Organo-catalyzed highly diastereo- and enantio-selective direct aldol reactions in water

The asymmetric direct aldol reactions of a wide scope of aromatic aldehydes, with unmodified ketones in the presence of 1 mol % of organocatalyst prepared from (2R,3R)-diethyl 2-amino-3-hydroxysuccinate and trans-4-hydroxy-l-proline, were performed in water, affording aldol products in high yields with excellent diastereoselectivities of up to >99:1 and enantioselectivities of up to 98%.     

Asymmetric cyano-ethoxycarbonylation of aldehydes catalyzed by self-assembled titanium catalyst

A new self-assembled catalyst based on titanium complex has been developed for the effective enantioselective cyano-ethoxycarbonylation of aldehydes. The self-assembled catalyst was readily prepared from (R)-3,3′-bis((methyl((S)-1-phenylethyl)amino)methyl)-1,1′-binaphthyl-2,2′-diol (1h), N-((1S,2R)-2-hydroxy-1,2-diphenylethyl)acetamide (2b), and tetraisopropyl titanate (Ti(OiPr)₄). A variety of aromatic aldehydes, aliphatic aldehydes, and α,β-unsaturated aldehydes were found to be suitable substrates in the presence of the self-assembled titanium catalyst (5 mol % 1h, 5 mol % 2b, and 5 mol % Ti(OiPr)₄). The desired cyanohydrin ethyl carbonates were afforded with high isolated yields (up to 95%) and moderate to good enantioselectivities (up to 92% ee) under mild conditions (at −15 °C). A possible catalytic cycle based on the experimental observation was proposed.     

Transition-metal complexes of phenoxy-imine ligands modified with pendant imidazolium salts: Synthesis, characterisation and testing as ethylene polymerisation catalysts

Reaction between 3-((1R,2R)-2-{[1-(3,5-di-tert-butyl-2-hydroxy-phenyl)-meth-(E)-ylidene]-amino}-cyclohexyl)-1-isopropyl-4-phenyl-3H-imidazol-1-ium bromide (1a) or the derivative 3-((1R,2R)-2-{[1-(2-hydroxy-5-nitro-phenyl)-meth-(E)-ylidene]-amino}-cyclohexyl)-1-isopropyl-4-phenyl-3H-imidazol-1-ium bromide (1b) and metal halides MCl_x.yTHF (M = Zr, x = 4, y = 2; M = V, x = y = 3; M = Cr, x = y = 3), in THF, at −78 °C gives the metal complexes of general formula [MCl_x(κ²-N,O-OC₆H₂R¹R²C(H)N-C₆H₁₀-Im)₂][Br]₂ (where M = Zr, x = 2, R¹ = R² = ^tBu, 2; M = Zr, x = 2, R¹ = H, R² = NO₂, 3; M = V, x = 1, R¹ = R² = ^tBu, 4; M = Cr, x = 1, R¹ = R² = ^tBu, 5; M = Fe, x = 0, R¹ = R² = ^tBu, 6; Im = 1-isopropyl-4-phenyl-3H-imidazol-1-ium-3-yl). ¹H and ¹³C NMR spectroscopy of 2 and 3 indicate κ²-N,O-ligand coordination via the phenoxy-imine moiety with pendant imidazolium salt that is corroborated by a single crystal structure of 6. Compounds 2, 3, 4 and 5 were tested as precatalysts for ethylene polymerisation in the presence of methylaluminoxane (MAO) cocatalyst, showing low activity. Selected polymer samples were characterised by GPC showing multimodal molecular weight distributions.     

Stereoselective synthesis of novel benzoins catalysed by benzaldehyde lyase in a gel-stabilised two-phase system

Asymmetric benzoin condensation was performed using recombinant benzaldehyde lyase (BAL) from Pseudomonas fluorescens Biovar I. To enable the conversion of hydrophobic substrates, the enzyme was entrapped in polyvinyl alcohol and suspended in hexane. Compared to the reported application of the biocatalyst in an aqueous phase containing 20% DMSO, the productivity of the resulting gel-stabilised two-phase system was 3-fold better. The entrapment process had an efficiency of >90%, no enzyme or cofactor was lost during reaction or storage. The entrapped enzyme was stable in hexane for 1 week at 4 °C and more than 1 month at −20 °C. Without preceding optimisation the novel benzoins (R)-1,2-di(3-furanyl)-2-hydroxyethanone, (R)-2-hydroxy-1,2-di(3-thienyl) ethanone, (R)-1,2-di(4-ethoxyphenyl)-2-hydroxyethanone, (R)-1,2-di(3-ethoxyphenyl)-2-hydroxyethanone, (R)-2-hydroxy-1,2-di(3-tolyl)ethanone, and (R)-1,2-di(benzofuran-2-yl)-2-hydroxyethanone were prepared with yields up to 31.8% and enantiomeric excess >99%.     

Enantioselective alkynylation to aldimines catalyzed by chiral 2,2′-di(2-aminoaryloxy)-1,1′-binaphthyl-copper(I) complexes

The enantioselective alkynylation of aldimines with terminal acetylenes catalyzed by chiral Cu(I) complexes with (R)-2,2′-di(2-aminoaryloxy)-1,1′-binaphthyl ligands (7) was examined. Chiral C₂-symmetric N,N-ligands 7, which have primary aniline moieties, were readily prepared from inexpensive (R)-1,1′-binaphthol (BINOL) as a chiral source. In particular, the reaction of N-benzylidenebenzeneamine 1a with phenylacetylene 2a proceeded smoothly in the presence of 5 mol % of (CuOTf)₂·C₆H₅CH₃ and 10 mol % of (R)-7d at room temperature for 24 h, and the corresponding propargylamine 3a was obtained with up to 82% ee.     

Ruthenium-catalysed asymmetric transfer hydrogenation of N-(tert-butanesulfinyl)imines

The ruthenium complex prepared from [RuCl₂(p-cymene)]₂ and (1S,2R)-1-amino-2-indanol is a very efficient catalyst for the asymmetric transfer hydrogenation of (R)-N-(tert-butanesulfinyl)ketimines in isopropanol. By carefully removing all possible moisture from the reaction medium, chiral primary amines with very high optical purities (up to >99% ee) can be easily prepared in excellent yields by the diastereoselective reduction of the imines followed by removal of the sulfinyl group under mild acidic conditions. Reaction times of 1-4 h were needed to complete the reduction reactions when they were performed at 40 °C.     

Infrared spectroscopy and outer product analysis for quantification of fat, nitrogen, and moisture of cocoa powder

The combination of the near infrared (NIR) and Fourier-transform infrared (FTIR) absorbance spectra (1100-2500 nm and 4000-600 cm⁻¹) of 100 cocoa powder samples was used to build calibration models for the determination of the content of fat, nitrogen, and moisture. The samples that comprised the dataset had an average composition of 13.51% of fat, 3.77% nitrogen, and 3.98% moisture. The fat content ranged from 2.42 to 22.00%, the nitrogen from 0.88 to 4.48%, and moisture from 1.60 to 7.80%. For NIR, the relative root mean square error of cross-validation (RMSECV) was 7.0% (R² = 0.96) for fat, 1.7% (R² = 0.98) for nitrogen, and 5.2% (R² = 0.94) for moisture. For FTIR, the relative RMSECV was 10.4% (R² = 0.94) for fat and 3.9% (R² = 0.95) for nitrogen. However, for moisture, it was not possible to build a calibration model with suitable predictability. The combination of the NIR and FTIR domains (data fusion) by outer product analysis PLS1 allowed to predict these parameters and to characterise frequencies in one domain based on the information of the other domain. This work allows to conclude that the second derivative of NIR is the recommended procedure to quantify fat, nitrogen, and moisture content in cocoa powders by infrared spectroscopy.     

Platinum(II) complex-catalyzed enantioselective aldol reaction with ketene silyl acetals in DMF at room temperature

[{(R)-binap}Pt(μ-OH)]₂2X is a weak Lewis acid, which can catalyze the enantioselective aldol reaction of aldehydes with ketene silyl acetals in DMF at room temperature. The platinum(II) complex-catalyzed the enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-(1-trimethylsilyloxy)propene gave the corresponding aldols in high yields with enantioselectivity up to 92%. With 5 mol % loading of the complexes, the enantioselective aldol reaction of aldehydes with 1-benzyloxy-1-(trimethylsilyloxy)propene smoothly proceeded in DMF containing 10% HMPA as to predominantly give anti-propionates with enantioselectivity up to 89%, irrespective of the silyl nucleophile geometry.     

Enantioselective allylation of alkyl glyoxylates catalyzed by (salen)chromium(III) complexes

The enantioselective addition of allylstannanes and allylsilanes to alkyl glyoxylates of type 1, catalyzed by chiral (salen)Cr(III) complexes 3, has been studied. We have found that the reaction proceeded smoothly for low loading (1-2 mol %) of (1R,2R)-(salen)Cr(III)BF₄3a or (1R,2R)-(salen)Cr(III)ClO₄3c, and allyltributyltin under simple, undemanding conditions, affording (R)-2-hydroxypent-4-enoic acid esters 2 in good yield (61-90%) and enantioselectivity (58-76% ee).     

Pd-catalyzed addition-carbocyclization of α,ω-diynes with H-P(O)R2 compounds

Chelating phosphines are much higher performing than mono-dentate phosphines in palladium-catalyzed reaction of α,ω-diynes with HP(O)R¹R² (R¹,R² = Ph, alkoxy) to afford (E)-3-(phosphorylmethylene)-2-methylcyclopentenes.     

Synthesis and reactivity towards carbon monoxide of an optically active endo five-membered ortho-cyclopalladated imine: X-ray molecular structure of trans-(μ-Cl)2[Pd(κ-C,N-(R)-C6H4-CHN-CHMe-Ph)]2

(R)-1-Phenylethyl-benzylidene-amine (1) reacted with Pd(OAc)₂ in acetic acid at 60 °C under nitrogen affording the acetato-bridged dinuclear endo five-membered ortho-cyclopalladated compound (μ-OAc)₂[Pd(κ²-C,N-(R)-C₆H₄-CHN-CHMe-Ph)]₂ (2) in 65% yield. Compound 2 was converted by a metathesis reaction with LiCl into the corresponding chloro-bridged dinuclear cyclopalladated compound (μ-Cl)₂[Pd(κ²-C,N-(R)-C₆H₄-CHN-CHMe-Ph)]₂ (3). ¹H NMR of CDCl₃ solutions of compounds 2 and 3 treated separately with py-d₅, (R)-1-phenylethylamine and racemic 1-phenylethylamine were consistent with the endo cyclopalladated structure and the R absolute configuration of the chiral carbon atoms of compounds 2 and 3. Compounds 2 and 3 reacted with carbon monoxide in methanol affording, as major compounds, methyl 2-formylbenzoate (91% chemical yield) and the epimers of 3-methoxy-2-[(R)-1-phenylethyl]isoindolin-1-one (64% chemical yield) in ca. 20% diastereomeric excess, respectively. The trans isomer of compound 3 crystallized in the P2₁ monoclinic space group with a = 10.430(4) Å, b = 12.082(8) Å, c = 11.168(4) Å and β = 95.20(3)° and presented C-H?Cl intramolecular and C-H?Pd intermolecular non-conventional hydrogen bonds.     

Highly diastereoselective chemoenzymatic synthesis of (2′R)- and (2′S)-2′-deoxy[2′-H]guanosines

In an effort to develop an efficient synthetic method of highly diastereoselective (2′R)- and (2′S)-2′-deoxy[2′-²H]guanosines, chemoenzymatic conversion was investigated. The synthesis of (2′R > 98% de)-2′-deoxy[2′-²H]guanosine was achieved by biological transdeoxyribosylation using (2′R > 98% de)-2′-deoxy[2′-²H]uridine, 2,6-diaminopurine, and Enterobacter aerogenes AJ-11125, followed by treatment with adenosine deaminase. (2′S > 98% de)-2′-Deoxy[2′-²H]guanosine was synthesized from (2′S > 98% de)-2′-deoxy[2′-²H]uridine and 2,6-diaminopurine using thymidine phosphorylase and purine nucleoside phosphorylase instead of E. aerogenes AJ-11125.     

A series of new zirconium complexes bearing bis(phenoxyketimine) ligands: Synthesis, characterization and ethylene polymerization

A series of new zirconium complexes bearing bis(phenoxyketimine) ligands, bis((3,5-di-tert-butyl-C₆H₂-2-O)R₁CN (2-R₂-C₆H₄))ZrCl₂ {R₁ = Me, R₂ = H (2a); R₁ = Et, R₂ = H (2b); R₁ = Ph, R₂ = H (2c); R₁ = 2-Me-Ph, R₂ = H (2d); R₁ = 2-F-Ph, R₂ = H (2e); R₁ = 2-Cl-Ph, R₂ = H (2f); R₁ = 2-Br-Ph, R₂ = H (2g); R₁ = Ph, R₂ = Me (2h); R₁ = Ph, R₂ = F (2i)}, have been prepared, characterized and tested as catalyst precursors for ethylene polymerization. Crystal structure analysis reveals that complex 2c has a six coordinate center in a distorted octahedral geometry with trans-O, cis-N, cis-Cl arrangement which possesses approximate C₂ symmetry. When activated with methylaluminoxane (MAO), complexes 2a-2i exhibited high ethylene polymerization activities of 10⁶-10⁸ g PE (mol M h)⁻¹. Compared with the bis(phenoxyimine) zirconium analogues bis((3,5-di-tert-butyl-C₆H₂-2-O)CHNC₆H₅)ZrCl₂ (3), the introduction of substituent on the carbon atom of the imine double bond enhanced the catalytic activity and molecular weight of prepared polyethylene. Especially, when the H atom at the carbon atom of the imine double bond was replaced by 2-fluoro-phenyl with strong electronic-withdrawing property, complex 2e displayed the highest catalytic activity, and the polyethylene obtained possessed the highest molecular weight and melt point.     

Desymmetrization of malonamides via an enantioselective intramolecular Buchwald-Hartwig reaction

A new form of enantioselective nitrogen arylation reaction is described. Beginning with symmetrical α-(2-bromobenzyl)malonamides, intramolecular palladium-catalyzed cross-coupling using a catalyst system including 3.3 mol % Pd(OAc)₂ and 6.6 mol % of the chiral biaryl monophosphine (R)-MOP, desymmetrized quinolinone products are obtained in nearly quantitative yields in enantiomeric ratios up to 88:12. This Letter represents a rare example of enantioselective Buchwald-Hartwig reaction.     

Palladium(II)-catalyzed 1,4-addition of arylboronic acids to β-arylenals for enantioselective syntheses of 3,3-diarylalkanals: a short synthesis of (+)-(R)-CDP 840

1,4-Addition of arylboronic acid to trans-β-arylenals proceeded smoothly in acetone-water (10/1) at 10-25 °C in the presence of [Pd(S,S-chiraphos)(PhCN)₂](SbF₆)₂ (0.5 mol %), AgX (X = BF₄, SbF₆, 10 mol %) and aqueous 42% HBF₄ to afford optically active 3,3-diarylalkanals with high enantioselectivities in a range of 86-97% ee. The protocol provided a method for short-step synthesis of optically active (+)-(R)-CDP 840.     

Chiral terpene auxiliaries. Part 1: Highly enantioselective reduction of ketones with borane catalyzed by an oxazaborolidine derived from (−)-β-pinene

(1R,2S,3R,5R)-3-Amino-6,6-dimethyl-2-hydroxybicyclo[3.1.1]heptane was synthesized in three steps from (−)-β-pinene. It was used for the in situ generation of a B-methoxy-oxazaborolidine catalyst for the asymmetric reduction of alkyl-aryl ketones with borane-dimethyl sulfide complex. In the presence of 3 mol % of the catalyst, the product alcohols were obtained in high yields and with enantiomeric excesses in the range of 93-98%.     

Synthesis and decarboxylation of N-acyl-α-triphenylphosphonio-α-amino acids: a new synthesis of α-(N-acylamino)alkyltriphenylphosphonium salts

4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF₄ at room temperature to give N-acyl-α-triphenylphosphonioglycines 3 (R² = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones 2 react with water in CH₂Cl₂/THF solution without any acidic catalyst at 0-5 °C in a few days yielding N-acyl-α-triphenylphosphonio-α-amino acids 3 (R² = Me) or α-(N-acylamino)alkyltriphenylphosphonium salt 4 (R² = CH₂OMe). α-Triphenylphosphonio-α-amino acids 3, on heating up to 105-115 °C under reduced pressure (5 mmHg) or on treatment with diisopropylethylamine in CH₂Cl₂ at 20 °C undergo decarboxylation to give the corresponding α-(N-acylamino)alkyltriphenylphosphonium salts 4, usually in very good yields.     

Study of ferrocenyl-substituted Co2(CO)6-bispropargylic alcohol complexes as substrates for the formation of chains and macrocycles

Treatment of [Fc-1-R¹-1′-R²] (R¹ = H, R² = CH(O); R¹ = H, R² = CMe(O); R¹ = R² = CMe(O)) with LiCCCH₂OLi (prepared in situ from HCCCH₂OH and n-BuLi) affords the ferrocenyl-substituted but-2-yne-1,4-diol compounds of general formula [Fc-1-R¹-1′-{CR(OH)CCCH₂OH}] (R¹ = R = H (1a); R¹ = H, R = Me (1b); R¹ = CMe(O), R = Me (1c)) in low to high yields, respectively (where Fc = Fe(η⁵-C₅H₄)₂). In the case of the reactions of [Fc-1-R¹-1′-R²] (R¹ = H, R² = CH(O); R¹ = R² = CMe(O)), the by-products [Fc-1-R¹-1′-{CR(OH)(CH₂)₃CH₃}] (R¹ = R = H (2a); R¹ = CMe(O), R = Me (2c)) along with minor quantities of [Fc-1,1′-{CMe(OH)(CH₂)₃CH₃}₂] (3) are also isolated; a hydrazide derivative of dehydrated 2c, [1-(CMeCHCH₂CH₂CH₃)-1′-(CMeNNH-2,4-(NO₂)₂C₆H₃)] (2c′), has been crystallographically characterised. Interaction of 1 with Co₂(CO)₈ smoothly generates the alkyne-bridged complexes [Fc-1-R¹-1′-{Co₂(CO)₆-μ-η²-CR(OH)CCCH₂OH}] (R¹ = R = H (4a); R¹ = H, R = Me(4b); R¹ = CMe(O), R = Me (4c)) in good yield. Reaction of 4a with PhSH, in the presence of catalytic quantities of HBF₄ · OEt₂, gives the mono- [Fc-1-H-1′-{Co₂(CO)₆-μ-η²-CH(SPh)CCCH₂OH}] (5) and bis-substituted [Fc-1-H-1′-{Co₂(CO)₆-μ-η²-CH(SPh)CCCH₂SPh}] (6) straight chain species, while with HS(CH₂)_nSH (n = 2,3) the eight- and nine-membered dithiomacrocylic complexes [Fc-1-H-1′-{cyclo-Co₂(CO)₆-μ-η²-CH(S(CH₂)_n-)CCCH₂S-}] [n = 2 (7a), n = 3 (7b)] are afforded. By contrast, during attempted macrocyclic formation using 4b and HSCH₂CH₂OCH₂CH₂SH dehydration occurs to give [Fc-1-H-1′-{Co₂(CO)₆-μ-η²-C(CH₂)CCCH₂OH}] (8). Single crystal X-ray diffraction studies have been reported on 2c′, 4b, 4c, 7b and 8.     

Titanium (IV) complexes based on substituted 2-[(2-hydroxyethyl)]aminophenols

Novel substituted 2-[(2-hydroxyethyl)]aminophenols, MeN(CHR¹CR²R³OH)(C₆H₄-o-OH) (2-5), were synthesized by the reaction of 2-methylaminophenol with corresponding oxiranes. Titano-spiro-bis(ocanes) [MeN(CHR¹CR²R³O)(C₆H₄-o-O)]₂Ti 6-9 (2, 6, R¹ = H, R² = R³ = Me; 3, 7, R¹ = R² = Ph (treo-), R³ = H; 4, 8, R¹ = Ph, R² = R³ = H; 5, 9, R¹ = R² = H, R³ = Ph) based on [ONO]-ligands have been synthesized. The obtained compounds were characterized by ¹H and ¹³C NMR spectroscopy and elemental analysis data. The complex [Ti(μ²-O){O-o-C₆H₄}{μ²-CMe₂CH₂}NMe]₆ (10) was obtained by controlled hydrolysis of 6. Molecular structure of 10 was determined by X-ray structure analysis.     

Trimethylaluminium-induced diastereoselective methylation onto ethyl 2-oxocyclopentane-1-carboxylate and isomerization between the dimethylaluminium-alkoxide products

Methylation of α-disubstituted cyclopentanone 1 with Me₃Al in CH₂Cl₂ at 0 °C for 30 min gave diastereoselectively a mixture of (1R*,2S*)-2 and (1R*,2R*)-2 in a 96:4 ratio and 83% total yield. When the same methylation was carried out at 0 °C for 1 h and then at room temperature for 120 h, a diastereomeric mixture of (1R*,2S*)-2 and (1R*,2R*)-2 was obtained in a 12:88 ratio and in 88% total yield. The stereochemistry of the two diastereomers was determined by the results of acetalization of their diol derivatives 3 and 5. Isomerization between the Me₂Al-alkoxides of (1R*,2S*)-2 and (1R*,2R*)-2 and its possible mechanism were investigated by HPLC analysis of the methylation reaction process at 0 °C for 1 h and then at room temperature for 56 h and also by their mutual epimerization reactions.