18797-90-5Relevant academic research and scientific papers
The kinetic resolution of oxazinones by alcoholysis: access to orthogonally protected β-amino acids
Cronin, Sarah A.,Connon, Stephen J.
supporting information, p. 7348 - 7352 (2021/09/07)
The catalytic, alcoholytic kinetic resolution of oxazinones is reported. A novel, stereochemically dense cinchona alkaloid-based catalyst can facilitate the highly enantiodiscriminatory (Sup to 101) ring-opening of oxazinones equipped with electrophilic aryl units to generate orthogonally protected β-amino acids for the first time.
Dynamic kinetic resolution of bis-aryl succinic anhydrides: Enantioselective synthesis of densely functionalised γ-butyrolactones
Claveau, Romain,Twamley, Brendan,Connon, Stephen J.
supporting information, p. 3231 - 3234 (2018/04/05)
The efficient Dynamic Kinetic Resolution (DKR) of disubstituted anhydrides has been shown to be possible for the first time. Using an ad hoc designed organocatalyst and an enantio- and diastereoselective cycloaddition process with aldehydes, stereochemically complex γ-butyrolactone derivatives can be obtained-with control over three contiguous stereocentres, one of which is all carbon quaternary.
Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines
Franchino, Allegra,Chapman, Jack,Funes-Ardoiz, Ignacio,Paton, Robert S.,Dixon, Darren J.
, p. 17660 - 17664 (2018/11/10)
Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3-rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.
The First Enantioselective Total Synthesis of (-)-Trans-Dihydronarciclasine
Varró, Gábor,Hegedus, László,Simon, András,Balogh, Attila,Grün, Alajos,Leveles, Ibolya,Vértessy, Beáta G.,Kádas, István
, p. 1909 - 1917 (2017/06/28)
A feasible and enantioselective total synthesis of (-)-Trans-dihydronarciclasine [(-)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(-)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-Amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (-)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-Trans-dihydronarciclasine, a highly potent cytostatic alkaloid.
Enantioselective Alkylative Kinetic Resolution of 2-Oxindole-Derived Enolates Promoted by Bifunctional Phase Transfer Catalysts
Sorrentino, Emiliano,Connon, Stephen J.
supporting information, p. 5204 - 5207 (2016/11/02)
The first strategy for bringing about highly enantioselective alkylative enolate kinetic resolutions using a simple phase-transfer protocol via SN2 chemistry has been developed. In the presence of a new squaramide-based quaternized cinchona alkaloid-derived catalyst and aqueous base, benzyl, allyl, and propargyl halides react with racemic substituted oxindoles to generate densely functionalized products with the two contiguous stereocenters, one of which is an all-carbon quaternary.
Cinchona alkaloid derivatives, their process of preparation and their use as catalysts
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Paragraph 0100; 0101, (2014/02/15)
The present invention provides a process for preparing a substantially stereochemically pure compound of formula (I), or a salt thereof wherein R1 and R2 are independently selected from the group consisting of H, -CH2-CH3, and -CH=CH2, the process comprising the step of demethylating the corresponding methylated compound of formula (II) in the presence of an alkaline or alkaline earth metal (C1-C10) alkylthiolate salt and a polar aprotic solvent.
Enantioselective synthesis of cis -3-fluoropiperidin-4-ol, a Building block for medicinal chemistry
Shaw, Simon J.,Goff, Dane A.,Boralsky, Luke A.,Irving, Mark,Singh, Rajinder
, p. 8892 - 8897 (2013/09/24)
The first enantioselective route to both enantiomers of cis-1-Boc-3-fluoropiperidin-4-ol, a highly prized building block for medicinal chemistry, is reported. An enantioselective fluorination is employed, taking advantage of the methodology reported by MacMillan, which uses a modified cinchona alkaloid catalyst. In studying the fluorination reaction, we have shown that the catalyst can be replaced by commercially available primary amines, including α-methylbenzylamine, with similar levels of enantioselectivity. The piperidinols are readily crystallized to obtain enantiopure material.
