Enantioselective Substitutions

Several ligands that have been useful in enantioselective allylic substitution have been mentioned previously in this chapter. In this section, a more detailed presentation of ligands that generate complexes that catalyze enantioselective allylic substitution chemistry are described. 

Some of the ligands that generate highly enantioselective catalysts for allylic substitution with pailadium, 

Dai and co-workers reported a related oxazoline ligand that contains a pendant binaphtholate group that catalyzes the selective formation of branched allylic amines and allylic alkylation products from linear or brandied allylic esters. Helmchen developed the phosphine ligand with a pendant carboxylic acid that is particularly enantioselective for the reactions of aliphatic cyclic allylic acetates.  

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As discussed in CbapL 6, copper-mediated diasteteoselective addition and substitution reactions ate well studied metliods for the construction of chiral centers in organic molecules. Tlie development of coppet-mediated enantioselective substitution reactions, however, is still at an early stage. 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

Scheme 8.8. Enantioselective substitution of oxazolin-2-yl and thiazolin-2-yl allyl thioethers.

Complex 2b also catalyzes the addition of imidazoles, benzimidazoles, and several purines to methyl allylic carbonates (Scheme 26) [76]. These reactions occurred with good yields and excellent enantioselectivities. -substituted heterocycles are found in a number of compounds that exhibit a range of biological activity. The syntheses of several pharmacologically active compounds were conducted with yields that were improved over those published previously. 

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