Loss of chirality

In most cases of diastereoselective nucleophilic addition reactions where achiral organometallic reagents are added to chiral carbonyl compounds, the chirulity inducing asymmetric center is in close vicinity to the newly created center and cannot be removed without the loss of chirality of either the inducing center or the newly formed center. This type of reaction is very useful in propagating chirality in a molecule from one center to an adjacent one, or in immolative processes. 

In order to establish the bridgehead carbon configuration with certainty and to demonstrate the usefulness of the method, desilylation and deprotection of 438b in acidic conditions have been performed. Since they are accompanied by double bond migration and loss of chirality, a dimethylcuprate alkylation has been carried out before acid hydrolysis (Scheme 59) [112]. 

Extension of this research was then delayed until two of us had returned to New Zealand. One of the first jobs of Tasker, a PhD student from Brisbane, was to use 3H-labeling methods to examine epimerization. At that time we were under the impression that reprotonation of carbanion intermediates would be diffusion controlled, as was subsequently reported for phenylglycine in phosphate buffers (18), so that no isotopic discrimination against 3H would be present. But then Wautier et al. reported (6) the complete loss of chirality in [Co(tren)(AA-(S)-AA OMe)]3+, prepared by treating [Co(tren)((S)-AAOMe)]3+ (AA = Ala, Leu) generated in situ in MeOH with (S)-AA OMe (AA = Leu, His, Ala, Val), although their reaction times and temperatures (1-15 h sometimes 35-50°C) and other experimental conditions ([Co(III)] —0.1 M L/V-ethylmorpholine salt of p-toluene sul-... 

Acyl azides (see Section 2.13) The acyl-azide method of coupling is unique for two reasons. First, it is the only case in which the immediate precursor of the activated form of the peptide is not the parent acid. The starting material is the peptide ester that is obtained from the amino acid ester by usual chain assembly (Figure 2.25, path A). Second, it is the only method that just about guarantees production of a peptide that is enantiomerically pure, provided scrupulous attention is paid to details of procedure. There is no danger for loss of chirality during conversion of the ester to the hydrazide and then the azide, but care must be taken to avoid contact of... 

In the case of the enantiomers of isopropylidene N-( 1 -substituted tetra-hydroisoquinolin-2-yl)aminomethylenemalonates (1258), complete loss of chirality was observed, with racemic tricyclic derivatives (1259) being... 

The alkene has a group attached to the chiral C which must react with H to give a group identical to one already attached, resulting in loss of chirality. 

Although optically active chloride is not racemized under the reaction conditions, and it will not add to IV (reverse reaction) to afford a complex of the type Illb, under forcing conditions (high temperature and/or long reaction times) the 7r-benzyl complex (VII in Reaction 5) is obtained which results in a loss of chirality. 

Murahashi alkylation. Murahashi alkylation (8, 346-347) of the optically active allylic alcohol 2 with butyllithium results in almost exclusive (99%) y-al-kylation to give a mixture of (S)-(E)-3 and (R)-(Z)-3 with only slight loss of chirality and with predominant syn-stereochemistry.1 This syn-stereochemistry is opposite... 

In addition to the spectroscopic investigations, there have been attempts to obtain structural and stereochemical information about radicals by chemical means.25 The approach generally taken is to generate radicals by one of the methods discussed in the next section at a carbon where stereochemistry can be determined. As an example, we may cite the experiment shown in Equation 9.6, in which an optically active aldehyde is heated in the presence of a source of radicals.26 The reaction follows the chain pathway indicated in Scheme 1 the loss of chirality indicates that the radical is either planar or, if pyramidal, undergoes inversion rapidly with respect to the rate (on the order of 10s sec-1) at which it abstracts a hydrogen atom from another molecule of aldehyde. 

The first dendrimers with chiral cores for studies on the influence of the stereo-genic centres of a core unit on the chiroptical properties of the overall molecule were presented by Seebach s group [18]. These workers first synthesised dendrimers based on a chiral tris(hydroxymethyl)methane core unit. To these were attached zeroth- to second-generation Frechet dendrons, either directly or separated from the core by an aliphatic (n-propyl) or an aromatic spacer (p-xylylene) (Fig. 4.62). Remarkably, the dendrimers with aliphatic spacer showed no significant optical activity. This loss of chiral information was attributed to a dilution effecf, resulting from linkage of the achiral dendron to the chiral core unit,... 

As a further test of the etched open tubular approach for the analysis of optical isomers, another column was fabricated based on the selector naphthylethylamine that had been attached to porous silica by the silanization/hydrosilation method for use in HPLC [70]. As in the HPLC experiments, this column was best suited for the resolution of the optical isomers of dinitrobenzoyl methyl esters of amino acids. The best separation (a = 1.14) was obtained for the alanine derivative. In addition, the peak symmetry and efficiency for the naphthylethylamine column was significantly better than that obtained on the cyclodextrin column. However, as shown in HPLC experiments, changes in the amino acid moiety (replacing alanine with valine, etc.) often results in a loss of chiral resolution. In the case of optical isomers, the separation mechanism in HPLC and CEC modes is identical since only interaction between the solute and the bonded phase can result in resolution of the enantiomers. 

Asymmetric -methylation of a, -enones. Chiral bidendate ligands derived from L-prolinol can be used for asymmetric Michael additions to a, 3-enones with cuprates of the type CH,L CuMgBr (10, 266). The highest optical yield in conjugate addition to chalcone is observed when L is (S)-N-methylprolinol (88% ee). The tridentate chiral ligand 1 is equally effective for asymmetric 3-methylation of chalcone with CH,L CuLi and CuBr the chemical yield is 95%. Reduction of the amide carbonyl group of 1 results in practically total loss of chiral induction. 

Note The palladium(II) carbene complex now has the asymmetric carbon atoms in close proximity to the catalytically active metal centre. However, there are no readily available free coordination sites for a substrate. Provision of free coordination sites only becomes possible after Pd-N bond fissure, accompanied by loss of chiral information on the catalytic centre. 

Ozone adsorbed on silica gel has also been found to be an effective cleavage reagentFor example, compound (8), which is normally very difficult to cleave, underwent the reaction indicated in equation (15) without loss of chirality. 

An intriguing enantioselective preparation of substituted quaternary 1,4-benzodiazepin-2-one scaffolds has been reported by Carlier et al. <03JA11482>. Enantioselective alkylation is used to prepare chiral products 64 (e.g. R = H R = Me, PhCH2 R = Me2CH) from non-racemic glycine-derived 1,4-benzodiazepinones. If the N1 substituent is sufficiently large (e.g. an isopropyl group) then the stereochemistry at the 3-position of the 3-substituted 1,4-benzodiazepinones is transmitted to the product despite the loss of chirality at C-3 on intermediate enolate anion formation. 

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