We report a method for the synthesis of chiral pyrrolidines using tin-lithium exchange and cyclization reactions. The precursors are formed readily from simple starting materials and undergo tin-lithium exchange by treatment with n-butyllithium. Subsequent intramolecular carbolithiation is stereoselective to give highly enantiomerically enriched pyrrolidines in excellent yields.
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http://dx.doi.org/10.1021/ol061615p | DOI Listing |
J Am Chem Soc
April 2022
Max-Planck-Institut für Kohlenforschung, Mülheim/Ruhr D-45470, Germany.
A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated and germylated) α-diazoacetate derivatives. A number of control experiments in combination with detailed computational studies provide compelling evidence that an interligand hydrogen bond between the -NH group of the amidate and the ester carbonyl group of the reactive rhodium carbene intermediate plays a quintessential role in the stereodetermining transition state. The penalty for distorting this array outweighs steric arguments and renders two of the four conceivable transitions states unviable.
View Article and Find Full Text PDFJ Org Chem
February 2019
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica , Universidade de Santiago de Compostela , 15782 Santiago de Compostela , Spain.
1,2-Aromatic diesters can be transformed into strained bridged polycyclic structures by a two-step procedure consisting of an initial reductive alkylation promoted by alkaline metals, followed by a reaction of the resulting unsaturated diesters with MeSnLi. We propose that a stanna-Brook rearrangement plays a fundamental role in the formation of the polycyclic organotin acetals obtained. These unusual compounds could be further functionalized by tin-lithium exchange followed by alkylation of the newly formed tertiary carbanion.
View Article and Find Full Text PDFChemistry
February 2018
Centrum für Molekulare Materialien, Fakultät für Chemie, Universität Bielefeld, Universitätsstraße 25, 33615, Bielefeld, Germany.
Pentafluoroethyllithium, LiC F , has been established as an efficient and versatile reagent for the transfer of the pentafluoroethyl unit to a number of electrophiles. Here, the stability of this species up to -40 °C is of advantage, particularly in comparison to its smaller congener LiCF . The usual production of LiC F , however, from gaseous HC F or IC F and strong bases requires specially designed apparatuses, which severely impeded its value as a laboratory reagent.
View Article and Find Full Text PDFJ Med Chem
August 2017
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , 1-1-1, Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan.
The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, E = 75%, EC = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1. We found that CO fixation after tin-lithium exchange at -20 °C afforded [C]1.
View Article and Find Full Text PDFChemistry
July 2015
Otto-Diels-Institute for Organic Chemistry, University of Kiel, Otto-Hahn-Platz 3-4, 24098 Kiel (Germany).
The lithiation of halogenated azobenzenes by halogen-lithium exchange commonly leads to substantial degradation of the azo group to give hydrazine derivatives besides the desired aryl lithium species. Yields of quenching reactions with electrophiles are therefore low. This work shows that a transmetalation reaction of easily accessible stannylated azobenzenes with methyllithium leads to a near-quantitative lithiation of azobenzenes in para, meta, and ortho positions.
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