Practical syntheses of 4-fluoroprolines

Routes have been developed for the economical, process-scale synthesis of the 2 S,4 R, 2 S,4 S, and 2 R,4 S diastereomers of 4-fluoroproline. ▪ 4-Fluoroprolines are among the most useful nonnatural amino acids in chemical biology. Here, practical routes are reported for the synthesis of the 2 S,4 R, 2 S,4 S, and 2 R,4 S diastereomers of 4-fluoroproline. Each route starts with (2 S,4 R)-4-hydroxyproline, which is a prevalent component of collagen and hence readily available, and uses a fluoride salt to install the fluoro group. Hence, the routes provide process-scale access to these useful nonnatural amino acids.