Competition of ester, amide, ether, carbonate, alcohol and epoxide ligands in the dirhodium experiment (chiral discrimination by NMR spectroscopy).

Thirty-eight derivatives of 3-hydroxy-2-methylpropanoic acid, each with two different oxygen functionalities, were synthesized and subjected to the standard dirhodium experiment (1H NMR in the presence of an equimolar amount of the chiral dirhodium tetracarboxylate complex Rh*). Their structures represent ester, amide, carbonate, ether, alcohol and/or epoxy groups. Significant selectivity in the binding of those oxygen groups to the complex were determined. From these results, a priority list in binding to a rhodium atom of Rh* was established: epoxides > primary alcohols > ethers > or = esters > or = amides > carbonates > tertiary alcohols. This sequence allows the prediction of the preferred binding site of oxygen-containing groups in polyfunctional compounds, which frequently occur among natural products, and, particularly, in asymmetric synthesis of such compounds. Differentiation of the enantiomers by the dirhodium experiment is easily accomplished due to numerous signal dispersions in nearly all cases.

Optimizing dirhodium(II) tetrakiscarboxylates as chiral NMR auxiliaries.

Thirteen enantiopure paddlewheel-shaped dirhodium(II) tetrakiscarboxylate complexes have been checked for their efficiency in the dirhodium method (differentiation of enantiomers by NMR spectroscopy); six of them are new. Their diastereomeric dispersion effects were studied and compared via so-called key numbers KN. Adducts of each complex were tested with five different test ligands representing all relevant donor properties from strong (phosphane) to very weak (ether). Only one of them, the dirhodium complex with four axial (S)-N-2,3-naphthalenedicarboxyl-tert-leucinate groups (N23tL), showed results significantly better for all ligands than the conventional complex Rh* [Rh(II)(2)[(R)-(+)-MTPA](4); MTPA = methoxytrifluoromethylphenylacetate]. On the basis of (1)H{(1)H} NOE spectroscopy and X-ray diffraction, a combination of favourable anisotropic group orientation and conformational flexibility is held responsible for the high efficiency of N23tL in enantiodifferentiation. Both complexes, Rh* and N23tL, are recommended as chiral auxiliaries for the dirhodium experiment.