191869-65-5Relevant articles and documents
Regio- and chemoselective Csp3-H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis
Ide, Takafumi,Barham, Joshua P.,Fujita, Masashi,Kawato, Yuji,Egami, Hiromichi,Hamashima, Yoshitaka
, p. 8453 - 8460 (2018)
We present a highly regio- and chemoselective Csp3-H arylation of benzylamines mediated by synergy of single electron transfer (SET) and hydrogen atom transfer (HAT) catalysis. Under well precedented SET catalysis alone, the arylation reaction of N,N-dimethylbenzylamine proceeded via aminium radical cation formation and selectively targeted the N-methyl group. In contrast, addition of PhC(O)SH as a HAT catalyst precursor completely switched the regioselectivity to Csp3-H arylation at the N-benzylic position. Measurement of oxidation potentials indicated that the conjugate base of PhC(O)SH is oxidized in preference to the substrate amine. The discovery of the thiocarboxylate as a novel HAT catalyst allowed for the selective generation of the sulfur-centered radical, so that the N-benzyl selectivity was achieved by overriding the inherent N-methyl and/or N-methylene selectivity under SET catalysis conditions. While visible light-driven α-C-H functionalization of amines has mostly been demonstrated with aniline derivatives and tetrahydroisoquinolines (THIQs), our method is applicable to a variety of primary, secondary and tertiary benzylamines for efficient N-benzylic C-H arylation. Functional group tolerance was high, and various 1,1-diarylmethylamines, including an α,α,α-trisubstituted amine, were obtained in good to excellent yield (up to 98%). Importantly, the reaction is applicable to late-stage functionalization of pharmaceuticals.
Late-Stage N-Me Selective Arylation of Trialkylamines Enabled by Ni/Photoredox Dual Catalysis
Shen, Yangyang,Rovis, Tomislav
supporting information, p. 16364 - 16369 (2021/10/21)
The diversity and wide availability of trialkylamines render them ideal sources for rapid construction of complex amine architectures. Herein, we report that a nickel/photoredox dual catalysis strategy affects site-selective α-arylation of various trialkylamines. Our catalytic system shows exclusive N-Me selectivity with a wide range of trialkylamines under mild conditions, even in the context of late-stage arylation of pharmaceutical compounds bearing this common structural motif. Mechanistic studies indicate the unconventional behavior of Ni catalyst upon intercepting the α-amino radicals, in which only the primary α-amino radical undergoes a successful cross-coupling process.
Targeting Alzheimer's disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238
Rizzo, Stefano,Bartolini, Manuela,Ceccarini, Luisa,Piazzi, Lorna,Gobbi, Silvia,Cavalli, Andrea,Recanatini, Maurizio,Andrisano, Vincenza,Rampa, Angela
experimental part, p. 1749 - 1760 (2010/05/17)
We report on a series of hybrid compounds structurally derived from donepezil and AP2238. This study was aimed at improving the activities of the reference compounds, donepezil and AP2238, and at broadening the range of activities of new derivatives as, due to the multifactorial nature of AD, molecules that modulate the activity of a single protein target are unable to significantly modify the progression of the disease. In particular, the indanone core from donepezil was linked to the phenyl-N-methylbenzylamino moiety from AP2238, through a double bond that was kept to evaluate the role of a lower flexibility in the biological activities. Moreover, SAR studies were performed to evaluate the role of different substituents in position 5 or 6 of the indanone ring in the interaction with the PAS, introducing also alkyl chains of different lengths carrying different amines at one end. Derivatives 21 and 22 proved to be the most active within the series and their potencies against AChE were in the same order of magnitude of the reference compounds. Compounds 15, 21-22, with a 5-carbon alkyl chain bearing an amino moiety at one end, better contacting the PAS, remarkably improved the inhibition of AChE-induced Aβ aggregation with respect to the reference compounds. They also showed activity against self-aggregation of Aβ42 peptide, the most amyloidogenic form of amyloid produced in AD brains, while the reference compounds resulted completely ineffective.
