1387576-65-9Relevant academic research and scientific papers
Metal-Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α-Substituted Enantiomerically Enriched Nitriles
Pirola, Margherita,Faverio, Chiara,Orlandi, Manuel,Benaglia, Maurizio
supporting information, p. 10247 - 10250 (2021/06/18)
A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral β-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and α-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral β-cyano esters, α-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).
Enantioselective Copper-Catalyzed Radical Ring-Opening Cyanation of Cyclopropanols and Cyclopropanone Acetals
Chen, Pinghong,Guo, Yin-Long,Liu, Guosheng,Wang, Lei,Wu, Lianqian
, p. 2189 - 2194 (2020/04/17)
A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper-catalyzed radical relay processes has been developed. Various cyclopropanols and cyclopropanone acetals are compatible to the catalytic conditions, providing β-carbonyl nitriles with excellent enantioselectivity. These products can be readily converted to chiral γ-amino acids derivatives and drugs such as (R)-baclofen. Preliminary mechanistic studies have supported a ring-opening process for cyclopropanoxy radicals followed by copper-catalyzed enantioselective cyanation of benzylic radicals to form the C?CN bonds in an enantioselective manner. (Figure presented.).
Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes
Song, Lu,Fu, Niankai,Ernst, Brian G.,Lee, Wai Hang,Frederick, Michael O.,DiStasio, Robert A.,Lin, Song
, p. 747 - 754 (2020/07/03)
Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and efficient approach for synthesizing these molecules. However, a generally applicable method featuring a broad substrate scope and high functional group tolerance remains elusive. Here, we address this long-standing synthetic problem using dual electrocatalysis. Using this strategy, we leverage electrochemistry to seamlessly combine two canonical radical reactions—cobalt-mediated hydrogen-atom transfer and copper-promoted radical cyanation—to accomplish highly enantioselective hydrocyanation without the need for stoichiometric oxidants. We also harness electrochemistry’s unique feature of precise potential control to optimize the chemoselectivity of challenging substrates. Computational analysis uncovers the origin of enantio-induction, for which the chiral catalyst imparts a combination of attractive and repulsive non-covalent interactions to direct the enantio-determining C–CN bond formation. This work demonstrates the power of electrochemistry in accessing new chemical space and providing solutions to pertinent challenges in synthetic chemistry. [Figure not available: see fulltext.]
Rhodium-catalyzed asymmetric hydrogenation of β-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position
Li, Xiuxiu,You, Cai,Yang, Yusheng,Yang, Yuhong,Li, Pan,Gu, Guoxian,Chung, Lung Wa,Lv, Hui,Zhang, Xumu
, p. 1919 - 1924 (2018/02/23)
With the assistance of hydrogen bonds, the first asymmetric hydrogenation of β-cyanocinnamic esters is developed, affording chiral β-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.
Opposite enantioselectivity in the bioreduction of (Z)-β-aryl-β-cyanoacrylates mediated by the tryptophan 116 mutants of old yellow enzyme 1: Synthetic approach to (R)- and (S)-β-aryl-γ-lactams
Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Monti, Daniela,Parmeggiani, Fabio,Powell, Robert W.,Santangelo, Sara,Stewart, Jon D.
, p. 1849 - 1860 (2015/06/02)
The Trp 116 mutants of Old Yellow Enzyme 1 that catalyse the reduction of (Z)-β-aryl-β-cyanoacrylates give the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g., alanine) make the substrate bind
Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent negishi arylations and alkenylations of racemic α-bromonitriles
Choi, Junwon,Fu, Gregory C.
supporting information; experimental part, p. 9102 - 9105 (2012/07/13)
The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation at a remarkably low temperature (-78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide.
