UC Irvine

Organozinc reagents are important tools for synthesis due to their highly nucleophilic nature and their ability to participate in transmetalation reactions, such as in Negishi coupling. Various methods for preparation of these compounds have been published, but the mechanisms of these published synthetic routes still remain poorly understood. This thesis will focus on two published methods for organozinc preparation and will document how fluorescence microscopy can be used to investigate these syntheses in ways that cannot be elucidated by traditional analytical tools.One method of organozinc preparation involves the use of lithium salts, which can promote the direct insertion of metallic zinc powder into an organohalide. Through a combined approach of single-metal-particle fluorescence microscopy with 1H NMR spectroscopy, it was found that the effectiveness of different lithium salts toward solubilizing zinc-surface intermediates establishes a previously unknown reactivity correlation that predicts the propensity of that salt to promote macroscale reagent synthesis and also predicts the solution structure of the ultimate organozinc reagent. This work unifies previously disparate observations under a single unified mechanistic framework. Another method of organozinc preparation involves the formation of an activated form of Zn (0) by the reduction of ZnCl2 with lithium naphthalenide, which coincidentally leaves behind a LiCl byproduct. This activated zinc could then be added to an organohalide, directly forming the corresponding organozinc. Our initial hypothesis speculated that this LiCl byproduct was effective at rapidly solubilizing organozinc reagent off of the zinc surface. Whereas, salts that are known to be ineffective at solubilization, such as NaCl, should not result in organozinc reagent being released off of the surface. This was investigated by imaging these activated zinc particles on a fluorescence microscope and by modifying the preparative procedure to form these zinc particles with different salt byproducts (i.e., LiCl and NaCl). Both images of the Zn*•2LiCl and Zn*•2NaCl showed absence of the oxidative addition intermediate which suggests that the rapid solubilization step may depend on factors beside the salt byproduct. Surface-bound reaction intermediates could not possibly be detected without an analysis method with astronomically low levels of detectability. Fluorescence microscopy is this novel method of instrumental analysis due to its high sensitivity and excellent spatiotemporal resolution.