10.1016/S0040-4039(00)73243-6
The research aimed to develop an efficient route to optically pure key intermediates of dihydromevinolin, which are biologically active compounds known for their ability to inhibit HMG CoA reductase, a rate-limiting enzyme in cholesterol synthesis in humans. The researchers focused on the intramolecular Diels-Alder (MDA) reaction as the most promising approach for constructing the decalin system present in mevinic acids. They successfully synthesized the key intermediate through a series of chemical reactions starting from (R)-5-methyl-2-cyclohexanone, involving vinylmagnesium bromide, MnO2, LiAlH4, propargyl bromide, t-BuOK, 10-camphorsulphonic acid (CSA), BH3*THF, NaOH, H2O2, Jones reagent, and other reagents.
10.1021/ja00029a049
The study explores the use of MAD (a bulky Lewis acid) in Diels-Alder reactions, demonstrating its ability to achieve high regioselectivity, endo selectivity, and diastereoselectivity in reactions involving unsymmetrical fumarates. MAD effectively discriminates between different acrylate carbonyls, such as tert-butyl and methyl acrylates, in chemoselective Diels-Alder reactions with cyclopentadiene. The study also describes an enantiodivergent synthesis of syn-1,3-polyols from a meso precursor through reagent-controlled diastereofacial selective allylation reactions. Key chemicals involved include MAD for asymmetric induction, tert-butyl and methyl acrylates as dienophiles, and cyclopentadiene as the diene. In the synthesis of syn-1,3-polyols, reagents like (+)- or (-)-diisopinylcamphyl allyl borane (Ipc,BAll) are used to introduce chirality, and camphorsulfonic acid is employed for selective acetonide formation. The study highlights the potential of these methods for versatile synthetic applications in organic chemistry.
10.1039/d0ob01149e
The study presents a novel nucleophilic methylthiolation methodology that enables the incorporation of the CH3S- group into activated carbons through either conjugate additions or substitutions reactions. The researchers utilized a range of chemicals, including chalcones, acyl ester derivatives, Morita-Baylis-Hillman acetates, and methylthiomethyl esters as the primary substrates and reagents. Methanethiol, traditionally used for methylthiolation, was replaced with these novel reagents due to its flammability and toxicity. The study aimed to develop a safer, low-cost, transition-metal-free method that exhibits good group tolerance and yields moderate to excellent results. Key chemicals involved in the reaction mechanism include potassium trichloroacetate, acetic acid, and camphorsulfonic acid (CSA) as an organocatalyst. The reaction products were further utilized to synthesize sulfoxides and sulfones, demonstrating the synthetic utility of the methodology. The study also involved theoretical calculations using Density Functional Theory to investigate the reaction mechanism, confirming the role of sulfurane and sulfonium ylide as key intermediates and the importance of a Pummerer rearrangement in the formation of the reagent.
10.1016/j.tetlet.2012.07.064
The research focuses on the synthesis and application of 4-isocyanopermethylbutane-1,1,3-triol (IPB), a new convertible isonitrile (isocyanide) for isocyanide-based multicomponent reactions (IMCRs) such as Ugi, Ugi-Smiles, and Passerini reactions. The purpose of this study is to develop a reagent that can generate highly activated N-acylpyrroles, which can then be transformed into various functionalities like carboxylic acids, esters, amides, alcohols, and olefins upon treatment with nucleophiles. The research concludes that IPB serves as a neutral carbanion equivalent to formate (HO2C) and carboxylates or carboxamides (RNu-CO), and it can be prepared in multigram scale from readily available starting materials with great stability in handling and storage. It shows good to excellent reactivity in different IMCRs and is compatible with numerous functionalities, making it applicable to many highly functionalized molecules. The generated N-acylpyrrole intermediates are stable and reactive, allowing for the transformation into other carbonyl functions in good yields. The research also demonstrates the utility of IPB in Ugi-Smiles and Passerini reactions, leading to the successful conversion of the IMCR products into the respective N-acylpyrroles and subsequently into carboxylic acids in good yield and chemoselectivity. Chemicals used in the process include IPB, various carboxylic acids, amines, aldehydes, and nucleophiles such as 4-fluorophenethylamine, piperidine, NH4OH, sodium methoxide, and lithium hydroxide. The study also involves the use of reagents like camphorsulfonic acid (CSA), quinoline, and trifluoroacetic acid (TFA) for the conversion of Ugi products into N-acylpyrroles.
10.1021/ol400207t
The research focuses on the efficient synthesis of enantioenriched R-substituted γ-hydroxy esters through a kinetic resolution process catalyzed by a chiral Br?nsted acid. The purpose of this study is to develop a method for producing these versatile and highly valuable molecules, which are important building blocks in the preparation of biological molecules, including natural products and drug candidates. The researchers achieved this by selectively lactonizing bulky racemic esters in the presence of a chiral Br?nsted acid catalyst, leading to the formation of a recoverable enantioenriched hydroxy ester and lactone. The process was found to be scalable and required only low catalyst loadings (0.5 mol %). The study successfully generated all-carbon quaternary centers with high enantioselectivity and demonstrated the versatility of these hydroxy esters by converting them into other synthetically useful materials. Key chemicals used in the process include various chiral Br?nsted acid catalysts, such as TADDOL, thiourea-based acids, camphor sulfonic acid, and BINOL phosphoric acid derivatives, as well as substrates like R-methyl hydroxy tert-butyl ester (()-1a and other ester functionalities.
10.1016/0040-4039(96)01924-7
The study presents the first synthesis of cis-enediynes from 1,5-diyne 7 through an acid-mediated allylic rearrangement using (+)-10-camphorsulfonic acid (CSA) in CH2Cl2 at 20 °C in the presence of ROH or RSH. The key chemicals involved include the starting material 1,5-diyne 7, which is prepared from a-bromocinnamaldehyde (5) via cross-coupling with H2C(CH2)4OMe and subsequent addition of LiCCCH2SiMe3. The reaction yields cis-enediyne 10 as the major product, along with trans-enediyne 8 and 1,5-diyne 9. The study also explores the allylic rearrangement in the presence of various nucleophiles (ROH and RSH), achieving high regioselectivity and trans/cis stereoselectivity. The synthesized cis-enediynes can be oxidized to form diradicals capable of DNA cleavage. Additionally, an 11-membered ring enediyne 15 is synthesized using a similar acid-promoted allylic rearrangement strategy, highlighting the potential for enediyne prodrug design and synthesis.
10.1016/0957-4166(94)80016-2
The study explores the enantioselective resolution of 1,2-diols using optically active 2,2’-diphenyl-3,3’,4,4’-tetrahydro-6,6’-bi-2H-pyran (PDHP) derivatives, specifically (2R,2’R) and (2S,2’S) PDHP (compounds 2 and 3). The researchers utilized these PDHP derivatives to selectively protect one enantiomer of racemic 1,2-diols through the formation of diastereomerically pure dispiroketals under thermodynamically controlled conditions. The process involves an initial reaction of the PDHP with the diol in the presence of camphorsulfonic acid (CSA) in toluene, followed by an equilibration step at elevated temperatures to form the more stable dispiroketal adducts. The study highlights the efficiency of this method for resolving various 1,2-diols and the subsequent deprotection of the resolved diols using lithium in liquid ammonia or through a ketal exchange process, which allows for the recycling of the chiral PDHP auxiliary. The study also discusses the limitations and optimizations of the reaction conditions to improve yields and enantiomeric purity.
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