- Para -C-H borylation of benzene derivatives by a bulky iridium catalyst
-
A highly para-selective aromatic C-H borylation has been accomplished. By a new iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C-H borylation of monosubstituted benzenes can be affected with para-selectivity up to 91%. This catalytic system is quite different from the usual iridium catalysts that cannot distinguish meta- and para-C-H bonds of monosubstituted benzene derivatives, resulting in the preferred formation of meta-products. The para-selectivity increases with increasing bulkiness of the substituent on the arene, indicating that the regioselectivity of the present reaction is primarily controlled by steric repulsion between substrate and catalyst. Caramiphen, an anticholinergic drug used in the treatment of Parkinsons disease, was converted into five derivatives via our para-selective borylation. The present [Ir(cod)OH]2/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, para-selective, aromatic C-H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.
- Saito, Yutaro,Segawa, Yasutomo,Itami, Kenichiro
-
p. 5193 - 5198
(2015/05/05)
-
- Synthesis of a potential M1 muscarinic agent [76Br] bromocaramiphen
-
[76Br]bromocaramiphen was prepared from the iodo-analogue by a Cu+ nucleophilic bromodeiodination exchange. The radiolabelling yield was 40-45%. The radiochemical and chemical purities assessed by radio-TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1-phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyclopemane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the pons tissues indicated that there was still 92% of unchanged radiotracer 30 mm p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pons, the cortex, the striatum and the cerebellum. These data suggest that [76Br]bromocaramiphen is not a potential probe for investigating the status of central M1 muscarinic receptors because of its high lipophilicity (log P7 4 = 2.4) and its affinity for sigma sites.
- Strijckmans,Hunter,Dolle,Coulon,Loc'h,Maziere
-
p. 471 - 481
(2007/10/03)
-
- Muscarinic Receptor Binding Profile of Para-Substituted Caramiphen Analogues
-
Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor.The purpose of the set to look for a possible relationshi
- Hudkins, Robert L.,DeHaven-Hudkins, Diane L.,Stubbins, James F.
-
p. 2984 - 2989
(2007/10/02)
-