Practical Synthesis of Chiral Building Blocks for Molecular Library of Organic Compounds

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Enantiomerically enriched mono-protected derivatives of 2-substitued 1,3-propanediols are useful chiral building blocks which have been frequently employed in natural product synthesis. One of the moststraightforward methods for their preparation involves asymmetric desymmetrization of parent prochiral propanediols or their derivatives and enzyme-mediated transesterification or hydrolysis has been used for this purpose. A few reports have been appeared on nonenzymatic approach which could be of wide generality allowing to prepare a tailor-made chiral building blocks appropriate for the molecular library of organic compounds. Nonenzymatic desymmetrization of 2-substitutcd 1,3-propanediols leading to the enantiomerically enriched 3-benzyloxy-1-propanols was achieved by using from N-tosyl-(L)-naphthylalanine-derived oxazaborolidinone-mediated enantioselective ring-cleavage reaction of the dioxane acetal derivatives as a key reaction. The method was found to be highly effective for propanediols bearing a relatively bulky substituent at the 2 position. Further survey of reaction conditions to reduce the amount of the oxazaborolidinone revealed that the use of diethyl ether as an additive is effective. In the presence of the additive, highly selective ring-cleavage reaction was realized even when 0.5 equiv of oxamborolidinone was employed. In addition to this, the use of dimethylsilyl ketene S,O-acetal as a nucleophile is also found to be effective for the catalytic enantioselective ring-cleavage reaction.