Synthesis of Cyclobutane Natural Products using Carbon-Hydrogen Functionalization Logic

C--H functionalization logic is rapidly permeating the way organic chemists approach synthesis and deconstruct targets molecules. With methodological advances developing at an increasing pace, new disconnections and strategies once thought impossible are now available for consideration during synthesis planning. While these methods have sporadically been utilized to great effect for decades, only recently have these strategies been formalized and articulated as an efficient and effective means to construct molecules of interest. When compared to traditional prefunctionalization approaches, there are inherent benefits to using C--H bonds as latent functional groups in terms of redox, atom and step economy.;This thesis begins with an overview of historical examples that exemplify the tenets of C--H functionalization logic, including specific case studies from our own lab. The following chapters outline the design and execution of this strategy to pseudodimeric cyclobutane natural products as an alternative to [2+2] photocycloaddition. Throughout all of the projects, methodological and strategic innovations were critical for success. During the studies toward dictazole A, a diastereoselective synthesis of 1,1- cyclobutanedicarboxylates was devised and an easily cleavable directing group for C--H functionalization was created. En route to piperarborenines, a one-pot synthesis of 1,3- cyclobutanedicarboxylates was invented and the structure of piperarborenine D was revised using sequential sp3 C--H cross coupling reactions. The synthesis of the proposed structure of pipercyclobutanamide A resulted in the first sp 3 C--H olefination on a cyclobutane, a new method to access all- cis-cyclobutanes and the direct conversion of an aminoquinoline amide to an aldehyde.