Amino diphenylphosphinates, which are commercially available or easily prepared from hydroxylamine, undergo ring expansion of cyclobutanones toward γ-lactams under mild conditions. A reaction pathway profoundly different from the common Beckmann reaction is achieved through the ambivalent character of the aminating agent. Thus, rearrangement occurs from a Criegee-like intermediate prior to the formation of the oxime species, which is corroborated by mechanistic experiments. Based on this observation, the migrating aptitude of the adjacent groups is analyzed and found to be in line with the parent Baeyer−Villiger reaction rendering a regioselective (up to >99:1 rr), stereospecific (>99% enantiospecificity), and chemoselective (>99%) insertion process possible. The method thus qualifies for late-stage skeletal editing as showcased by the synthesis of Rolipram and its N-alkylated analogs.

Methylenecyclobutanes are found to undergo Wacker oxidation via a semi-pinacol-type rearrangement. Key to a successful process is the use of tert-butyl nitrite as oxidant, which not only enables efficient catalyst turn-over but also ensures high Markovnikovselectivity under mild conditions. Thus, cyclopentanones (26 examples) can be accessed in an overall good yield and excellent selectivity (up to 97 % yield, generally > 99 : 1 ketone:aldehyde ratio). Stereochemical analysis of the reaction sequence reveals migration aptitudes in line with related 1,2-shifts. By introducing a pyox ligand to palladium, prochiral methylenecyclobutanes can be desymmetrized, thus realizing the first enantioselective Wacker oxidation.

The first synthesis of hebelophyllene Eispresented, along with assignment of its previously unknown relative configuration through synthesis of epi-ent-hebelophyllene E. Development of ac atalytic enantioselective [2+ +2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes.K ey to its success is the identification of an ovel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional-group tolerance (9 examples,u pt o9 7:3e .r.). Thus,alate-stage cycloaddition using af ully functionalized alkene,f ollowed by ad iastereoselective reduction allows ac oncise entry to this class of natural products.

Enantioselective methylene insertion into prochiral cyclobutanones is described providing access to chiral β-substituted cyclopentanones as important structural motif in synthesis and natural products. Commercially available trimethylsilyl as well as other silyl diazomethanes act as one-carbon synthon and scandium triflate is found to be a potent Lewis acid catalyst. By using bis(oxazoline) ligands, enantioinduction is achieved for a number of β-substituted cyclopentanones including examples bearing all-carbon quaternary stereocentres.

Methylencyclobutane werden der Wacker Oxidation über eine semi-pinakolartige Umlagerung unterzogen. Der Schlüssel zu einem erfolgreichen Prozess ist die Verwendung von tert-Butylnitrit als Oxidationsmittel, das nicht nur eine effiziente Katalyse ermöglicht, sondern auch eine hohe Markovnikov-Selektivität unter milden Bedingungen gewährleistet. Auf diese Weise können Cyclopentanone (26 Beispiele) in guter Ausbeute und ausgezeichneter Selektivität (bis zu 97 % Ausbeute und generell > 99 : 1 Keton:Aldehyd-Verhältnis) zugänglich gemacht werden. Die stereochemische Analyse der Reaktionssequenz zeigt ein Wanderungsverhalten, das mit verwandten 1,2-Umlagerungen übereinstimmt. Des Weiteren können durch die Einführung eines Pyox-Liganden an Palladium prochirale Methylencyclobutane desymmetrisiert werden, was der ersten enantioselektiven Wacker-Oxidation entspricht.