Stereochemical preference

The rate-determining expulsion of bromide ion through a bridged intermediate requires an anti orientation of the two bromides. The nucleophilic attack of iodide at one bromide enhances its nucleophilicity and permits formation of the bridged ion. The stereochemical preference in noncyclic systems is also anti, as indicated by the fact that /neso-stilbene... 

A chemical synthesis of prostaglandins by a free radical pathway through an endoperoxide intermediate showed a strong stereochemical preference for the formation of the endoperoxides having cis alpha and omega appendages. 

Base-promoted E2 eliminations involving 1,2-dibromo-1,2-diphenylethane have been used to learn about the stereochemical preferences of this reaction. The meso starting material gives one alkene and the dl starting material gives another. 

All the trimethylplatinum(IV) species have a fac-arrangement of the methyls this is enforced in the [PtMe3X]4 oligomers, but nevertheless appears to reflect a genuine stereochemical preference (e.g. the isoelectronic /aoIr(PMe2Ph)3Me3, section 2.13.5). 

In all the reported examples, the enzyme selectivity was affected by the solvent used, but the stereochemical preference remained the same. However, in some specific cases it was found that it was also possible to invert the hydrolases enantioselectivity. The first report was again from iQibanov s group, which described the transesterification of the model compound (13) with n-propanol. As shown in Table 1.6, the enantiopreference of an Aspergillus oryzae protease shifted from the (l)- to the (D)-enantiomer by moving from acetonitrile to CCI4 [30]. Similar observations on the inversion of enantioselectivity by switching from one solvent to another were later reported by other authors [31]. 

Scheme 1.4 Asymmetric hydrolysis of dihydropyridine diesters influence of solvent on lipase stereochemical preference.

Which isomer is predominantly formed depends on R, R, and on the method by which the carbene or carbenoid is generated. Most studies have been carried out on monosubstituted species (R = H), and in these studies it is found that aryl groups generally prefer the more substituted side (syn addition) while carbethoxy groups usually show anti stereoselectivity. When R = halogen, free halocarbenes show little or no stereochemical preference, while halocarbenoids exhibit a preference for syn addition. Beyond this, it is difficult to make simple generalizations. 

The stereochemical preference (for syn addition) can now also be understood. The step above represents a concerted process. Both BH2 and H are adding simultaneously, so they must end up on the same face of the alkene. In other words, the reaction must be a syn addition. 

Once again (just like the attack of the bromonium ion in the previous section), water must attack from the back side, which explains the observed stereochemical preference for anti addition. 

When there is also a stereogenic center in the silyl enol ether, it can enhance or detract from the underlying stereochemical preferences. The two reactions shown below possess reinforcing structures with regard to the aldehyde a-methyl and the enolate TBDMSO groups and lead to high stereoselectivity. The stereochemistry of the (3-TBDMSO group in the aldehyde has little effect on the stereoselectivity. 

Recently, Porter et al. (1986b, 1988) have reported the synthesis of both meso- and ( )-forms of a series of two-chain carbonyl diacids made by joining two pentadecanoic acid units by a carbonyl group at the 3,3, 6,6, 9,9 and 12,12 positions, 3,5-didodecyl-4-oxoheptanedioic acid (C-15 3,3 ), 6,8-dinonyl-7-oxotridecanedioic acid (C-15 6,6 ), 9,11-dihexyl-10-oxononadecanedioic acid (C-15 9,9 ) and 12,14-dipropyl-13-oxopentacosanedioic acid (C-15 12,12 ), respectively. The diacids were used to probe further the question of stereochemical preference in two-chain amphiphiles. The method used for examining the diastereomeric preference was equilibration by base-catalyzed epimerization in homogeneous, bilayer and micellar media. This method allows for stereoselection based on hydrophobic/hydrophilic considerations rather than classic steric size effects. 

Table 12 shows the equilibrium spreading pressures of each diacid. It is immediately apparent that for three of the diastereomeric pairs there are statistically significant differences. These distinctions relate stereochemical preferences in the spontaneous spreading of (+)- versus meso-monolayers in equilibrium with their respective crystalline phases. However, there appears to be no discernible trend in either the ( )- or meso-ESPs as a function of carbonyl position despite clear trends seen in their monolayer properties in the absence of any bulk crystalline phase. 

In comparison to sulbactam, penam sulfones 12a and b exhibited excellent activity against TEM-1 and AmpC enzymes, respectively, with over 2500-fold improvement against the class C enzyme. Within the same series, 12a and 12b are appreciably more potent than their corresponding diastereomers. In particular, they are potent against the AmpC enzyme suggesting the stereochemical preference of the alkoxy substituent of the cyclopropyl ring, which plays a critical role in binding with the enzymes. Further, in vitro evaluations in a cell-based assay (MIC) established the effectiveness of 12a. hi... 

In several cases (including the present example) where diastereoiso-meric aldol products are possible, there is a preference for the formation of the tAreo-diastereoisomer. This stereochemical preference presumably arises because the six-membered cyclic zinc chelate of the ffereo-isomer can exist in a chair conformation with both substituents in equatorial positions. Table I summarizes the results obtained in several aldol condensations performed by the present procedure. 

The (E)-alkene (74) is formed from Wittig reaction of the corresponding phenyl 3-pyridyl ketone the stereochemical preference is determined by an interaction (either hydrogen bonding or salt bridging) between the carboxylic acid chain being introduced and the amide tether provided by the reactant." ... 

Similar, but more extensive, studies of the co-ordination behaviour of the bifunctional ligands (70a) and (70b) with a range of metals have revealed both P,N and P,P bonding. For the Pd" complexes [PdXjL] (X = Cl, Br, or I), i.r. data indicate that both ligands employ P,P co-ordination. The choice of donor atom is discussed in terms of chelate ring size and stereochemical preferences of the various metals. "... 

NADH. These experiments were pioneering with respect to contemporary enzymology, especially with regard to early recognition that coenzymes are held within enzyme active sites in stereochemically preferred ways. One typically utilizes NADH that contains a tritium or deuterium atom in the 4R or 45 position, and the success or failure of substrate deuteration/tritiation indicates the stereochemistry. Westheimer has tabulated the known examples of dehydrogenases that exhibit specificity for a particular face of NADH. Creighton and Murthy have reproduced this tabulation in their comprehensive review on the stereochemistry of enzyme-catalyzed reactions at carbon. 

The stereochemical preferences are such that it is possible to prepare either enantiomer of a chiral epoxide in high... 

Langlois and co-workers (179) found the same exo stereochemical preference through double asymmetric induction of a related ene-lactone (1 )-145 with their well-explored and efficient camphor-derived oxazoline nitrone (150-146 (Scheme 1.32). They found the cycloaddition components form a matched pair and allowed kinetic resolution of the racemic lactone in up to 70% enantiomeric excess (ee). They suggest the selectivity for exo adduct 147 arises through destabilization of the endo transition state by a steric clash between dipolarophile ring hydrogens and the bornane moiety. 

The combination of the geometrical preference of the tether and the stereochemical preference of the dipolarophile substituent can be seen in the intramolecular cycloadditions of alkyl nitronates, (Scheme 2.6) (99). When the tether is restricted to two atoms, only the endo approach of the tether is observed in up to a 100 1 ratio, independent of the configuration of the disubstituted dipolarophile. However, in the case of a three-atom linker, there exists a matched and mismatched case with respect to the observed stereoselectivities. With a (Z)-configured dipolarophile, only the exo isomer was observed since the ester moiety also approaches on the exo to the nitronate. However, with an ( )-configured dipolarophile, the ester group is forced to approach in an endo manner to accommodate an exo approach of the tether, thus leading to lower selectivity. 

Regio and stereochemical preferences in kinetically-controlled reactions may also be expressed as isodesmic processes. For example, the regioselectivity of (endo) addition of 2-methylcyclopentadiene with acrylonitrile comes down to the difference in energy the transition states leading to meta and para products, respectively. 

All levels of calculation (including semi-empirical calculations) provide a qualitatively correct account of the experimental regio and stereochemical preferences. The only (apparent) exceptions are that both B3LYP/6-31G and MP2/6-31G models show modest preferences for meta products in cycloaddition of 2-methylcyclopentadiene and acrylonitrile. Note, in particular, the success of the calculations in properly assigning the more crowded syn product for the cycloaddition of 5-methoxycyclopentadiene and acrylonitrile. Also note the large magnitude for the preference. Clearly factors other than sterics are at work. 

LUMO maps, which reveal the most electron deficient sites on a molecule, that is, those which are most susceptible to attack by a nucleophile, should be able to account for differences in direction of nucleophilic attack among closely-related systems. They will be employed here first to verify the above-mentioned preferences and then to explore stereochemical preferences in a number of related systems. 

Lipases from porcine pancreas (PPL) and from Aspergillus niger are uniquely suited for oxazolone hydrolysis since they catalyze the ring-opening reaction with a high degree of enantioselectivity. Moreover, these lipases exhibited opposite stereochemical preference, thus providing access to both enantiomers of A -benzoyl... 

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