DUDDECK AND DIAZ GOMEZ Thus,the underlying mechanism is replacement (b) s1ike56-58 do not sh H.C+1 027 sion pparenty.the ligand exchang A△H alent s54 and 55.Tou 0、5 mentioned earli H,C.1 isreasonable to assume that all ys two factors 2e (4-hvd ity duringtransition state formation.Since but why of two mole tions,compiled heer d he 5032-trio in was i.Mixing entropy:both 54 and 56 are racemates.So "H and e Scheme 20 (bottom right).Th ore.be e. in th prisingly.the ne an n a lowered temperatures large AAScontribution.In contrast the monoether 56 the of 5aibd the other one represent the 1 AGo is ch e/mo and the NMR behavior was recognized is a trival ethe R molecule TS ligand mol MG# ble for the coal each and 4Go=RT In K bound l:l be This,hov is not atte ssess C.svmmetry Chirality DOI 10.1002/chir strates with unusually high barriers, which are due to mo￾lecular entropy. Racemic 2,8,12-trioxahexacyclo[8.3.0.03,9.04,6.05,13.07,11]- tridecane (54) 96 and 4,7,11-trioxapentacyclo [6.3.0.02,6. 03,10.05,9]undecane (55) 96 were investigated in the pres￾ence of an equimolar amount of 52. This experiment was successful in terms of enantiodifferentiation (Scheme 20).97 In addition, it became apparent that some 1 H and 13C NMR signals were somewhat broadened even at room temperature; see Scheme 20 (bottom right). Therefore, variable-temperature experiments were performed and, surprisingly, the spectra displayed a nearly complete coa￾lescence behavior at moderately lowered temperatures (Scheme 21).98 A comparison with the signals of the free ligand (top traces in Scheme 21) shows that one of the two signal sets of 54, visible at low temperatures, belongs to the free ligand itself, whereas the other one represents the 1:1- adduct 54?52; both exist in approximately equal amounts indicating that DG0 is close to 0 kJ/mol, and the equilibrium constant is K  100 . This is indeed typical for category IV ligands. The energy barrier is DDG# 5 44 6 2 kJ/mol, estimated for the coalescence temperature Tc. The ligand 54, as well as 55 for which an analogous NMR behavior was recognized is a trivalent ether. Two ligand exchange mechanisms are conceivable: (a) an adduct opens its Rh

O bond, the ligand molecule rotates and forms a new Rh

O bond with another oxygen of the same ligand molecule (internal rotation), and (b) an adduct opens and another free ligand molecule forms a new adduct (replacement). If mechanism (a) is responsi￾ble for the coalescence behavior, each 1 H and 13C signal of the bound 54 should be split into three with relative intensities of 1:1:1 because 54 would loose its C3 symme￾try. This, however, is not observed; the signal patterns of the free and the bound 54 are very similar (Scheme 21) as if the bound molecule still would possess C3 symmetry. Thus, the underlying mechanism is replacement (b) whereas internal rotation (a) is a much faster process giv￾ing time-averaged signals, which cannot be frozen even at 210 K. (Scheme 22). Interestingly, NMR signals of monoethers like 56–58 do not show an analogous VT-NMR behavior although their NMR signals display similar coordination (Dd) and dispersion (Dm) as well. Apparently, the ligand exchange barrier DDG# (5 DDH# 2 TDDS# ) is much lower for these ethers than for the trivalent ethers 54 and 55. Thus, the question arises: Why is that barrier so exceptionally high for the symmetrical ethers? As mentioned earlier, it is reasonable to assume that activation enthalpies DDH# are generally low for all types of ethers. Thus, it must be the activation entropy DDS# which is responsible. Basically, two factors influence DDS# , namely loss or restriction of symmetry and of mobil￾ity during transition state formation. Since adduct forma￾tion is the combination of two molecules, DDS# is expected to be negative, but why can its magnitude be so different? A comparison of estimated DDS# contributions, compiled in Table 3, reveals that indeed a much higher energy bar￾rier is expected for a chiral triether than for a monoether; the caged triether 54 and the asymmetric acyclic ether 56 are taken as representatives for the following discus￾sion. Since a quantitative estimate is very difficult and unsafe, we restrict our discussion to general trends. i. Mixing entropy: both 54 and 56 are racemates. So, activation entropy contributions due to the existence of isomers are very similar in both cases and can, there￾fore, be neglected in the estimation. ii. Symmetry number: the triether 54 loses its C3-symme￾try (three indistiguishable orientations in space) in the transition state because it is fixed to a rhodium atom by one and only one oxygen atom (C3 ? C1) creating a large DDS# contribution. In contrast, the monoether 56 Scheme 18. Racemic 2,3-trans-dihydro-(4-hydroxy-3-methoxyphenyl)- 3-(hydroxymethyl)-1,4-benzodioxin-6-yl]-2(E)-propenoic acid ethyl ester (53) investigated by the dirhodium method; top: significant complexation induced shifts Dd (in ppm), bottom: diastereomeric dispersions Dm (in Hz, recorded at 9.4 Tesla).93,94 Values for 13C are in italics; favoured complexa￾tion sites are indicated by ‘‘Rh...’’ (symbolizing 52). Scheme 19. Equilibria of the free component molecules S and 52 in the ligation (top) and ligand exchange reaction (below), energy level diagram (bottom); ‘‘TS’’: transition state. 60 DUDDECK AND DI´AZ GO´ MEZ Chirality DOI 10.1002/chir