The Chemical Catalysis Program in the Chemistry Division supports Professor Michael J. Krische of the University of Texas- Austin in the US. The international collaborator, Professor Bernhard Breit of Albert-Ludwigs-Universität in Germany is supported by the German funding agency, DFG, in a collaboration that will design new routes to commodity and fine chemicals. The proposal for which this award was granted was submitted in response to Program Announcement NSF 09-608: International Collaboration in Chemistry (ICC) between US investigators and their Counterparts Abroad. The researchers propose to develop catalytic processes that enable byproduct-free manufacture of chemical products from abundant, renewable resources. The Breit Group will design and prepare a series of novel phosphine ligands that incorporate supramolecular recognition elements specifically tailored for the activation of carbonyl groups, including carbon dioxide. These "first-generation metal complexes" will be assayed in C-C bond forming hydrogenations developed by the Krische Group in order to establish key structure-reactivity and structure-selectivity trends that will allow Krische and Breit to design improved second-generation catalysts that will be prepared by the Breit Group and assayed by the Krische Group. The collaboration between the Krische and Breit groups is an ideal combination of scientific expertise that will enhance both groups through direct exposure to research techniques, approaches, philosophies, and networks across the Atlantic.
The proposed research intends to achieve the high catalyst activities and selectivities necessary to activate new substrates efficiently on a large scale, which will enhance fine chemical applications, including the manufacture of pharmaceuticals. The largest impact of this proposal will be in education through research. The requested funds are for undergraduate and graduate students, who will benefit from the unique opportunity to acquire skills across the disciplines of synthetic organic chemistry, physical organic chemistry, and transition metal inorganic chemistry. Students from groups historically underrepresented in the sciences will also be recruited to participate. The Krische Group participates in programs such as the "Pfizer Research Fellowship for Under-Represented Minorities" and the NIH sponsored "Bridges to the Future" program, which facilitates the transition of minority students from BS/MS to Ph.D. degree granting institutions. Additionally, Professor Krische has mentored several students using NIH-sponsored "Research Supplements to Promote Diversity in Health-Related Research."
Alkene hydroformylation, the reaction of carbon monoxide, hydrogen and alkenes to form aldehydes, has emerged as one of the largest volume applications of homogenous metal catalysis (>10 million metric tons/annually). Although the hydroformylation of alkenes is highly efficient, the hydroformylation of related π-unsaturated reactants (dienes, alkynes and allenes) suffers from incomplete regioselectivity and "over-hydroformylation" to form dialdehyde products. Additionally, the vast majority of industrial hydroformylation processes utilize catalysts based on rhodium, which is the rarest transition metal (that is not radioactive) and, consequently, exceptionally expensive. Paraformaldehyde is an abundant and renewable one-carbon feedstock (14 million metric tons, estimated global annual production) that could potentially serve as a safe, inexpensive alternative to carbon monoxide in one carbon homologations of dienes, alkynes and allenes. Under the aegis of this NSF-sponsored collaborative research (Award 1021640), the Krische Group and the Breit Group succeeded in developing ruthenium catalysts that enable highly selective reactions of paraformaldehyde to dienes, alkynes and allenes to furnish products of "hydrohydroxymethylation" (Chem. Sci. 2013, 4, 1876; Angew. Chem. Int. Ed. 2011, 50, 5687). Further, it was found that methanol (35 million metric tons, estimated global annual production) could be used as a one-carbon building block in such processes (Nature Chem. 2011, 3, 287). A review article summarizing the results of this NSF-funded collaborative research will soon be published in the journal Angewandte Chemie in a special issue commemorating the 150th anniversary of the chemical company BASF, the world’s largest practitioner of hydroformylation ("Paraformaldehyde and Methanol as C1-Feedstocks in Metal Catalyzed C-C Couplings of π-Unsaturated Reactants: Beyond Hydroformylation," Sam, B.; Breit, B.; Krische, M. J. Angew. Chem. Int. Ed. 2014, 53, DOI: 10.1002/anie.201407888). The outcomes of this research are significant, as (a) the hydroformylation of dienes, alkynes and allenes cannot be accomplished selectively under the conditions of rhodium catalyzed hydroformylation, meaning these new transformations represent the only catalytic methods available to accomplish these particular one-carbon homologations, (b) the paraformaldehyde-mediated one-carbon chain extensions employ catalysts based on ruthenium, which is far less expensive than rhodium, and (c) paraformaldehyde poses a much lower safety hazard than carbon monoxide. Among the broader impacts of this proposal, one of them – "designing new routes to commodity and fine chemicals" as given by the Division Director in 2002 – connects directly to our research outcomes. Finally, one of the greatest outcomes of this collaborative work resides in the training of students – undergraduates, graduate students and postdoctoral researchers – in the broad areas of organic chemistry, organometallic chemistry and transition metal catalysis.
