Perspectives | The RajanBabu Group

New Methodology for Stereoselective Synthesis
Discovery of efficient catalytic processes for activation and selective incorporation of abundantly available, feedstocks such as ethylene, butadiene, styrene, HCN, CO, H₂ could have enormous impact on how chemical intermediates are synthesized in the lab, and eventually manufactured on an industrial scale. Among these, processes that yield practical levels of asymmetric induction will be especially attractive to synthetic chemists. Seldom has chemistry seen an area where the scientific goals are so challenging, the economic and environmental benefits so obvious, and the ethical reasons for doing the research so compelling. Through an approach that relies primarily on mechanistic insights, and a systematic examination of ligand effects, we have discovered a number of highly efficient and selective protocols for heterodimerization of ethylene with vinylarenes, 1,3-dienes and strained olefins. As the initial results indicate these discoveries might provide facile entry into broad classes of biologically relevant compounds in fewer steps than previously described. Our current research examines the full scope and limitations of the new synthetic methods and, seeks new applications for the synthesis of complex molecules like pseudopterosins and helioporins. Another major objective is to examine novel aspects of recently discovered catalytic methods for intramolecular cyclization of α,ω-diynes, allenynes and allene-aldehydes using [X-Y] (X-Y, silicon, tin and boron) reagents. Since the X and Y groups are incorporated into the products as the respective vinyl or allyl derivatives, there is an increase in the number of functionalizable groups and serviceable stereochemical elements (including uncommon axial chirality in a diene) after the reaction. New ways of exploiting the high chemo-, regio- and stereoselectivity observed in many of these reactions are being explored. Examples of conceptually new ideas under consideration include: (a) generation of axially chiral 1,3-diene using asymmetric catalysts; (b) use of resident axial chirality to control atropselectivity elsewhere in a molecule; (c) stereoselective reactions of axially chiral 1,3-dienes. Applications for the syntheses of helical polyolefins, and molecules such as antitumor aryltetralins, and highly functionalized, axially chiral dibenzocyclooctadienes are being pursued. A unifying theme in all our projects is the use of transition metal complexes and the ligand-dependent selectivities associated with their reactions. The basic knowledge (e. g., electronic and steric effects of ligands, unusual salt effects, mechanistic details) that is created while addressing the challenging problems should have value beyond the current work. Any enabling chemistry that uses feedstocks in catalytic processes for the synthesis of chemical intermediates should contribute to cleaner manufacturing methods. In addition, this research demands knowledge and skill in several areas of chemistry: synthetic-, physical-, and metallo-organic chemistry, computational chemistry, analytical and spectroscopic techniques. It has been a very fertile area for learning and teaching.

New Methodology for Stereoselective Synthesis

Discovery of efficient catalytic processes for activation and selective incorporation of abundantly available, feedstocks such as ethylene, butadiene, styrene, HCN, CO, H₂ could have enormous impact on how chemical intermediates are synthesized in the lab, and eventually manufactured on an industrial scale. Among these, processes that yield practical levels of asymmetric induction will be especially attractive to synthetic chemists. Seldom has chemistry seen an area where the scientific goals are so challenging, the economic and environmental benefits so obvious, and the ethical reasons for doing the research so compelling. Through an approach that relies primarily on mechanistic insights, and a systematic examination of ligand effects, we have discovered a number of highly efficient and selective protocols for heterodimerization of ethylene with vinylarenes, 1,3-dienes and strained olefins. As the initial results indicate these discoveries might provide facile entry into broad classes of biologically relevant compounds in fewer steps than previously described. Our current research examines the full scope and limitations of the new synthetic methods and, seeks new applications for the synthesis of complex molecules like pseudopterosins and helioporins.

Another major objective is to examine novel aspects of recently discovered catalytic methods for intramolecular cyclization of α,ω-diynes, allenynes and allene-aldehydes using [X-Y] (X-Y, silicon, tin and boron) reagents. Since the X and Y groups are incorporated into the products as the respective vinyl or allyl derivatives, there is an increase in the number of functionalizable groups and serviceable stereochemical elements (including uncommon axial chirality in a diene) after the reaction. New ways of exploiting the high chemo-, regio- and stereoselectivity observed in many of these reactions are being explored. Examples of conceptually new ideas under consideration include: (a) generation of axially chiral 1,3-diene using asymmetric catalysts; (b) use of resident axial chirality to control atropselectivity elsewhere in a molecule; (c) stereoselective reactions of axially chiral 1,3-dienes. Applications for the syntheses of helical polyolefins, and molecules such as antitumor aryltetralins, and highly functionalized, axially chiral dibenzocyclooctadienes are being pursued.

A unifying theme in all our projects is the use of transition metal complexes and the ligand-dependent selectivities associated with their reactions. The basic knowledge (e. g., electronic and steric effects of ligands, unusual salt effects, mechanistic details) that is created while addressing the challenging problems should have value beyond the current work. Any enabling chemistry that uses feedstocks in catalytic processes for the synthesis of chemical intermediates should contribute to cleaner manufacturing methods. In addition, this research demands knowledge and skill in several areas of chemistry: synthetic-, physical-, and metallo-organic chemistry, computational chemistry, analytical and spectroscopic techniques. It has been a very fertile area for learning and teaching.