Dynamic asymmetric multicomponent resolution: lipase-mediated amidation of a double dynamic covalent system.
The Strecker reaction is one of the most important multicomponent reactions developed, leading to alpha-aminonitriles that are versatile substrates for many synthetic applications. In the present study, this reaction type has been applied to a double dynamic covalent resolution protocol, leading to efficient C-C- and C-N-bond generation as well as chiral discrimination. The combination of transimination with imine-cyanation enabled the dynamic exchange in more than one direction around a single stereogenic center of restricted structure. This multiple exchange process could generate a vast range of compounds from a low number of starting materials in very short time. The resulting double dynamic covalent systems, created under thermodynamic control, were subsequently coupled in a one-pot process with kinetically controlled lipase-mediated transacylation. This resulted in complete resolution of the dynamic systems, yielding the optimal N-acyl-alpha-aminonitriles for the enzyme, where the individual chemoenzymatic reactions could produce enantiomerically pure acylated N-substituted alpha-aminonitriles in good yields.
Vongvilai
Pornrapee
P
KTH-Royal Institute of Technology, Department of Chemistry, Teknikringen 30, S-10044 Stockholm, Sweden.
Ramström
Olof
O
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D003486:Cyanides / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D007700:Kinetics; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry; D013816:Thermodynamics
D000577:Amides; D003486:Cyanides; D007097:Imines; D009570:Nitriles; D008049:Lipase