Chelate conformations

With the amide 8 (R1 = C 11,) derived from 2-oxopropanoic acid and amine E, the (2 R)-diastereomer is predominantly formed, regardless of the solvent, through chelation-controlled Re-side attack of the organometal14. Presumably, the weaker steric interaction between the pyrrolidine moiety and the methyl substituent of the amide (R1 = CH3) compared to the phenyl substituent (R1 = C6H5) facilitates the preferential formation of the chelated conformer S-m-8. 

A similar trend was observed in the reaction of tri- and tetrasubstituted etiolates derived from 2-unsubstituted or 2-bromo substituted 3,4-dihydro-6-methoxy-1(2//)-naphthalenone16. The trisubstituted cnolate underwent addition to (—)-(2 )-2-(4-methylphenylsulfinyl)-2-cyclopen-tenone via attack on the nonchelated conformation to give an adduct of d.r. [(2S)/(2/ )] 77 23. The tetrasubstituted enolate underwent addition to the corresponding ( + )-(5)-enone via attack on the chelated conformation to give an adduct with the same absolute configuration at C-2 but with d.r. [(2R) (2S)] 95.5-97 4.5-3. 

M. M. Bhadbhade, and D. Srinivas, Effects on molecular association, chelate conformation and reactivity toward substitution in Cu(5-X-salen) complexes, salen = N,N -ethylenebis (salicyli-denaminato), X = H, CH3O and Cl synthesis, X-ray structures and ERR investigations, Inorg. Chem. 32, 5458-5466 (1993). 

It should also be noted that there is a strong conformational bias for only one of the product chelate conformers. For example, erythro chelate D should be strongly disfavored by both 1,3-diaxial Rj L and CH3 Xq steric control elements. Consequently, it is assumed that the transition states leading to either adduct will reflect this conformational bias. Further support for these projections stems from the observations that the chiral acetate enolates derived from 149a exhibit only poor diastereoface selection. In these cases the developing Rj CH3 interaction leading to diastereomer A is absent. Similar transition state allylic strain considerations also appear to be important with the zirconium enolates, which are discussed below. 

Metal Chelates, Conformational Analysis and Steric Effects in (Buckingham and Sargeson) 6 219... 

Crabtree and coworkers prepared a series of complexes with a methylene linker and different wingtips. Changing the bulk of the wingtip groups has a strong influence on whether a chelating conformation is achieved. For example, in the case of the terhbutyl group a monocarbene complex was formed (Scheme 3.5) instead of the chelate complex [21]. 

Diastereomeric 1,3-amino alcohols 1 have been obtained by reduction of 4,5-dihydroisoxa-zoles350-353. 3C chemical shifts allow a stereochemical differentiation due to the formation of energetically preferred chelated conformations. Similar to /3-hydroxy carbonyl compounds and 1,3-diol derivatives, the chemical shifts of the backbone carbons are larger in the syn 1,3-amino alcohols than in the awn -isomers353. 

At this stage, very little is known about the stabilities of various isomers in coordination chemistry and obviously much less about the reasons for them. It is not clear in many instances whether the chelate conformations have any great influence on isomer stability, or how the influence is exerted in the few instances where it has been established. It is conceivable that the conformation exerts its influence through the entropy term rather than as a AH effect. On the other hand, the conformers may have quite different effects on the solvation energies of the complex isomers, and the stability difference may be reflected through this term. 

FIGURE 5.35 Absolute configuration of (S)-propylenediamine (upper) and its chelate conformations (A and ) with axial and equatorial orientations (lower). 

The addition of organometallics to aldehyde substrates incapable of populating intramolecularly chelated conformations preferentially results in a Cram selective process. This result is most easily rationalized by considering an aldehyde conformation that maintains the incoming organometallic reagent and the largest substituent of the aldehyde in an antiperiplanar disposition, as represented by (5). ... 

Both reactions were inhibited by PPhs, which suggests that phosphine dissociation and alkyne coordination are required for insertion to occur. It was estimated that the alkyne-coordinated species generated in reaction (1) inserts 65 times more rapidly than the corresponding intermediate of reaction (m). This differential was explained by assuming that chelate conformations favor the alkyne bound in the coordination plane for the former case and perpendicular to the plane for the latter. 

Chb is classically defined as the energy difference between the open and chelate conformations, i.e., it denotes the stabilization experienced by the open conformation when the OH group rotates by 180° to close a hexatomic or pentatomic... 

Consequently, Fhb is the difference between the OH barrier calculated in the chelate conformation and the same barrier calculated in a molecule structurally close to the examined compound but hydrogen bond free. In most of our calculations, the reference molecule was attained by substituting the hydrogen bond acceptor fragment with a H atom. When tested on malonaldehyde and acetylacetone the approach worked very well [185]. The method was then applied with discrete success to many other molecules as formazan [186], carbonylamine [187], hexafluoro-acetylacetone [184], glyoxaloxime [188], 2-nitroresorcinol, 4,6-dinitroresorcinol and 2-nitrophenol in vacuum and in solution [189], malonamide and nitromalonamide [158] and ort/zo-halophenols [190]. 

Additivity of the various contributions has been demonstrated for many complexes. The contributions are from the chiral configuration of chelate rings (configurational effect), the chiral chelate conformation (conformational effect), and the presence of asymmetric centers in the ligands. As expected, the contributions are considerably greater for asymmetric atoms which are coordinated to the chromophore than for others (see below). The contributions from chiral ring conformations and from asymmetric centers on the ligands often are inseparable. Complexes of 2,2 -diaminobiphenyl (dabp) of the type [Co(dabp) (en)2H+ have been of interest (], 8) since the coordinated non-planar dabp is chiral without an asymmetric center. 

In the sequel, we will discuss a generalization of the chelation hypothesis as it applies to reactions other than hydrogenation of Schiff bases of a-keto acids with chiral amines. The catalytic hydrogenation of pyruvic acid amide resulted in the formation of lactcimide in high optical purity (75-99% diastereomeric excess)(] ). This might be explained by the chelate conformation of the substrate-catalyst complex shown in Scheme 8. 

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