3113-96-0

Biocatalytic asymmetric reduction of ketone is an efficient method for the production of chiral carbinols. The study indicates selective bioreduction of different ketones (1–8) to their respective (R)-alcohols (1a–8a) in low to high selectivity (0- >99%) with good yields (11–96%). In this work, whole-cell of Lactobacillus kefiri P2 catalysed enantioselective reduction of various prochiral ketones was investigated. (R)-4-Phenyl-2-butanol 2a, which is used as a precursor to antihypertensive agents and spasmolytics (anti-epileptic agents), was obtained using L kefiri P2 in 99% conversion and 91% enantiomeric excess (ee). Moreover, bioreduction of 2-methyl-1-phenylpropan-1-one substrate 8, containing a branched alkyl chain and difficult to asymmetric reduction with chemical catalysts as an enantioselective, to (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was carried out in excellent yield (96%). The gram-scale production was carried out, and 9.70 g of (R)-2-methyl-1-phenylpropan-1-ol (8a) in enantiomerically pure form was obtained in 96% yield. Also especially, the yield and gram scale of (R)-2-methyl-1-phenylpropan-1-ol (8a) synthesised through catalytic asymmetric reduction using the biocatalyst was the highest report so far. The efficiency of L kefiri P2 for the conversion of the substrates and ee of products were markedly influenced by the steric factors of the substrates. This is a cheap, clean and eco-friendly process for production of chiral carbinols compared to chemical processes.

Transition-metal catalysts are powerful tools for carbon-carbon bond-forming reactions that are difficult to achieve using native enzymes. Enzymes that exhibit inherent selectivities and reactivities through host-guest interactions have inspired widesprea

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral PxNy-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)5] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP2N4 (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.

Two cis-1,2-diol-type chiral ligands (T1 and T2) and their tri-coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dati

The invention discloses a chiral amino-pyridine-phosphine tridentate ligand, a manganese complex, and a preparation method and application thereof. The chiral amino-pyridine-phosphine tridentate ligand is shown as a formula II, and the manganese complex of the chiral amino-pyridine-phosphine tridentate ligand can be used for efficiently catalyzing and hydrogenating ketone compounds to prepare chiral alcohol compounds in a high enantioselectivity mode. The chiral amino-pyridine-phosphine tridentate ligand and the manganese complex are simple in synthesis process, good in stability, high in catalytic activity and mild in reaction conditions.

Asymmetric Transfer Hydrogenation (ATH) has been an attractive way for the reduction of ketones to chiral alcohols. A great number of novel and valuable synthetic pathways have been achived by the combination usage of organometallic and coordination chemistry for the production of important class of compounds and particularly optically active molecules. For this aim, four boron containing Schiff bases were synthesized by the reaction of 4-formylphenylboronic acid with chiral amines. The boron containing structures have been found as stable compounds due to the presence of covalent B–O bonds and thus could be handled in laboratory environment. They were characterized by 1H NMR and FT-IR spectroscopy and elemental analysis and they were used as catalyst in the transfer hydrogenation of ketones to the related alcohol derivatives with high conversions (up to 99%) and low enantioselectivities (up to 22% ee).

The ability of alkali metal complexes featuring functionalized BINOL-derived ligands to catalyze ketone hydroboration reactions was explored. The reduced products were formed in excellent yields and with variable enantioselectivities dependent upon the nature of the ligand and the alkali metal cation.

A series of Mn(I) catalysts containing imidazole-based chiral PNN tridentate ligands with controllable 'side arm' groups have been established, enabling the inexpensive base-promoted asymmetric hydrogenation of simple ketones with outstanding activities (up to 8200 TON) and good enantioselectivities (up to 88.5percent ee). This protocol features wide substrate scope and functional group tolerance, thereby providing easy access to a key intermediate of crizotinib.

Iridium-catalyzed enantioselective transfer hydrogenation of ketones with formic acid was developed using a prolinol-phosphine chiral ligand. Cooperative action of the iridium atom and the ligand through alcohol-alkoxide interconversion is crucial to facilitate the transfer hydrogenation. Various ketones including alkyl aryl ketones, ketoesters, and an aryl heteroaryl ketone were competent substrates. An attractive feature of this catalysis is efficient discrimination between the alkyl and aryl substituents of the ketones, promoting hydrogenation with the identical sense of enantioselection regardless of steric demand of the alkyl substituent and thus resulting in a rare case of highly enantioselective transfer hydrogenation of tert-alkyl aryl ketones. Quantum chemical calculations revealed that the sp3-C?H/π interaction between an sp3-C?H bond of the prolinol-phosphine ligand and the aryl substituent of the ketone is crucial for the enantioselection in combination with O?H???O/sp3-C?H???O two-point hydrogen-bonding between the chiral ligand and carbonyl group. (Figure presented.).

The bis(carbonyl) manganese(I) complex [Mn(CO)2(1)]Br (2) with a chiral (NH)2P2 macrocyclic ligand (1) catalyzes the asymmetric transfer hydrogenation of polar double bonds with 2-propanol as the hydrogen source. Ketones (43 substrates) are reduced to alcohols in high yields (up to >99 %) and with excellent enantioselectivities (90–99 % ee). A stereochemical model based on attractive CH–π interactions is proposed.

In this study, a total of 10 bacterial strains were screened for their ability to reduce cyclohexyl(phenyl)methanone 1 to its corresponding alcohol. Among these strains, Lactobacillus paracasei BD101 was found to be the most successful biocatalyst to redu

In this study, four bacterial strains were tested for their ability to reduce acetophenones to its corresponding alcohol. Among these strains Weissella paramesenteroides N7 was found to be the most successful biocatalyst to reduce the ketones to the corresponding alcohols. The reaction conditions were systematically optimized for W. paramesenteroides N7 that resulted in high enantioselectivity and conversion rates for the bioreduction. The scale-up asymmetric reduction of 1-(4-methoxyphenyl) propan-1-one (1r) by W. paramesenteroides N7 gave (R)-1-(4-methoxyphenyl) propan-1-ol (2r) with 94% yield and >99% enantiomeric excess. This is the first report showing the synthesis of (R)-1-(4-methoxyphenyl) propan-1-ol (2r) in enantiopure form using a biocatalyst on a gram scale. The whole cell catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that W. paramesenteroides N7 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest as a promising and alternative green approach.

The synthesis of different metal pincer complexes coordinating to the chiral PNP ligand bis(2-((2R,5R)-2,5-dimethyl-phospholanoethyl))amine is described in detail. The characterized complexes with Mn, Fe, Re and Ru as metal centers showed good activities regarding the reduction of several prochiral ketones. Comparing these catalysts, the non-noble metal complexes produced best selectivities not only for aromatic substrates, but also for different kinds of aliphatic ones leading to enantioselectivities up to 99% ee. Theoretical investigations elucidated the mechanism and rationalized the selectivity. (Figure presented.).

The combination of [3-[(2S)-2-[(diphenylphosphanyl)oxy]-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride] with [Ru(η6-arene)(μ-Cl)Cl]2, Ir(η5-C5Me5)(μ-Cl)Cl]2 or [Rh(μ-Cl)(cod)]2, in the presence of KOH/isoPrOH, has been found to generate catalysts that are capable of enantioselectively reducing alkyl, aryl ketones to the corresponding (R)-alcohols. Under optimized conditions, when the catalysts were applied to the asymmetric transfer hydrogenation, we obtained the secondary alcohol products in high conversions and enantioselectivities using only 0.5 mol% catalyst loading. In addition, [3-[(2S)-2-{[(chloro(?4-1,5-cyclooctadiene)rhodium)diphenyl phosphanyl] oxy}-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride], (6) complex is much more active than the other analogous complexes in the transfer hydrogenation. Catalyst 6 acts as excellent catalysts, giving the corresponding (R)-1-phenyl ethanol in 99% conversion in 30 min (TOF ≤ 396 h?1) and in high enantioselectivity (92% ee).

An experimental protocol to achieve the Meerwein-Ponndorf-Verley (MPV) reduction of ketones under mildly basic conditions is reported. The transformation is tolerant of a range of ketone substrates, including O- and S-containing heterocycles, is scalable, and shows potential to be used as a platform to access enantioenriched products. These studies provide a general method for achieving the reduction of ketones under mildly basic conditions and offer an alternative protocol to more well-known Al-based MPV reduction conditions.

Manganese catalysts derived from tridentate P,N,N ligands can be activated easily using weak bases for both ketone and ester hydrogenations. Kinetic studies indicate the ketone hydrogenations are 0th order in acetophenone, positive order in hydrogen and 1st order in the catalyst. This implies that the rate determining step of the reaction was the activation of hydrogen. New ligand systems with varying donor strength were studied and it was possible to make the hydrogen activation significantly more efficient; a catalyst displaying around a 3-fold increase in initial turn-over frequencies for the hydrogenation of acetophenone relative to the parent system was discovered as a result of these kinetic investigations. Ester hydrogenations and ketone transfer hydrogenation (isopropanol as reductant) are first order for both the substrate and catalysts. Kinetic studies also gained insight into catalyst stability and identified a working range in which the catalyst is stable throughout the catalytic reaction (and a larger working range where high yields can still be achieved). The new more active catalyst, combining an electron-rich phosphine with an electron-rich pyridine is capable of hydrogenating acetophenone using as little as 0.01 mol% catalyst at 65 °C. In all, protocols for reduction of 21 ketones and 15 esters are described.

This manuscript describes the design and synthesis of Ru catalysts that feature only a single stereogenic element, yet this minimal chirality resource is demonstrated to be competent for effecting high levels of stereoinduction in the asymmetric transfer hydrogenation over a broad range of ketone substrates, including those that are not accommodated by known catalyst systems. The single stereogenic center of the (1-pyridine-2-yl)methanamine) is the only point-chirality in the catalysts, which simplifies this catalyst system relative to existing literature protocols.

The asymmetric transfer hydrogenation (ATH) of ketones catalyzed by Rh-based macrocycles proceeded smoothly in the presence of air with high catalytic activity and enantioselectivity. Even though the S/C ratio (substrate to catalyst molar ratio) was incre

The PNNP ligand (R,R)-{PPh2(2-C6H4)CH=N(pyrrolidine-NBn)-}2 2 was prepared by condensation between 2-diphenylphosphino benzaldehyde and the pyrrolidine-substituted diamine 1. Reduction with NaBH4 in MeOH afforded (R,R)-{PPh2(2-C6H4)CH–NH(pyrrolidine-NBn)-}2 3. The corresponding iron(II) complexes [FeCl2(2)] (4), [Fe(CH3CN)2(2)](BF4)2 (5) and [Fe(CH3CN)2(2)](PF6)2 (6) were synthesized and fully characterized by NMR, ESI-HRMS, and EA. DFT calculations for complexes [FeCl2(2)] (4) and [Fe(CH3CN)2(2)](BF4)2 (5) were carried out in order to investigate the stability of related structures. The PNNP ligands 2 and 3 in combination with Fe3(CO)12 as iron source were tested as catalysts in the asymmetric transfer hydrogenation of a variety of ketones with conversions higher than 95 % and enantioselectivities up to 97 %.

A hybrid transition-metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.

Chiral square-planar Rh(I) complexes based on new C2-symmetric NHC ligands have been synthesized selectively in a few steps as single diastereoisomers. These chiral precatalysts were applied to the asymmetric transfer hydrogenation of 1-phenylp

A series of MnI complexes containing lutidine-based chiral pincer ligands with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON=turnover number), broad substrate scope (81 examples), good functional-group tolerance, and excellent enantioselectivities (85–98 % ee) in the hydrogenation of various ketones. These aspects are rare in earth-abundant metal catalyzed hydrogenations. The utility of the protocol have been demonstrated in the asymmetric synthesis of a variety of key intermediates for chiral drugs. Preliminary mechanistic investigations indicate that an outer-sphere mode of substrate–catalyst interactions probably dominates the catalysis.

An enantioselective aryl transfer is promoted using chiral tricoordinated lithium amido aryl zincates that are easily accessible reagents and whose chiral appendage is simply recovered for reuse. The arylation reaction is run in good yields (60 % average on twenty substrates) and high enantiomeric excesses (95 % ee average). This occurs whatever the ortho, meta, or para substituent borne by the substrate and a complete chemoselectivity is observed with respect to the aldehyde function. Sensitive groups such as nitriles, esters, ketones, and enolisable substrates resist to the action of the ate reagent, warranting a large scope to this methodology.

Chiral C2-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes have been synthesized and used as catalysts in the ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic, methyl alkyl and alkyl/aryl ketones using 2-propanol as both the hydrogen source and solvent in the presence of KOH. Under optimized conditions, all complexes showed high catalytic activity as catalysts in the reduction of various ketones to corresponding chiral secondary alcohols. Products were obtained with high conversions (99%) and moderate to good enantioselectivities (82% ee). Furthermore, C2-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes were characterized by multinuclear NMR spectroscopy, FT-IR spectroscopy, LC/MS-MS and elemental analysis.

The imidazolium salt [(S,S)-tBuNC3H3NCHPhCHPhNH2]PF6, (S,S)-11·HPF6 is a precursor to the enantiopure "Kaibene" ligand, tBu-Kaibene, (S,S)-11 featuring a tert-butyl group on the N-heterocyclic carbene (NHC) ring-nitrogen atoms. It has been prepared in high yield and purity by refluxing a chiral cyclic sulfamidate with 1-tert-butylimidazole. Similarly (S,S)-12·HPF6 with a mesityl group at the imidazolium ring-nitrogen atom has been prepared in the same fashion and serves as a source of Mes-Kaibene, (S,S)-12. These bidentate Kaibene ligands feature an NHC and a primary amine separated by a chiral linker. Salts (S,S)-11·HPF6 or (S,S)-12·HPF6 react with base and AgI or CuI to give a total of four M(Kaibene)2I compounds (M = Ag or Cu). At 22 °C, the amine-functionalized imidazolium cations undergo oxidative addition to iridium(I) in [IrCl(cod)]2 (cod = 1,5-cyclooctadiene) to generate iridium(III) hydride R-Kaibene compounds [IrHCl(cod)((S,S)-11)](PF6) (17) and [IrHCl(cod)((S,S)-12)](PF6) (18), respectively, each as a mixture of six configurational isomers. In contrast, the salt (S,S)-11·HPF6 reacts with [Ir(OtBu)(cod)]2 to produce a bimetallic iridium compound with (S,S)-11 as the bridging ligand. This compound contains interesting NH···Cl and NH···Ir noncovalent intramolecular interactions. Salt (S,S)-12·HPF6 reacts with silver oxide to yield [Ag2((S,S)-12)2](PF6)2 (20). Reagent 20 serves as an efficient transmetalation reagent to deliver to each rhodium in [RhCl(cod)]2 1 equiv of (S,S)-12 as a bidentate ligand to give [Rh(cod)((S,S)-12)](PF6). In the reaction between [IrCl(cod)]2 and 20, (S,S)-12 ends up coordinated in an iridium(III) hydride complex (22) as a tridentate ligand via the NHC, NH2, and a cyclometalated phenyl group. The two iridium hydride compounds, 18 and 22, are catalysts for the hydrogenation of a range of ketones (turnover number up to 499, turnover frequency up to 249 h-1, with er (enantiomeric ratio) up to 35:65 R:S).

A pair of novel optically pure phosphinite ligands were synthesized by ring opening reaction of chiral amines with (R)-styrene oxide or (S)-glycidyl phenyl ether oxide using a straightforward method in high yields and their ruthenium complexes were described in detail. The ruthenium complexes proved to be highly efficient catalysts for the enantioselective hydrogenation of ketones, affording products up to 99% ee. The results showed that the corresponding chiral alcohols could be obtained with high activity and excellent enantioselectivities at the desired temperature. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinito[dichloro(η6-benzene)ruthenium (II)] acts an excellent catalyst in the reduction of ketones, giving the corresponding alcohol up to 99% ee.

1-Hydrosilatrane, a safe and easy-to-handle reducing reagent that can be inexpensively accessed, has been shown to reduce prochiral ketones asymmetrically in the presence of chiral 1,2-aminoalcohols with ees ranging from 8% to 86%. The best result was achieved using ephedrine as the source of chirality, which is readily commercially available. The additive can be recovered through extraction and reused without any erosion of enantioselectivity.

The invention comprises novel chiral metal complex compounds of the formula (I) wherein M, PR2, R3 and R4 are outlined in the description, its stereoisomers, in the form as a neutral complex or a complex cation with a suitable counter ion. The chiral metal complex compounds can be used in asymmetric reactions, particularly in asymmetric reductions of ketones, imines or oximes.

Three new manganese complexes trans-[Mn(P-NH-NH-P)(CO)2][Br], (14) P-NH-NH-P = (S,S)-PPh2CH2CH2NH-CHPhCHPhNHCH2CH2PPh2), fac-[Mn(P′-NH-NH2)(CO)3][Br], (15) P′-NH-NH2 = (S,S)-PPh2(C6H4)NHCHPhCHPhNH2, and syn-mer-Mn(P-NH-NH2)(CO)2Br, (16) P-NH-NH2 = (S,S)-PPh2CH2CH2NHCHPhCHPhNH2 were synthesized and tested for the asymmetric transfer hydrogenation (ATH) of acetophenone in 2-PrOH. The ligands have stereogenic centers derived from the starting diamine, (S,S)-DPEN. Complex 16 was shown by NOE NMR experiments to have Mn-Br syn to the N-H of the secondary amine. Only the precatalyst 16, upon reaction with potassium tert-butoxide (KOtBu) in 2-PrOH, generated an active system at 80 °C for the ATH of acetophenone to 1-phenylethanol in an enantiomeric excess (ee) of 42% and thus was selected for further investigation into the mechanism of transfer hydrogenation. The corresponding amido complex Mn(P-N-NH2)(CO)2 (17), a borohydride complex syn-mer-Mn(P-NH-NH2)(CO)2(BH4) (18), and an ethoxide complex anti-mer-Mn(P-NH-NH2)(CO)2(OEt) (19′) were independently synthesized and tested in the ATH of acetophenone. The amido complex 17 and the borohydride complex 18 displayed similar activity to 16 activated in basic 2-PrOH, but the anti NH OEt complex 19′ was completely inactive. This result suggested that the NH effect, as described by Noyori, was required to obtain catalytic activity. The syn NH BH4 manganese complex is one of the most active manganese ATH catalysts to date and can hydrogenate a variety of aromatic ketones, including base-sensitive substrates such as p-acetylbenzoate ethyl ester.

This study aims to propose a simple procedure for the development of enantioselective hydrosilylation of a ketone using catalytic amounts of [Ir(cod)2]BF4 and chiral azolium salt. Previously, catalytic asymmetric hydrosilylation reac

Nickel-catalyzed cross-coupling has emerged as the most versatile approach to date for achieving enantioconvergent carbon–carbon bond formation using racemic alkyl halides as electrophiles. In contrast, there have not yet been reports of the application of chiral nickel catalysts to the corresponding reactions with heteroatom nucleophiles to produce carbon–heteroatom bonds with good enantioselectivity. Herein, we establish that a chiral nickel/pybox catalyst can borylate racemic secondary benzylic chlorides to provide enantioenriched benzylic boronic esters, a highly useful family of compounds in organic synthesis. The method displays good functional group compatibility (e.g., being unimpeded by the presence of an indole, a ketone, a tertiary amine, or an unactivated alkyl bromide), and both of the catalyst components (NiCl2?glyme and the pybox ligand) are commercially available.

Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of acylsilanes are reported. The acylsilanes were activated via an addition of fluoride on the silicon to form a penta-coordinate anionic silicate intermediate. The silicate then underwent alkyl or aryl group migration from the silicon atom to the neighboring carbonyl carbon atom (1,2-anionotropic rearrangement), followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high yields with excellent enantioselectivities (up to 95% ee). The isolation of an α-silylcarbinol intermediate as well as DFT calculations revealed that the 1,2-anionotropic rearrangement occurred via a bisguanidinium silicate ion pair, which is the stereodetermining step. The chiral center formed is then retained without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl acylsilanes were smoothly transformed into homoallylic linear crotyl alcohols with retention of E/Z geometry, and no branched alcohols were detected. This clearly suggested that the 1,2-anionotropic rearrangement occurred through a three-membered instead of a five-membered transition state.

Kinetic resolution of secondary alcohols by benzoylation using a phosphinite derivative of (1S,2R)-1-amino-2-indanol as the catalyst was investigated. The aminophosphinite catalyst is effective for the kinetic resolution of aryl cycloalkyl carbinols with a small number of examples for organocatalytic kinetic resolution to achieve resolution with s = up to 44. Although the benzoylation of phenylalkanols proceeded with a low selectivity, 1-arylalkanols bearing at least one substituent at the ortho position on the benzene ring or a branched alkyl group on the carbinol carbon were resolved with acceptable selectivity.

The highly efficient catalytic oxidation and oxidative kinetic resolution (OKR) of secondary alcohols has been achieved using a synthetic manganese catalyst with low loading and hydrogen peroxide as an environmentally benign oxidant in the presence of a small amount of sulfuric acid as an additive. The product yields were high (up to 93%) for alcohol oxidation and the enantioselectivity was excellent (>90% ee) for the OKR of secondary alcohols. Mechanistic studies revealed that alcohol oxidation occurs via hydrogen atom (H-atom) abstraction from an α-CH bond of the alcohol substrate and a two-electron process by an electrophilic Mn-oxo species. Density functional theory calculations revealed the difference in reaction energy barriers for H-atom abstraction from the α-CH bonds of R- and S-enantiomers by a chiral high-valent manganese-oxo complex, supporting the experimental result from the OKR of secondary alcohols.

Abstract: Metal-catalyzed enantioselective transfer reduction of ketones to enantiomerically enriched chiral alcohols has recently attracted attention. Therefore, a series of methyl alkyl or alkyl/aryl ketones have been reduced by using Ru(II), Rh(I) and Ir(III) catalysts based on C2-symmetric chiral ferrocenyl phosphinite ligands. The corresponding optically active secondary alcohols were obtained in excellent conversions and moderate-to-good enantioselectivities. The best results were obtained with an iridium catalyst, giving up to 98% conversion and 80% ee.

The reductive amination of α-dialkylphosphine acetaldehydes with enantiopure β-aminophosphines is a new, versatile route to unsymmetrical tridentate (pincer) ligands P-NH-P′. Four new ligands PR2CH2CH2NHCHR′CHR′′PPh2 (R=iPr, Cy, R′=Ph, CH(CH3)2, R′′=Ph, H) prepared in this way are used to make the iron(II) complexes mer-FeCl2(CO)(P-NH-P′) and mer-FeCl(H)(CO)(P-NH-P′). The hydride complex with the rigid ligand with R′=R′′=Ph is an efficient and highly enantioselective homogeneous asymmetric pressure hydrogenation (APH) catalyst. Prochiral aryl ketones are reduced under mild conditions (THF, 0.1 mol % catalyst, 1 mol % KOtBu, 5–10 bar, 50 °C) to the (S)-alcohols, usually in enantiomeric excess (ee) greater than 90 %. DFT calculations provided transition-state structures for the enantiodetermining hydride-transfer step.

The catalytic potential of new N-heterocyclic carbene ligands, derived from a chiral fused bicyclic ring scaffold with restricted rotation along the C–N bond bearing the chiral auxiliary, has been explored in the transition-metal-mediated asymmetric transfer hydrogenation reactions of ketones. In particular, the chiral oxazolidine-fused N-heterocyclic carbene precursors (3S)-3-R-6-methyl-7-phenyl-2,3-dihydroimidazo[5,1-b]oxazol-6-ium iodide [R = sec-butyl (1f), i-butyl (2f), isopropyl (3f)] were synthesized from commercially available optically pure amino acids in a multistep sequence that avoids tedious chiral resolution. The reactions of the chiral imidazolium iodide salts 1f–3f with Ag2O yielded the corresponding silver complexes 1g–3g, which were treated with [(COD)MCl]2 (M = Rh, Ir; COD = 1,5-cyclooctadiene) to afford the rhodium(I) and iridium(I) complexes (1h–3h and 1i–3i, respectively). The rhodium(I) and iridium(I) complexes conveniently catalyze the asymmetric transfer hydrogenation of acetophenones for a wide variety of substrates ranging from electron-rich ones such as 4-methylacetophenone, 3,4-dimethylacetophenone, 4-tert-butylacetophenone, and 4-(methylthio)acetophenone to electron-deficient ones such as 4-bromoacetophenone, 4-chloroacetophenone, 4-fluoroacetophenone, 4-nitroacetophenone, and 3-fluoroacetophenone in moderate-to-good yields (ca. 18–95 %) but with low enantioselectivities (ca. 4–41 % ee).

Metal-catalyzed asymmetric transfer hydrogenation is a powerful and practical method for the reduction of ketones to produce the corresponding secondary alcohols, which are valuable building blocks in the pharmaceutical, perfume, and agrochemical industries. Hence, a series of novel chiral β-amino alcohols were synthesized by chiral amines with regioselective ring opening of (S)-propylene oxide or reaction with (S)-(+)-2-hydroxypropyl p-toluenesulfonate by a straightforward method. The chiral ruthenium catalytic systems generated from [Ru(arene)(μ-Cl)Cl]2 complexes and chiral phosphinite ligands based on amino alcohol derivatives were employed in asymmetric transfer hydrogenation of ketones to give the corresponding optically active alcohols; (2S)-1-{[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-phenylethyl]amino}propan-2-yldiphenylphosphinitobis[dichol-oro(η6-benzene)ruthenium(II)] acts an excellent catalyst in the reduction of α-naphthyl methyl ketone, giving the corresponding alcohol with up to 99% ee. The substituents on the backbone of the ligands were found to have a remarkable effect on both the conversion and enantioselectivity of the catalysts. Furthermore, this transfer hydrogenation is characterized by low reversibility under these conditions.

The asymmetric transfer hydrogenation (ATH) of ketones is an efficient method for producing enantio-enriched alcohols which are used as intermediates in a variety of industrial processes. Here we report the synthesis of new iron ATH precatalysts (S,S)-[FeBr(CO)(Ph2PCH2CH2NHCHPhCHPhNC=CHCH2PR′2)][BPh4] (R′=Et, and ortho-tolyl (o-Tol)) where one of the phosphine groups is modified with small alkyl and large aryl substituents to probe the effect of this change on the activity and selectivity of the catalytic system. A simple reversible equilibrium kinetic model is used to obtain the initial TOF and the inherent enantioselectivity S=kR/kS of these catalysts along with those for the previously reported catalysts with R′=Ph and Cy for the ATH of acetophenone. With an increase in the size of the PR′2 group, the TOF goes through a maximum at PPh2 while the S value goes through a maximum of 510 at R′=Cy. The complex with R′=o-Tol starts with a high S value of 200 but is rapidly changed to a second catalyst with an S value of 28. For the reduction of acetophenone to (R)-1-phenylethanol, turnover numbers of up to 5200 and ee up to 98 % were achieved. The chemotherapeutic pharmaceutical precursor (R)-(3′,5′-bis(trifluoromethyl))-1-phenylethanol is synthesized in up to 95 % ee. Several other alcohols can be prepared in greater than 90 % ee by choosing the precatalyst with the correctly matched steric properties. A hydride complex derived from the catalyst with R′=Cy is characterized by NMR spectroscopy. It is proposed that low concentration trans-hydride carbonyl complexes with the FeH parallel to the NH of the ligand are the active catalysts in all of these systems.

Highly enantioselective arylation of aryl aldehydes catalyzed by (S)-H8-BINOL-Ti(Oi-Pr)2 complex in the presence of N-methylmorpholine (NMM) as an effective and inexpensive additive is described for the first time. We found high enan

Novel chiral multidentate P3N4-type ligand has been synthesized and characterized by NMR and HRMS. Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand (R,R,R,R)-3 and IrCl(CO)(PPh3)2exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee.

The invention discloses a reduction alcoholization and resolution method of cyclohexyl phenyl ketone. The reduction alcoholization and resolution method takes the cyclohexyl phenyl ketone as a raw material; the cyclohexyl phenyl ketone is subjected to hyd

The zinc acetate promoted asymmetric hydrosilylation of various ketones and imines under solvent-free conditions was examined by using an unprecedented low catalyst loading. Exposure of ketones to 0.05 mol % Zn-based chiral diamine complex in the presence of triethoxysilane afforded enantioenriched alcohols in excellent yields (up to 98 %) and enantioselectivities (up to 97 % ee). This methodology also allowed for the chemoselective 1,2-reduction of α,β-unsaturated ketones and imines.

Chiral, triangular poly-azamacrocycles (trianglimines) readily available from enantiomerically pure trans-1,2-diaminocyclohexane and various aromatic dialdehydes, differ in their nature and substitution pattern. The highly symmetrical macrocycle having two electron-donating groups attached to the aryl moieties is formed under thermodynamic control that fulfilled the so called entropy of symmetry rule. Conversely, from the 2-nitroterephthaldehyde a kinetic product of trivial C1 symmetry is solely obtained, whereas from 2-methoxyterepthaldehyde a mixture of C3- and C1-symmetrical macrocycles are formed. The factors that contribute to the mechanism of the macrocycle formation were determined on the basis of an experimental/theoretical approach. The non-symmetrical structure of the macrocycle resulted from a symmetrical intermediate that appeared during cyclocondensation. The chiroptical properties of the trianglimines were studied by means of experimental ECD and VCD methods supported by quantum-chemical calculations. The nitro-substituted trianglimine appeared to be a simple, low molecular weight supergelator forming in polar media of stable chiral organogels. The structure of the gel is affected by the nature and chirality of the dopant. The hexaimine macrocycles after reduction of the CN imine bonds formed trianglamines-useful chiral ligands in stereoselective synthesis. The Zn-trianglamine complexes were employed as catalysts for asymmetric hydrosilylation of prochiral ketones, providing products of enantiomeric excess up to 98%. This remains the best result obtained for Zn-diamine catalysed asymmetric hydrosilylation of ketones so far.

An axially chiral, cyclic borane decorated with just one C6F5 group at the boron atom promotes the highly enantioselective hydrosilylation of acetophenone derivatives without assistance of an additional Lewis base (up to 99% ee). The reaction is an unprecedented asymmetric variant of Piers' B(C6F5)3-catalyzed carbonyl hydrosilylation. The steric congestion imparted by the 3,3′-disubstituted binaphthyl backbone of the borane catalyst as well as the use of reactive trihydrosilanes as reducing agents are keys to success.

Known Ru(II), Rh(I) and Ir(III) complexes of C2-symmetric ferrocenyl based chiral bis(phoshinite) ligands were catalyzed the asymmetric transfer hydrogenation of alkyl/aryl or alkyl methyl ketones. Corresponding secondary alcohols were obtained with high enantioselectivities up to 98% ee and reactivities using iso-propanol as the hydrogen source.

The asymmetric reduction of prochiral ketones is a pivotal reaction for the preparation of chiral alcohols which form an extremely important class of intermediates for fine chemicals and pharmaceuticals. Especially, iridium-based asymmetric reduction of ketones to enantiomerically enriched alcohols has recently attracted important attention by a number of research groups and interest in this area is growing. Therefore, a series of novel neutral mononuclear iridium(III) ferrocenyl-phosphinite complexes have been prepared and applied in the iridium(III)-catalyzed asymmetric transfer hydrogenation (ATH) of ketones to give corresponding secondary alcohols with outstanding enantioselectivities and reactivities using 2-propanol as the hydrogen source (up to 99% ee and 99% conversion). It was seen that the substituents on the backbone of the ligands resulted in a significant effect on both the activity and % enantioselectivity. Furthermore, the structural elucidation of the complexes was carried out by elemental analysis, IR and multi-nuclear NMR spectroscopic data.

For the first time, an iron(ii) catalyst is used in the biphasic asymmetric transfer hydrogenation (ATH) of ketones to enantioenriched alcohols employing water and potassium formate as the proton and hydride source, respectively. The precatalyst [FeCl(CO)(P-NH-N-P)]BF4 (P-NH-N-P = (S,S)-PPh2CH2CH2NHCHPhCHPhNCHCH2PPh2) in the organic phase with the substrate is activated by base to produce a system that rivals the best ruthenium biphasic ATH catalysts in activity but not enantioselectivity. Biorenewable 2-methyltetrahydrofuran as a cosolvent and biodegradable TWEEN80 as a surfactant were added to the reaction mixture to greatly decrease the mass-transfer limitations caused by the biphasic reaction mixture. The enantioselectivity of the reduction was as high as 76% depending on the substitution pattern of the arylketone employed. NMR studies verified the formation of an iron hydride [FeH(CO)(PPh2CH2CH2NHCHPhCHPhNCHCHPPh2)] intermediate as was observed in our 2-propanol-based ATH studies.

The application describes catalytic materials for hydrogenation or asymmetric hydrogenation. In particular, the application describes iron(ll) complexes containing tridentate diphosphine PNP ligands useful for catalytic hydrogenation.

Enantioselective reduction of ketones with (EtO)2MeSiH catalyzed by an in-situ generated N-heterocyclic carbene (NHC) Ir complex at room temperature has been developed. A series of benzimidazolium salts were synthesized and screened in the asymmetric hydrosilylation reaction. As a result, propiophenone was efficiently reduced by the combined catalytic system of [IrCl(cod)]2 and NHC-Ag complex derived from N-(1-naphthalenylmethyl)-substituted benzimidazolium salt L12, affording the corresponding alcohol in 92% yield and with 92% ee. Moreover, the evaluation of an Ir catalyst precursor showed that cationic [Ir(cod)2]BF4 complex could be used. Furthermore, the introduction of a chiral hydroxyamide side arm into the benzimidazolium salt was critical for the successful design of the NHC ligand.