Catalytic Enantioselective Claisen Rearrangements of O-Allyl β-Ketoesters

Claisen rearrangement; organocatalysis; asymmetric catalysis; Density-functional calc; H bondingThe selective construction of contiguous quaternary stereogenic centers, a motif found inmany complex natural products, represents a significant synthetic challenge.[1] Among thelimited number of approaches for the formation of bonds between such sterically-congestedcarbon atoms, intramolecular processes such as polyene cyclizations,[2a,b] intramolecularcycloadditions,[2c] and sigmatropic rearrangements[2d,e] have been particularly effective.For addressing vicinal quaternary carbons, these transformations have only been applied in adiastereocontrolled manner using substrates containing pre-existing stereogenic centers,either as part of cleavable auxiliaries or structural features of the target molecule. Thedevelopment of catalytic asymmetric methods for the direct and selective formation of suchstereochemical arrays represents a highly desirable and challenging goal.Since its discovery in 1912,[3] the [3,3]-sigmatropic rearrangement of allyl vinyl ethers (theClaisen rearrangement) has emerged as a proven strategy for the formation of carbon–carbon bonds between vicinal stereogenic centers.[4] Diastereoselectivity is generallypredictable and high in these processes because of the concerted nature of the C–O bond-breaking and C–C bond-forming events as well as the large energetic preference for chair-like over boat-like transition states. Furthermore, important examples of enantioselectivemethods for Claisen rearrangements involving Lewis acid catalysis[5] have been identifiedrecently for select substrates with chelating functional groups.We reported recently that the achiral guanidinium ion