Contributors: Tverdiy, Dmytro, Chekanov, Maksym, Savitskiy, Pavlo, Syniugin, Anatolii, Yarmoliuk, Sergiy, Fokin, Andrey
... Abstract We report a novel and efficient approach to the synthesis of imidazo[1,5-a]pyridine-1-carboxylic acids. By using the reaction of 2-(aminomethyl)pyridine with acyl chlorides followed by one-pot treatment with trifluoroacetic anhydride, 2,2,2-trifluoro-1-imidazo[1,5-a]pyridin-1-ylethanones were obtained, which were then converted into imidazo[1,5-a]pyridine-1-carboxylic acids in high preparative yields through haloform cleavage.
Novel Synthesis of α-Keto Esters and Amides by an sp3 C–H Oxidation of Nitromethyl Aryl Ketones Promoted by Ion-Supported (Diacetoxyiodo)benzene
Contributors: Jiang, Xiaoying, Gan, Bing, Liu, Jiwei, Xie, Yuanyuan
... Abstract A simple and efficient method is described for the preparation of α-keto esters or amides from nitromethyl aryl ketones. In the presence of nucleophiles (alcohols or amines), the ion-supported (diacetoxyiodo)benzene-promoted sp3 C–H oxidation of nitromethyl aryl ketones proceeded efficiently under mild conditions to give the corresponding α-keto esters and amides in moderate to good yields. This is the first reported use of (diacetoxyiodo)benzene in the synthesis of α-keto esters and amides. The reaction is ecofriendly and has the advantages of mild conditions, short reaction times, and a recyclable reagent.
Contributors: Sirvent, Juan, Bierer, Donald, Webster, Robert, Lücking, Ulrich
... Abstract Sulfoximines have recently gained considerable recognition as an important structural motif in the life sciences. This is especially true for (hetero)aryl-substituted S,S-dimethylsulfoximine derivatives, such as the marketed insecticide sulfoxaflor, as well as the clinical candidates PTEFb inhibitor BAY 1143572 and ATR inhibitor AZD 6738 for the treatment of cancer. Herein, the first palladium-catalyzed direct α-arylation of p-methoxybenzyl-protected S,S-dimethylsulfoximine using readily available (hetero)aryl bromides is reported. This new method provides a safe, short, and efficient approach to (hetero)aryl-substituted S,S-dimethylsulfoximine derivatives, an important class of bioactive compounds, demonstrated by application of this methodology to an improved synthesis of PTEFb inhibitor BAY 1143572.
Synthesis of Supramolecular Iridium Catalysts and Their Use in Enantioselective Visible-Light-Induced Reactions
Contributors: Böhm, Alexander, Bach, Thorsten
... Abstract Iridium complexes were prepared which are covalently linked via a bipyridine ligand to a chiral octahydro-1H-4,7-methanoisoindol-1-one skeleton. The skeleton allows for two-point hydrogen bonding to prochiral lactams, which can be processed in iridium-catalyzed photochemical reactions. Attempts to use the iridium complexes in reactions, which typically involve photoinduced electron transfer, failed to provide the desired enantioselectivity. If employed as triplet sensitizers the complexes showed an improved performance and moderate enantioselectivities (up to 29% ee) were achieved in a photochemical epoxide rearrangement.
Contributors: Pal, Sujit, Dumbre, Shrinivas
... Abstract A conformationally restricted polyhydroxylated 1-azabicyclo[4.2.0]octane core has been synthesized in search for a potent selective glycosidase inhibitor. The key feature of the synthesis involves the high stereoselective photoelectron-transfer-promoted cyclization of the strained α-trimethylsilylmethylazetidine moiety to the tethered π functionality.
Bowl-to-Bowl Inversion Accelerated by the Introduction of Bulky 1,1,4,4-Tetramethylbutane-1,4-diyl Groups on Sumanene
Contributors: Amaya, Toru, Katoh, Shun, Hirao, Toshikazu
... Abstract A variable-temperature 1H NMR study revealed that the bowl-to-bowl inversion of sumanene is accelerated by the introduction of bulky 1,1,4,4-tetramethylbutane-1,4-diyl groups on the peripheral aromatic ring. This is likely to be induced by a bowl flattening, as shown in the DFT-optimized structures.
Contributors: Moragas, Toni, Martin, Ruben
... Abstract A nickel-catalyzed reductive carboxylation technique for the synthesis of cyclopropanecarboxylic acids has been developed. This user-friendly and mild transformation operates at atmospheric pressure of carbon dioxide and utilizes either organic halides or alkene precursors, thus representing the first example of catalytic reductive carboxylation of secondary counterparts lacking adjacent π-components.
An NHC-Catalyzed Cross-Benzoin–Esterification Sequential Reaction for the Synthesis of Trifluoromethyl-Substituted α,β-Unsaturated Esters
Contributors: Zhao, Qian, Feng, Li-Ying, Huang, Wei, He, Xiang-Hong, Peng, Cheng, Han, Bo
... Abstract Efficient preparation of synthetically important CF3-containing α,β-unsaturated esters is described using an NHC-catalyzed multicomponent reaction. This approach combines sequential NHC-mediated HOMO and LUMO activation to produce a C–C bond and C–O bond in a one-pot operation.
Practical Synthesis of Fluorinated Piperidine Analogues Based on the 2-Azaspiro[3.3]heptane Scaffold
Contributors: Chernykh, Anton, Tkachenko, Anton, Feskov, Illia, Daniliuc, Constantin, Tolmachova, Nataliya, Volochnyuk, Dmitriy, Radchenko, Dmytro
... Abstract The synthesis of a set of conformationally restricted fluorinated analogues of piperidine, based on a 2-azaspiro[3.3]heptane scaffold, is reported. Different pattern of fluorine substitution within the rigid skeleton make the analogues excellent candidates for use in drug design. The overall simplicity of the experimental procedures and the availability of inexpensive starting materials allow for multigram-scale syntheses of the described compounds.
Stereoselective Synthesis of a Highly Oxygenated δ-Lactone Related to the Core Structure of (–)-Enterocin
Contributors: Wegmann, Marcus, Bach, Thorsten
... Abstract The title compound was prepared in a concise route starting from an appropriately protected (S)-glyceraldehyde. A highly diastereoselective (d.r. >95:5) Mukaiyama aldol reaction of an acetoacetate-derived silyl enol ether served as the initial step of the synthetic sequence. It was found that protection of the glyceraldehyde as a butane-2,3-dione acetal is required to achieve the desired diastereoselectivity. Upon lactonization, a Tsuji–Trost allylation and a subsequent one-pot reaction cascade including an ozonolysis and an α-hydroxylation gave diastereoselective access to the desired α-hydroxy-β-oxo-δ-lactone. Alternative synthetic approaches are discussed and proof for the configuration of the product is presented.