We have calculated the optical rotation at λ = 589 nm for 45 fluorinated alcohols, amines, amides, and esters using both time-dependent density functional theory (TDDFT) with the CAM-B3LYP functional and the second-order approximate coupled-cluster singles and doubles (CC2) method, where the aug-cc-pVDZ basis set was adopted in both methods. Comparison of CAM-B3LYP and CC2 results to experiments illustrates that both methods are able to reproduce the experimental optical rotation results for both sign and magnitude. Several conformers for molecules containing the benzyloxy and naphthalene groups needed to be considered to obtain consistent signs with experiments, and these conformers are discussed in detail. We have also used a two-point inverse power extrapolation of the basis set to investigate the optical rotation in the basis set limit at the CC2 level, however, we only found small differences compared to the aug-cc-pVTZ results. Our results demonstrate that the least computationally expensive method investigated here, the CAM-B3LYP functional with the aug-cc-pVDZ basis set, is a reliable method to predict the optical rotation for large molecules and thereby the absolute configuration of chiral molecules.