Chemoselective Cleavage

CHEMO- AND REGIOSELECTIVITY ENHANCEMENT IN SOLID-SUPPORTED REACTIONS 

It can be concluded that solid supports have been successfully employed in order to enhance the selectivity or organic transformations and to facilitate the isolation of desired products from multistep reaction sequences. Several different approaches to take advantage of these opportunities have been discussed in this chapter, without comprehensively reviewing every reaction that displays an enhanced selectivity when conducted on a solid support. The presented examples should allow researchers to gauge if solid-supported chemistry has the potential to solve selectivity issues encountered in their research. 

Blanco-Urgoiti, L. Anorbe, L. Perez-Serrano, G. Dominguez, J. Perez-Castells, Chem. Soc. Rev. 2004, 33, 32. 

Garibay, P. Vedso, M. Begtmp, T. Hoeg-Jensen, J. Comb. Chem. 2001, 3, 332. 

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Nal, CeCl3 7H20, CH3CN, rt, 0.5-21 h, 84-96% yield. Chemoselective cleavage of ketone derivatives is observed in the presence of aldehyde derivatives, and enone ketals are cleaved in the presence of simple ketone ketals. 

In continuation of our efforts to explore the utility of the SAMP/RAMP hydra-zone methodology, we developed the first asymmetric synthesis of a-phosphino ketones via formation of a carbon-phosphorus bond in the a-position to the carbonyl group [70]. The key step of this asymmetric C—P bond formation is the electrophilic phosphinylation of the ketone SAMP hydrazone 87, giving rise to the borane-adduct of the phosphino hydrazone 88 with excellent diastereoselectiv-ity (de = 95-98%). Since these phosphane-borane adducts are stable with respect to oxidation, the chemoselective cleavage of the chiral auxiliary by ozonolysis leading to the a-phosphino ketones (R)-89 could be accomplished with virtually no racemization. Using RAMP as a chiral auxiliary, the synthesis of the enantiomer (S)-89 was possible (Scheme 1.1.25). 

The potency of this strategy relies ultimately in the sturdiness, and yet the possibility for chemoselective cleavage, of pentenyl arabinofuranosides (e. g. 175) [90]. Its value has been demonstrated recently with the synthesis of the pentenyl glycoside of mannose-capped dode-... 

Chemoselective cleavage of anomeric thioacetates to the thioaldose in the presence of O-acetyl groups is possible under various conditions, e. g., methanolic sodium methoxide at low temperatures [121], phenylmercury acetate followed by demercuration [122], 2-aminoethanethi-ol [123], or hydrazinium acetate [124], and these methods have therefore often been used in the synthesis of thiooligosaccharides (O Sect. 3.2.1). As mentioned, glycosyl thioacetates can also be prepared from the 2-acetoxyglycal derivative (see Scheme 24). 

Since the electrophilic ozone preferentially attacks a more nucleophilic double, it is possible to achieve chemoselective cleavage in compounds containing two or more double bonds by limiting the amount of ozone. The relative reactivity of double bonds toward ozone decreases in the following order ... 

Scheme 33 illustrates the use of two standard persistent auxiliaries. The Evans oxazolidinone 33-1 [83] is highly versatile, i.e., suitable for enolate reactions and double bond additions alike. In the enolate alkylation case [reaction (99)] the high diastereoselectivity depends on the formation of a chelate 33-2 which fixes the reaction site in a defined conformation in which one of the diastereofaces is efficiently shielded. The removal of the auxiliary requires the chemoselective cleavage of the exo cyclic amide bond which is sometimes difficult to achieve. In boron mediated aldoltype additions [Scheme 34, reaction (100)] no chelate can be formed so that the extremeley high diastereoselectivity with which the syn-adduct 34-1 is formed must be due to some other effect, presumably allyl 1,3-strain on the stage of the enol borinate 34-1. 

The synthesis of penems has been the object of intensive research in the last decade. Stereoselective synthesis of azetidinones, chemoselective cleavage of the thiazolidine ring of penicillins, hydroxy-ethylation at the lactam a carbon, and penem annulation reactions are the important issues addressed in this work. By confronting possibilities with achievements, a comprehensive but readable survey of this chapter of antibiotic chemistry is attempted. 

B. Carboni, L. Toupet, G. Dujardin, Chem. Commun. 2003, 276-277. A novel diastereoseleetive route to a-hydroxyalkyl dihydropyrans using an hetero Diels-Alder/allylboration sequence, (h) B. B. Toure, D. G. Hall, Angew. Chem. Int. Ed. 2004, 43, 2001-2004. Three-component sequential aza[4+2] cycloaddition/allylboration/retro-sulfinyl-ene reaetion a new stereocontrolled entry to palustrine alkaloids and other 2,6-disubstituted piperidines, (i) B. B. Toure, D. G. Hall, J. Org. Chem. 2004, 69, 8429-8436. Design of a nonreductive method for chemoselective cleavage of hydrazines in the presence of unsaturations application to a steieoconveigent three-component synthesis of (-)-methyl palustramate. 

Others have also employed this metathetical cleavage approach toward the chemoselective cleavage of oleflnic substrates. For example, a similar approach was taken using an octenediol-based linker system 26 toward the cleavage of saccharides 27 (Scheme 6.6). ... 

Although the reactivity with different carbon electrophiles has been widely documented, there are not many examples of synthetically useful carbon-sulfur bond formation at the thiazole carbons. For instance, the regio- and chemoselective cleavage of the carbon-silicon bond of 2-TST (1) by trifluoromethyl-sulfenyl chloride was reported to take place at —78 °C. The expected 2-(trifluoromethylthio)thiazole was obtained with satisfactory 3uelds (eq 27). ... 

SCHEME 23.1 Chemoselective cleavage of trityloxy ethers using boron trichloride. 

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