Substrate controlled directing groups

Alternatively, substrate control of diastereoselectivity can rely on attractive catalyst substrate interactions. This requires in general special functional groups which allow for a directed hydroformylation, which is summarized in Sect. 6 (vide infra). 

Scheme 1. Concept of a specifically introduced reagent-directing group into an organic substrate as a selectivity control instrument.

These results can be understood on the basis of a Felkin-Ahn transition state arrangement for the BF3 experiments and a chelation transition state arrangement with MgBt2 as the promoter. The matched transition states are pictured in Fig. 12. The latter additions are strongly substrate-controlled, which accounts for the formation of (Z) products as the minor adducts. Evidently the methyl substituent is an efficient facially directing group in the chelated aldehyde substrate. 

Both these syntheses of oleandolide relied upon substrate-controlled aldol reactions of dipropionate reagents (5)-18 and ent-25. Substrate control is also evident in the way both groups incorporated the exocyclic epoxide with greater than 95% ds. While we chose to use macrocyclic control for this transformation, the Evans synthesis used acyclic stereocontrol and the directing influence of a nearby hydroxyl group. 

Peracids m-CPBA and CF3CO3H have been used in epoxidations of substrates with two mnable allylic directing groups expected to direct the peracids to opposite faces of the alkene. Control of face selectivity was observed and attributed to the different binding abilities of the two peracids to the various allylic functionalities, carbamate on one side of the alkene and alcohol, methyl ester, acetate, trifluoroacetate, or TBS-ether on the other. The conversion of A-mono-protected and A-di-protected cyclopent-... 

An important strategy for achieving substrate control is the use of chiral auxiliaries, which are structures incorporated into reactants for the purpose of influencing the stereochemistry. Two of the most widely used systems are oxazolidinones " derived from amino acids and sultams derived from camphorsulfonic acid. These groups are most often used as carboxylic acid amides. They can control facial stereoselectivity in reactions such as enolate alkylation, aldol addition, and Diels-Alder cycloadditions, among others. The substituents on the chiral auxiliary determine the preferred direction of approach. 

Substrate Controlled Directing Groups in Cross-Dehydrogenative Coupling 177... 

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