Reduction Of Acetophenone Research Articles

Synthesis of Chiral Aza Crown Ethers Having Exocyclic Hydroxy Groups and Their Use in Asymmetric Reduction of Ketones with Sodium Tetrahydridoborate

New chiral diaza crown ethers with exocyclic hydroxy groups were synthesized by reactions of (2S,3S)-1,4-dibenzyloxy-2,3-bis(2-oxiranylmethoxy)butane with N,N'-dibenzyl-1,2-ethanediamine and (4S,5S)-4,5-bis(benzylaminomethyl)-2,2-dimethyl-1,3-dioxolane. Catalytic debenzylation of the products gave the corresponding derivatives having secondary amino groups. The obtained diaza crown ethers, as well as some known crown ethers, were used as asymmetric catalysts in the reduction of pinacolone and acetophenone with sodium tetrahydridoborate in methylene chloride. Depending on the catalyst structure, the optical yield of the reduction products ranged from 5 to 90%.

Supported Organometallic Complexes. XXXVIII [1] Bis(methoxyethyldimethylphosphine)ruthenium(II) Complexes as Transfer Hydrogenation Catalysts

AbstractDiamineruthenium(II) complexes containing the hemilabile methoxyethyldimethylphosphine ligand, [Cl2Ru(Ln)(η1‐Me2PCH2CH2OMe)2] (2Ln) (n = 1‐12, Scheme 1), have been synthesized from the starting materials Me2PCH2CH2OMe, [Ru(COD)Cl2]n, and the respective diamines L1‐L12. The structure of complex 2L5 reveals that two chlorides are in trans position, while in complex 2L11 the two chlorides favor a cis configuration. Most of the complexes are highly catalytic active in the hydrogen transfer reduction of acetophenone. The experimental study indicates that the replacement of phenyl groups for methyl functions in the ether‐phosphine ruthenium(II) complexes resulted in a switch of the hydrogenation mechanism from direct hydrogenation to transfer hydrogenation. The reason is attributed to the better donor ability of methyl groups compared to phenyl substitutents. Thus the metal center becomes more electron‐rich and inhibits the binding of dihydrogen to the ruthenium(II) complex fragment.

Evaluating the role of solvent and borane on the enantioselectivity of the oxazaborolidine reduction of prochiral ketones using catalysts derived from cis-(1 R,2 S)-1-amino-indan-2-ol

The dependency of the enantioselectivity on the solvent and hydride source for the asymmetric reduction of acetophenone catalysed by the oxazaborolidine derived from cis-(1 R,2 S)-1-amino-indan-2-ol have been investigated. 11B NMR studies have implied that monomer/dimer ratios are important for achieving high enantioselectivities.

Reduction of acetophenone using supercritical 2-propanol: the substituent effect and the deuterium kinetic isotope effect

The reductions of several substituted acetophenones using supercritical 2-propanol were carried out to estimate the Hammett's reaction constant ( ρ=0.33). Also, the reduction of acetophenone using supercritical deuteriated 2-propanol was carried out to determine the rate-determining step. The kinetic isotope effects were observed in the reduction using 2-deuterio-2-propanol ( k H/ k D=1.6) and O-deuterio-2-propanol ( k H/ k D=2.0). These findings suggest that the reaction proceeds via a cyclic transition state between acetophenone and 2-propanol similar to that of the Meerwein–Ponndorf–Verley reduction.

Contribution of DFT Calculations to the Understanding of an Asymmetric Reaction, the Hydrogen Transfer Reduction of Ketones by a Rhodium(I) Complex

AbstractThe density functional theory (DFT) calculations presented here allow us to understand the mechanism of an asymmetric reaction, the hydride transfer reduction of acetophenone by a RhI complex bearing a chiral diamine ligand, RhH(diam)(COD). The mechanism which accounts for the enantioselectivity is a concerted one, where both the hydride and one hydrogen carried by a nitrogen are transferred simultaneously to the ketone. The two diastereoisomeric transition states leading to the R and S alcohols have been determined, the former being the most stable. The activation free energies, the kinetic constants and the enantiomeric excesses ee have been calculated, giving values in good agreement with the experiments. Two conditions ensure the enantioselectivity. The first is the existence of a unique isomer of the starting complex, which is achieved by the presence of bulky substituents on the diamine asymmetric carbons. The second is the presence of one hydrogen on the diamine nitrogens (secondary amines) and the existence of a C2 axis for the diamine ligand, which means that only one of these hydrogens points in the same direction as the Rh−H bond, a condition necessary for a low‐energy concerted transfer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Asymmetric Synthesis of anti‐ and syn‐β‐Amino Alcohols by Reductive Cross‐Coupling of Transition Metal‐Coordinated Planar Chiral Arylaldehydes with Aldimines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic Reduction of Carbonyl Functional Groups in 2-Propanol by Molybdocene Hydrides

The catalytic reduction of acetophenone in 2-propanol by the organometallic complex [Cp2Mo(μ-OH)2 MoCp2](OTs)2 (I) proceeds through a molybdocene hydride intermediate. Activation parameters for the reduction of acetophenone to 1-phenylethyl alcohol in 2-propanol-d8 are 19 kcal mol-1 and −26 cal mol-1 K-1 for ΔH⧧ and ΔS⧧, respectively. These parameters suggest 2-propanol and I are involved in a C−H activation step to form a molybdocene monohydride that may be the active species in the hydrogenation catalysis. When the catalysis reaction was performed with (CH3)2CHOD as the solvent, 1-deuterio-1-phenylethyl alcohol was almost quantitatively formed. This is consistent with a mechanism where a Cp2Mo hydride, formed in the C−H activation of (CH3)2CHOD, is converted to the deuteride by the solvent's alcoholic deuteron. The labeling experiment further supports the a molybdocene hydride as the catalytic species.

Practical Synthesis of Optically Active Styrene Oxides via Reductive Transformation of 2‐Chloroacetophenones with Chiral Rhodium Catalysts.

A practical method for the synthesis of optically active styrene oxides has been developed via formation of optically active 2-chloro-1-phenylethanols generated by reductive transformation of ring-substituted 2-chloroacetophenones. The optically active alcohols with up to 98% ee are obtainable from the asymmetric reduction of acetophenones with an S/C = 1000−5000 with a formic acid triethylamine mixture containing a well-defined chiral Rh complex, Cp*RhCl[(R,R)-Tsdpen].

Synthesis and evaluation of new chiral diols based on the dicyclopentadiene skeleton

The resolution by Lipase PS of rac- 5 (from reduction of ketone 6 , obtained from dicyclopentadiene with a new environment-friendly synthesis) gives (2 S)- 5 , which was further reduced to the endo (2 R)- 1a alcohol. The endo (2 S)- 1b alcohol was obtained from camphor with a multistep synthesis. Pinacol couplings of 3a, b , carried out with Mg/Hg or Corey's general procedure respectively, afforded with high diastereoselectivity the C 2 symmetry diols (2 R,2′ R)- 2a and (2 S,2′ S)- 2b , with endo oriented OH functions. The enantiogenic power of the endo alcohol (2 R)- 1a and (2 S)- 1b and of the diols (2 R,2′ R)- 2a and (2 S,2′ S)- 2b was tested towards the LiAlH 4 reduction of acetophenone. The C 2 symmetry appears to play a fundamental role.

Axially Chiral 3,3'-Bi(1-benzothiophene)-2,2'-dicarboxylic Acid and Its Derivatives

Ullmann dimerization of substituted methyl 3-X-1-benzothiophene-2-carboxylates 1-7 (X = Cl, Br) gave rise to the corresponding dimeric 3,3'-bi(1-benzothiophene) esters 8-13. Resolution of the title acid 20 by fractional crystallization of its mono- and bisquininium salt afforded pure (R)- and (S)-enantiomers, the optical purity and absolute configuration of which was confirmed by CD spectrometry and by X-ray crystallography. Ullmann dimerization of chiral oxazolines 23 and 24 derived from 2 proceeded without any diastereodifferentiation. Reduction of (R)- and (S)-20 afforded the corresponding (R)- and (S)-diols 29, which served as chiral ligands in a model enantioselective reduction of acetophenone. (R)- and (S)-1-phenylethan-1-ol were formed in 28 and 29% e.e., respectively.

Catalytic hydrogenation by recyclable supported Pd(II)-amino acid complex

L-phenyl alanine was anchored to P(S-DVB) resin and its complex with PdCl2 was prepared. The newly synthesized catalyst was found to be a versatile and recyclable catalyst for the hydrogenation of 1-octene and acetophenone. This chiral catalyst induced moderate enantioselectivity during the asymmetric reduction of acetophenone.

Asymmetric reduction of acetophenone and propiophenone by NaAl(IPTOLate)H2 combined with enantiomeric enrichment of the reaction product as an inclusion complex with IPTOL

An improved procedure was developed for asymmetric reduction of acetophenone and propiophenone by the chiral reagent NaAl(IPTOLate)H2. This procedure is based on isolation of the chiral alcohol that formed as a crystalline host—guest complex with the IPTOL ligand. The enantiomeric enrichment of the product was as high as 97% ee. The ability of IPTOL and its analogs to form host—guest complexes with a number of ether-type solvents, 1-phenylethanol, and 1-phenylpropan-1-ol as well as thermal stabilities of IPTOL-containing complexes with these alcohols were studied.

Asymmetric synthesis of anti- and syn-beta-amino alcohols by reductive cross-coupling of transition metal-coordinated planar chiral arylaldehydes with aldimines.

Samarium iodide-mediated cross-coupling of N-tosyl ferrocenylideneamine with planar chiral ferrocenecarboxaldehydes or benzaldehyde chromium complexes gave diastereoselectively the corresponding anti-beta-amino alcohol derivatives in good yields, while N-tosyl benzylideneamine produced syn-beta-amino alcohols by coupling with planar chiral arylaldehydes. Dynamic kinetic resolution of a configurationally equilibrated reactive species generated from achiral N-tosyl ferrocenilideneamine and benzylideneamine by reduction with samarium iodide was observed in the cross-coupling with planar chiral arylaldehydes giving both antipodes of beta-amino alcohols depending on the planar chirality. The obtained anti-beta-amino alcohol with the ferrocene ring was utilized as a chiral ligand for catalytic asymmetric reduction of acetophenone.

Practical synthesis of optically active styrene oxides via reductive transformation of 2-chloroacetophenones with chiral rhodium catalysts.

[reaction: see text] A practical method for the synthesis of optically active styrene oxides has been developed via formation of optically active 2-chloro-1-phenylethanols generated by reductive transformation of ring-substituted 2-chloroacetophenones. The optically active alcohols with up to 98% ee are obtainable from the asymmetric reduction of acetophenones with an S/C = 1000-5000 with a formic acid triethylamine mixture containing a well-defined chiral Rh complex, CpRhCl[(R,R)-Tsdpen].

One‐Pot Lipase‐Catalyzed Synthesis of Enantiopure Secondary Alcohols from Carbonyl Compounds: A New Protocol for Lipase‐Mediated Resolution.

Abstract Reduction of acetophenones with sodium borohydride in the presence of neutral alumina in hexane followed by enantioselective acylation catalyzed by Pseudomonas cepacia lipase has been achieved in one-pot. Further, immobilized lipase offered a high degree of selectivity with spontaneity.

Catalytic reduction of acetophenone with transition metal systems containing chiral bis(oxazolines)

The catalytic behaviour of several Ru, Rh and Ir systems containing bis(oxazoline) ligands ( 1– 6) has been tested in the asymmetric reduction of acetophenone ( 7) to give 1-phenylethanol ( 8) by hydrogenation (Ir systems), transfer hydrogenation (Ir and Ru systems) and hydrosilylation (Ir and Rh systems). Ligands 1 and 3 gave good activities, obtaining the best asymmetric induction with Ir– 1 system in the hydrosilylation (ee up to 50% ( S) of 8). In order to identify the catalytic precursors, Ru ( 9– 11) and Ir ( 12) complexes were synthesised and characterised. NMR studies of ruthenium complexes showed the existence of two main isomers in a ca. ratio 3/1, in agreement with the PM3(tm) calculations carried out for 10.

Ab initio Study on Enantioselective Reduction of Ketones Catalyzed by Thiazolidino [3, 4‐c ] oxazaborolidines

AbstractThe ab initio molecular orbital method is employed to study the enantioselective reduction of acetophenone with borane catalyzed by thiazolidino [3, 4‐c] oxazaborolidine. Computation resuit shows that the controlling step for the reduction is the decomposition of the catalyst‐alkoxyborane adduct and the reduction leads to S‐alcohols. The transition state of the hydride transfer from the borane moiety to the carbonyl carbon of acetophenone is a twisted chair structure with a B (2)—N (3)—BBH3—HBH3—CCO—OCO 6‐membered ring.

One-pot lipase-catalyzed synthesis of enantiopure secondary alcohols from carbonyl compounds: a new protocol for lipase-mediated resolution

Reduction of acetophenones with sodium borohydride in the presence of neutral alumina in hexane followed by enantioselective acylation catalyzed by Pseudomonas cepacia lipase has been achieved in one-pot. Further, immobilized lipase offered a high degree of selectivity with spontaneity.

Voltammetric Reductions of Ring-Substituted Acetophenones. 2. A Senior-Level Experiment Requiring Classification of an Electrochemical Mechanism as Stepwise or Concerted

An experiment suitable for upper-level undergraduates in which they determine the characteristics of a chemically coupled electron transfer (EC) mechanism is described. Students examine the free-energy barrier between an unstable radical anion and the products of its decomposition for ring-substituted and alpha-substituted acetophenones, acetanilides, and alkyl halides. Digital simulation is used to estimate the value of the standard potential, E°. Calculation of the electrochemical transfer coefficient, α, allows a determination of whether the electron transfer occurs in a single step (concerted) or follows the generation of the intermediate radical anion (stepwise).

Plants in organic synthesis: an alternative to baker's yeast

The reduction of acetophenone 1 and the hydrolysis of 1-acetoxy-2-methylcyclohexene 3 with various commercially available plants to the corresponding S-carbinol 2 and S-ketone 4 are described. The further incubation of 2-methylcyclohexanone 4 with some plants affords the enantiomerically pure trans- and/or cis-alcohol 5 and 6 , respectively.