Asymmetric Transition Metal Catalyzed Cyclopropanations

Kristen Berger, Purdue University

Abstract

Cyclopropanes are found in an array of synthetic and natural products. The Simmons-Smith reaction has been one of the most common methods used to synthesize cyclopropanes since it was first discovered in the 1950s. The Simmons-Smith reaction entails the transfer of a carbene (:CH2) from a zinc carbenoid to an alkene, forming a cyclopropane. However, there are still many limitations to the Simmons–Smith method, including poor functional group tolerance and poor regioselectivity in polyalkene substrates. To address the weaknesses in the Simmons-Smith reactions, we have pursued a transition metal-catalyzed method. Our group has reported a cobalt pyridinediimine (PDI) catalyst system to carry out cyclopropanation reactions using gem-dichloroalkanes and gem-dibromoalkanes in order to access nonstabilized carbenes. This method also offers an advantage over diazo transfer chemistry since diazo chemistry requires a stabilizing group to be present in most cases. This established work has demonstrated a complimentary reactivity to the Simmons–Smith reaction. In this work, we demonstrate that we could expand upon the existing methods of dimethylcyclopropanation to access spirocyclopropanated products by changing the identity of the dichloroalkane. In addition to this reactivity, an enantiopure catalyst that is able to catalyze an enantioselective cyclopropanation was found. We were able to show a broad scope of this new reaction, and mechanistic experiments are carried out in order to probe the mechanism of this reaction. Overall, this thesis offers a new way to access enantiopure dimethylcyclopropane and spirocyclopropanated products.

Degree

Ph.D.

Advisors

Lipton, Purdue University.

Subject Area

Organic chemistry

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