Cyclocondensation, chelate-controlle

Furthermore, the chelation-controled facially selective cyclocondensation of chiral alkoxy aldehyde 194 with diene mixture 195 in the presence of magnesium bromide in benzene gave the carbon-linked disaccharide (196) as a single product in 79% yield (Scheme 28). 

Since the investigations which used ZnCb and BF3-OEt2 as catalysts, other Lewis acids have been shown to catalyze the cyclocondensation reaction. MgBr2, for example, was used by Pearson and Danishefsky to add the power of chelation control to the reaction. When chiral a-alkoxy aldehydes are condensed with dienes under the influence of MgBr2, products derived from an ACF transition state predominate. The chelation of the metal by the a-alkoxy group of the aldehyde forces the aldehyde side chain to occupy the same side of the aldehyde as the metal. The diene, therefore, can attack the aldehyde from the least hindered exo face giving rise to the trans-KC product (Scheme 5). When an aldehyde is used that cannot form a chelate to the metal (such as benzaldehyde) syn (endo) selectivity is observed. 

The use of simple aryl or alkyl ketones in the synthesis of a variety of substituted S-lactones via Lewis acid-catalyzed cyclocondensations has been reported (Midland and Graham, 1984). In addition, it was shown that changes in substitution pattern on the diene (1,1-dialkoxy- in the case of Brasard s diene, single alkoxy substitution at the 1-position of Danishefsky s diene) were reflected in changes in diastereoselec-tivity induced by particular Lewis acids. Europium(III) catalysts improved diastereoselectivity in the cyclocondensation of Brasard s diene, implying a chelation-controlled addition that was much more efficient than additions catalyzed by zinc chloride or boron trifluoride etherate. 

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