120695-60-5Relevant academic research and scientific papers
Palladium-catalyzed synthesis of nitriles from N-phthaloyl hydrazones
Ano, Yusuke,Higashino, Masaya,Yamada, Yuki,Chatani, Naoto
, p. 3799 - 3802 (2022/04/07)
The Pd-catalyzed transformation of N-phthaloyl hydrazones into nitriles involving the cleavage of an N-N bond is reported. The use of N-heterocyclic carbene as a ligand is essential for the success of the reaction. N-Phthaloyl hydrazones prepared from aromatic aldehydes or cyclobutanones are applicable to this transformation, which gives aryl or alkenyl nitriles, respectively.
E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis
Mu, Yucheng,Nguyen, Thach T.,Koh, Ming Joo,Schrock, Richard R.,Hoveyda, Amir H.
, p. 478 - 487 (2019/04/08)
Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for the preparation of di- or tri-substituted alkenyl nitriles. Related approaches that are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z- or E-di-substituted cyano-substituted alkenes or their corresponding tri-substituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy to apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to the synthesis of biologically active compounds.
Photocatalytic E → Z isomerization of polarized alkenes inspired by the visual cycle: Mechanistic dichotomy and origin of selectivity
Metternich, Jan B.,Artiukhin, Denis G.,Holland, Mareike C.,Von Bremen-Kuhne, Maximilian,Neugebauer, Johannes,Gilmour, Ryan
, p. 9955 - 9977 (2018/05/31)
Iteratively executed with exquisite spatial and temporal control, the selective isomerization of polarized alkenes underpins a plethora of complex biological processes ranging from natural product biosynthesis through to the mammalian visual cycle. However, nature's proficiency conceals the inherent difficulties in replicating this contrathermodynamic transformation in the laboratory. Recently, we disclosed the first highly Z-selective isomerization of polarized alkenes, employing the cinnamoyl chromophore as a retinal surrogate under UV-irradiation (402 nm) with (-)-riboflavin (Vitamin B2) as an inexpensive, organic photocatalyst (J. Am. Chem. Soc. 2015, 137, 11254-11257). This study was inspired by the propensity of crystalline (-)-riboflavin in the eyes of vertebrates to invert the intrinsic directionality of retinal isomerization. Herein, we extend this methodology to include a bioinspired, catalytic E → Z isomerization of α,β-unsaturated nitriles, thereby mimicking the intermediate Opsin-derived, protonated Schiff base in the visual cycle with simple polarized alkenes. Replacement of the iminium motif by a cyano group is well tolerated and gives an additional degree of versatility for postisomerization functionalization. Broad substrate scope is demonstrated (up to 99:1 Z:E) together with evidence of mechanistic dichotomy via both singlet and triplet energy transfer mechanisms. Kinetic studies, temperature dependent photostationary state correlations and investigation of substituent-based electronic perturbation of the alkene identified polarization combined with increased Z-isomer activation barriers as the selectivity governing factors in catalysis. This investigation demonstrates the importance of internal structural preorganization on photostationary composition and explicates the augmented Z-selectivity upon hydrogen-alkyl exchange at the β-position of the alkene.
Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
Zhang, Jianye,Dong, Zhiqian,Mundla, Sreenivasa Reddy,Hu, X. Eric,Seibel, William,Papoian, Ruben,Palczewski, Krzysztof,Golczak, Marcin
supporting information, p. 477 - 491 (2015/01/30)
All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
Asymmetric hydrogenation of α,β-unsaturated nitriles with base-activated iridium N,P ligand complexes
Mueller, Marc-Andre,Pfaltz, Andreas
supporting information, p. 8668 - 8671 (2014/08/18)
Although many chiral catalysts are known that allow highly enantioselective hydrogenation of a wide range of olefins, no suitable catalysts for the asymmetric hydrogenation of α,β-unsaturated nitriles have been reported so far. We have found that Ir N,P ligand complexes, which under normal conditions do not show any reactivity towards α,β-unsaturated nitriles, become highly active catalysts upon addition of N,N- diisopropylethylamine. The base-activated catalysts enable conjugate reduction of α,β-unsaturated nitriles with H2 at low catalyst loadings, affording the corresponding saturated nitriles with high conversion and excellent enantioselectivity. In contrast, alkenes lacking a conjugated cyano group do not react under these conditions, making it possible to selectively reduce the conjugated C=C bond of an α,β-unsaturated nitrile, while leaving other types of C=C bonds in the molecule intact.
Synthetic application of intramolecular cyanoboration on the basis of removal and conversion of a tethering group by palladium-catalyzed retro-allylation
Ohmura, Toshimichi,Awano, Tomotsugu,Suginome, Michinori,Yorimitsu, Hideki,Oshima, Koichiro
, p. 423 - 427 (2008/09/17)
A new synthetic strategy, involving utilization of a tethered intramolecular reaction with a removable tether, was demonstrated by the intramolecular cyanoboration-retro-allylation sequence. Georg Thieme Verlag Stuttgart.
TWO CONVENIENT SYNTHESES OF 2-ARYL-1-CYANO-1-PROPENES FROM QUATERNARY AMMONIUM SALTS
Gupton, John T.,Zembower, David,Miller, John
, p. 1891 - 1903 (2007/10/02)
Two readily available and different quaternary ammonium salts have been prepared by the alkylation of vinamidinium salt reduction products.These salts have been successfully converted to 2-aryl-1-cyano-1-propenes and this methodology represents a clean an
