191328-04-8Relevant academic research and scientific papers
Catalytic Regioselective Olefin Hydroarylation(alkenylation) by Sequential Carbonickelation-Hydride Transfer
Liu, Chen-Fei,Luo, Xiaohua,Wang, Hongyu,Koh, Ming Joo
supporting information, p. 9498 - 9506 (2021/07/19)
Alkene hydrocarbofunctionalization represents one of the most important classes of chemical transformations, but related branched-selective examples with unactivated olefins are scarce. Here, we report that catalytic amounts of a dimeric Ni(I) complex and an exogenous alkoxide base promote Markovnikov-selective hydroarylation(alkenylation) of unactivated and activated olefins using organo bromides or triflates derived from widely available phenols and ketones. Products bearing aryl- and alkenyl-substituted tertiary and quaternary centers could be isolated in up to 95% yield and >99:1 regioisomeric ratios. Contrary to previous dual-catalytic methods that rely on metal-hydride atom transfer (MHAT) to the olefin prior to carbofunctionalization with a cocatalyst, our mechanistic evidence points toward a nonradical reaction pathway that begins with site-selective carbonickelation across the C═C bond followed by hydride transfer using alkoxide as the hydride source. Utility of the single-catalyst protocol is highlighted through the synthesis of medicinally relevant scaffolds.
Substituted piperidine derivatives as selective agonists of 5-HT receptors
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, (2008/06/13)
PCT No. PCT/GB96/02765 Sec. 371 Date May 13, 1998 Sec. 102(e) Date May 13, 1998 PCT Filed Nov. 13, 1996 PCT Pub. No. WO97/18202 PCT Pub. Date May 22, 1997A compound of formula (I), or a salt or prodrug thereof, is described, wherein G is attached at posit
Fluorination of 3-(3-(piperidin-1-yl)propyl)indoles and 3-(3-(piperazin- 1-yl)propyl)indoles gives selective human 5-HT(1D) receptor ligands with improved pharmacokinetic profiles
Van Niel, Monique B.,Collins, Ian,Beer, Margaret S.,Broughton, Howard B.,Cheng, Susan K. F.,Goodacre, Simon C.,Heald, Anne,Locker, Karen L.,MacLeod, Angus M.,Morrison, Denise,Moyes, Christopher R.,O'Connor, Desmond,Pike, Andrew,Rowley, Michael,Russell, Michael G. N.,Sohal, Baibinder,Stanton, Josephine A.,Thomas, Steven,Verrier, Hugh,Watt, Alan P.,Castro, José L.
, p. 2087 - 2104 (2007/10/03)
It has previously been reported that a 3-(3-(piperazin-1- yl)propyl)indole series of 5-HT(1D) receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pK(a) of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4- fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT(1D) receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pK(a) of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.
