Enantioselective desymmetrisation of prochiral four membered carbocycles

Abstract

Over the course of this work, three new methods for the enantioselective desymme-trisation of prochiral four-membered carbocycles have been investigated. In the first research project a method for the enantioselective one-carbon ring ex-pansion of prochiral cyclobutanones has been developed. The optimisation of reac-tion conditions revealed Scandium triflate as a potent Lewis acid catalyst using silyl diazomethanes as one-carbon synthons. Enantioinduction was achieved by the evo-lution of the employed chiral bis(oxazoline) ligands. Thereby, enantioselective ac-cess to β-substituted cyclopentanones was enabled, which was demonstrated for a number of examples including ones bearing all-carbon quaternary stereocentres. A second part of the work dealt with oxidative ring expanding Wacker-Tsuji oxida-tion of prochiral methylenecyclobutanes. The substrate scope for functionalised methylenecyclobutanes was explored and stereochemical analysis of the reaction provided support for the assumed reaction pathway. Furthermore, the existing re-action conditions were adapted to enable the use of chiral pyridine-oxazoline lig-ands. The application of weakly coordinating anions as ligands for the chiral palla-dium catalyst resulted in the achievement of the first enantioselective Wacker-Tsuji oxidation of 1,1-distubstituted alkenes. A third research project was the desymmetrisation of prochiral methylenecyclobu-tanes via Mizoroki-Heck arylation. Successive optimisation of the reaction conditions was conducted for methylenecyclobutane model substrates bearing tertiary as well as quaternary carbon centres in 3-position. High dependency of the electronic na-ture of the employed phosphine ligands was found. Furthermore, the addition of sil-ver(I) salts forcing a cationic pathway of the reaction was found crucial to obtain reasonable yields. Initial attempts to use chiral ligands to achieve enantioinduction were not successful so far.