Racemic methylations, order

For weak acids, the proton is directly transferred from the acid to the substrate in a reagent-controlled manner and, in order to increase the selectivity, extremely shielded 2 -substituted m-terphenyls have been developed as concave protonating reagents inspired by the geometry of enzymes. Thus, the diastereoselective protonation by a series of substituted phenols of endocyclic keto enolates, obtained by the stereocontrolled 1,4-addition of lithiocuprates onto substituted cyclohexenones, was reported by Krause and coworkers354 355 and applied to the synthesis of racemic methyl dihydroepijasmonate356. 

Figure 17 shows the 11/A isotherms of racemic and enantiomeric films of the methyl esters of 7V-stearoyl-serine, -alanine, -tryptophan, and -tyrosine on clean water at 25°C. Although there appears to be little difference between the racemic and enantiomeric forms of the alanine surfactants, the N-stearoyl-tyrosine, -serine, and -tryptophan surfactants show clear enantiomeric discrimination in their WjA curves. This chiral molecular recognition is first evidenced in the lift-off areas of the curves for the racemic versus enantiomeric forms of the films (Table 2). As discussed previously, the lift-off area is the average molecular area at which a surface pressure above 0.1 dyn cm -1 is first registered. The packing order differences in these films, and hence their stereochemical differentiation, are apparently maintained throughout the compression/expansion cycles. 

The propensity of S-S dications to undergo dealkylation was found to decrease in the order of methyl > ethyl > benzyl. This order of reactivity parallels the increase in the stability of the corresponding carbocations.94 Dealkylation of dication 77 affords thiosulfonium salt 78 in quantitative yield.95 Kinetic studies suggest SN1 mechanism of dealkylation. In addition, reaction of sulfoxide 79 with a substituent chiral at the a-carbon results in racemic amide 80 after hydrolysis. 

Extractions of aqueous solutions of racemic amino-acid ester salts with solutions of / -6/s(dinaphthyl)-22-crown-6 [284] in chloroform revealed the dependence of the enantiomeric distribution constant on the structure of the amino acid ester (Table 64). In order to limit the concentrations of complex in the aqueous phase, inorganic salts were added. In the case of tyrosine, serine and alanine no extraction of salt was observed obviously these salts form very hydrophilic complexes. The highest degree of chiral recognition was found with [284] and p-hydroxyphenylglycine methyl ester hexafluorophosphate [A(AG°)... 

Racemization of chiral a-methyl benzyl cation/methanol adducts. The rate of exchange between water and the chiral labeled alcohols as a function of racemization has been extensively used as a criterion for discriminating the Sn2 from the SnI solvolytic mechanisms in solution. The expected ratio of exchange vs. racemization rate is 0.5 for the Sn2 mechanism and 1.0 for a pure SnI process. With chiral 0-enriched 1-phenylethanol in aqueous acids, this ratio is found to be equal to 0.84 0.05. This value has been interpreted in terms of the kinetic pattern of Scheme 22 involving the reversible dissociation of the oxonium ion (5 )-40 (XOH = H2 0) to the chiral intimate ion-dipole pair (5 )-41 k-i > In (5 )-41, the leaving H2 0 molecule does not equilibrate immediately with the solvent (i.e., H2 0), but remains closely associated with the ion. This means that A inv is of the same order of magnitude of In contrast, the rate constant ratio of... 

All diaryl sulfoxides, some alkyl aryl sulfoxides (e.g., methyl p-tolyl sulfoxide, 41), and some dialkyl sulfoxides (e.g., methyl 1-adamantyl sulfoxide), were found to undergo racemization according to the pyramidal inversion mechanism. Mislow and co-workers (248) have found that for most of the compounds investigated, irrespective of the nature of the substituents attached to sulfur, the first-order rate constant for racemization in p-xylene at 210 C is about 3 X 10" sec", corresponding to a half-life of about 6 hr. Moreover, the activation parameters do not show significant differences and their values were contained in a narrow range 35 to 42 kcal/mol and... 

Vlhen the chiral methylation is carried out with 30% aqueous NaOH the indanone is deprotonated at the interface but does not precipitate as the sodium enolate (Figure 11). In this system there are 3 to 4 molecules of H2O per molecule of catalyst available while in the 50% NaOH reactions the toluene is very dry with only 1 molecule of H2O available per catalyst molecule thus forcing the formation of tight ion pairs. Solvation of the ion pairs in the toluene/30% NaOH system should decrease the ee which we indeed observe with an optimum 78% versus 94% in the 50% NaOH reaction. In the 30% NaOH reactions the ee decreases from 78% to 55% as the catalyst concentration increases from 1 mM to 16 mM (80 mM 5, 560 mM CH3CI, 20 C). Based on these ee s rates of formation of (-h)-enantiomer and racemic product can be calculated. When the log of these rates are plotted versus the log of catalyst concentrations (Figure 13) we find an order of about 0.5 in the catalyst for the chiral process similar to that found using 50% NaOH consistent with a dimer-monomer pre-equilibrium. The order in catalyst for the... 

Figure 13. Order in catalyst for racemic (1.0) and chiral (0.5) methylations using 30% NaOH.

Table 4.6 shows that, while the correlation functions of the meso form change within less than one order of magnitude when the alkyl group R increases from methyl to tert-butyl, the corresponding values in the racemic series decrease by four to six orders of magnitude for the same variations in the alkyl group. 

In order to obtain a commercially viable process it is necessary to racemize the unwanted amine enantiomer, preferably in situ in a so-called DKR. The paUadium-on-charcoal-catalyzed racemization of amines was first reported by Murahashi et al. [23] and was later combined with Upase-catalyzed acylation, to afford a DKR, by Reetz [24] and others [25]. We were able to achieve a DKR of a-methyl benzyl-amine by performing the hpase-catalyzed acylation in the presence of a palladium nanoparticle catalyst (Scheme 6.10). 

Fig. 17.4 Chromatographic behaviour of dihydroactinidiolide (DHA) enantiomers synthetic racemate (a) DHA fractionation by enantioselective high-performance liquid chromatography (HPLC) (b). Chiral selectors used in enantio-GC DIME-jS-CD (30%) in SE 52 DIAC-jS-CD (30%) in PS 268 DIAC-/1-CD (50%) in OV 1701. Order of elution R (I), S (II) in all cases [13], DIME heptakis(2,3-di-0-methyl), CD cylclodextrin, DIAC heptakis(2,3-di-0-acetyl)...

Unsubstituted 3-hydroxythiophene is less stable than 2-hydroxythiophene (63AHC(l)l). This instability may be due to oxidative coupling. In order to confirm this, 2,5-dimethyl-3-hydroxythiophene was subjected to ferricyanide oxidation (72ACS31). Racemic and meso forms of 2,2, 5,5 -tetramethyl-bi-4-thiolen-3-one (445) were isolated. When the a-substituent was r-butyl instead of methyl, exposure to air gave 2-(2,5-di-r-butyl-4-thiolen-3-one) 3-(2,5-di-r-butylthienyl) ether (446), formed by carbon-oxygen coupling. 

The failure in separating in fractions possessing optical activity of opposite sign the stereoregular polymers of racemic 5-methyl-l-heptene, polymerized in the presence of the same catalyst as that used to prepare polymers from racemic 3-methyl-l-pentene and 4-methyl-1-hexene (75), might be an indication that, in order to obtain prevailingly (R) and (S) separable polymers instead of random copolymers from racemic vinyl monomers, the asymmetric carbon atom of the monomer must be in a or in / position with respect to the double bond. 

This is a modification of the method originally used by Chan and Levett (1977). The following elution order is obtained (1) methyl 13-hydroxy-9(Z), 11 (E)-octadecadienoate, (2) methyl I3-hydroxy-9(E),l 1 (E)-octadecadienoate, (3) methyl 9-hydroxy- 10(E), 12(Z)-octadecadienoate, and (4) methyl 9-hydroxy- 10(E), 12(E)-octadecadienoate (Figure C4.2.4A). Peaks 1 and 3 are collected for CP-HPLC analysis peaks 2 and 4 are racemic... 

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