Anti aldols, summary

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

In summary, boryl enolate 38 can be obtained via in situ O-borylation of N-propionylsultam 37 and converted to aldol product 40 upon treatment with aliphatic, aromatic, or a,/l-unsaturatcd aldehdyes at - 78°C in the presence of TiCU- As aldol product 40 can normally be obtained in crystalline form, in most cases diastereomerically pure anti- Ao 40 can also be obtained after the recrystallization. 

In summary, several factors determine the stereochemical outcome of aldol addition reactions. The diastereochemical preference of the syn or anti isomer is determined by the configuration of the enolate and the orientation of the aldehyde within the TS. Chirality in either reactant introduces another stereochemical influence. The use of chiral auxiliaries can promote high facial selectivity in the approach of the aldehyde and thus permit the preparation of enantiomerically enriched products. The same outcome can be achieved using chiral Lewis acids as reaction catalysts. 

In summary, 1,3-diols are prominent motives in polyketides, and they can be constmcted by various advanced methods. A practical access to 1,3-diols starts often with an aldol reaction. This aldol reaction can already construct a 1,3-diol if one hydroxyl group is already present in the starting material. Alternatively, syn- or anti-selective reductions of carbonyl groups offer an easy to predict stereoselective way to 1,3-diols. As we have seen in particular in the synthesis of roxaticin, direct reduction of diketones or p-keto esters proves an efficient entry into 1,3-diol segments. 

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