DUDDECK AND DIAZ GOMEZ CH,O CH-O-CH, 36:R=CF 37:R=CF2CF2CF OCH, 44 EU 13 CH,O of the chiral anide shift tsEu 2,2.6-trime xymethy-bipheny 36)and Euhim) ed in the follow ently because of the lower steric shielding by o of the CSA com 6m6 A the m of 1.2 bomane derivative ted (Scheme 12 nes 49 and 50 are milar,i ide 48.This is not a surprise when consid e latter (se earlier). On the other dging o ygen atom s ing strong NMR signal re tals by mentio ld bere are poc 1 eth 3.4.-trimethoxypheny age of most chral e is the fact not effec in binding o soft subtrates.On this back ence of)a.Pr(fo soft Lewis acic So.the dirhodium dime Indeed.52 atom)slenides phosphanes.phosphane and OCH. OCH 38 39 0 41 Scheme 13.Some methaxylated benzenes and Chirality DOI 10.1002/chir method soon; a number of reviews appeared in the follow￾ing years.21–24,27–29 Principal features are similar to those of the CSA complexes (see earlier). The most popular reagents are tris(3-trifluoroacetylcamphorato)europium [Eu(tfc)3; 36] and tris(3-heptafluoropropylhydroxymeth￾ylene)europium [Eu(hfm)3; 37] but a few others, also with ligands based on the camphor skeleton, have been tested (Scheme 12). In analogy to CSAs, ethers bind weakly with CLSR73 and shift reagents with fluorinated ligands should be used due to their higher Lewis acidity.74,75 Positive results have been reported for tetrahydrofurane (18) 75,76 whereas fur￾ane (23) failed, probably because of the electron pair delocalization in the latter (see earlier).76 On the other hand, molecules with several ether oxygen atoms close to each other form chelates producing strong NMR signal re￾solution. So, constitutions and configurations of such com￾pounds have been studied. For example, ortho-dimethoxy￾benzene (39) binds well whereas methoxybenzene (38) as well as meta- and para-dimethoxybenzenes (40 and 41, respectively) and methoxynaphthalenes (42 and 43) are poor donors (Scheme 13).77,78 Analogous observations were reported for some glycol ether derivatives79 and and 3,4,5-trimethoxyphenyl-substituted lignans.80 The advantage of chelation has been utilized by Diaz et al.81 for differentiating successfully the enantiomers of 2,20 ,6-trimethoxy-60 -methoxymethyl-biphenyl (44) in the presence of Eu(tfc)3, Pr(tfc)3, and Pr(hfm)3 with an effi- ciency not far away from that of other 2,20 -dimethoxybi￾phenyl derivatives bearing one or two hydroxyl or car￾bonyl functions. It should be noted, however, that some￾what higher molar proportions of the CLSR had to be added (Scheme 14). Like in the case of CSA application, oxiranes (epoxides) are generally better donors to CLSR than open-chain ethers or cyclic ethers with more than four ring members, apparently because of the lower steric shielding by a￾hydrogens (see earlier). Among them are phenyloxirane (45) 82 and 1,2-epoxy-3-methylpentane (46),83 the d- and l￾enantiomers were discerned from the meso-form of 1,2- dimethyloxirane (47).84 An intriguing series of benzonor￾bornane derivatives has been described: benzonorborna￾diene-exo-oxide (48), 7-oxa-benzonorbornene (49), and 7- oxa-benzonorbornadiene (50).85 Interestingly, the donor ability of the 7-oxa-norbornanes 49 and 50 are similar, if not even better, than that of the structurally related epox￾ide 48. This is not a surprise when considering the posi￾tions of the two next-nearest hydrogens, because of the unique geometry of the norbornane skeleton, all hydro￾gens are directed away from the bridging oxygen atom so that its steric shielding is less than in any other open-chain or less-strained cyclic ethers; compare Scheme 6 and the pertinent text (Scheme 15). Finally, a solitary report on chiral discrimination of ace￾tals by NMR spectroscopy should be mentioned: synthetic (1)-, (2)- and rac-a-multistriatin (51) were differentiated: a slight C-1 NMR signal splitting could be observed in the presence of the strongly acidic Eu(hfc)3 (37).86 Dirhodium tetracarboxylate complexes. The disadvant￾age of most chiral axiliaries described earlier is the fact that they are hard Lewis acids (or bases) and, therefore, not effective in binding to soft subtrates. On this back￾ground, a dinuclear complex offers an alternative because it is a soft Lewis acid itself.59,60 So, the dirhodium tetracar￾boxylate complex 52, Rh(II) 2[(R)-(1)-MTPA]4 (MTPA-H 5 methoxytrifluoromethylphenylacetic acid : Mosher’s acid; Scheme 16),87 has been introduced. Indeed, 52 offers excellent chiral resolution of soft Lewis base sub￾strates like sulfides, sulfoxides (complexation at the sulfur atom), selenides, phosphanes, phosphane sulfides, and selenides30 as well as olefins,87 iodides, nitriles, phos￾phane borane complexes,88 and silanes89 (hydridic hydro￾Scheme 12. Structures of the chiral lanthanide shift reagents Eu(tfc)3 (36) and Eu(hfm)3 (37). Scheme 13. Some methoxylated benzenes and naphthalenes 38–43. Scheme 14. Structure of 2,20 ,6-trimethoxy-60 -methoxymethyl-biphenyl 44. 58 DUDDECK AND DI´AZ GO´ MEZ Chirality DOI 10.1002/chir