Complete Relative Stereochemistry of Multiple Stereocenters Using Only Residual Dipolar Couplings

Residual dipolar couplings (RDCs), in combination with molecular order matrix calculations, were
used to unambiguously determine the complete relative stereochemistry of an organic compound with five
stereocenters. Three simple one-dimensional experiments were utilized for the measurements of 13C−1H,
13C−19F, 19F−1H, and 1H−1H RDCs. The order matrix calculation was performed on each chiral isomer
independently. The fits were evaluated by the comparison of the root-mean-square deviation (rmsd) of
calculated and measured RDCs. The order tensor simulations based on two different sets of RDC data
collected with phage and bicelles are consistent. The resulting stereochemical assignments of the
stereocenters obtained from using only RDCs are in perfect agreement with those obtained from the single-crystal X-ray structure. Six RDCs are found to be necessary to run the simulation, and seven are the
minimum to get an acceptable result for the investigated compound. It was also shown that 13C−1H and
1H−1H RDCs, which are the easiest to measure, are also the most important and information-rich data for
the order matrix calculation. The effect of each RDC on the calculation depends on the location of the
corresponding vector in the structure. The direct RDC of a stereocenter is important to the configuration
determination, but the configuration of stereocenters devoid of protons can also be obtained from analysis
of nearby RDCs.