Stereochemical Strategies—Polycyclic Systems

At the opposite end of the topological spectrum are stereocenters in terminal rings that are eligible for disconnection. Stereocenters in such rings which are elements of a retron or partial retron for a ring disconnective transform should be cleared preferentially by application of that transform. Examples 156, 157 and 158 illustrate such stereocenters (starred). 

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. 

Reduce stereochemical complexity and molecular size concurrently by applying diastereoselective or enantioselective transforms which are also disconnective. 

Apply stereoselective transforms to clear stereocenters by removal or interchange of functional groups with the establishment of the retron for a disconnective transform, especially with retrosynthetic generation of the core groups C=C, C=0 or C=N. 

Apply stereoselective, FG-transposing transforms which convert a 1,4- or other l,n-stereorelationship into a 1,2-stereorelationship and allow the operation of disconnective transforms. 

Apply disconnective transforms which do not alter stereocenters but which separate stereocenters by molecular cleavage. 

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When stereochemical complexity is embedded in topological complexity, such as in complex polycyclic structures, the stereochemical strategies which are most effective are those which are linked to both complexities. A decidedly different strategic approach is appropriate for topologically simpler systems. 

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