Diastereoselective reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane with prochiral ketones using the Ti(OiPr)4/NaBH4 system

A simple and convenient one-pot method for the reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane by prochiral ketones using a Ti(OⁱPr)₄/NaBH₄ system to obtain the corresponding alkyl amine derivatives in 76–95% yields with good diastereoselectivity (dr = up to 23:1:1) is reported.     

Asymmetric synthesis of methyl bacteriopheophorbide-d and analogues by stereoselective reduction of the 3-acetyl to the 3-(1-hydroxyethyl) group

Asymmetric borane-reduction of 3-acetyl-13¹-oxo-tetrapyrroles (=bacteriochlorin, chlorin and porphyrin) in the presence of a chiral source gave selectively chiral 3-(1-hydroxyethyl)-13¹-oxo-tetrapyrroles. Oxazaborolidines were effective as chiral auxiliaries. Reduction with (S)-oxazaborolidines led to the (3¹S)-alcohol as the major product, whose stereoselectivity was the opposite of that in the same asymmetric reduction of usual prochiral ketones ArCOR. The asymmetric reduction of the 3-acetyl group in methyl bacteriopyropheophorbide-a and the 7,8-oxidation afforded 3¹-epimeric methyl (3¹S)-bacteriopheophorbide-d (89% de).     

The mechanism of asymmetric reduction catalyzed by a C2 symmetric bis-amino alcohol catalyst

By means of¹H,¹³C,¹¹B NMR, polar transfer DEPT135, DEPT90 and 2D NMR experiments, IR, etc, the structure of the diaminodihydroxyl ligand and its derivatives used in the asym-metric reduction of prochiral ketones were detected. The catalysts derived from the ligand and borane formedin situ were also studied and the structure transformations in solution were monitored. The structure of the catalyst was proved to be a new type of dual-centered catalyst — bisoxazaborolidine.     

Aerobic oxidative desymmetrization of meso-diols with bifunctional amidoiridium catalysts bearing chiral N-sulfonyldiamine ligands

Asymmetric aerobic oxidation of a range of meso- and prochiral diols with chiral bifunctional Ir catalysts is described. A high level of chiral discrimination ability of Cp^∗Ir complexes derived from (S,S)-1,2-diphenylethylenediamine was successfully demonstrated by desymmetrization of secondary benzylic diols such as cis-indan-1,3-diol and cis-1,4-diphenylbutane-1,4-diol, providing the corresponding (R)-hydroxyl ketones with excellent chemo- and enantioselectivities. Enantiotopic group discrimination in oxidation of symmetrical primary 1,4- and 1,5-diols gave rise to chiral lactones with moderate ees under similar aerobic conditions.     

S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids: efficient organocatalysts for enantioselective sodium borohydride reductions of prochiral ketones

Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of (?)-menthol or (?)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthesized chiral ionic liquids have been characterized by ¹H, ¹³C NMR and Mass spectrometry. Moderate to excellent enantiomeric excess (ee > 99%) has been obtained in asymmetric sodium borohydride reduction of prochiral ketones using these salts as chiral catalysts.     

Daucus carota and baker’s yeast mediated bio-reduction of prochiral ketones

Stereoselective reduction of prochiral ketones to the corresponding alcohols using biocatalysts has attracted much attention, from the viewpoint of green chemistry. Asymmetric reduction of indanone, tetralone and hydroxyl trimonoterpene ketones to the corresponding enantiomerically pure (S)-alcohols, using Daucus carota plant homogenate and fermented baker’s yeast cells, is described. The present study illustrates the broad substrate selectivity of the dehydrogenase enzymes present in the D. carota in the synthesis of a wide range of chiral secondary alcohols of biological importance.     

Asymmetric transfer hydrogenation of acetophenone derivatives with novel chiral phosphinite based η-p-cymene/ruthenium(II) catalysts

Enantioselective reduction of prochiral ketones to optically active secondary alcohols is an important subject in synthetic organic chemistry because the resulting chiral alcohols are extremely useful, biologically active compounds. The new chiral ligands (2R)-2-[benzyl{(2-((diphenylphosphanyl)oxy)ethyl)}amino]butyldiphenylphosphinite, 1 and (2R)-2-[benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, 2 and the corresponding ruthenium(II) complexes 3 and 4 have been prepared. The structures of these complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. ³¹P-{¹H} NMR, DEPT, ¹H-¹³C HETCOR or ¹H-¹H COSY correlation experiments were used to confirm the spectral assignments. These ruthenium(II)-phosphinite complexes have been used as catalysts for the asymmetric transfer hydrogenation of acetophenone derivatives. Under optimized conditions, aromatic ketones were reduced in good conversions and in moderate to good enantioselectivities (up to 85% ee).     

31P NMR assays for rapid determination of enantiomeric excess in catalytic hydrosilylations and transfer hydrogenations

Chiral chlorophosphine (S)-(1,1′-binaphthalen-2,2′-dioxy)chlorophosphine (S)-2 was tested for its performance as a chiral-derivatizing agent (CDA) using solutions of various alcohols, amines, and N-BOC amino acids. Based on ³¹P NMR spectroscopy, the enantiomeric excess was determined within less than 5 min per sample, reaching an accuracy of ±1%. One-pot procedures for a combination of the method with typical homogenous catalytic transformations of prochiral ketones were established. Hydrosilylation products may be analyzed after conversion into alcohols using HF bound to PS-vinyl pyridine co-polymer beads. Transfer hydrogenations simply require solvent evaporation prior to the use of the CDA.     

Asymmetric reduction of prochiral ketones using in situ generated oxazaborolidine derived from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol. An efficient synthesis of enantiopure (R)-tomoxetine

Catalytic asymmetric reduction of prochiral ketones was examined in the presence of chiral oxazaborolidine catalyst 2 prepared in situ from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol (1). The optically active secondary alcohols were generally obtained in moderate to high enantiomeric excesses (ee 43-95%) and good yields (75-94%), except for ketones bearing electron-withdrawing groups. The methodology was applied to the synthesis of enantiopure (R)-tomoxetine, a potent anti-depressant drug.     

Chiral diamides as efficient catalytic precursors for the borane-mediated asymmetric reduction of prochiral ketones

Chiral diamides [(2S)-5-oxo-2-(arylamino)carbonylpyrrolidines] derived from the abundantly available (S)-glutamic/(S)-pyroglutamic acids were successfully utilized as effective chiral catalytic precursors in the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene, to provide the corresponding secondary alcohols with up to 91% enantiomeric purities.     

Asymmetric reduction of ketones by employing Rhodotorula sp. AS2.2241 and synthesis of the β-blocker (R)-nifenalol

A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity in the reduction of various aromatic ketones and acetylpyridines (>97% ee), but moderate to high enantioselectivity in the reduction of α- and β-keto esters. (R)-Nifenalol, a β-adrenergic blocker, was also synthesized using 2-bromo-1(R)-(4-nitrophenyl)ethanol (97% ee) which was prepared through the asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turned this system into a versatile tool for organic synthesis.     

Enantioselective borane reduction of aromatic ketones catalyzed by chiral aluminum alkoxides

The asymmetric borane reduction of prochiral ketones with an alkoxide catalyst prepared in situ from aluminum tri-iso-propoxide and (R)-binaphthol was examined. Using these conditions, alcohols were obtained in high yield and e.e.'s of up to 83%.     

Asymmetric reduction of prochiral ketones using in situ generated oxazaborolidines derived from amino alcohols of (1R)-camphor as catalysts

Chiral oxazaborolidines generated in situ from 1,2-amino alcohols and amino alcohol derivatives derived from (1R)-(+)-camphor and borane or trimethyl borate were used as catalysts for the enantioselective reduction of prochiral ketones.     

(2S)-2-Anilinomethylpyrrolidine: an efficient in situ recyclable chiral catalytic source for the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene

(2S)-2-Anilinomethylpyrrolidine was successfully utilized as a chiral catalytic source in the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene to provide the corresponding secondary alcohols with enantiomeric excesses up to 91%. The potential of (2S)-2-anilinomethylpyrrolidine as an in situ recyclable chiral catalytic source in the borane-mediated chiral reduction processes has also been demonstrated.     

Asymmetric hydrogenation of enol phosphinates catalyzed by a chiral ferrocenylphosphine-rhodium complex. Asymmetric synthesis of optically active secondary alkyl alcohols

Catalytic asymmetric synthesis of secondary alkyl alcohols (up to 78% ee) was accomplished by asymmetric hydrogenation of enol diphenylphosphinates, derived from prochiral ketones such as acetophenone, 3-methyl-2-butanone, and 2-octanone, in the presence of a cationic rhodium complex of (R)-1-[(C)-1′,2-bis(diphenylphosphino)ferrocenyl]ethanol (BPPFOH).     

A convenient method for the preparation of oxazaborolidine catalyst in situ using (S)-α,α-diphenylpyrrolidinemethanol,tetrabutylammonium borohydride,and methyl iodide for the asymmetric reduction of prochiral ketones

An oxazaborolidine catalyst is readily prepared in situ at 25 °C in THF using (S)-α,α-diphenylpyrrolidinemethanol and borane generated from tetrabutylammonium borohydride/CH₃I reagent system. The oxazaborolidine/BH₃ reagent system prepared in this way is useful for the reduction of prochiral ketones to the corresponding alcohols with up to 99% ee.     

Synthesis of a water-soluble cationic chiral diamine ligand bearing a diguanidinium and application in asymmetric transfer hydrogenation

A novel water-soluble cationic N-monosulfonated chiral diamine ligand diguanidinium 1c was easily prepared from (R,R)-DPEN and its rhodium complex and was successfully applied in the asymmetric transfer hydrogenation of prochiral ketones and imines in water by using sodium formate and formic acid as co-hydrogen donors. Various substrates were reduced with high yields and good to excellent enantioselectivities (up to >99% ee).     

Chiral Borate Esters in Asymmetric Synthesis. Part 2

Asymmetric catalytic activity of the chiral spiroborate esters 1 – 9 with a O₃BN framework (see Fig. 1) toward borane reduction of prochiral ketones was examined. In the presence of 0.1 equiv. of a chiral spiroborate ester, prochiral ketones were reduced by 0.6 equiv. of borane in THF to give (R)‐secondary alcohols in up to 92% ee and 98% isolated yields (Scheme 1). The stereoselectivity of the reductions depends on the constituents of the chiral spiroborate ester (Table 2) and the structure of the prochiral ketones (Table 1). The configuration of the products is independent of the chirality of the diol‐derived parts of the catalysts. A mechanism for the catalytic behavior of the chiral spiroborate esters (R,S)‐ 2 and (S,S)‐ 2 during the reduction is also suggested.     

Stereoselective reduction of C=X by a chiral 1,4-dihydropyridine (NADH-MIMIC) in a self-immolative process

A series of prochiral ketones and a prochiral imine was reduced with high absolute stereoselectivity using an optically active 4-methyl-1,4-dihydropyridine in the presence of Mg(ClO₄)₂.     

Catalytic asymmetric borane reduction of prochiral ketones by the use of diazaborolidine catalysts prepared from chiral β-diamines

The catalytic asymmetric borane reduction of prochiral ketones was examined in the presence of chiral diazaborolidine catalysts prepared in situ from chiral β-diamines and borane. Chiral secondary alcohols were obtained with modest to high enantiomeric excesses (up to 92% ee) using (S)-2-[(4-trifluoromethyl)anilinomethyl]indoline 2f.