Active Secondary Alcohols Research Articles

ChemInform Abstract: Preparation of Optically Active Secondary Alcohols by Combination of Enzymatic Hydrolysis and Chemical Transformation.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Catalytic Asymmetric Synthesis of Optically Active Secondary Alcohols Deuterated on the Secondary Carbon by the Enantioselective Alkylation of Aldehydes.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Catalytic Enantioselective Borane Reduction of Aromatic Ketones with Sulfonyl (S)-Prolinol.

Abstract The asymmetric reduction of aromatic ketones was catalyzed by a class of recoverable and highly stable chiral sulfonamides derived from (S)-proline to yield optically active secondary alcohols in high yields and with enantiomeric excesses of up to 91%.

A Novel D2‐Symmetrical Chiral Tetraoxazoline Ligand for Highly Enantioselective Hydrosilylation of Aromatic Ketones

AbstractA novel D2‐symmetrical chiral tetraoxazoline ligand was synthesized from 1,2,4,5‐benzenetetracarboxylic acid and L‐valinol via a one‐pot reaction, and the asymmetric hydrosilylation of aromatic ketones was carried out in dichloromethane in the presence of 1.0 mol% of a bivalent copper ion catalyst with the tetraoxazoline to give optically active secondary alcohols. The chiral catalyst showed excellent activities and enantioselectivities in the hydrosilylation of aryl ketones with up to 99% ee.

Easy Separation of Optically Active Secondary Alcohols by Enzymatic Hydrolysis of Soluble Polymer-Supported Carbonates

Abstract The enzyme-mediated enantioselective hydrolysis of middle molecular weight poly(ethylene glycol) (PEG)-supported carbonates is disclosed. The representative water-soluble substrate was prepared by the immobilization of (±)-1-phenylethanol onto a monomethoxy PEG (MPEG, av. Mw 5000) or PEG (av. Mw 4600) through a carbonate linker. Porcine pancreas lipase (PPL) enantioselectively catalyzed the hydrolysis of the polymer-supported substrate in a mixed solvent (hexane/buffer = 9/1) at 0 °C to afford the corresponding optically active compounds. In this system, the separation of the remaining (S)-substrate and the resulting (R)-alcohol was achieved by a simple procedure without any laborious column chromatography. The substrate was easily hydrolyzed with NaOH in MeOH–H2O to give the (S)-alcohol. This procedure was also applicable to the preparation of other optically active secondary alcohols. As expected, an introduction of a hydrophobic spacer between the MPEG moiety and the carbonate linker affected both the reactivity and enantioselectivity. An o-substitution produced a lower conversion than those of the reaction of the m- and p-substituted substrates. While the substrate with a p-phenylethyl spacer gave the best E value (>200) with low conversion, the reaction of the substrate with a p-phenylmethyl spacer smoothly proceeded with high enantioselectivity (E value = 151).

Synthesis, characterization, and structures of arylaluminum reagents and asymmetric arylation of aldehydes catalyzed by a titanium complex of an N-sulfonylated amino alcohol

A series of phenylaluminum reagents AlPh x Et 3− x (L) ( x = 1–3) containing adduct ligand L [Et 2O, THF, OPPh 3, or 4-dimethylaminopyridine (DMAP)] were synthesized and characterized. NMR studies showed that AlPh x Et 3− x (L) ( x = 1 or 2) exists as an equilibrium mixture of 3–4 species in solution. Solid-state structures of the phenylaluminum reagents reveal a distorted tetrahedral geometry. Asymmetric additions of phenylaluminum to 2-chlorobenzaldehyde were examined employing a titanium(IV) complex [TiL ∗(OPr i ) 2] 2 10 (H 2L ∗ = (1 R,2 S)-2-( p-tolylsulfonylamino)-1,3-diphenyl-1-propanol) as a catalyst precursor. It was found that the adduct ligand L had a strong influence on the reactivity and the enantioselectivity in asymmetric phenyl additions to aldehydes. The phenylaluminum reagents with OPPh 3 or DMAP were unreactive toward aldehydes, and AlPh 3(THF) was found to be superior to AlPh 3(OEt 2) or AlPhEt 2(THF). Asymmetric aryl additions of AlAr 3(THF) to aldehydes employing a loading of 5 mol % titanium(IV) complex 10 with a strategy of a slow addition of the aldehydes over 20 min were conducted, and the reactions produced optically active secondary alcohols in high yields with excellent enantioselectivities of up to 94% ee.

Addition of Diethylzinc to Aromatic Aldehydes Catalyzed by Hydrolase

Abstract A novel application of hydrolase as catalyst for the addition of diethylzinc to aromatic aldehydes is reported. Optimum conditions were screened out. Under the optimum conditions (i.e., reaction at 40 °C using hyperthermophilice esterase APE1547, 4-Cl-benzaldehyde substrate, and trichloromethane solvent), this reaction provided optically active secondary alcohol with an enantiomeric excess up to 56% and a yield up to 78%. The possible mechanism was proposed based on experimental observations and molecular dynamics simulation. These observations extend the phenomenon of enzyme promiscuity.

Preparation and preliminary biological screening of cholic acid–juvenoid conjugates

Steroidal compounds have been utilized as carriers and for modification of physico-chemical properties of model biologically active secondary alcohols – juvenoids. Juvenoids are juvenile hormone analogues – environmentally safe insecticides, possessing significant biological activity towards different arthropods groups in focus on insect pest species. Structure modification of juvenoids plays important role to control the rate of liberation and decomposition of juvenoid in digestive system and can also play important role in the mode of action towards selected insect. This study presents an approach to the synthesis of steroidal monomers and dimers carrying one and two molecules of a juvenoid in their structures. The prepared compounds were tested for their inhibition activity on reproduction of the blowfly Neobellieria ( Sarcophaga) bullata. These steroid–juvenoid conjugates showed promising possibilities in synthesis of new unique biochemical insecticides. Preliminary biological test results of prepared compounds are presented.

Highly Enantioselective Organocatalytic Oxidative Kinetic Resolution of Secondary Alcohols Using Chirally Modified AZADOs

A highly enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols has been accomplished using asymmetric organocatalysis. A panel of chirally modified 2-azaadamantane N-oxyls (AZADOs) exhibit superior catalytic activity and high enantioselectivity, allowing us to obtain optically active secondary alcohols with a k(rel) value up to 82.2.

Asymmetric transfer hydrogenation of aromatic ketones with chiral diamino-thiophene/iridium catalyst systems

The chiral diamino-bis(bithiophene) ligands were firstly employed in the iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. The new catalyst systems, generated in situ from chiral diamino-bis(bithiophene) ligands and IrCl(CO)(PPh 3) 2 in i PrOH, gave the corresponding optically active secondary alcohols with high yield and fair to good enantioselectivities (up to 90% ee). The chiral Ir(I)/diamino-bis(bithiophene) complexes were also synthesized and characterized. The XPS spectra showed that the potentially multidentate ligands coordinated to the Ir atom through the nitrogen atoms, while the thiophene pendants did not participate in coordination to the Ir atom.

Chiral Schiff Bases as Highly Active and Enantioselective Catalysts in Catalytic Addition of Dialkylzinc to Aldehydes

We have developed chiral Schiff base catalysts based on the ONO-tridentate ligand for the catalytic enantioselective addition of dialkylzinc to aldehydes. Various aldehydes were smoothly converted into corresponding optically active secondary alcohols with high enantioselectivity (up to 98 % ee) in high yield. Furthermore, we have succeeded in decreasing the catalyst loading minimum to 0.1 mol % in the chiral Schiff base-catalyzed enantioselective alkylation of aldehydes.

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by 14-hydroxylsubstituted morphinans

Enantioselective addition reactions of diethylzinc to aromatic aldehydes were performed with catalytic amounts of 14-hydroxylsubstituted morphine alkaloids. The reaction conditions such as catalyst loading, time and temperature were optimized to obtain the highest enantiomeric excess. Optically active secondary alcohols were synthesized with ee up to 95%.

Asymmetric Borane Reduction of Prochiral Ketones Catalyzed by α,α-Disubstituted Aziridinemethanols

A series of novel α,α-disubstituted aziridinemethanols have been developed for the enantioselective reduction of ketones in refluxing tetrahydrofuran. The optically active secondary alcohol products were obtained in good enantiomeric excess (~96.8%) and excellent yields. The results showed that the substituent groups on the hydroxyl-bearing carbon of aziridinemethanols obviously affected the enantioselectivity.

Chiral ligand 2-(2′-piperidinyl)pyridine: synthesis, resolution and application in asymmetric diethylzinc addition to aldehydes

Chiral ligand 2-(2′-piperidinyl)pyridine 1 has been synthesized in good overall yield by sequential benzylation, hydrogenation and debenzylation of 2,2′-bipyridine. Its enantiomerically pure enantiomers have been obtained by resolution of 2-(1-benzyl-2-piperidinyl)pyridine 2 with d-tartaric acid (or l-tartaric acid) followed by debenzylation. The absolute configuration was determined by X-ray analysis of the ( S)- 2 d-tartrate. It was demonstrated that 1 can be used as an effective enantioselective catalyst in the addition of diethylzinc to aldehydes. Optically active secondary alcohols with up to 100% enantiomeric excess were obtained in high yields.

Asymmetric borane reduction of prochiral ketones catalyzed by C3-symmetric sulfonamide

A novel, recoverable, C 3-symmetric sulfonamide L- 1 has been developed for the asymmetric borane reduction of prochiral ketones in refluxing THF. The optically active secondary alcohols were obtained in excellent enantiometric excesses (up to 97% ee) and good yields. The C 3-symmetric sulfonamide L- 1 can be easily recovered and reused four times without any significant loss of catalytic activity.

3‐Substituted BINOL Schiff bases and their reductive products for catalytic asymmetric addition of diethylzinc to aldehydes

Three new chiral 3-substituted BINOL Schiff bases and their reductive 3-arylaminomethyl BINOL products have been synthesized and used for the asymmetric addition reaction of diethylzinc to aldehydes in the presence of titanium tetraisopropoxide. The reaction provided optically active secondary alcohols in high yield (86-100%) and good enantioselectivity (up to 92% ee).

Catalytic enantioselective organozinc addition toward optically active tertiary alcohol synthesis

A highly enantioselective organozinc (R2Zn) addition to a series of aldehydes and ketones was developed based on conjugate Lewis acid-Lewis base catalysis. Optically active secondary and tertiary alcohols were obtained in high yields with high enantioselectivities without Ti(IV) compounds. Bifunctional chiral 3,3'-diphosphoryl-BINOL ligands were designed and prepared through a phospho-Fries rearrangement as a key step. On the other hand, bifunctional chiral phosphoramide ligands were designed and prepared from L-valine. Mechanistic studies were performed by X-ray analyses of Zn(II) cluster and chiral ligands, a 31P NMR experiment on Zn(II) complexes, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition state assembly that includes monomeric active intermediates.

Novel chiral tetraaza ligands: synthesis and application in asymmetric transfer hydrogenation of ketones

Novel chiral tetraaza ligands, N 1, N 2-bis(2-(piperidin-1-yl)benzylidene)cyclohexane-1,2-diamine 1 and N 1, N 2-bis(2-(piperidin-1-yl)benzyl)cyclohexane-1,2-diamine 2, have been synthesized and fully characterized by analytical and spectroscopic methods. The structure of ( R, R)- 1 has been established by X-ray crystallography. Asymmetric transfer hydrogenation of aromatic ketones with the catalysts prepared in situ from [IrHCl 2(COD)] 2 and the chiral tetraaza ligands in 2-propanol gave the corresponding optically active secondary alcohols in high conversions and good ees (up to 91%) under mild reaction conditions.

Asymmetric Reduction and Oxidation of Aromatic Ketones and Alcohols Using W110A Secondary Alcohol Dehydrogenase from Thermoanaerobacter ethanolicus

An enantioselective asymmetric reduction of phenyl ring-containing prochiral ketones to yield the corresponding optically active secondary alcohols was achieved with W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (W110A TESADH) in Tris buffer using 2-propanol (30%, v/v) as cosolvent and cosubstrate. This concentration of 2-propanol was crucial not only to enhance the solubility of hydrophobic phenyl ring-containing substrates in the aqueous reaction medium, but also to shift the equilibrium in the reduction direction. The resulting alcohols have S-configuration, in agreement with Prelog's rule, in which the nicotinamide-adenine dinucleotide phosphate (NADPH) cofactor transfers its pro-R hydride to the re face of the ketone. A series of phenyl ring-containing ketones, such as 4-phenyl-2-butanone (1a) and 1-phenyl-1,3-butadione (2a), were reduced with good to excellent yields and high enantioselectivities. On the other hand, 1-phenyl-2-propanone (7a) was reduced with lower ee than 2-butanone derivatives. (R)-Alcohols, the anti-Prelog products, were obtained by enantiospecific oxidation of (S)-alcohols through oxidative kinetic resolution of the rac-alcohols using W110A TESADH in Tris buffer/acetone (90:10, v/v).

Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones

Towards the synthesis of sterically hindered optically active secondary alcohol 2, yeast strains ( Candida floricola IAM 13115 and Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone 1 were developed by screening. Strains with complementary re-facial selectivity ( Pichia angusta IAM 12895 and Pichia minuta IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3 S,5 S)-2,6-dimethyl-3,5-heptanediol 12a.