- Electrochemical Oxidative Decarboxylation of Malonic Acid Derivatives: A Method for the Synthesis of Ketals and Ketones
-
A novel electrochemical oxidative decarboxylation of disubstituted malonic acids leading to dimethoxy ketals is described. In the presence of NH3, a wide range of disubstituted malonic acids was transformed into the corresponding ketals in good to excellent yields under electrochemical conditions. When the crude reaction mixture, obtained after electrolysis, was directly treated with 1 M aq HCl, the initially generated ketals were smoothly transformed into the corresponding ketones in a single vessel operation.
- Ma, Xiaofeng,Luo, Xiya,Dochain, Simon,Mathot, Charlotte,Markò, István E.
-
-
Read Online
- Electrochemical synthesis of versatile ammonium oxides under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions
-
An electrochemical oxidative cross-coupling reaction between 2.5-substituted-pyrazolin-5-ones and ammonium thiocyanate has been developed, which resulted in a series of unprecedented cross-coupling products under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions. It is worth noting that since the resulting cross-coupling products are nearly insoluble in MeCN, the pure product could be afforded without silica gel column purification. In addition, the prepared ammonium oxides are versatile building blocks for synthesizing functionalized pyrazole derivatives.
- Yuan, Yong,Li, Liang-Sen,Zhang, Lin,Wang, Feng,Jiang, Lin,Zuo, Lin,Wang, Qi,Hu, Jian-Guo,Lei, Aiwen
-
supporting information
p. 2768 - 2771
(2021/03/23)
-
- Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis
-
Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.
- Liu, Hao-Nan,Cao, Hao-Qiang,Cheung, Chi Wai,Ma, Jun-An
-
supporting information
p. 1396 - 1401
(2020/02/22)
-
- α-Alkylidene-γ-butyrolactone Formation via Bi(OTf)3-Catalyzed, Dehydrative, Ring-Opening Cyclizations of Cyclopropyl Carbinols: Understanding Substituent Effects and Predicting E/Z Selectivity
-
A Bi(OTf)3-catalyzed ring-opening cyclization of (hetero)aryl cyclopropyl carbinols to form α-alkylidene-γ-butyrolactones (ABLs) is reported. This transformation represents different chemoselectivity from previous reports that demonstrated formation of (hetero)aryl-fused cyclohexa-1,3-dienes upon acid-promoted cyclopropyl carbinol ring opening. ABLs are obtained in up to 89% yield with a general preference for the E-isomers. Mechanistically, Bi(OTf)3 serves as a stable and easy to handle precursor to TfOH. TfOH then catalyzes the formation of cyclopropyl carbinyl cations, which undergo ring opening, intramolecular trapping by the neighboring ester group, subsequent hydrolysis, and loss of methanol resulting in the formation of the ABLs. The nature and relative positioning of the substituents on both the carbinol and the cyclopropane determine both chemo- and stereoselective outcomes. Carbinol substituents determine the extent of cyclopropyl carbinyl cation formation. The cyclopropane donor substituents determine the overall reaction chemoselectivity. Weakly stabilizing or electron-poor donor groups provide better yields of the ABL products. In contrast, copious amounts of competing products are observed with highly stabilizing cyclopropane donor substituents. Finally, a predictive model for E/Z selectivity was developed using DFT calculations.
- Sandridge, Matthew J.,McLarney, Brett D.,Williams, Corey W.,France, Stefan
-
p. 10883 - 10897
(2017/10/27)
-
- Inversion of cpADH5 Enantiopreference and Altered Chain Length Specificity for Methyl 3-Hydroxyalkanoates
-
Expanding the substrate scope of enzymes opens up new routes for synthesis of valuable chemicals. Ketone-functionalized fatty acid derivatives and corresponding chiral alcohols are valuable building blocks for the synthesis of a variety of chemicals including pharmaceuticals. The alcohol dehydrogenase from Candida parapsilosis (cpADH5) catalyzes the reversible oxidations of chiral alcohols and has a broad substrate range; a challenge for cpADH5 is to convert alcohols with small substituents (methyl or ethyl) next to the oxidized alcohol moiety. Molecular docking studies revealed that W286 is located in the small binding pocket and limits the access to substrates that contain aliphatic chains longer than ethyl substituent. In the current manuscript, we report that positions L119 and W286 are key residues to boost oxidation of medium chain methyl 3-hydroxy fatty acids; interestingly the enantiopreference toward methyl 3-hydroxybutyrate was inverted. Kinetic characterization of W286A showed a 5.5 fold increase of Vmax and a 9.6 fold decrease of Km values toward methyl 3-hydroxyhexanoate (Vmax: 2.48 U mg? and Km: 4.76 mm). Simultaneous saturation at positions 119 and 286 library yielded a double mutant (L119M/W286S) with more than 30-fold improved activity toward methyl 3-hydroxyoctanoate (WT: no conversion; L119M/W286S: 30 %) and inverted enantiopreference (S-enantiomer ≥99 % activity decrease and R-enantiomer >20-fold activity improvement) toward methyl 3-hydroxybutyrate.
- Ensari, Yunus,Dhoke, Gaurao V.,Davari, Mehdi D.,Bocola, Marco,Ruff, Anna Jo?lle,Schwaneberg, Ulrich
-
p. 12636 - 12645
(2017/09/18)
-
- Regioselective synthesis of substituted piperidine-2,4-diones and their derivatives via Dieckmann cyclisations
-
Abstract A flexible route to piperidine-2,4-diones variously substituted at the 6-, 5,6- and 2,6-positions, both with and without 1-substitution, is described; no N-protective group is required. A related regioselective Dieckmann cyclisation is also described that uses Davies' α-methylbenzylamine auxiliary and affords 6-substituted piperidine-2,4-diones enantioselectively.
- Marson, Charles M.,Yau, Kin Cheung
-
p. 7459 - 7469
(2015/08/24)
-
- Gold/copper-catalyzed activation of the aci-form of nitromethane in the synthesis of methylene-bridged bis-1,3-dicarbonyl compounds
-
Activation of the aci-form of nitromethane using Lewis acids for the attack of carbon nucleophiles was studied. 1,3-Dicarbonyl compounds in the presence of catalytic amounts of AuCl3 or Cu(OTf)2 in nitromethane solvent could be converted into methylene-bridged bis-1,3-dicarbonyl compounds.
- Balamurugan, Rengarajan,Manojveer, Seetharaman
-
supporting information; experimental part
p. 11143 - 11145
(2011/11/05)
-
- Triclorosilane-mediated stereoselective synthesis of β-amino esters and their conversion to highly enantiomerically enriched β-lactams
-
A highly stereoselective trichlorosilane-mediated reduction of N-benzyl enamines was developed; the combination of a low cost, easy to make metal-free catalyst and an inexpensive chiral auxiliary allowed to perform the reaction on substrates with different structural features often with total control of the stereoselectivity. By easy deprotection through hydrogenolysis followed by conversion of β-aminoester to 2-azetidinones, the synthesis of enantiomerically pure β-lactams (>98% e.e.) was successfully accomplished.
- Guizzetti, Stefania,Benaglia, Maurizio,Bonsignore, Martina,Raimondi, Laura
-
supporting information; experimental part
p. 739 - 743
(2011/04/22)
-
- Discovery of a potent nicotinic acid receptor agonist for the treatment of dyslipidemia
-
Nicotinic acid has been used clinically for decades to control serum lipoproteins. Nicotinic acid lowers very low-density lipoprotein (VLDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa), and it is also effective in raising high-density lipoprotein (HDL)-cholesterol. However, nicotinic acid has several side effects in clinical use. The most notable is intense cutaneous vasodilation "flushing"+ on the upper body and face. We discovered a pyranopyrimidinedione series to be nicotinic acid receptor agonists. A potent nicotinic acid receptor agonist from this series {5-(3-cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d] pyrimidine-4,7-dione}with reduced flushing side effect in dogs was identified.
- Qin, Jun,Rao, Ashwin,Chen, Xiao,Zhu, Xiaohong,Liu, Zhidan,Huang, Xianhai,Degrado, Sylvia,Huang, Ying,Xiao, Dong,Aslanian, Robert,Cheewatrakoolpong, Boonlert,Zhang, Hongtao,Greenfeder, Scott,Farley, Constance,Cook, John,Kurowski, Stan,Li, Qiu,Van Heek, Margaret,Chintala, Madhu,Wang, Ganfeng,Hsieh, Yunsheng,Li, Fangbiao,Palani, Anandan
-
scheme or table
p. 171 - 176
(2011/03/23)
-
- Silica-supported HgSO4/H2SO4: A convenient reagent for the hydration of alkynes under mild conditions
-
The silica-supported aqueous-phase catalyst (SAPC) approach has proven convenient for efficiently performing the hydration of alkynes with HgSO 4/H2SO4 to give the corresponding carbonyl compounds in dichloromethane under mild conditions. The use of this solid reagent significantly improves the reaction work-up as it merely involves filtering and evaporating the solvent.
- Mello, Rossella,Alcalde-Aragonés, Ana,González-Nú?ez, María Elena
-
scheme or table
p. 4281 - 4283
(2010/09/07)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 121
(2010/11/04)
-
- Synthesis and antifungal activity of (-)-(Z)-dysidazirine
-
(Chemical Equation Presented) A short, flexible synthesis of the marine natural product (2R)-(Z)-dysidazirine (-)-1 has been completed. (-)-1 shows significant antifungal activity across a panel of seven human pathogens, whereas the structural analogue (-)-2, featuring a terminal tert-butyl group, is essentially inactive.
- Skepper, Colin K.,Dalisay, Doralyn S.,Molinski, Tadeusz F.
-
scheme or table
p. 5269 - 5271
(2009/06/18)
-
- Microwave assisted rapid and efficient synthesis of aryl methyl ketones and β-keto esters using Meldrum's acid
-
Microwave mediated rapid and efficient synthesis of aryl methyl ketones and β-keto esters from acyl Meldrum's acid by hydrolysis and alcoholysis, respectively, has been reported.
- More,Mahulikar
-
p. 823 - 825
(2007/10/03)
-
- Method for preparing chiral diphosphines
-
The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
- -
-
-
- Process for preparing malonate derivatives or beta -keto esters from epoxide derivatives
-
A process for preparing a malonic acid monoester or β-ketoester from an epoxide includes the steps of reacting an epoxide with carbon monoxide and an alcohol in the presence of a catalytic amount of a cobalt compound and at least one promoter to produce a β-hydroxyester, separating the β-hydroxyester from the cobalt compound and the promoter, and oxidizing the β-hydroxyester to produce a malonic acid monoester or β-ketoester.
- -
-
-
- Asymmetric hydrogenation method of a ketonic compound and derivative
-
The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1
- -
-
-
- Process for the preparation of β-ketocarboxylic acid esters
-
The invention relates to a process for the preparation of β-ketocarboxylic acid esters of the general formula STR1 in which R1 is an alkyl radical having 1 to 4 C atoms, R2 is an alkyl radical or alkenyl radical having 2 to 15 C atoms or a phenyl radical and R3 is hydrogen or an alkyl or alkenyl radical having 1 to 6 C atoms, characterized in that acetocarboxylic acid esters of the general formula STR2 in which R1 and R3 are as defined, are reacted with calcium hydroxide or calcium oxide in the presence of an organic solvent and in the absence of water, the calcium chelate complexes formed are acylated with carboxylic acid chloride and the products are then cleaved with aqueous ammonium salt solution to form the β-ketocarboxylic acid esters of formula (I). The β-ketocarboxylic acid esters readily accessible by the process according to the invention can be used as important intermediates in the synthesis of pharmaceutically active ingredients or plant protection agents.
- -
-
-
- Process for the production of 3-oxocarboxylic acid esters
-
3-Oxocarboxylic acid esters are produced by acylation of the magnesium enolates of acetoacetic acid esters with carboxylic acid chlorides and cleavage of the acetyl group from the acylacetoacetic acid esters formed as the intermediate product. The yields and purity of the products are considerably improved by adding a tertiary amine during the acylation.
- -
-
-
- A Simple Synthesis of Anthracyclinones from 2-Acetylquinizarin
-
Reaction of 2-acetyl-1,4-dihydroxyanthraquinone with a variety of β-keto esters in presence of tertiary amine in MeOH afforded anthracyclinone derivatives in a one-pot addition-oxidation-aldol sequence.
- Mullah, Khairuzzaman B.,Sutherland, James K.
-
p. 1237 - 1244
(2007/10/02)
-
- Antihypertensive dihydropyridine derivatives
-
Compound of formula 1 are calcium entry antagonists useful for treating hypertension, congestive heart failure, angina, and vasospastic disorders: STR1 wherein n is an integer from 1 to 4; R1 and R2 are lower alkyl; R3 is lower alkyl or alkoxyalkyl; A is alkylene of two to eight carbon atoms; X1 and X2 are each independently --NO2, --CF3, CH3 O--, --CN, --H, lower alkyl or halo; Y is --O--, --S--, --S(O)--, or --S(O)2 --; and R is H, lower alkyl, cycloalkyl, alkoxyalkyl, cycloalkyloxy-alkyl, alkoxycycloalkyl, acyl, or saturated or unsaturated 5- or 6-membered heterocyclyl optionally substituted with lower alkyl or alkoxy, wherein the heteroatom is one oxygen atom.
- -
-
-
- Knoevenagel Reactions with β-Oxo Acids. Regiospecific Enol Equivalents for Syntheses of α,β-Unsaturated Ketones and of Some β-Ketols
-
3-Oxobutanoic acid reacts with aliphatic aldehydes in the presence of pyridine to give α,β-unsaturated methyl ketones in good yields.Analogous results were obtained with a series of other β-oxo acids.Synthesis of (E)-7-methyloct-4-en-3-one, a major constituent of the marine sponge Plakortis zygompha, has been carried out using this methodology.Aromatic aldehydes are generally less reactive under these conditions but give β-ketols when the phenyl ring bears an electron-withdrawing substituent.Some observations on the mechanism of the reaction between 3-oxobutanoic acid and benzaldehyde are presented.
- Grayson, David H.,Tuite, Mathew R. J.
-
p. 2137 - 2142
(2007/10/02)
-
- Process for the producton of 4-substituted acetoacetic acid derivatives
-
Process for the production of 4-substituted acetoacetic acid derivatives. An acetoacetic acid derivative having the formula: STR1 wherein R is alkoxy having 1 to 6 C atoms, phenoxy, --NR'2, wherein R' is alkyl having 1 to 6 C atoms or aryl, or NR'2, which is azetidine, pyrrolidine or piperidine, is treated with a secondary amine at an elevated temperature and in the presence of an organic solvent. The water formed is separated. The intermediate is converted into the corresponding 3-enamine carboxylic acid derivative. The derivative is converted by treatment with sodium amide in liquid ammonia into the corresponding sodium salt. The sodium salt is converted by treatment with a halogen compound having the formula R1 CH2 X or R1 R2 CHX, wherein R1 and R2 each are alkyl, alkenyl, alkinyl or aryl and X is chlorine, bromine or iodide, into the corresponding 4-substituted enamino derivative. The derivative is hydrolyzed into the 4-substituted acetoacetic acid derivative.
- -
-
-
- Substituted 1-Azaadamantanes
-
Substituted 1-azaadamantanes of type 14 are facilely prepared from the six-membered rings 2.Functionalized derivatives 2 of cyclohexane are easily synthesized from α,β-unsaturated ketones and dimethyl malonate or by similar procedures.With hexamethylenetetramine as partner the azatricyclic products 14 are formed in one step from 2.The Mannich-type mechanism of the key reaction is discussed, and the 1H NMR data are analyzed.
- Risch, Nikolaus
-
p. 4073 - 4085
(2007/10/02)
-
- α-Carboxylation reaction of carbonyl compounds with bromomagnesium ureide-carbon dioxide adducts
-
Bromomagnesium ureide-carbon dioxide adducts, models of the carboxylated biotin complex, undergo caboxylation of a variety of carbonyl compounds in good yield.
- Sakurai, Hideki,Shirahata, Akihiko,Hosomi, Akira
-
p. 1967 - 1970
(2007/10/02)
-