145821-58-5Relevant articles and documents
Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic Applications
Krautwald, Simon,Bezdek, Máté J.,Chirik, Paul J.
supporting information, p. 3868 - 3875 (2017/03/20)
A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B2Pin2) is described. The reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron reagent PinB-BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that exhibit differential reactivity. One example prepared by diboration of 1-octyne was crystallized, and its stereochemistry established by X-ray crystallography. The utility and versatility of the 1,1-diborylalkene products was demonstrated in a number of synthetic applications, including a concise synthesis of the epilepsy medication tiagabine. In addition, a synthesis of 1,1,1-triborylalkanes was accomplished through cobalt-catalyzed hydroboration of 1,1-diborylalkenes with HBPin. Deuterium-labeling and stoichiometric experiments support a mechanism involving selective insertion of an alkynylboronate to a Co-B bond of a cobalt boryl complex to form a vinylcobalt intermediate. The latter was isolated and characterized by NMR spectroscopy and X-ray crystallography. A competition experiment established that the reaction involves formation of free alkynylboronate and the two boryl substituents are not necessarily derived from the same diboron source.
A convergent approach to (R)-Tiagabine by a regio- and stereocontrolled hydroiodination of alkynes
Bartoli, Giuseppe,Cipolletti, Roberto,Di Antonio, Giustino,Giovannini, Riccardo,Lanari, Silvia,Marcolini, Mauro,Marcantoni, Enrico
experimental part, p. 3509 - 3517 (2010/08/21)
The occurrence of unsaturated systems in natural products combined with the mildness and the wide range of applicability of CeCl3 promoted methodologies suggest several potential future synthetic applications within the field of total synthesis of biologically active molecules. On this concept, the use of CeCl3·7H2O-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 1, named (R)-Tiagabine, which is a potent and selective γ-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. The Royal Society of Chemistry 2010.
The Synthesis of Novel GABA Uptake Inhibitors. 1. Elucidation of the Structure-Activity Studies Leading to the Choice of (R)-1--3-piperidinecarboxylic Acid (Tiagabine) as an Anticonvulsant Drug Candidate
Andersen, Knud Erik,Braestrup, Claus,Groenwald, Frederik C.,Joergensen, Anker S.,Nielsen, Erik B.,et al.
, p. 1716 - 1725 (2007/10/02)
A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties.The in vitro value for inhibition of 3H>-GABA uptake in rat synaptosomes was determined for each compound.It was found that the most potent examples are those having a substituent in an "ortho" position in one or both aromatic/heteroatomic groups.The majority of the compounds described are structurally related to tiagabine, (R)-1--3-piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized.
