Organometallic Approaches to [3.1.0] Bicycles in Process Chemistry

Within the field of process chemistry, all available methods of synthesis are typically considered for the preparation of complex targets. Early in development, speed and flexibility are paramount, but as larger quantities of clinical candidates are required later in development, a route is typically chosen based on process robustness, product quality, and its overall efficiency with respect to several metrics. In this chapter we will highlight the preparation of active pharmaceutical compounds and intermediates containing [3.1.0] bicycles for which stoichiometric main group or catalytic transition metals were utilized to construct C-C bonds. We will focus on four broad classes of reactions: Intermolecular metallocarbenoid cyclopropanation, Michael-initiated ring closures, intramolecular metallocarbenoid cyclopropanation, and those utilizing nucleophilic displacements. A comparative method assessment is presented to illustrate which targets are most amenable to a particular chemistry for obtaining high yields and controlling stereochemistry.