Preparative Organic Synthesis Research Articles

Specificity of Penicillin Acylases in Deprotection of N-Benzyloxycarbonyl Derivatives of Amino Acids.

Changes in the structure of the N-acyl group in N-acylated amino acid derivatives significantly affect both the recognition and activity of penicillin acylases on this series of substrates. However, penicillin acylases from both Alcaligenes faecalis and Escherichia coli are capable of removing the N-benzyloxycarbonyl protecting group in amino acid derivatives under mild conditions without the use of toxic reagents. Efficiency in using penicillin acylases in preparative organic synthesis can be improved by utilizing modern rational enzyme design methods.

Hyperbaric reactions in organic synthesis. Progress from 2006 to 2021.

This comprehensive review summarizes the published literature data concerning above 1 kbar reactions for the purposes of preparative organic synthesis (more than 50 mg of the initial substance) from 2006 to the beginning of 2021 and highlights the obstacles, which were overcome by the use of a high-pressure technique. The review covers around 100 references.

Halogen-Bridged Methylnaphthyl Palladium Dimers as Versatile Catalyst Precursors in Coupling Reactions.

Halogen‐bridged methylnaphthyl (MeNAP) palladium dimers are presented as multipurpose Pd‐precursors, ideally suited for catalytic method development and preparative organic synthesis. By simply mixing with phosphine or carbene ligands, they are in situ converted into well‐defined monoligated complexes. Their catalytic performance was benchmarked against state‐of‐the‐art systems in challenging Buchwald–Hartwig, Heck, Suzuki and Negishi couplings, and ketone arylations. Their use enabled record‐setting activities, beyond those achievable by optimization of the ligand alone. The MeNAP catalysts permit syntheses of tetra‐ortho‐substituted arenes and bulky anilines in near‐quantitative yields at room temperature, allow mono‐arylations of small ketones, and enable so far elusive cross‐couplings of secondary alkyl boronic acids with aryl chlorides.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity.

Challenges in the selective manipulation of functional groups (chemoselectivity) in organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites of reactivity (protecting groups). Although electrochemistry offers precise redox control to achieve unique chemoselectivity, this approach often becomes challenging in the presence of multiple redox-active functionalities. Historically, electrosynthesis has been performed almost solely by using direct current (DC). In contrast, applying alternating current (AC) has been known to change reaction outcomes considerably on an analytical scale but has rarely been strategically exploited for use in complex preparative organic synthesis. Here we show how a square waveform employed to deliver electric current-rapid alternating polarity (rAP)-enables control over reaction outcomes in the chemoselective reduction of carbonyl compounds, one of the most widely used reaction manifolds. The reactivity observed cannot be recapitulated using DC electrolysis or chemical reagents. The synthetic value brought by this new method for controlling chemoselectivity is vividly demonstrated in the context of classical reactivity problems such as chiral auxiliary removal and cutting-edge medicinal chemistry topics such as the synthesis of PROTACs.

A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation

We report an engineered panel of ene-reductases (ERs) from Thermus scotoductus SA-01 (TsER) that combines control over facial selectivity in the reduction of electron deficient CC double bonds with thermostability (up to 70 °C), organic solvent tolerance (up to 40 % v/v) and a broad substrate scope (23 compounds, three new to literature). Substrate acceptance and facial selectivity of 3-methylcyclohexenone was rationalized by crystallisation of TsER C25D/I67T and in silico docking. The TsER variant panel shows excellent enantiomeric excess (ee) and yields during bi-phasic preparative scale synthesis, with isolated yield of up to 93 % for 2R,5S-dihydrocarvone (3.6 g). Turnover frequencies (TOF) of approximately 40 000 h−1 were achieved, which are comparable to rates in hetero- and homogeneous metal catalysed hydrogenations. Preliminary batch reactions also demonstrated the reusability of the reaction system by consecutively removing the organic phase (n-pentane) for product removal and replacing with fresh substrate. Four consecutive batches yielded ca. 27 g L−1 R-levodione from a 45 mL aqueous reaction, containing less than 17 mg (10 μM) enzyme and the reaction only stopping because of acidification. The TsER variant panel provides a robust, highly active and stereocomplementary base for further exploitation as a tool in preparative organic synthesis.

Easy Access to Enantiomerically Pure Heterocyclic Silicon-Chiral Phosphonium Cations and the Matched/Mismatched Case of Dihydrogen Release.

Phosphonium ions are widely used in preparative organic synthesis and catalysis. The provision of new types of cations that contain both functional and chiral information is a major synthetic challenge and can open up new horizons in asymmetric cation‐directed and Lewis acid catalysis. We discovered an efficient methodology towards new Si‐chiral four‐membered CPSSi* heterocyclic cations. Three synthetic approaches are presented. The stereochemical sequence of anchimerically assisted cation formation with B(C6F5)3 and subsequent hydride addition was fully elucidated and proceeds with excellent preservation of the chiral information at the stereogenic silicon atom. Also the mechanism of dihydrogen release from a protonated hydrosilane was studied in detail by the help of Si‐centered chirality as stereochemical probe. Chemoselectivity switch (dihydrogen release vs. protodesilylation) can easily be achieved through slight modifications of the solvent. A matched/mismatched case was identified and the intermolecularity of this reaction supported by spectroscopic, kinetic, deuterium‐labeling experiments, and quantum chemical calculations.

RECENT TRENDS IN CONVERSION OF C6-SUGARS INTO VALUE-ADDED CHEMICALS OVER SOLID CATALYSTS

In recent decades, the energy demand is ever increasing. Biomass energy is a viable option as an alternative due to reduced CO 2 emissions and depletion of fossil fuels at a faster rate. Therefore, the substitution of non-renewable fossil resources by renewable biomass as a sustainable feedstock has been focused on researchers to develop useful green fuels and other platform chemicals such as biofuels, commodity chemicals, and new bio-based materials. For the conversion of sugars, several methodologies have been investigated through chemocatalysis from plant-derived biomass feedstocks. This review critically overviewed the latest advancement regarding reaction conditions, product yields, and selectivity on the conversion of C 6 -sugars into important chemicals like 5- hydroxymethylfurfural, levulinic acid, lactic acid, formic acid, glyceraldehyde, 1,3-dihydroxyacetone and furan-2,5-dicarboxylic acid, etc. This review describes green chemistry principles includes the main reactions used to convert renewable biomass into industrially important products that are applicable as raw materials with emphasis on preparative organic synthesis.

Lyophilized extracts from vegetable flours as valuable alternatives to purified oxygenases for the synthesis of oxylipins

In this work, the whole aqueous extracts of soybean flour and oat flour have been used as valuable alternatives to purified oxygenase enzymes for the preparation of oxylipins derived from (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid (EPA). The lipoxygenase activity in the aqueous extracts of soybean (Glycine max. L.) flour was monitored with linoleic acid as substrate and compared with the commercially available purified enzyme (LOX-1). Oat flour extracts (Avena sativa L.) were evaluated for their peroxygenase activity by comparing different enzyme preparations in the epoxidation of methyl oleate. It was found that lyophilization of the aqueous extracts from these vegetable flours offers advantages in terms of enzyme stability, reproducibility and applicability to preparative organic synthesis. The lyophilized enzyme preparations were tested for the oxyfunctionalization of EPA and the formed products were isolated in satisfactory yields. In the presence of lyophilized extract from soybean, EPA gave 15S-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoic acid in enantiopure form as exclusive product. Peroxygenase from oat flour was less selective and catalyzed the formation of different epoxides of EPA. However, the biocatalyzed epoxidation of EPA under controlled conditions allowed to obtain optically active (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoic acid (65% ee) as the main monoepoxide, among the five possible ones.

How a Solvent Molecule Affects Competing Elimination and Substitution Dynamics. Insight into Mechanism Evolution with Increased Solvation.

Competiting SN2 substitution and E2 elimination reactions are of central importance in preparative organic synthesis. Here, we unravel how individual solvent molecules may affect underlying SN2/E2 atomistic dynamics, which remains largely unclear with respective to their effects on reactivity. Results are presented for a prototype microsolvated case of fluoride anion reacting with ethyl bromide. Reaction dynamics simulations reproduce experimental findings at near thermal energies and show that the E2 mechanism dominates over SN2 for solvent-free reaction. This is energetically quite unexpected and results from dynamical effects. Adding one solvating methanol molecule introduces strikingly distinct dynamical behaviors that largely promote the SN2 reaction, a feature which attributes to a differential solute-solvent interaction at the central barrier that more strongly stabilizes the transition state for substitution. Upon further solvation, this enhanced stabilization of the SN2 mechanism becomes more pronounced, concomitant with drastic suppression of the E2 route. This work highlights the interplay between energetics and dynamics in determining mechanistic selectivity and provides insight into the impact of solvent molecules on a general transition from elimination to substitution for chemical reactions proceeding from gas- to solution-phase environments.

ChemInform Abstract: Enantioseparations in Achiral Environments and Chromatographic Systems

AbstractReview: [109 refs.

Enantioseparations in Achiral Environments and Chromatographic Systems

AbstractSince the very first resolution of racemic tartaric acid by Pasteur, the importance of resolution and methodology has been on a path of continuous understanding and expansion. The science and chemistry of achieving such targets has changed a lot. The advent of chromatography changed the direction by involving synthetic, semisynthetic, or naturally occurring chiral materials for a direct approach to resolution, where rapid and reversible association occurs to form diastereomers with different stabilities and partition coefficients responsible for overall enantioseparation. It has now reached a stage where the separation of excess enantiomers from nonracemic mixtures has been achieved in a totally achiral environment, which does not appear to be in line with the prevalent concepts of basic stereochemistry. Caution should be exercised when enantiomerically enriched mixtures – obtained by enantioselective synthesis – are chromatographed for purification in preparative organic synthesis.

ChemInform Abstract: Metal‐Free One‐Pot Synthesis of 1,3‐Diazaheterocyclic Compounds via I2‐Mediated Oxidative C—N Bond Formation.

ChemInformVolume 46, Issue 48 Preparative Organic Chemistry ChemInform Abstract: Metal-Free One-Pot Synthesis of 1,3-Diazaheterocyclic Compounds via I2-Mediated Oxidative C—N Bond Formation. Xianhai Tian, Xianhai Tian Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorLina Song, Lina Song Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorErtong Li, Ertong Li Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorQiang Wang, Qiang Wang Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorWenquan Yu, Wenquan Yu Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorJunbiao Chang, Junbiao Chang Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this author Xianhai Tian, Xianhai Tian Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorLina Song, Lina Song Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorErtong Li, Ertong Li Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorQiang Wang, Qiang Wang Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorWenquan Yu, Wenquan Yu Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this authorJunbiao Chang, Junbiao Chang Coll. Chem. Mol. Eng., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. ChinaSearch for more papers by this author First published: 12 November 2015 https://doi.org/10.1002/chin.201548038Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue48December, 2015 RelatedInformation

ChemInform Abstract: Copper‐Catalyzed Direct Synthesis of Furans and Thiophenes via Decarboxylative Coupling of Alkynyl Carboxylic Acids with H2O or Na2S.

ChemInformVolume 46, Issue 42 Preparative Organic Chemistry ChemInform Abstract: Copper-Catalyzed Direct Synthesis of Furans and Thiophenes via Decarboxylative Coupling of Alkynyl Carboxylic Acids with H2O or Na2S. Francis Mariaraj Irudayanathan, Francis Mariaraj Irudayanathan Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this authorGabriel Charles Edwin Raja, Gabriel Charles Edwin Raja Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this authorSunwoo Lee, Sunwoo Lee Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this author Francis Mariaraj Irudayanathan, Francis Mariaraj Irudayanathan Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this authorGabriel Charles Edwin Raja, Gabriel Charles Edwin Raja Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this authorSunwoo Lee, Sunwoo Lee Dep. Chem., Chonnam Natl. Univ., Gwangju 500-757, S. KoreaSearch for more papers by this author First published: 01 October 2015 https://doi.org/10.1002/chin.201542043Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue42October, 2015 RelatedInformation

Exploring nicotinamide cofactor promiscuity in NAD(P)H-dependent flavin containing monooxygenases (FMOs) using natural variation within the phosphate binding loop. Structure and activity of FMOs from Cellvibrio sp. BR and Pseudomonas stutzeri NF13

Flavin-containing monooxygenases (FMOs) catalyse asymmetric oxidation reactions that have potential for preparative organic synthesis, but most use the more expensive, phosphorylated nicotinamide cofactor NADPH to reduce FAD to FADH2 prior to formation of the (hydro)peroxy intermediate required for substrate oxygenation. A comparison of the structures of NADPH-dependent FMO from Methylophaga aminisulfidivorans (mFMO) and SMFMO from Stenotrophomonas maltophilia, which is able to use both NADPH and NADH, suggested that the promiscuity of the latter enzyme may be due in part to the substitution of an Arg–Thr couple in the NADPH phosphate recognition site in mFMO, for a Gln–His couple in SMFMO (Jensen et al., 2012, Chembiochem, 13, 872–878). Natural variation within the phosphate binding region, and its influence on nicotinamide cofactor promiscuity, was explored through the cloning, expression, characterisation and structural studies of FMOs from Cellvibrio sp. BR (CFMO) and Pseudomonas stutzeri NF13 (PSFMO), which possess Thr–Ser and Gln–Glu in the putative phosphate recognition positions, respectively. CFMO and PSFMO displayed 5- and 1.5-fold greater activity, respectively, than SMFMO for the reduction of FAD with NADH, and were also cofactor promiscuous, displaying a ratio of activity with NADH:NADPH of 1.7:1 and 1:1.3, respectively. The structures of CFMO and PSFMO revealed the context of the phosphate binding loop in each case, and also clarified the structure of the mobile helix–loop–helix motif that appears to shield the FAD-binding pocket from bulk solvent in this class of FMOs, a feature that was absent from the structure of SMFMO.

Green synthesis from biomass

This review describes how to apply green chemistry principles to transform biomass into several types of molecules. On the basis of selected papers published over the last three to four years, it includes the main reactions used to convert renewable feedstocks into chemical products that are potentially applicable as raw materials or synthetic intermediates in fine chemical industries with emphasis on preparative organic synthesis.

ChemInform Abstract: Solvent‐Free Synthesis of Substituted Five Membered Heterocycles: One‐Pot Reaction of Primary Amine and Alkyl Propiolate or Isothiocyanate in the Presence of Oxalyl Chloride.

ChemInformVolume 45, Issue 28 Preparative Organic Chemistry ChemInform Abstract: Solvent-Free Synthesis of Substituted Five Membered Heterocycles: One-Pot Reaction of Primary Amine and Alkyl Propiolate or Isothiocyanate in the Presence of Oxalyl Chloride. Zinatossadat Hossaini, Zinatossadat Hossaini Dep. Chem., Islamic Azad Univ., Qaemshahr, IranSearch for more papers by this author Zinatossadat Hossaini, Zinatossadat Hossaini Dep. Chem., Islamic Azad Univ., Qaemshahr, IranSearch for more papers by this author First published: 26 June 2014 https://doi.org/10.1002/chin.201428044Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume45, Issue28July 15, 2014 RelatedInformation

Síntese Ambientalmente Correta a partir de Biomassa

This review describes how to apply green chemistry principles to transform biomass into several types of molecules. On the basis of selected papers published over the last three to four years, it includes the main reactions used to convert renewable feedstock into chemical products that are potentially applicable as raw materials or synthetic intermediates in fine chemical industries with an emphasis on preparative organic synthesis.

The taming of oxygen: biocatalytic oxyfunctionalisations.

The scope and limitations of oxygenases as catalysts for preparative organic synthesis is discussed.

ChemInform Abstract: One‐Pot Synthesis of S‐Alkyl Dithiocarbamates via the Reaction of N‐Tosylhydrazones, Carbon Disulfide and Amines.

ChemInformVolume 45, Issue 1 Preparative Organic Chemistry ChemInform Abstract: One-Pot Synthesis of S-Alkyl Dithiocarbamates via the Reaction of N-Tosylhydrazones, Carbon Disulfide and Amines. Qiang Sha, Qiang Sha Sch. Chem. Eng., Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorYun-Yang Wei, Yun-Yang Wei Sch. Chem. Eng., Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this author Qiang Sha, Qiang Sha Sch. Chem. Eng., Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this authorYun-Yang Wei, Yun-Yang Wei Sch. Chem. Eng., Nanjing Univ. Sci. Technol., Nanjing 210094, Peop. Rep. ChinaSearch for more papers by this author First published: 12 December 2013 https://doi.org/10.1002/chin.201401056Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume45, Issue1January 7, 2014 RelatedInformation

Surfing the ω-transaminase and ene reductase wave: Biocatalytic asymmetric transformations for preparative organic synthesis

Surfing the ω-transaminase and ene reductase wave: Biocatalytic asymmetric transformations for preparative organic synthesis