The LANCA three-component reaction of lithiated alkoxy­allenes (LA), nitriles (N), and carboxylic acids (CA) smoothly provides β-alkoxy-β-ketoenamides in broad structural variety. The subsequent cyclocondensation of these compounds with hydroxylamine hydrochloride afforded a large library of pyrimidine N-oxides under mild conditions and in good yields. Their synthetic utility was further increased by the Boekelheide rearrangement leading to 4-acetoxymethyl-substituted pyrimidines. With trifluoroacetic anhydride the rearrangement proceeds even at room temperature and directly furnishes 4-hydroxymethyl-substituted pyrimidine derivatives. The key reactions are very robust and work well even in the presence of sterically demanding substituents.

An asymmetric synthesis of the C-homoterpenoid (+)-Greek tobacco lactone is developed starting from readily available (R)-linalool. The synthesis is comprised of four operations and features a diastereoablative epoxidation and an oxidative tetrahydropyran formation using vanadium-, palladium-, and selenium-catalyzed cyclizations.

Coordination-driven self-assembly of differently shaped di- to hexavalent crown-ether host molecules is described. A series of [21]crown-7- and [24]crown-8-substituted bipyridine and terpyridine ligands was synthetized in a "toolbox" approach. Subsequent coordination to 3d transition metal and ruthenium(II) ions provides an easy and fast access to host assemblies with variable valency and pre-defined orientations of the crown-ether moieties. Preliminary isothermal calorimetry (ITC) titrations provided promising results, which indicated the host complexes under study to be suitable for the future investigation of multivalent and cooperative binding. The hosts described herein will also be suitable for the construction of various multiply threaded mechanically interlocked molecules.

A total synthesis of 3-epi-hypatulin B, a highly oxygenated and densely functionalized bicyclic scaffold, is reported. The carbon skeleton was prepared by functionalization of a cyclopentanone core and an intramolecular Mukaiyama aldol reaction. The synthesis features a late-stage photo-oxidation of a methoxyallene intermediate for the installation of an ester functionality. Problems encountered during the batch process were solved by translation of the transformation into a flow protocol. Our synthesis highlights the value of flow chemistry to enable challenging steps in natural product synthesis.

A protecting-group-free synthesis of two endoperoxide natural products, plakortolide E and plakortolide I, is reported. Key-steps feature the use of earth-abundant transition metals, consisting of a vanadium-mediated epoxidation, an iron-catalyzed allylic substitution, and a cobalt-induced endoperoxide formation. Our approach combines redox-economy, chemoselective bond-forming reactions, and telescoping into one-pot operations to forge an overall efficient synthesis.