Dynamic Covalent Resolution: Applications for System Screening and Asymmetric Synthesis

Combined thermodynamic/kinetic events amount to a kinetically controlled Dynamic Combinatorial Resolution (DCR) process, where the lability of the molecules/aggregates are used to generate dynamics, and the species experiencing the lowest activation energy is selected via kinetic process. Both interand intramolecular processes can be performed using this concept, resulting in complete resolution and associated amplification of the selected species. When intermolecular processes are resolved using this method, an additional advantage is that only a catalytic amount of selector is required to control the system. In this thesis, the Henry and Strecker reactions were developed as efficient C– C bond-forming routes to single and multi-level dynamic covalent systems. These methods efficiently provided a vast variety of substrates from small numbers of starting compounds. These dynamic systems, generated under thermodynamic control at mild conditions, were coupled in one-pot processes with kinetically controlled lipase-mediated transacylation. The enzymemediated resolution of the dynamic nitroaldol system led to enantiomerically pure β-nitroacetates in high yield. Furthermore, combination of multi-level dynamic Strecker systems and lipase-mediated acylation resulted in the resolution of specific α-aminonitriles from the pool. In addition, the asymmetric synthesis of discrete β-nitroalkanol derivatives was simply achieved, resulting in high yields and high enantiomeric purities through the direct one-pot procedure. Moreover, racemase type activity of lipase enzyme through N-substituted α-aminonitrile structure has been discovered. By use of control experiments together with molecular modeling, the mechanism of the racemization process has been established. Asymmetric synthesis of N-methyl α-aminonitriles was also performed through the dual function of lipase, resulting in high yield and good enantioselectivity.