The project focuses on the asymmetric hydrogenation of unfunctionalized alkenes. There are two specific aims. One is to use asymmetric hydrogenation of largely unfunctionalized alkenes to prepare widespread fragments in chiral, acyclic molecules and the other is to optimize and refine the optically active carbene oxazoline catalyst developed previously to facilitate enantioselective hydrogenation of a more diverse set of largely unfunctionalized alkenes. These studies will be applied to form all stereochemical permutations of difunctionalized chirons that correspond to some of the most fundamental building blocks in chiral, acyclic molecules.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Kevin Burgess in the Department of Chemistry at Texas A&M University. Professor Burgess will focus his work on the development of methodology for the asymmetric hydrogenation of unfunctionalized alkenes. A great range of genuinely useful chiral building blocks will be prepared. The work has the potential for broader impact in the pharmaceutical industry and the project serves as an excellent venue for the training of undergraduates, graduate students, and postdoctoral fellows.
Throughout the featured chiron syntheses are scalable, green, practical routes to chirons that are widely used in synthetic chemistry. We are continuing with our theme that coupling catalyst and substrate directing effects to obtain key materials is a useful and under-utilized strategy in contemporary organic methodology. As a direct result of the methodologies outlined above we were able to prepare several materials to illustrate our hydrogenation approach to polyketide-derived natural products (Figure 3). Exercises like this are necessary to demonstrate to the natural products syntheses community that the methodology is practical. However, we do not waste time by making complex molecules via routes that involve many peripheral steps, particularly if the only "showcase" hydrogenation is near the end of the synthesis. Instead we chose strategies to demonstrate the hydrogenation steps at an early stage in the procedure. We also made an unexpected observation that acidity in catalytic hydrogenation processes is important because the generated acid may influence the outcome of catalysis by changing or decomposing the substrate or reactant, or impacting enantioselectivities in more subtle ways (Figure 4). Our carbene catalyst is superior to the corresponding phosphine insofar as it is less inclined to generate acid under hydrogenation conditions. This project facilitated the syntheses of complex organic materials with useful and well-defined three dimensional architectures as illustrated in Figure 1.
