Relayed introduction

G. S. Bethell and R. J. Ferrier, The relayed introduction of alkylthio-groups into carbohydrates derivatives A novel synthesis of amicetose, J. Chem. Soc. Perkin / (1993) 1400-1405. 

Despite the planar conformation of nitrogens, several possibilities are available for the introduction of chirality. It is possible to prepare benzim-idazolylidenes, triazolylidenes, imidazolylidenes or unsubstituted-backbone imidazolinylidenes with a stereogenic center on one or two N-substituents (carbenes I and II). The other possibility is to relay the imidazolinylidenes backbone stereogenecity via the N-substituents or to combine stereogenic N-substituents with a chiral backbone (carbenes III or IV). It is at least possible to prepare bis-carbenes of type V with one (or two) stereogenic link between the two carbenes (Fig. 7). 

This has been nicely demonstrated and exploited by Woodward s syntheses of bicyclic systems of the penem type. They are typically formed in moderate to good yields upon refluxing the requisite substituted starting -lactams in toluene or xylene for extended periods. The key step is the introduction of the ylidic moiety into the 1-position of a 4-functionalized azetidin-2-one which itself can be obtained as a relay substance by degradation of natural penicillins or from easily available 4-acetoxyazetidin-2-one. The ester ylide function is built up by reaction first with alkyl hemiacetals of glyoxylates to give a hemiaminal and then successive replacement of the OH-group of the latter by Cl with thionyl chloride and finally of the chlorine atom by triphenylphosphane under basic conditions. 

Another significant application of the concept of relay deprotection comes from a synthesis of the antitumour macrolides Cryptophycins 1 and 8.644 The penultimate step required a mild method for the introduction of the epoxide ring in the side chain [Scheme 4.340]. A variant of a direct method for the conversion of diols to epoxides developed by Kolb and Sharpless645 was cleverly adapted to the case at hand. Thus diol 340.1 was treated with the 4-azido-1 1,1-tri-methoxybutane in the presence of chlorotrimethylsilane to give the cyclic orthoester 340.2, which decomposed under the reaction conditions with loss of Me SiOMe to give the chlorohydrin ester 3403 (inversion). Selective reduction... 

The selectivity of the radical relay chlorination is striking. In the case of the enone (13 Sdieme 18), and in related compounds with A-ring dienones, the m-iodobenzoate template at C-17 directs chlorination to C-9 and not to die preexisting functional groups of (13). The selective chlorination of C-9 seems to be quantitative, although in the first report the A "Lalkene (14) was isolated in only 77% yield. Later work has shown that the overall introduction of this double bond can have yields in the 90-93% range, and good yields for this reaction have also been reported from another laboratory. Template-directed radical relay chlorination on the a-face of steroids has also been successful in the a/b cu-coprostanol steroid series,and in the cholestanol series with iodophenyl templates linked by amide, ether, or sulfonate functions rather than carboxylic esters. ... 

The use of sulfones as relays can be extended to the introduction of a large variety of appendages. Vinylation is especially important because of the general difficulty of performing vinylations on sp centres using transition metal chemistry. The examples assembled in Scheme 14 thus acquire a special significance [31]. It is also noteworthy that both the allylation and vinylation reactions, as well as some of the more exotic transformations discussed later in this section, all of which employ sulfone-based reagents, can be applied not just to aliphatic xanthates but also to iodides and tellurides [29,37-44]. 

The studies at solid electrodes showed that the introduction of delocalized conjugated units and aromatic groups in a molecular monolayer affects the ET rate (32b). The SECM has been used to compare the ET rate across C-16 and similarly sized dipalmytoyl phosphocholine (DPHC) (Fig. 13). The latter phospholipid has a fra .s,/ra/7.y,fram-l, 6-diphenyl-l,3,5-hexatrieiie chain. This prototype of polyene systems has been previously used as a fluorescent probe (45). Its nonpolar hydrocarbon structure is compatible with membranes and can serve as an electron relay in a blocking monolayer film. In addition to its conjugated chain, DPHC also contains one saturated C-16 alkyl chain, which is easily incorporated into the C-16 monolayer. 

Summary. It is pointed out that, in order to avoid misconceptions, the introduction of ions is very important ions have been dealt with as basic particles of matter according to Dalton s atomic model (see Chap. 5). In order to understand the charges of ions and the change of ions and atoms by electron transfer, the differentiated atomic model with nucleus and electron shells should be introduced. With the assistance of a clear terminology, it is easy to formulate half-reaction for the oxidation and reduction steps, the number of electrons to be transferred can be clearly recognized. Finally, if mental models -for instance, from involved atoms or ions in Galvanic cells or in batteries - are relayed and drawn by the students themselves, then they could more easily see through the redox processes or even perhaps be able to repeat them independently. In all explanations, one should pay attention that the observations should be done at the substance level, but that the interpretations and discussions of reaction equations should consequently take place at the level of the smallest particles as atoms, ions and molecules. 

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