Bachelor's Degree(s): California Institute of Technology, 1982
PhD: Yale University, 1988
PostDoc: MIT, 1988-90
Area of Interest
Our research program in organic and organometallic chemistry is aimed at the mechanism-based design of new carbon-carbon bond forming reactions catalyzed by transition metal complexes. We are also interested in utilizing such reactions to develop new, efficient strategies for the synthesis of molecular or macromolecular targets of medicinal interest (including biologically active natural products and "unnatural" structural analogs). Two primary focus areas have been the titanium-catalyzed multi-component coupling reactions of tethered enals and the molybdenum-catalyzed metathetical coupling of terminal olefins.
Using titanium-catalyzed multi-component coupling reactions we have developed, simple acyclic substrates such as 1 can be converted to a variety of complex, polycyclic products such as 2-6. Product 2 results from the three-component coupling of olefin + aldehyde + carbon monoxide (cyclocarbonylation). Products 3-6, which can be made when carbon monoxide is replaced with an isonitrile, result from an unusual (and unexpected) cyclopentadienyl reductive elimination reaction.
We have recently discovered a catalytic version of the cyclocarbonylation reaction 1 ® 2 and are using this reaction to devise efficient routes to complex natural products such as asteriscanolide, ginkgolide A, and prostaglandin F2a. Our catalytic reaction uses the ansa-titanocene complex 7 as chiral catalyst that is generated from an air stable precursor. The major enantiomer formed (up to 90% ee) corresponds with the most stable diastereomer of the metallacycle intermediate.
Using molybdenum catalyzed olefin metathesis we developed processes for the metathetical cross-coupling reactions of a olefins with styrenes, allylsilanes and acrylonitrile will be presented. Acrylonitrile is an example of a directly functionalized olefin which had eluded all previous attempts at productive olefin metathesis. Cross-metathesis of acrylonitrile with a olefins is proposed to arise from a pathway where alkyl substituents are selectively incorporated into the b position and cyano substituents are selectively incorporated into the a position of metallacyclobutane intermediates. The key to successful olefin metathesis reactions of acrylonitrile appears to be the presence of an electron-rich olefin in the reaction mixture to intercept the cyano-substituted alkylidene intermediate (electron-deficient acrylonitrile being too weak a Lewis base to fulfill this role). Another interesting feature of the acrylonitrile cross-metathesis reactions is the high selectivity for the less stable cis olefin product.
We are actively continuing our studies in titanium-catalyzed multi-component coupling reactions and molybdenum-catalyzed cross-metathesis through mechanistic studies, ligand and catalyst design, and total synthesis, as well as pursuing new directions inspired by emerging ideas and collaborations and by new discoveries from our current research.