174310-75-9Relevant articles and documents
Ligand-controlled β-selective C(sp3)-H arylation of N-Boc-piperidines
Millet, Anthony,Larini, Paolo,Clot, Eric,Baudoin, Olivier
, p. 2241 - 2247 (2013)
We report a general palladium-catalyzed β-arylation of Boc-piperidines, which yields a variety of valuable 3-arylpiperidines in a simple and direct manner. The β- vs. α-arylation selectivity was controlled by the ligand, with flexible biarylphosphines providing mainly the desired β-arylated products whereas more rigid biarylphosphines mainly furnished the more classical α-arylated products. The computed reaction mechanism (DFT), studied from the common α-palladated intermediate, indicated that the reductive elimination steps leading to the α- and β-arylated products are selectivity-determining. Moreover, the experimental trend obtained with different ligands was well reproduced by the calculations.
Enantioselective intramolecular C-H amination of aliphatic azides by dual ruthenium and phosphine catalysis
Qin, Jie,Zhou, Zijun,Cui, Tianjiao,Hemming, Marcel,Meggers, Eric
, p. 3202 - 3207 (2019/03/21)
The catalytic enantioselective intramolecular C(sp3)-H amination of aliphatic azides represents an efficient method for constructing chiral saturated cyclic amines which constitute a prominent structural motif in bioactive compounds. We report a dual catalytic system involving a chiral-at-metal bis(pyridyl-NHC) ruthenium complex and tris(4-fluorophenyl)phosphine (both 1 mol%), which facilitates the cyclization of aliphatic azides to chiral α-aryl pyrrolidines with enantioselectivities of up to 99% ee, including a pyrrolidine which can be converted to the anti-tumor alkaloid (R)-(+)-crispine. Mechanistically, the phosphine activates the organic azide to form an intermediate iminophosphorane and transfers the nitrene unit to the ruthenium providing an imido ruthenium intermediate which engages in the highly stereocontrolled C-H amination. This dual catalysis combines ruthenium catalysis with the Staudinger reaction and provides a novel strategy for catalyzing enantioselective C-H aminations of unactivated aliphatic azides.
Cobalt-Porphyrin-Catalysed Intramolecular Ring-Closing C?H Amination of Aliphatic Azides: A Nitrene-Radical Approach to Saturated Heterocycles
Kuijpers, Petrus F.,Tiekink, Martijn J.,Breukelaar, Willem B.,Broere, Dani?l L. J.,van Leest, Nicolaas P.,van der Vlugt, Jarl Ivar,Reek, Joost N. H.,de Bruin, Bas
supporting information, p. 7945 - 7952 (2017/06/19)
Cobalt-porphyrin-catalysed intramolecular ring-closing C?H bond amination enables direct synthesis of various N-heterocycles from aliphatic azides. Pyrrolidines, oxazolidines, imidazolidines, isoindolines and tetrahydroisoquinoline can be obtained in good to excellent yields in a single reaction step with an air- and moisture-stable catalyst. Kinetic studies of the reaction in combination with DFT calculations reveal a metallo-radical-type mechanism involving rate-limiting azide activation to form the key cobalt(III)-nitrene radical intermediate. A subsequent low barrier intramolecular hydrogen-atom transfer from a benzylic C?H bond to the nitrene-radical intermediate followed by a radical rebound step leads to formation of the desired N-heterocyclic ring products. Kinetic isotope competition experiments are in agreement with a radical-type C?H bond-activation step (intramolecular KIE=7), which occurs after the rate-limiting azide activation step. The use of di-tert-butyldicarbonate (Boc2O) significantly enhances the reaction rate by preventing competitive binding of the formed amine product. Under these conditions, the reaction shows clean first-order kinetics in both the [catalyst] and the [azide substrate], and is zero-order in [Boc2O]. Modest enantioselectivities (29–46 % ee in the temperature range of 100–80 °C) could be achieved in the ring closure of (4-azidobutyl)benzene using a new chiral cobalt-porphyrin catalyst equipped with four (1S)-(?)-camphanic-ester groups.
