Development of Novel Fluorous Tagging Reagents and Progress Towards (4S,8S,12S)-4,8,12-Trimethylnonadecanol

The configuration of methyl groups within polyisoprenoid motifs of natural products continue to be difficult to assign. The syn/anti relationships of methyl groups within oligoisoprenoids have been shown to produce reliable differences in 1H and 13C NMR spectra. However, the data set requires expanion to include longer polyisoprenoid motifs and the stereopurity of these samples needs to be higher. Herein, we describe the advancements towards making a more comprehensive data set of oligoisoprenoids in high stereopurity through a fluorous mixture synthesis. Four new fluorous tagging reagents were synthesized and demonstrated to separate otherwise identical compounds. From which a simple method was developed to evaluate the potential of future fluorous tags. Additionally, the known reaction conditions for aryl thionocarbonate ester formation were optimized to reduce the presence of byproduct; increasing the isolatable yield. Finally, an iterative reaction scheme utilizing a highly selective (96 % de, +99 % ee) iridium catalyzed crotylation reaction was used towards the synthesis of (4S,8S,12S)-4,8,12,-trimethyl-nonadecanol