Title : Organocatalyzed domino reactions for asymmetric organic synthesis
Abstract:
A concise and catalytic preparation of multi-functionalized scaffolds in a stereoselective manner is highly desired in organic synthesis. This can be achieved via one-pot multicomponent reactions or domino reactions. The most of the success in this arena has come using toxic and highly expensive transition metal catalysts. Over the last decade or so, organocatalysis has emerged as an alternate and often better mode of activation due to their inherent properties. Among different organocatalysts, N-Heterocyclic Carbenes (NHC) and Hypervalent Iodine-based catalysts have received increasing attention due to their unique mode of activation. For example, NHCs generate three different reactive intermediates from enals namely, enolates, homoenolates and acylanions. These all three intermediates allow for an access to completely three different class of products from the same substrate, which is unparalleled for any other mode of catalysis. The diversity of these catalysts further multiplies in combination with co-catalysts like Bronsted acids, Lewis acids, etc. Similarly, hypervalent iodine-based catalysts lead to exclusive rearrangements through migration of substituents, expansion or contraction of rings to produce new stereocentres selectively. These properties of NHCs and hypervalent iodines have enabled the discovery of a wide range of new and novel reactions.
On the other hand, the preparation of organo-selenides/selenones has been revisited in the recent past because of their biological properties as well as unique reactivity. The organoselenide/selenones often undergoes a self-induced interesting, transformations like vicinal group functionalization, and the formation of rings/stereocentres via rearrangement because of a weaker C-Se σ-bond. Despite these attractive properties, metal-free catalytic asymmetric synthesis of oganoselenones has remained less explored.
With organocatalysis as the guiding principle of our research, we have reported several new and novel asymmetric transformations using NHCs and Hypervalent Iodine organocatalysts. These include a one-pot stereoselective construction of 2,3-dihydroxy-2,3-diaryl tetrahydrofurans via NHC-catalysed domino reactions of aldehydes and vinyl selenone (Figure), first NHC-catalyzed phospha-Brook rearrangement, first NHC-catalyzed synthesis of 3-phosphonate-derived heterocycles, first NHC-catalysed preparation of chiral organoselenones, etc. In addition, we have developed method for the asymmetric dihydroxylation of chalcones using hypervalent reagent.
