Integrity of the stereocenters

Microwave irradiation greatly improved the reaction between the lactim ethers 157 and anthranilic acid, as regards yields, reaction time and also the integrity of the stereocenter, as shown by the results obtained for compounds 158 (R1 = (R)-Me R4 = H R2 = Me, 4-MeO-Bn, (CH2)2Ph, 2-naphthylmethyl) and 158 (R =(R)-Me R4 = Me R2 = indol-3-ylmethyl), prepared by both the conventional thermal and the microwave-assisted methods <2004SL803>. 

With the Corey lactone four of the stereocenters (8,9,11,12) are defined in the lactone synthon, although there could be a slight concern with the integrity of the stereocenter at position 12 because as an aldehyde intermediate there is some chance of epimerization at that center via its enol. The main problem with this approach is the control of the stereocenter at position 15, which has to be introduced late into the process. Inevitably, there is some diastereoisomer formed, which can be... 

The total synthesis of the complex bioactive indole alkaloid ditryptophenaline, having two contiguous quaternary stereocenters related by C2 symmetry, was accomplished in the laboratory of L.E Overman.In the late stages of the synthetic effort the complex diol substrate was oxidized to the dicarboxylic acid using a two-step procedure first, a Dess-Martin oxidation to the dialdehyde followed by the Pinnick oxidation. The mild reaction condition ensured that the integrity of the stereocenters at the a-positions was preserved. 

The mechanism of this defunctionalization was discussed in connection with Figure 1.14. It took place via approximately planar radical intermediates. This is why in the reduction of alkyl mercury(II) acetates, the C—Hg bond converts to a C—H bond without stereocontrol. The stereochemical integrity of the mercury-bearing stereocenter is thus lost. When the mer-curated alcohol in Figure 3.48 is reduced with NaBD4 rather than NaBH4, the deuterated cyclohexanol is therefore produced as a mixture of diastereomers. 

Other methods of esterification that do not utilize a carbodi-imide coupling method have also been explored. For example, the stereoselective esterification of 20-(S)-camptothecin, a hindered 3 ° alcohol, with amino acid derivatives was accomplished with the use of scandium triflate (Sc(OTf)3) in high yields while retaining the integrity of the amino acid stereocenter (eq 9). ... 

The cleavage of the chiral auxiliary requires an oxidative decomplexation with bromine, chlorine, iodine, or cerium(IV) salts and others in the presence of water, alcohols, and amines yielding carboxylic acids, esters, and amides, respectively. In all cases, the stereochemical integrity of the newly created stereocenter is maintained, whereas the iron-based chirality is "sacrificed upon the decomplexation. For example, the decomplexation with bromine leads to a substitution of the acyl group by bromide under retention at the iron atom. However, the complex [(PPh3)(CO)(Cp)FeBr] is susceptible to racemization in solution [61]. 

Another important factor to deduce the involvement of radicals in a transition metal-catalyzed process is the integrity of stereocenters. In oxidative addition or Sr 2-type processes the stereochemical information - retention or inversion, respectively - is preserved for optically active substrates like sec-butyl bromide (Sect. 2.2), while racemic products are observed when radical intermediates are generated. On the other hand, stereochemical convergence is observed for strongly biased diastereomeric substrates, such as exo- and endo-norbomyl substrates 25 (Fig 9) The reactions occur almost exclusively at the exo-face of the norbomyl... 

A new stereocenter is established in the Claisen condensation whenever the carbanionic carbon center that is undergoing acylation bears two different groups. Normally, however, the basic conditions of the reaction result in the formation of the enolate of the 3-dicarbonyl system and the loss of stereochemical integrity. Two groups have now reported the asymmetric acylation of optically active imide enolates. 

If the chiral auxiliary (adjuvant) is an integral part of the starting material, the chiral center (or other chirality element) generated in the asymmetric synthesis must be readily separable from the auxiliary without racemization [of the new stereocenter]. 

Asymmetric reactions and processes give rise to two kinds of stereoisomeric products diastereomers and enantiomers. The physical separation of these isomers with simultaneous analysis of isomer distribution (peak integration) is an excellent way to determine the selectivity of a reaction. For the analysis of diastereomers, standard chromatographic techniques suffice, although the chromatographic method should be accompanied by another technique that determines the configuration of the new centers. Diastereomer analysis also ensues in cases of double asymmetric induction, and the configuration of known centers in the reactants may be used as a point of reference for determination of the new stereocenter(s) by NMR or X-ray. 

R)-Ma ic acid supplies one of the integral stereocenters of hypusine (903), an unusual amino acid isolated from bovine brain. Its name is derived from the two components hydroxyputrescine and lysine (Scheme 132) [195]. 

A cascade carbopalladation-carbonylation sequence for substrates possessing P-hydrogens was explored by Seashore-Ludlow and Somfai [19] (Scheme 6.10). This allows for the construction of complex architectures with vicinal stereocenters in a concise and rapid fashion via the stereocontrolled formation of two carbon-carbon bonds. An integral aspect of this domino reaction is the ability to control P-hydride elimination of the organopalladium intermediate and instead form the carbonylation product. 

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