydrogenated smoothly, affording the corresponding β-hydroxy esters in good to excellent enantioselectivities (up to 95% ee).     

Immobilized microorganisms in the reduction of ethyl 4-chloro acetoacetate

Microorganisms were used to reduce ethyl 4-chloroacetoacetate (CAAE) to ethyl (S)-4-chloro-3-hydroxybutanoate [(S)-CHBE]. Mucor ramannianus provided 98% conversion with 84% ee. Free cells of Kluyveromyces marxianus led to 95% conversion with 81% ee. After a fractionary factorial design to study the reaction conditions, calcium alginate immobilized cells of K. marxianus furnished the product with 99% conversion with 91% ee.     

Approach to the stereoselective synthesis of melatonin receptor agonist Ramelteon via asymmetric hydrogenation

Asymmetric synthesis of a novel non-benzodiazepine hypnotic drug Ramelteon (TAK-375) was accomplished via asymmetric hydrogenation. Development of the substrate design revealed that a novel class of substrate, allylic acylamine 4a, was hydrogenated with a Ru-BINAP catalyst in 95% ee and 98% yield. The effectiveness and robustness of the reaction were demonstrated on a 700-g scale.     

Highly enantioselective Pd-catalyzed asymmetric hydrogenation of activated imines

Pd/bisphosphines complexes are highly effective catalysts for asymmetric hydrogenation of activated imines in trifluoroethanol. The asymmetric hydrogenation of N-diphenylphosphinyl ketimines 3 with Pd(CF3CO2)/(S)-SegPhos indicated 87-99% ee, and N-tosylimines 5 could gave 88-97% ee with Pd(CF3CO2)/(S)-SynPhos as a catalyst. Cyclic N-sulfonylimines 7 and 11 were hydrogenated to afford the useful chiral sultam derivatives in 79-93% ee, which are important organic synthetic intermediates and structural units of agricultural and pharmaceutical agents.     

Rhodium-catalyzed asymmetric hydrogenation of functionalized olefins using monodentate spiro phosphoramidite ligands

Novel chiral monodentate phosphorus ligands, SIPHOS, were conveniently synthesized from 1,1'-spirobiindane-7,7'-diol. The Rh complexes of SIPHOS can catalyze the hydrogenation of alpha-dehydroamino esters in mild conditions, providing alpha-amino acid derivatives in up to 99% ee. Enamides and beta-dehydroamino esters can also be hydrogenated in good to excellent enantioselectivities (up to 99% and 94% ee, respectively). The SIPHOS ligand with smaller alkyl groups on the N-atom afforded higher enantioselectivity. The X-ray analysis of single crystal showed that the structure of Rh/SIPHOS catalyst is [Rh(COD)((S)-SIPHOS-Me)(2)](+), which clarified the configuration of the catalyst with the monodentate chiral phosphorus ligand in Rh-catalyzed asymmetric hydrogenation. A positive nonlinear effect in the relationship of the optical purities of ligand and product was observed in the hydrogenation of dehydroamino acid derivatives. The kinetic study of hydrogenation showed that the reaction is zero order in the concentration of substrate and first order in the concentration of Rh catalyst and the hydrogenation pressure. The rate of hydrogenation decreased when the Rh/L ratio changed from 1:1 to 1:4.     

Preparation of d-amino acids by enzymatic kinetic resolution using a mutant of penicillin-G acylase from E. coli

We have demonstrated for the first time that d-glutamine (d-Gln) and d-glutamic acid (d-Glu) can be efficiently obtained in high ee (97% and 90%, respectively) by enzymatic kinetic resolution of d,l-Gln and d,l-Glu. This was achieved by enantioselective conversion of the l-enantiomers to their N-phenylacetyl derivatives in aqueous solution, using a mutant of penicillin-G acylase (PGA) from E. coli and phenylacetic acid methylester as the acyl donor. Kinetic modeling studies suggest that the high ee values obtained are both due to a strong enantiopreference for the l-amino acid in the deacylation step of the covalent enzyme intermediate, as well as to completeness of conversion that is transiently obtained as a result of the distinct preference of the mutant PGA for phenylacetic acid methylester over the N-phenylacetyl-l-amino acid product. For the other amino acids tested (Asn, Asp, and Ser), the highest ee values that were obtained for the remaining d-enantiomer are moderate (50–80%) because of lower enantioselectivity in the enzyme deacylation step and due to less complete conversion of the l-amino acid caused by competition for the active site between the acyl donor and the N-phenylacetyl-l-amino acid that is produced. The results demonstrate that the mutated PGA has great potential for the production of optically active d-amino acids by kinetic resolution.     

Asymmetric hydrogenation of aromatic ketones using an iridium(I) catalyst containing ferrocene-based P–N–N tridentate ligands

Six ferrocene-based P–N–N tridentate ligands have been synthesized and applied in the Ir-catalyzed asymmetric hydrogenation of aromatic ketones. A wide range of ketones are hydrogenated enantioselectively to afford the corresponding optically active alcohols in the enantioselectivities of up to 86.6% ee. The substituent groups on the P-phenyl and pyridine rings play an important role with regard to the enantioselectivity.     

Pd-Catalyzed asymmetric hydrogenation of 3-(toluenesulfonamidoalkyl)indoles

A series of 2-substituted 3-(toluenesulfonamidoalkyl)indoles was synthesized by application of (EtO)(2)POH or iodine as the catalyst, and was hydrogenated using chiral Pd catalyst, giving the 2,3-disubstituted indolines with up to 97% ee.     

Ir-catalyzed asymmetric hydrogenation of simple ketones with chiral ferrocenyl P,N,N-ligands

The Ir-catalyzed asymmetric hydrogenation of simple aromatic ketones with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of ketones were hydrogenated to afford the corresponding chiral alcohols in good to excellent enantioselectivities (up to 98%?ee).     

Organolithium-mediated conversion of beta-functionalised aziridines into alkynyl amino alcohols and diamines

The direct conversion of dihydrofuran and dihydropyrrole N-triisopropylbenzenesulfonyl aziridines into alkynyl amino alcohols and diamines respectively can be achieved using 3 equiv. sec-butyllithium-PMDETA in THF; use of n-butyllithium and (-)-sparteine in Et2O gave an alkynyl amino alcohol in 60% ee.     

Ruthenium-catalyzed enantioselective hydrogenation of aryl-pyridyl ketones

Various substituted aryl-pyridyl ketones were hydrogenated in the presence of Ru-XylSunPhos-Daipen bifunctional catalytic system with enantiomeric excesses up to 99.5%. Upon introduction of a readily removable ortho-bromo atom to the phenyl ring, enantiomerically enriched 4-chlorophenylpyridylmethanol was obtained by hydrogenation method with 97.3% ee, which provided an important chiral intermediate for some histamine H(1) antagonists.     

Highly enantioselective bioreduction of 4-bromoacetophenone

Microorganisms were used to reduce 4-bromoacetophenone to (S)-4-bromophenylethanol and (R)-4-bromophenylethanol. After a fractional factorial design to identify the important variables for this reaction, Geotrichum candidum provided a 98.9% conversion with >99% ee of the (R)-isomer, while Rhodotorula rubra led to a 97.6% conversion with a 98.8% ee of the S-isomer.