Stereoselectivity retention

In regard to the stereoselectivity of the insertion process, Murray and coworkers have shown that the CH oxidation of substituted cyclohexanes by dioxiranes is, like the already discussed epoxidation, highly stereo-controUed . A specific case is c -decalin, which gives only the cis alcohol, as exemplarily displayed in equation 27. A similar stereoselective retention of configuration was also obtained for frawi-decalin and cis- and frawi-dimethylcyclohexanes"°. In fact, complete retention of configuration was demonstrated in the CH oxidation of chiral alkanes ". For example, the optically active (f )-2-phenylbutane was converted by either DMD or TFD" to (5 )-2-phenylbutan-2-ol (equation 28) without any loss of the enantiomeric purity (ep) in the product. 

A concerted, spiro-structured, oxenoid-type transition state has been proposed for C-H oxidation by dioxiranes (Scheme 5). This mechanism is based mainly on the stereoselective retention of configuration at the oxidized C-H bond [20-22], but also kinetic studies [29], kinetic isotopic effects [24], and high-level computational work support the spiro-configured transition structure [30-32], The originally proposed oxygen-rebound mechanism [24, 33] was recently revived in the form of so-called molecule-induced homolysis [34, 35] however, such a radical-type process has been experimentally [36] and theoretically [30] rigorously discounted. 

Cycloadditions. Cycloheptenones are prepared from 1-alkenylcyclopropane derivatives via a [5 -(- 2]cycloaddition. Improvement of stereoselectivity (retention) by the use of [Rh(CO)2Cl]2 is recognized. A synthesis of (-l-)-aphanamol I has been realized based on such a cycloaddition involving an allenic double bond as the two-carbon component. ... 

Mo [24], W [24-25], Mn [26-32], Fe [26-28] porphyrins have been reported. Mn and Fe porphyrins, in the presence of imidazole or other donor axial ligands, catalyse epoxidation with high yields and stereoselectivity (retention of... 

Several interesting syntheses of oxazolidinones have been published. The most outstanding is a Rh-catalysed C-H insertion reaction for the oxidative conversion of carbamates to oxazolidinones <01AG(E)598>. The reaction allowed the synthesis (generally 74-85% yield) of structurally diversified oxazolidinones (e.g. 198) starting from easily available carbamates (e.g. 197). The reaction is stereoselective (retention of configuration)... 

Peracids can react with alkanes to give hydroxylated products, as shown in equation (66). This may be an electrophilic reaction because the rate increases with increasing acidity of the peracid. Radical side reactions were thought to be inhibited by added l2. CF3CO3H is also an effective oxidant. The reaction of franj-l,2-dimethylcyclohexane with PhC03H is reported to be 97% stereoselective (retention) and 97% regioselective for tertiary hydroxylation. ... 

The C—C double bond in the cyclopentene ring can be cleaved by the osmium tetroxide-periodate procedure or by photooxygenation. The methoxalyl group on C-17 can, as a typical a-dicarbonyl system, be split off with strong base and is replaced by a proton. Since this elimination occurs with retention of the most stable configuration of the cyclization equi-hbrium, the substituents at C-17 and C-18 are located trans to one another. The critical introduction of both hydrogens was thus achieved regio- and stereoselectively. 

Carboxylate anions are better nucleophiles for allylation. The monoepoxide of cyclopentadiene 343 is attacked by AcOH regio- and stereoselectively via tt-aliylpalladium complex formation to give the m-3,5-disubstituted cyclopen-tene 344[212]. The attacks of both the Pd and the acetoxy anion proceed by inversion (overall retention) to give the cis product. 

Retention and stereoselectivity on the BSA columns can be changed by the use of additives to the aqueous mobile phase (30). Hydrophobic compounds generally are highly retained on the BSA, and a mobile-phase modifier such as 1-propanol can be added to obtain reasonable retention times. The retention and optical resolution of charged solutes such as carboxyUc acids or amines can be controlled by pH and ionic strength of the mobile phase. 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

When this prior stereoi merization is accounted for, the rearrangonent is found to have resulted fixtm a mixture of all possible suprafacial, antarafacial, inversion, and retention combinations in reughly equal amounts, indicating that no stereochemical pathway is strongly preferred. Substituted systems, however, show higher stereoselectivity. Theoretical modeling of the reaction finds no intermediate, but tire titumtinn state is diradical in character. ... 

Changes in pressure typically have a greater impact on retention than on selectivity. Most studies of CSPs have indicated little effect of pressure on stereoselectivity [28, 31]. However, Bargmann-Leyder et al. reported pressure-related changes in selectivity for an amylose-based CSP, though the magnitude of the pressure effect was not the same for all the compounds studied [58]. Pressures in the range of 15-20 MPa are common for chiral SFC. 

Due to mechanistic requirements, most of these enzymes are quite specific for the nucleophilic component, which most often is dihydroxyacetone phosphate (DHAP, 3-hydroxy-2-ox-opropyl phosphate) or pyruvate (2-oxopropanoate), while they allow a reasonable variation of the electrophile, which usually is an aldehyde. Activation of the donor substrate by stereospecific deprotonation is either achieved via imine/enamine formation (type 1 aldolases) or via transition metal ion induced enolization (type 2 aldolases mostly Zn2 )2. The approach of the aldol acceptor occurs stereospecifically following an overall retention mechanism, while facial differentiation of the aldehyde is responsible for the relative stereoselectivity. 

The smooth cyclizations of ( )- and (Z)-/V-( 3-alkenyl/ethoxy lac tarns with formation of a six-membered ring (via a chair-like transition state) occur completely stereoselectively in quantitative yield with retention of the geometry of the double bond913. 

The complete retention of optical activity in the starting sulfinates recovered at any stage of the reaction, and the high stereoselectivity of the rearrangement are further evidence for the concertedness of the [2,3]sigmatropic rearrangement, in complete agreement with the results presented in equation 15. 

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

Typically, lyases are quite specific for the nucleophilic donor component owing to mechanistic requirements. Usually, approach of the aldol acceptor to the enzyme-bound nucleophile occurs stereospedfically following an overall retention mechanism, while the facial differentiation of the aldehyde carbonyl is responsible for the relative stereoselectivity. In this manner, the stereochemistry of the C—C bond formation is completely controlled by the enzymes, in general irrespective of the constitution or configuration of the substrate, which renders the enzymes highly predictable. On the other hand, most of the lyases allow a reasonably broad variation of the electrophilic acceptor component that is usually an aldehyde. This feature... 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

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