Preserve stereocenter

Skeletal bonds directly to remote stereocenters or to stereocenters removed from functional groups by several atoms are preserved. Those between non-stereocenters or double bonds which lie on a path between stereocenters are strategic for disconnection, especially if that path has more than two members. 

Of the two carbocyclic rings in 272 or in simpler precursors such as 275, ring A, which has no independent stereocenters, is more strategic for disconnection. Indeed, ring B and the carbon stereocenter bearing the /-butyl (C-8) qualify for preservation as initial or origin structural units for the synthesis. The stereocenter at C(8) with its bulky... 

Notice the overall result. When R migrates over, the net result is to place oxygen in between B and R. Focus your attention on the stereocenter of the alkyl group (R). As R migrates, the configuration of the stereocenter is unaffected by the migration. In other words, the configuration of the stereocenter is preserved. This happens to all three B—R bonds ... 

Amino acids can be used as azomethine yhde precursors, although the stereo-genic center is by necessity lost and require reaction with chiral dipolarophiles to circumvent the problem of absence of stereocontrol. Harwood et al. (57) demonstrated that the chirality of the original amino acid could be preserved by derivatization to give back not only the original stereocenter, but further stereoinduction. 

Although 8 consisted of two diastereomers, only one of the stereocenters in 8, C(8), was to be preserved beyond the next stage of the synthesis. As a result, the synthesis of 1 could have been rendered enantioselective by beginning with enantiopure 9 or, for example, the ditosylate of enantiopure 1,3-butanediol. At this stage, however, we did not feel that it was necessary to pursue an enantioselective synthesis of 1. 

The addition of hydrogen cyanide to a carbonyl group results in the formation of an a-hydroxy nitrile, a so-called cyanohydrin (A, Scheme 6.1) [1]. Compounds of this type have in many instances served as intermediates in the synthesis of, e.g., a-hydroxy acids B, a-hydroxy aldehydes C, fS-amino alcohols D, or a-hydroxy ketones E (Scheme 6.1) [1], In all these secondary transformations of the cyanohydrins A, the stereocenter originally introduced by HCN addition is preserved. Consequently, the catalytic asymmetric addition of HCN to aldehydes and ketones is a synthetically very valuable transformation. Besides addition of HCN, this chapter also covers the addition of trimethylsilyl cyanide and cyanoformate to car-... 

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... 

Homoallylic type alcohols (67), on the other hand, give predominantly cyclopentenones independent of substitution (equation 37). In Ae 3-hydroxyalkyl-substituted systems, presumably allene oxide (68) is the intermediate. Thus it would appear Aat the initial site of allene oxidation is not critical to the success of the reaction. Either precursor (58) or (59) is expected to give the observed stereochemical relationships of the newly formed stereocenters by the concerted mechanism. Finally, Cha has noted that the two intermediates may lead to different stereochemical relationships by the zwitterionic mechanism. This assumes a specific pathway for breakdown of (58) or (59). That stereochemical information is preserved in the reaction is shown by the selective transformations in equation (38). 

To avoid complications with the reactive enolates and to preserve the stereochemistry it has proven practical to employ the derived silyl enol ethers, formed by trapping the enolates with chlorotrialkyl-silane instead of the enolates themselves. The rearrangement of the silyl enol ethers takes place under mild conditions, too, often at room temperature, and exhibits all the characteristics of 3,3-sigmatropic rearrangements, namely high stereoselectivity in the formation of double bonds and stereocenters. 

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. 

Felkin product (69% ds, 2-anti). A (Z)-titanium enolate usually favours the anti-Felkin adduct, and the subsequent Oppolzer synthesis of denticulatins A (see Scheme 9-69) highlights this behaviour (see also Scheme 9-30) however, exceptions can be found (Scheme 9-45). Oxidation of the C3 and Cn hydroxyls of 258, and cyclization, under carefully controlled conditions to preserve the configuration of the Cio stereocenter, then allowed the selective synthesis of denticulatin B. 

The tandem intermolecular-[4 + 2]/intermolecular-[3 + 2] cycloadditions create bicyclic nitroso acetals with up to six stereogenic centers in a predictable fashion (Scheme 16.53). Because both cycloadditions are usually conceited and the geometry of the components is preserved, the relationship between those substituents in the nitroso acetal will also be preserved. For example, in Scheme 16.53 the substituents A and B, as well as E and F in nitroso acetal 237 will take up a cis relationship to each other. However, the relationships B/C, C/D, and D/E are established by the topicity of the cycloaddition events as described below. Upon hydrogenol-ysis, those stereocenters in product 239 are also preserved unless further reactions follow, the most important of which is the loss of the C(6) stereogenic center during reductive alkylation when substituent F is an alkoxy group. 

In most enamine processes, the stereointegrity of the a-carbonyl stereocenters can be preserved because most of the products are kinetically stable in the presence of enamine catalysts. 

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