Diastereoisomeric chelates

In contrast to the early theoretical work of Rank and coworkers , C-NMR investigations had revealed that the metallated carbon atom in the a-sulphinyl carbanion is nearly planar . A four-centre chelate structure 315 has been proposed for a-lithiosulphoxides, and it is believed to be responsible for the planar configuration of the anionic carbon atom and for the greater stability of o(-sulphinyl carbanions in comparison with a-sulphenyl carbanions This chelation favours one of the two diastereoisomeric carbanions and for this reason a-sulphinyl carbanions react with electrophiles in a highly stereoselective manner (see below). 

The dynamic behavior of the model intermediate rhodium-phosphine 99, for the asymmetric hydrogenation of dimethyl itaconate by cationic rhodium complexes, has been studied by variable temperature NMR LSA [167]. The line shape analysis provides rates of exchange and activation parameters in favor of an intermo-lecular process, in agreement with the mechanism already described for bis(pho-sphinite) chelates by Brown and coworkers [168], These authors describe a dynamic behavior where two diastereoisomeric enamide complexes exchange via olefin dissociation, subsequent rotation about the N-C(olefinic) bond and recoordination. These studies provide insight into the electronic and steric factors that affect the activity and stereoselectivity for the asymmetric hydrogenation of amino acid precursors. 

Reaction of two equivalents of 2-[(dimethylamino)methyl]ferrocenyUithium with ZnCl2 affords the corresponding diorganozinc compound (68) in which two 2-[(dimethylamino) methyl]ferrocenyl ligands are C,Af-chelate bonded to zinc. Due to the chirality of the bidentate ligands 68 exists in two diastereoisomeric forms. Indeed, in solution a meso one and an S,S)/ R,R) enantiomeric parr in a 1 4 ratio were observed by H and C NMR spectroscopy. However, it is only the S,S)/ R,R) enantiomeric pair that preferentially crystallizes from solution. An X-ray crystallographic study of such crystals afforded the structure of (R,R)/(S,S)-6S in the solid state (Figure 35). 

Separation of diastereoisomeric peptides by HPLC is more common. Since each diastereo-isomer has different physicochemical and biological properties, this is of great interest. Separations of diastereoiosomeric di- and tripeptides have usually been performed on reversed-phase columns. Cahill et al. (119) separated diastereoisomeric amino acids and derivatized dipeptides using esters of the /V-hydroxysuccinamide of f-butyl carbonyl-L-amino acid on Cl8 and C8 columns. Linder et al. (120) separated amino acid and peptide derivatives on an RP-C8 column, adding a metal chelate. Mixtures of DL and LD-dipeptides can be separated by RP-HPLC into two peaks, one containing LL- and DD-isomers, the other containing LD and DL-isomers. Sep-... 

Diastereoisomerism is observed when two or more chiral elements appear in the same system. Isolation and characterization of enantiomers or diastereoisomers depend on the structural stability of the chiral element. Therefore the conformation of a chelate ring must generally be considered as labile. The structural stability of the configuration around the metal center and the stability of an asymmetric coordination atom depends on the nature of the central metal atom. In most cases an optically active ligand molecule can be considered as configurationally stable. The presence of a stable chiral element can induce definite chirality in another element which, taken separately, would be labile. 

The enhanced reactivity of chelated amino acid esters towards attack by other nucleophiles has been used to advantage in the sequential synthesis of small peptides equation (4l).225 Formation of the amide bond takes only seconds to minutes at room temperature in DMSO as solvent, and the peptide can be easily recovered by reducing the metal to the Co" state. Recent studies have shown that the A and A diastereoisomeric reactants are selective in their couplings to (2 ) and (S) amino acid esters and that mutarotation at the asymmetric centre of the chelated ester reactant varies from 0-6%.226 Isied and coworkers have described the use of the Co(NH3)3+ as a C-terminal protecting group for the sequential synthesis of peptides (equation 42).227 This procedure has advantages over other methods in some cases. 

Coordinated thioether S is often asymmetric. In (302) the asymmetry is frozen by the configuration of the attached chelate rings but in (301) it is not and inversion is fast. Conventional resolution via diastereoisomeric salts has never been substantiated for a purely enantiomeric Co—SR Ril+ system devoid of other chirality. I3C and H studies on diastereoisomeric systems1079 however show that inversion rates are normally of the order 0.1-10 s1, which makes coordinated thioethers decidedly more configurationally labile than organic sulfonium salts. The effects of asymmetry in (302) are readily seen in diastereoisomeric systems where the lone pair on S is often stereospecifically orientated. It usually directs stereochemical change and ligand replacement processes. 

The reactions proceed with retention of configuration at phosphorus. Various classical routes to alkylphosphine oxides have been applied in the synthesis of a range of potentially chelating and pincer-like ligands, e.g., (233), the binaphthyl system (234), the hybrid phosphine oxide-N-oxide (235), and the chiral pyridine bis(phosphine oxide) (236). A route to diarylmethylphosphine oxides is afforded by the palladium-catalysed reaction of aryl bromides with tet-rakis(hydroxymethyl)phosphonium chloride in the presence of a base. The diastereoisomeric system (237) has been isolated from the reaction of a cyclic... 

If the P-hydroxy acid derivative is a lactone, the chain is turned the other way and no chelation is possible. The lactone 65 can be prepared from malic acid 64 (either enantiomer) and the dilithium derivative 66 cannot be chelated. Instead the solvated (THF is the solvent) LiO group blocks the top face of the almost planar enolate. The selectivity is anti as before but when the chain is opened out 68 by hydrolysis of the lactone it is clear that the other diastereoisomeric relationship to that in 60 has been made.11... 

The introduction of chiral ligands on a reagent or a catalyst induces asymmetry that will be transmitted to the corresponding diastereoisomeric transition states. In most of the cases, the ligands favor rigidified chelates, and there are only a few low-energy conformers to consider. 

The presence of a chiral acetal, aminal or oxathiane in the vicinity of a carbonyl group can direct the reduction of a ketone toward a diastereoisomeric alcohol, whether or not chelation is operative. For example, the LiAlHf or Li 5-BU3BH reductions shown in Figure 6.13 give predominantly the diastereoisomer predicted by the Felkin-Ahn model while reductions with DIBAL or LiAlH4/MgBr2 give predominantly the diastereoisomer predicted by the chelation model [87,94, 213, 226],... 

The classic case of diastereoisomerism that arises among chelate ligand derivatives is Ihe tris(didentate) complexes in which the two donor atoms of the identical ligands are different. Clycinate, NH2CH2C02, and 2-aminoethanethiolate, NH2CH2CH2S-, illustrate this. For complexes of either ligand, the facial and meridional labels described previously could be applied, but the more systematic configuration indexes are OC-6-22 and OC-6-21. 

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