In an effort to understand better the curious effect imparted by sodium iodide on the stereochemical course of the Wittig reaction, a thorough investigation of the influence of various sodium salts has been carried out. It is known that, in general, nonstabilized triphenylphosphonium ylides produce predominantly cis alkenes in reactions with aldehydes, while stabilized ylides produce trans alkenes and semi-stabilized ylides produce mixtures of both cis and trans alkenes. Among other factors, the choice of solvent and the temperature can also influence the stereochemical outcome of Wittig reactions. To minimize the variables involved, reaction conditions have been restricted to the use of semi-stabilized ylides with THF as the solvent at relatively low temperatures. The observation that the presence of sodium iodide in the reaction mixture of the types of Wittig reactions specified above caused a higher cis/trans alkene ratio to result was used as a starting point for the development of highly cis selective Wittig reaction systems. The information obtained in the initial part of the study with relatively simple systems was subsequently applied to polymeric systems, and thus led to the development of cis selective polymer-bound Wittig reagents. The above studies also led to the investigation of Wittig reactions in which salt-free conditions were imposed or in which an insoluble metal halide was formed in the preparation of the ylide. This was a follow-up investigation to the recently proposed hypothesis of a spin-paired diradical mechanism of certain Wittig reactions by McEwen and Ward. Based on competition experiments, radical trapping experiments, and theoretical calculations, it seems that the Wittig reactions of unstabilized ylides involve an initial concerted $\pi$2s + $\pi$2s cycloaddition to form oxaphosphetanes, but that some degree of asynchronousness arises in the reactions of semi-stabilized and stabilized ylides.

Polyynes represent a class of naturally occurring products that have been linked to a variety of forms of cytotoxicity, including antibacterial and anti-cancer activity. Because these molecules could represent an advancement in modern medical treatments of a variety of ailments, they have been studied much more frequently in the last decade as the need for new antimicrobial treatments has increased. By investigating the structure-activity relationship of the biologically active polyyne, dodeca-2,4-diyn-1-ol, we determined that key structural features such as polyyne conjugation and hydroxyl presence are necessary for the compounds to be biologically active. Using this known molecule as a scaffold and varying chain length, and placement of the conjugation in the chain, we found that diynes around 10-12 carbons showed cytotoxic activity with E. coli while P. fluorescens was only affected by specific molecules that showed no noticeable trend. Further investigation into the trend of molecules that affect E. coli found that increasing the number of alkynes in the conjugation tended to make the molecules more effective than their diyne analogs in most cases.

The first systematic experimental study of diradical 1,1,2,3,3-pentamethylenepropane (PMP) systems has been carried out. A series of PMP precursors based on the bicyclo (3.1.0) hexan-3-one framework was synthesized. The precursors were photolyzed and thermolyzed with the goal of generating a derivative of PMP. Evidence for the formation of a PMP diradical came when 2,4-bis(phenylmethylene)-exo-6-methyl-bicyclo (3.1.0) hexan-3-one (84) was found to epimerize photochemically and thermally. The thermodynamic parameters, E$\sb{\rm a}$ = 30.99 $\pm$ 0.51 kcal/mol and log A = 11.20 $\pm$ 0.27, were calculated for the range 164.3-204.5$\sp\circ$C. These values are evidence for a PMP intermediate in comparison to the predicted values obtained from a Benson analysis and the parameters for similar known cyclopropane thermal rearrangements. Two experimental efforts to identify directly the reaction intermediate were inconclusive. However, the kinetic analysis is only consistent with PMP formation. We unsuccessfully attempted to observe spectroscopically the PMP-like species by low-temperature ESR and UV-Vis. Olefinic trapping studies also proved to be inconclusive in identifying a PMP-like species. The cyclic bis-enamines (118, 119, 121, 122) were found to phosphoresce brightly upon photolysis in frozen matrix at 77K. This phenomenon is unique to the bis-enamines as the mono-enamine (120) failed to phosphoresce under identical conditions. The UV absorption, fluorescence, the phosphorescence spectra for the bis-enamines are reported.

My research work focused on the development of methodologies to enable efficient synthesis of natural products. In the Andrade lab I developed N-sulfinyl metallodienamine (NSMD) and metalloenamine (NSME) methodologies for the asymmetric synthesis of natural products. In 2017, our first report of a novel diastereoselective hydroxylation protocol for metallodienamine (with 4:1 dr) in concise 14-step synthesis of (−)-albocycline warranted further exploration of the method. By screening different metal bases, I was able to observe a unique diastereoselective switch. DFT computational modeling assisted with experimental analysis suggested a favoritism of metallodienamine geometry by choice of metal bases as the origin of the diastereoselective switch. The method worked well with a diverse set of N-sulfinyl aldimines and ketimines with 50-99% yield and 3:1 to 98:2 diastereoselectivity. A one-pot protocol was developed to access 1,2 amino alcohols with high diastereoselectivity. With a good understanding of the diastereoselective reaction with NSMD and NSMEs, I joined with Dr. Po-Cheng Yu to develop a highly diastereoselective domino Michael/Michael/Mannich reaction for the concise total synthesis of (+)- epiibogamine. The domino reaction enabled us to set all the stereocenters in the natural product in a single step with high diastereoselectivity enabling access to the natural product in a concise 7 steps. I also worked briefly on developing diastereoselective oxidative coupling with N-sulfinyl imine for the synthesis of (+)-chimonanthine. At the beginning of my fourth year I Joined the Kim lab, where I developed photoredox catalyzed process to synthesize y-lactones. These motifs are found in various natural products and require multistep to access. I developed a method that enables quick access to these motifs in one step. / Chemistry

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