Refernces
10.1021/jm300170m
The research focuses on the optimization of (2,3-dihydro-1-benzofuran-3-yl)acetic acids, with the aim of discovering a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) agonist that serves as a glucose-dependent insulinotropic agent for the treatment of type 2 diabetes. The study identified compound 16, also known as TAK-875, as a promising candidate due to its low lipophilicity, high resistance to β-oxidation, and long-acting pharmacokinetic profile, which resulted in significant reduction of plasma glucose and increased insulin secretion in type 2 diabetic rats. The research involved the synthesis and evaluation of various (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivatives, utilizing chemicals such as ADDP, P(n-Bu)3, toluene, NaOH, m-CPBA, oxone, TBAF, and a range of biphenylylmethanols and phenols, among others, to optimize the compounds' pharmacokinetic profiles and reduce undesirable lipophilic properties associated with free fatty acids. The successful identification of TAK-875 as a potential anti-diabetic drug candidate concludes the study, highlighting its potential in human clinical trials for the treatment of type 2 diabetes.
10.1021/om00084a013
The study investigates the photochemical reactions of phosphine-substituted cobalt carbonyl complexes, specifically focusing on [Co(CO)3L2][Co(CO)4] and Co2(CO)8L2 (L = tributylphosphine). The major photochemical reactions are initiated by the photolysis of the cation Co(CO)3L2?, which leads to ligand dissociation, electron transfer, and metal-metal bond cleavage. In the presence of CO, H2, or excess phosphine, various products are formed, including Co2(CO)8L2, HCo(CO)3L, HCo(CO)4L2, and [Co(CO)2L3]?. The neutral complex Co2(CO)8L2 is photostable in the absence of phosphine but undergoes photosubstitution or photodisproportionation in the presence of excess phosphine, depending on the solvent (hexane or methanol). The study provides insights into the mechanisms of these photochemical processes and their potential applications in catalysis.
10.1021/ja111389r
The research investigates the mechanism of the Ru-catalyzed hydroamidation of terminal alkynes, aiming to understand the coordination type of the alkyne during the reaction, how the regio- and stereochemistry are controlled, and to identify the rate-determining step of the catalytic cycle. The study employs deuterium-labeling, in situ IR, in situ NMR, in situ ESI-MS experiments, and computational studies to explore the reaction pathway. The results support a mechanism involving ruthenium-hydride and ruthenium-vinylidene species as key intermediates. The proposed catalytic cycle includes oxidative addition of the amide, insertion of a p-coordinated alkyne into a ruthenium-hydride bond, rearrangement to a vinylidene species, nucleophilic attack of the amide, and reductive elimination of the product. Tri-n-butylphosphine (P(n-Bu)3) plays a crucial role as a ligand in the catalyst system. It is used in combination with bis(2-methallyl)(cycloocta-1,5-diene)ruthenium(II) [(cod)Ru(met)2] and 4-dimethylaminopyridine (DMAP) to form an active catalyst that facilitates the addition of amides to terminal alkynes. The study concludes that the reaction proceeds via a mechanism closely related to the proposed Mechanism D, which is supported by all experimental results and confirmed by DFT calculations.
10.1016/S0040-4039(00)85218-1
The research investigates a method for converting secondary alcohols into hydrocarbons through a radical deoxygenation process. The purpose of this study is to develop an efficient and practical method for the reduction of hydroxyl groups in secondary alcohols to hydrocarbons, which is typically challenging due to the stability of alcohols towards common reducing agents. The key chemicals used in this research include tributyltin hydride (Bu?SnH), 2,2'-dibenzothiazolyl-disulfide, and tributylphosphine. The method involves two main steps: first, the transformation of secondary alcohols into benzothiazolylsulfides using 2,2'-dibenzothiazolyl-disulfide and tributylphosphine, and second, the desulfurization of these sulfides to hydrocarbons using tributyltin hydride under radical conditions initiated by azobisisobutyronitrile (AIBN). The study concludes that this method offers several practical advantages: it proceeds smoothly under neutral conditions without side reactions such as rearrangement or disproportionation, and it yields high-quality hydrocarbons in good yields. Additionally, the method is applicable to alcohols containing other functional groups without the need for protection, and it shows potential for the deoxygenation of natural products, such as cholesterol and sugar derivatives.
10.1021/ja052146+
The research explores a novel intramolecular variant of the Morita-Baylis-Hillman (MBH) reaction that utilizes allylic leaving groups as electrophilic partners in an entirely organomediated process. The study aims to develop a high-yielding, selective method for synthesizing densely functionalized cyclic enones through this reaction. The researchers initially tested various leaving groups and organocatalysts, finding that tertiary phosphines, particularly Bu3P, were effective in promoting cyclization. They optimized the reaction conditions using KOH as a base and BnEt3NCl under phase transfer conditions, achieving impressive yields of up to 80% for the desired cyclization products. The study demonstrated that both primary and secondary allylic chlorides, as well as aryl and alkyl enones, were tolerated in the reaction, allowing for the formation of both five- and six-membered rings with excellent selectivity. The conclusions highlight the successful development of a convenient, organomediated method for synthesizing cyclic enones without the need for transition metal catalysts, suggesting potential applications in the synthesis of complex organic molecules. Future work will focus on exploring related transformations and further modifications of the electrophilic partner and the tether.
10.1039/c1ob06187a
The research explores the development of two phosphine-catalyzed reactions involving 1,4-dien-3-ones and 1,1-dicyanoalkenes. The purpose of the study is to investigate efficient and atom-economical carbon–carbon bond forming reactions that can rapidly construct molecular complexity. The researchers found that under the catalysis of PBu3 (Tri-n-butylphosphine) (20 mol %), 1,4-dien-3-ones such as styryl ketones readily undergo a formal [4 + 2] cycloaddition reaction with 2-aryl 1,1-dicyanoalkenes, producing polysubstituted cyclohexanones in good yield and diastereoselectivity. Additionally, when the doubly activated alkenes have an acidic methyl or methylene at the 2-position, a vinylogous Michael addition of 1,4-dien-3-ones occurs under the same conditions, yielding non-cyclized multifunctional adducts. The study concludes that these transformations are highly chemoselective and atom economical, representing significant advancements in the field of organic synthesis. The phosphine-catalyzed reactions provide a convenient and efficient method for constructing complex molecular structures, which could have applications in the synthesis of natural products and pharmaceutical compounds.
C; 
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