Developing a Methodology for Catalytic Asymmetric Crotylation of Aldehydes

Asymmetric crotylation has firmly earned a place among the set of valuable synthetic tools for stereoselective construction of carbon skeletons. For a long time the field was heavily dominated by reagents bearing stoichiometric chiral auxiliaries, but now catalytic methods are gradually taking center stage, and the area continues to develop rapidly. This account focuses primarily on preformed organometallic reagents based on silicon and, to some extent, boron. It narrates our endeavors to design new and efficient chiral Lewis base catalysts for the asymmetric addition of crotyl(trichloro)silanes to aldehydes. It also covers the development of a novel protocol for kinetic resolution of racemic secondary allylboronates to give enantio- and diastereomerically enriched linear homoallylic alcohols. As a separate topic, cross-crotylation of aldehydes by using enantiopure branched homoallylic alcohols as a source of crotyl groups is discussed. Finally, the synthetic credentials of the developed methodology are illustrated by total syntheses of marine natural products, in which crotylation plays a key role in setting up stereogenic centers.1 Introduction2 Pyridine N-Oxides as Lewis Base Catalysts3 Bipyridine N,N′-Dioxides as Lewis Base Catalysts4 Chiral Allylating Reagents5 Synthetic Applications6 Concluding Remarks

Latent (Pro)Nucleophiles in Enantioselective Lewis Base Catalyzed Allylic Substitutions

The use of latent nucleophiles, which are molecules that are not nucleophilic but can be activated to act as a nucleophile at an opportune time during the reaction, expands the scope of Lewis base catalyzed reactions. Here, we provide an overview of the concept and show examples of applications to N- and C-centered nucleophiles in allylic substitutions. N- and C-silyl compounds are superior latent (pro)nucleophiles in Lewis base catalyzed reactions with allylic fluorides in which the formation of the strong Si–F bond serves as the driving force for the reactions. The latent (pro)nucleophiles ensure high regio­selectivity in these reactions and enable enantioselective transformations of Morita–Baylis–Hillman adducts by the use of common chiral Lewis base catalysts.1 Introduction2 Substitution of MBH Carbonates3 The Concept of Latent (Pro)Nucleophiles4 Enantioselective Allylation of N-Heterocycles5 Enantioselective Phosphonyldifluoromethylation of Allylic Fluorides6 Conclusion

Polarity Inversion Catalysis by the 1,4-Addition of N-Heterocyclic Carbenes

Polarity inversion is the hallmark of N-heterocyclic carbene (NHC) organocatalysis, with the generation and reaction of acyl anion equivalents known for more than 70 years. In contrast, polarity inversion through 1,4-addition of NHCs to conjugate acceptors was first applied in a catalytic reaction in 2006. This sub-field of NHC-organocatalysis has developed steadily over the subsequent years, enabling novel coupling reactions, enantioselective cycloisomerizations, polymerizations, and other reactions. In this review, this emerging area of NHC-organocatalysis is discussed with comprehensive coverage. In addition, notes regarding the use of other Lewis base catalysts for related reactions, and comments regarding NHC selection for this type of catalysis, are provided.

Studies on Thiourea Catalysed Bromocycloetherification and Bromolactonisations

Lewis base catalysed halofunctionalisation reactions of alkenes are well established and allow access to, among others, various oxygen containing heterocycles. By exploiting the known conversion of N-heterocyclic carbenes into the corresponding thioureas it has been possible to prepare and study a range of chiral and non-chiral Lewis base catalysts for such reactions. Although all thiourea catalysts were found to mediate bromocycloetherification and bromolactonisation reactions, they could not be achieved with enantioselectivity.

Multifunctional catalysis: stereoselective construction of α-methylidene-γ-lactams via an amidation/Rauhut–Currier sequence

Novel chiral organocatalyst 5a, which can simultaneously act as Brønsted and Lewis base catalysts, leads to a one-pot amidation/Rauhut–Currier sequence that affords highly functionalized α-methylidene-γ-lactams with chiral tetrasubstituted carbon stereogenic centers.