Development of novel asymmetric domino reactions through the utilization of multiple transition metal catalysts cooperatively in one pot reactions
Final Report Abstract
This post-doctoral research resulted in the development of a fourth generational rhodium catalytic system [Rh(cod)2OH] for asymmetric ring opening (ARO) reactions of oxabicyclic alkenes. While the rhodium catalyzed ARO reaction has been intensively pursued by the scientific community for a wide variety of nucleophiles, instances utilizing soft carbon nucleophiles are rare and challenging. In this research, a total of three projects were successfully completed. The first two projects involved the utility of novel carbon nucleophiles such as anthrones and cyanocoumarins, which contain biologically relevant scaffolds in the rhodium catalyzed ARO reaction. A third project demonstrating the first instance of desymmetrization of meso-oxabicycles bearing bridgehead tethered internal nucleophiles was also successfully concluded. In the first project, an unprecedented benzylic functionalization of anthrones through the rhodium catalyzed ARO reaction was developed, yielding anthrone functionalized hydronapthalenes with excellent yields and ee. Challenges in enantioselectivities encountered using known catalyst systems prompted a development of a fourth generational rhodium catalyst system that gave superior yields and ee. In the second project, I demonstrated that vinylogous nucleophiles such as cyanocoumarins can be effectively utilized to effect distal C-C bond formations by exploiting gamma-reactivity of dienolates. The success of this methodology also showcases the first instance in the literature where the concept of vinylogy can be utilized in ring opening reactions on any strained cyclic system. In the final project, the author established an unprecendented rhodium catalyzed asymmetric cycloisomerization of meso-oxabicyclic alkenes tethered to bridgehead nucleophiles. This work demonstrated that C-O, C-N and C-C bond forming reactions can be executed with excellent enantioselectivities utilizing mild reaction conditions, hence opening up a new protocol towards enantio-enriched tricyclic hydronapthalenes. Furthermore, the author also discovered that racemic oxabicylic alkenes bearing two different nucleophiles on the bridgehead substituent undergoes a parallel kinetic resolution, whereby two different constitutional isomers can be generated enantio-selectively arising from differential nucleophilic attack.
