Ligand-Dependent Regiodivergent Enantioselective Allylic Alkylations of α-Trifluoromethylated Ketones

The asymmetric introduction of CF3 unit is a powerful tool for modifying pharmacokinetic properties and slowing metabolic degradation in medicinal chemistry. A catalytic and enantioselective addition of α-CF3 enolates allows for expeditious access to functionalized chiral building blocks with CF3-containing stereogenicity. The computational studies reveal that the choice of ligand in a designed palladium-complex system regulates the regioselectivity and stereoselectivity of the asymmetric allylic alkyation (AAA) of α-CF3 ketones and Morita–Baylis–Hillman (MBH) adducts. Multiple C-H···F interactions are involved in the transition states.

Unconventional Transformations of Morita–Baylis–Hillman Adducts

Morita–Baylis–Hillman (MBH) adducts are versatile starting materials widely employed in Lewis base catalysis. A myriad of different transformations have been reported based on either allylic alkylations with stabilised nucleophiles or annulations with diverse dipolarophiles. Apart from these two conventional types of reactivity, MBH adducts have recently been implemented in alternative and complementary catalytic strategies, including: (i) one-pot and cascade transformations, where additional chemical bonds are formed following the asymmetric allylic alkylation event in a single synthetic operation; (ii) regioselective α-allylations for the synthesis of trisubstituted alkenes; and (iii) dual activation strategies, involving Lewis base catalysis together with transition metal complexes or light, enabling allylic alkylations with nonstabilised nucleophiles and cascade processes. The present Short Review summarises the most significant unconventional catalytic transformations of racemic MBH adducts reported within the last decade.1 Introduction2 Multi-Step Single-Vessel Transformations (path iii)2.1 One-Pot Transformations2.2 Cascade Transformations3 α-Allylations (path iv)3.1 SN2′ Mechanism3.2 SN2′–SN2 Mechanism3.3 Miscellaneous Mechanisms4 Dual Activation (path v)4.1 MBH Adduct as Electrophile4.2 MBH Adduct as Nucleophile5 Summary and Outlook

Peptide Modifications: Versatile Tools in Peptide and Natural Product Syntheses

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion