921936-93-8Relevant articles and documents
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.
Direct catalytic enantio- and diastereoselective Mannich reaction of isocyanoacetates and ketimines
Ortin, Irene,Dixon, Darren J.
, p. 3462 - 3465 (2014/04/03)
A catalytic asymmetric synthesis of imidazolines with a fully substituted β-carbon atom by a Mannich-type addition/cyclization reaction of isocyanoacetate pronucleophiles and N-diphenylphosphinoyl ketimines has been developed. When a combination of a cinchona-derived aminophosphine precatalyst and silver oxide was employed as a binary catalyst system, good reactivity, high diastereoselectivities (up to 99:1 d.r.), and excellent enantioselectivities (up to 99 % ee) were obtained for a range of substrates. Binary catalyst system: A catalytic asymmetric synthesis of imidazolines with a fully substituted β-carbon atom through a Mannich-type addition/cyclization reaction of isocyanoacetate pronucleophiles and N-diphenylphosphinoyl ketimines has been developed. By employing a cinchona-derived aminophosphine precatalyst and silver oxide as a binary catalyst system, good reactivity and high diastereo- and enantioselectivities were obtained.
