A convergent approach to (R)-Tiagabine by a regio- and stereocontrolled hydroiodination of alkynes

Abstract

The occurrence of unsaturated systems in natural products combined with the mildness and the wide range of applicability of CeCl(3) promoted methodologies suggest several potential future synthetic applications within the field of total synthesis of biologically active molecules. On this concept, the use of CeCl(3).7H(2)O-NaI system as an efficient heterogeneous promoter has been highlighted in the iodofunctionalization of carbon-carbon triple bonds. The study has shown that this method would be particularly interesting for the stereoselective formation of trisubstituted (Z)- or (E)-iodoalkenes by simply changing the nature of the solvent. The methodology has been successfully applied to the synthesis of (R)-1-[4,4-bis-(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid , named (R)-Tiagabine, which is a potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans.

Identifying Early Dehydration Risk With Home-Based Sensors During Radiation Treatment: A Feasibility Study on Patients With Head and Neck Cancer

“…Remote collection and transmission of patient health-related data to facilitate clinical decision making have been used in the management of chronic diseases other than cancer (7)(8)(9)(10)(11)(12), and this has been shown to improve patient quality of life and symptom control, decrease emergency room visits and unplanned hospitalizations, and decrease overall health-care costs (12)(13)(14)(15).…”

Microwave‐Assisted Cerium(III)‐Promoted Cyclization of Propargyl Amides to Polysubstituted Oxazole Derivatives

“…Only when the ester moiety was directly bound to the triple bond was the corresponding oxazole 5k obtained in poor yield; in this case, LC/MS analysis of the reaction mixture showed significant amounts of hydroiodination reaction and subsequent hydrolysis to the carbonyl moiety (Scheme 2). [24] We were also interested in examining the utility of our method with different substituents on the carboxamide moiety, and were pleased to find that the reaction tolerates alkyl, heteroaryl, and aryl substituents. The presence of electron-withdrawing or -donating substituents had little influence on the reactivity.…”

“…[21] In particular, the combination of CeCl 3 ·7H 2 O and NaI has been shown to be a highly versatile reagent system [22] that is capable of promoting threecomponent, diastereoselective syntheses of various potentially pharmacologically relevant heterocycles. [23] This wide variety of applications, together with the ability of the Lewis acid system to promote the regio-and diastereoselective addition to alkynes, [24] led us to explore whether the application of the CeCl 3 ·7H 2 O/NaI system can promote cyclization of functionalized propargyl amides to oxazoles, which are otherwise unapproachable by conventional routes. Thus, as a result of our efforts, we can herein report a mild and efficient microwave-assisted synthesis of oxazoles through a 5-exo-dig cyclization of functionalized Npropargyl carboxamides.…”

4.05 Addition of HX Reagents to Alkenes, Alkynes, and Allenes without Transition Metal

“…The methodology tolerated alkyl-, aryl-, and heteroaryl substituents on the alkyne moiety, and in the case of internal alkynes, the hydroiodination proceeded in a highly stereoselective manner, with preferential formation of the thermodynamically more stable (Z)-alkenyl iodides (equation 88). 56 The reaction was initiated by coordination of Ce(III) to the triple bond, giving an organocerium intermediate by the nucleophilic attack of iodide anion, which followed by rapid protodemetalation to afford the products. …”