Dynamic Asymmetric Multicomponent Resolution: Lipase-Mediated Amidation of a Double Dynamic Covalent System
2009 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 40, 14419-14425 p.Article in journal (Refereed) Published
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 iminecyanation 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.
Place, publisher, year, edition, pages
2009. Vol. 131, no 40, 14419-14425 p.
strecker reaction; combinatorial libraries; enantioselective synthesis; catalytic addition; amino-acids; imines; chemistry; receptors; selection; molecules
IdentifiersURN: urn:nbn:se:kth:diva-18907DOI: 10.1021/ja9052015ISI: 000271271500081ScopusID: 2-s2.0-70349914540OAI: oai:DiVA.org:kth-18907DiVA: diva2:336954
QC 201005252010-08-052010-08-052011-01-17Bibliographically approved