93379-07-8

Upstream product

• 58889-89-7 (Z)-1-methoxy-1-(4-methoxyphenyl)-1-propene 
• 143215-10-5 (Z)-1-(4-methoxyphenyl)-1-(tert-butyldimethylsiloxy)-1-propene 
• 10557-27-4 1-(4-methoxy-phenyl)-propane-1,2-dione 
• 73208-70-5 ethyl (2S)-2-(tetrahydropyran-2-yloxy)propionate 
• 121-97-1 4-Methoxypropiophenone 
• 123-11-5 4-methoxy-benzaldehyde 
• 75-07-0 acetaldehyde 
• 530085-88-2 phosphoric acid diethyl ester 1-(4-methoxyphenyl)-propenyl ester 
• 14774-77-7 p-methoxyphenyllithium 
• 104-46-1 anethole 
• 200353-84-0 1-(4-methoxyphenyl)-1-oxopropan-2-yl acetate 
• 111199-12-3 (S)-2-methoxymethoxy-1-(4-methyoxyphenyl)-1-propanone 
• 111199-15-6 (S)-2-(1-Ethoxy-ethoxy)-1-(4-methoxy-phenyl)-propan-1-one 

Downstream Products

• 111197-84-3 (S)-2-hydroxy-1-(4-methoxyphenyl)-1-propanone dimethyl acetal 
• 93397-63-8 (S)-4-methoxy-β-methylbenzeneethanol 
• 103593-55-1 (S)-2-methylsulfonyloxy-1-(4-methoxyphenyl)-1-propanone 2,2-dimethyl-trimethylene acetal 
• 103593-54-0 (S)-2-methylsulfonyloxy-1-(4-methoxyphenyl)-1-propanone dimethyl acetal 
• 111004-04-7 (1R,2S)-1-(4'-methoxyphenyl)-1,2-propanediol 
• 111197-88-7 (S)-2-hydroxy-1-(4-methoxyphenyl)-1-propanone 2,2-dimethyl-trimethylene acetal 
• 93397-57-0 Methanesulfonic acid (S)-2-(4-methoxy-phenyl)-1-methyl-2-oxo-ethyl ester 

Relevant academic research and scientific papers

Continuous enzymatic stirred tank reactor cascade with unconventional medium yielding high concentrations of (S)-2-hydroxyphenyl propanone and its derivatives

The implementation of biocatalysis in flow chemistry offers synergistic synthesis advantages in line with green chemistry principles. Yet, the conversion of high substrate concentrations is in many cases hindered by insolubility issues or substrate toxicity. Here, the continuous synthesis of (S)-2-hydroxyphenyl propanone (2-HPP) from inexpensive benzaldehyde and acetaldehyde in a methyltert-butyl ether based organic reaction environment, namely micro-aqueous reaction system, has been established. Kinetic parameters of the applied whole cell catalyst were identified to design a continuous process for (S)-2-HPP synthesis. This revealed a necessity to distribute acetaldehyde over a spatial coordinate to remain below a toxic concentration threshold. Hence, three continuous stirred tank reactors (cSTR) were conjugated in a technical cascade with an additional influx of acetaldehyde into each unit. The catalytic behaviour of this reaction setup was described based on mass balances and a kinetic model. Enzyme deactivation was described by a novel staged model and compared to a simple generic model. The optimized continuous setup yielded 190 mM (S)-HPP with an ee > 98% over 8 h. The product was easily recovered from the organic reaction environment by crystallization with an isolated yield of 68% and a purity of >99%. Further, the substrate range of the applied catalystPseudomonas putidabenzoylformate decarboxylase variant L461A was analysed. This revealed numerous halogenated, methoxylated and nitro-derivatives inortho,meta, andparaposition, which can in principle be gained by the established process. As an example, the applied cSTR concept was transferred top-methoxy benzaldehyde with good results even without further optimization.

Rearrangement of N- tert-Butanesulfinyl Enamines for Synthesis of Enantioenriched α-Hydroxy Ketone Derivatives

Treating chiral N-tert-butanesulfinyl ketimines with potassium hexamethyldisilazide (or potassium tert-butoxide) and methyl triflate gives N-methylated N-tert-butanesulfinyl enamine intermediates that undergo stereoselective [2,3]-rearrangement to afford α-sulfenyloxy ketones with excellent enantiopurities. This cascade of enamination-N-methylation-rearrangement was even used to generate acyclic tertiary α-hydroxy ketones bearing two α-substituents showing negligible differences in bulkiness, such as methyl and ethyl groups.

Biocatalytic route to chiral acyloins: P450-catalyzed regio- and enantioselective α-hydroxylation of ketones

P450-BM3 and mutants of this monooxygenase generated by directed evolution are excellent catalysts for the oxidative α-hydroxylation of ketones with formation of chiral acyloins with high regioselectivity (up to 99%) and enantioselectivity (up to 99% ee). This constitutes a new route to a class of chiral compounds that are useful intermediates in the synthesis of many kinds of biologically active compounds.

Asymmetric oxidation of enol phosphates to α-hydroxy ketones using Sharpless reagents and a fructose derived dioxirane

The asymmetric oxidation of a variety of differently substituted, acyclic and cyclic enol phosphates using the Sharpless AD-reagents AD-mix-α and AD-mix-β, and a fructose derived chiral ketone as a catalyst, afforded the corresponding α-hydroxy ketones in high enantioselectivity and good yield. The influence of steric and electronic factors of the substrates on the facial stereoselectivity in the reported oxidations was studied.

Studies towards the stereoselective α-hydroxylation of flavanones. Biosynthetic significance

The enolates of various propiophenones, chromanones, and also analogues of naturally occurring flavanones were stereoselectively hydroxylated at the ?-position, by employing commercially available enantiopure oxaziridines, to afford the desired ?-hydroxylated target molecules in good to exceptional stereoselectivities and in moderate to good chemical yields. A mechanistic rationale is presented to account for the stereoselectivities achieved. These in vitro results were tentatively related to the stereoselective biosynthesis of enantio-enriched dihydroflavonols while questions were raised about the authenticity of certain natural compounds. CSIRO 2008.

Asymmetric oxidation of enol phosphates to α-hydroxy ketones by?(salen)manganese(III) complex. Effects of the substitution pattern of enol phosphates on the stereochemistry of oxygen?transfer

This paper presents a study of enantioselective catalytic oxidation of a variety of differently substituted, cyclic (E) and acyclic (Z)-enol phosphates. The asymmetric oxidation of acyclic (Z)-enol phosphates containing alkoxy substituents in the phosphate group 2a, c, e-g, i, and j and Z-configured enol phosphates containing aryloxy substituents in the phosphate group 2b, d, and h afforded optically active α-hydroxy ketones 4a-j of opposite configuration with good to high enantioselectivity. The influence of electronic and steric effects of the enol phosphate substituents on the stereoselectivity of oxidation was studied.

α-Hydroxy ketones in high enantiomeric purity from asymmetric oxidation of enol phosphates with (salen) manganese(III) complex

Optically active α-hydroxy ketones 4 have been prepared in high enantioselectivity by the catalytic, enantioselective oxidation of easily available and stable (E)-enol phosphates 2 by (salen) Mn(III) complex.

Stereoselective Synthesis of Optically Active α-hydroxy Ketones and anti-1,2-diols via Asymmetric Transfer Hydrogenation of Unsymmetrically Substituted 1,2-diketones

Formula Represented A well-defined chiral Ru catalyst RuCl(N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine)(η6-arene) effectively promotes asymmetric transfer hydrogenation of 1-aryl-1,2-propanedione with HCOOH/N(C2H5)3, leading preferentially to optically active 1-aryl-2-hydroxy-1-propanone with up to 99% ee and 89% yield at 10°C. The reaction at 40°C gives anti-1-aryl-1,2-propanediol with up to 95% ee and 78% yield. This is a highly efficient procedure for the synthesis of optically active anti-diols.

Benzoylformate decarboxylase from Pseudomonas putida as stable catalyst for the synthesis of chiral 2-hydroxy ketones

The thiamin diphosphate-and Mg2+-dependent enzyme benzoylformate decarboxylase (BFD) from Pseudomonas putida was characterized with respect to its suitability to catalyze the formation of chiral 2-hydroxy ketones in a benzoin-condensation type reaction. Carboligation constitutes a side reaction of BFD, whereas the predominant physiological task of the enzyme is the non-oxidative decarboxylation of benzoylformate. For this purpose the enzyme was obtained in sufficient purity from Pseudomonas putida cells in a one-step purification using anion-exchange chromatography. To facilitate the access to pure BFD for kinetical studies, stability investigations, and synthetical applications, the coding gene was cloned into a vector allowing the expression of a hexahistidine fusion protein. The recombinant enzyme shows distinct activity maxima for the decarboxylation and the carboligation beside a pronounced stability in a broad pH and temperature range. The enzyme accepts a wide range of donor aldehyde substrates which are ligated to acetaldehyde as an acceptor in mostly high optical purities. The enantioselectivity of the carboligation was found to be a function of the reaction temperature, the substitution pattern of the donor aldehyde and, most significantly, of the concentration of the donor aldehyde substrate. Our data are consistent with a mechanistical model based on the X-ray crystallographic data of BFD. Furthermore we present a simple way to increase the enantiomeric excess of (S)-2-hydroxy-1-phenyl-propanone from 90% to 95% by skillful choice of the reaction parameters. Enzymatic synthesis with BFD are performed best in a continuously operated enzyme membrane reactor. Thus, we have established a new enzyme tool comprising a vast applicability for stereoselective synthesis.

Asymmetric reduction of α-keto esters and α-diketones with a bakers' yeast keto ester reductase

Optically pure α-hydroxy esters and α-hydroxy ketones have been synthesized by the reduction of the corresponding ketones with a keto ester reductase isolated from bakers' yeast (YKER-I). The reduction of α-keto esters affords the corresponding (S)- or (R)-hydroxy esters selectively, where the stereochemical course depends on the chain length of the alkyl substituent on the carbonyl group. An α-keto short alkanoic ester affords the corresponding (S)-hydroxy ester, whereas a long alkanoate yields the corresponding (R)-hydroxy ester. The reduction of α-diketones affords the corresponding (S)-2-hydroxy ketones regio- and stereoselectively.