NHC-catalyzed transformations: Stetter, benzoin, and ring expansion reactions
N-Hetereocyclic carbenes (NHC) have been intensively investigated since Ukai et al had reported the first NHC-catalyzed coupling of two equivalents of benzaldehyde, to form what is known as the benzoin product. A plethora of reports have since been published on NHC-catalyzed reactions, such as the cross-benzoin, Stetter, redox reactions, and many others. An attractive feature of NHCs is their ability to effect the umpolung (inversion of reactivity) of aldehydes. The efforts in the introduction of β,γ-unsaturated-α-ketoesters as acceptors for the Stetter reaction have led to the first highly enantioselective intermolecular Stetter reaction with β-aryl substituted Stetter acceptors (up to >99% ee). The synthetic applications of the Stetter adducts generated from the α-ketoester acceptors were demonstrated to give access to a diverse number of useful building blocks. Furthermore, the α-ketoester substrates were found to also be applicable for the cross-benzoin reaction. Through the development of a new electron-deficient, morpholine-based triazolium-derived carbene, a highly chemo- and enantioselective cross-benzoin reaction was achieved using aliphatic aldehydes and α-ketoesters. This methodology constitutes as the first highly enantioselective intermolecular cross-benzoin reaction with aliphatic aldehydes (up to 93% ee). In addition, a highly divergent synthesis of Stetter adducts and cross-benzoin products could be achieved in excellent regioselectivity. Interested in utilizing NHCs as organocatalysts for the development of new reactions, tetrahydrofuran and prolinal derivatives were found to undergo efficient ring-expansions. This methodology gives access to highly functionalized lactones and lactams, which could serve as synthetically useful building blocks for the synthesis of natural products and biologically active compounds.
DegreeDoctor of Philosophy (Ph.D.)
CommitteeMajewski, Marek; Wilson, Lee; Attah-Poku, Sam; Pedras, Soledade M.
Copyright DateJune 2012
organocatalysis, carbenes, umpolung