Enantiomers conformationally locked

To this point, all the examples presented have been ones in which the origin of the asymmetric induction has been unimolecular in nature, that is, the molecules adopt homochiral conformations in the solid state that favor the formation of one enantiomer over the other, usually through the close intramolecular approach of reactive centers bimolecular crystal packing effects appear to play little or no role in governing the stereochemical outcome of such reactions. This raises the interesting question of whether the soUd-state ionic chiral auxiUary approach to asymmetric synthesis could be made to work for conformationally unbiased reactants, i.e., those possessing symmetrical, conformationally locked structures. Two such cases are presented and discussed below. 

A diene system with unsymmetrical 1,4-disubstitution is converted to the iron carbonyl complex 1 which is resolved into its enantiomers. The aldehyde function is conformationally locked in the transoid position and is diastereofacially shielded from the bottom face. Nucleophiles attack from the top face with high selectivity. Alternatively, chain elongation leads to the triene 2 which is reacted with diazomethane. Cerium(IV) oxidation removes the metal and furnishes the substituted cyclopropane 3. 

N-Benzoyl-Lalanine methyl ester is in turn about eight times more reactive than is its D enantiomer). The open-chain compounds may not bind to the enzyme in the same manner, however, as does the locked substrate. The conformation around the amido bond of the open-chain compounds, for example, can be transoid rather than cisoid (81). In addition, if equatorial 24 is considered to be the reactive conformer for both the Dand L enantiomers, and if the alanine methyl group is attracted to the hydrophobic aromatic binding subsite, then structures 34 and 38 would result. The L enantiomer of N-benzoyl-phenylalanine methyl ester 38 in this representation has approximately the same conformation as equatorial L-24. But attraction of the methyl of the D enantiomer to the location occupied by the methyl group of the L enantiomer causes the carbomethoxy group to move from the position it occupies in D-24. 

Conformational enantiomerism. trans-Cyclooctene is strained, unable to achieve a symmetric planar conformation. It is locked into one of these two enantiomeric conformations. Either pure enantiomer is optically active, with [a] = 430°. 

The chemical structure and numbering system for ABA is shown in Fig. 4 structure 3-1. ABA can exist in two forms - the naturally occurring S-ABA and its enantiomer R-ABA (3-2). Two conformations of the ABA ring are possible, one with the side chain axial (3-4), which is the preferred conformation in solution, and the other with the side-chain equatorially oriented. In PA, the side chain is locked in the axial position (Figs. 3-5). 

This molecule lacks a plane of symmetry. It is chiral when locked in this conformation. A ring flip leads to the mirror image (enantiomer) of the above conformation, however (try it ). Therefore, c/r-l,2-dimethylcy-clohexane is actually a mixture of enantiomeric chairs rapidly interconverting via ring flips. Because of this interconversion, the compound displays no optical activity, just like any ordinary meso compound. Although neither chair has a plane of symmetry, notice that one of the boat transition states for chair-chair interconversion does, just like a true meso structure ... 

In comparison to the hybrid squares [Pd(/ )-(+)-BINAP)(58)2] [OTfls (5.88) and [Pt (7 )-(+)-BINAP)(58)2][OTf]g (5.89), the all metal squares were formed in significantly greater diastereomeric excesses and were conformationally much more rigid. This was confirmed by VT H-NMR studies carried on these chiral squares with only metal corners. In brief the C2h-symmetrical connector ligands are locked into a chiral conformation in the square assemblies and must be restricted in rotation due to the presence of two - of just one - metal comers. As expected the use of the opposite chiral metallo-corners based on the (5)-(—)-BINAP ligand allowed the preparation of the opposite enantiomers of chiral molecular squares. The CD spectra of these chiral species confirmed the expected enantiomeric relationship. 

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