Chiral barrier

The structural variations reported by Cram and coworkers relate to an appreciable extent to the various ancillary functions which have been appended to the binaphthyl units or elsewhere in the macrocyclic system. Enhancements of the chiral barrier or functionalization through arms has generally been effected at the 3-or 6-positions. These positions are adjacent to the hydroxyl group or directly across the second ring from it, respectively. 

The incorporation of chiral units within the macrocyclic skeleton is an important route to the design of macrocyclic receptors capable of enantiomeric or chiral substrate recognition. In order to achieve this goal, the receptor must display a fine structure as a result of chiral barriers, which then allows diastereomeric receptor-substrate interactions, in addition to maintaining the desired cavity properties.18,30,51... 

Attachment of bulky chiral barriers to achieve enantiomeric selection is exemplified by ligands (61),204 (63)69 and (64).19 Ligands of type (61) are especially efficient chiral compounds with binap-thyl hinges . The orientation of the binaphthyl rings for (61) is shown more explicitly in (62).234 With optically pure (61), complete enantiomeric separation of ammonium salt racemates such as (67) is obtained.235-237 The structure has been determined crystallographically for the less stable d form of the PF6- salt of (67) with the (S,S) host (61). The results indicate that the receptor, substrate, counterion and solvent have undergone several steric concessions in order to relieve the strain imposed on the system by the visit of an unwanted guest.238... 

Pioneering studies by Cram and co-workers employed crown ether arrays 35a-c incorporating a 2,2 -dihydroxy-l,l -binaphthyl unit as the chiral barrier <1975PAC327>. Enhancements in the chiral recognition of amino acids were obtained by placing large substituents, at the 3,3 -positions of the binaphthyl moiety, so as to raise its steric barrier. 3,3 -Diphenyl derivative 35c is often the benchmark to which other chiral crown ethers are compared <1981JOC393>. 

Chiral recognition in these phases is achieved when a chiral center is introduced into the crown ether to serve as a barrier to one enantiomer of the guest amine. The chiral barrier is usually a large bulky group that selectively affects the association of one enantiomer of the amine. 

The macrocycle (81), synthesized by Cram and Cram in the early 1970s, contains the appropriate features to achieve this goal (i) a complexation site ensured by the ether functions and (ii) chiral barriers conferred by the chiral binaphthyl units. Enantioselective recognition of 1-phenyl-ethylammonium salts was performed with (81) <73JA2692, B-94MI929-03). 

An investigation of the complexation of this class of molecules with various ionic species may lead to important insights into the catalytic nature of enzymes. For example, fhe crown ether similar to that above containing two 2,2 -substituted 1,1 -binaphthyl groups as chiral barriers complexes preferentially with one enantiomer of some primary amine salfs ... 

In this chapter we have, in our opinion, presented the most important motifs that have been used to construct anion receptors effective in chiral recognition. The carbohydrates have been successfully applied for modification of binding pocket of anion receptors as well as chiral barriers modulating discrimination of enantiomers. The works described in this chapter illustrate that in the design of new enantioselective receptors, important are not only individual anion binding motifs but also their arrangement in the space. 

It is rather easy to understand now why the S-isomer was preferentially selected and hydrolyzed. The side chain R being away from the chiral barrier minimizes the steric factors and leads to the formation of a more stable intermediate. 

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