4-Fluoroprolines are among the most useful nonnatural amino acids in chemical biology. Here, practical routes are reported for the synthesis of the 2S, 4R, 2S, 4S, and 2R,4S diastereomers of 4-fluoroproline. Each route starts with (2S,4R)-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. (c) 2008 Elsevier B.V. All rights reserved.