Clearability

Some examples of directly clearable (CL) and non-clearable (nCL) stereocenters with respect to a particular transform follow. 

Relationships between stereocenters vary between two extremes. On the one hand, stereocenters may interact strongly in a spatial sense if they are directly joined, proximate to one another, or part of a compact rigid-ring structure. On the other hand, two stereocenters which are remote from one another and/or flexibly connected may be so independent that one cannot be used to provide substrate spatial control for the other. Nonetheless, this latter type of stereorelationship may still be clearable if the target molecule can be disconnected to divide the two stereocenters between two precursors or if an appropriate enantioselective transform is available. 

Stereocenters in a ring which can be severed by a disconnective transform, but which are not part of the retron, can be eliminated prior to disconnection if they are clearable. Removal of such stereocenters may convert a non-strategic bond into a strategic one. Stereocenters should also be cleared if that sets up the retron for a disconnective transform. Such strategic stereocenter eliminations commonly involve transforms which remove a 3 ° or 4 ° stereocenter to generate C=C (endo- or exocyclic), C=0 or C=N. Elimination of two clearable vicinal stereocenters to generate C=C retrosynthetically is strategically indicated whether or not that leads to a disconnectable retron. 

These strategies guide the retrosynthetic conversion of 272 to 278 and the further conversion of 278 via 279 to 282. The r-butyl substituent actuates the clearability of the stereocenters in 279. Further retrosynthetic simplification as dictated by basic FG-, stereochemical and topological strategies then leads from 280 to 281 and to 282, a previously described substance. The successful synthesis followed closely the above outlined retrosynthetic scheme. An enantioselective process was devised for the synthesis of 281 from 282 (see Section 10.12).67, 83... 

Clearable Stereocenter(s). Stereocenter(s) which can be eliminated retrosynthetically by application of a transform with stereocontrol (stereoselectivity). 

RP-HPLC found application in the monitoring of the alkali hydrolysis kinetics of alkali-clearable azo disperse dyes containing a fluorosulphonyl group. The chemical structures of dyes included in the experiments are shown in Fig. 3.85. Samples for RP-HPLC analysis were neutralized to pH 4.0 - 4.5 with diluted HC1 mixed with five volumes of ACN and injected without any other sample preparation step. Separation was carried out in an ODS column at ambient temperature. The isocratic mobile phase consisted of ACN-water (80 20, v/v) and dyes were detected at their absorption maxima. HPLC measurements indicated that dyes are easily hydrolysed under relatively mild alkaline conditions, and the hydrolysis follows a pseudo first-order kinetics [148],... 

Various liquid chromatographic methods have found application in the control of the synthesis of new dye molecules. Thus, an alkali-clearable azo disperse dye with a fluorosulphonyl group was synthesized and it stability was checked by RP-F1PLC. The synthesis route is depicted in Fig. 3.133. The purity control and the hydrolysis rate of the new dye was followed by RP-F1PLC using an ODS column and an ACN-water (80 20, v/v)... 

J. Koh, Alkali hydrolysis kinetics of alkali-clearable azo disperse dyes containing a fluorosulpho-nyl group and their fastness properties on PET/cotton blends. Dyes Pigm., 64 (2005) 17-23. 

J. Koh and A.J. Greaves, Synthesis and application of an alkali-clearable azo disperse dye containing a fluorosulfonyl group and analysis of its alkali-hydrolysis kinetics. Dyes Pigm., 50 (2001) 117-126. 

A good example of clearable and non-clearable stereocentres is found in the two following stereoisomers of bicylo[3.3.0]octan-2-one, in which the shape of the molecule forces the attack of the nucleophile to the carbonyl group from the convex face (attack at the (3-face). 

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