Applications of 2,3-Diketoesters in Organic Synthesis and Stereoselective Transformations

Abstract

Dimethyldioxyrane oxidation of δ-hydroxy-α-diazo-β-ketoesters that are prepared by zinc triflate catalyzed Mukaiyama-aldol condensation of methyl diazoacetoacetates with aldehydes, occurred in quantitative yield to form dihydrofuranols that undergo acid catalyzed dehydration under mild conditions to generate 3-methoxyfuran-2-carboxylates in good yield. Oxidation of ζ-keto-α-diazo-β-ketoesters that are formed by zinc triflate catalyzed Mukaiyama-Michael condensation of methyl diazoacetoacetate enones procduced their 2,3,7-diketoester derivative in quantitative yield. The intramolecular acid catalyzed aldol cyclization of 2,3,7-triketoesters provides highly functionalized cyclopentanones with good diastereoselectivity in high overall yields via kinetically controlled and stereodivergent catalytic processes. Lewis acid catalysis gives high selectivity for the 1,3-anti tetrasubstituted cyclopentanones, whereas Brønsted acid catalysis produces the corresponding 1,3-syn diastereomer. The first enantioselective transformation of 2,3-diketoesters was demonstrated in carbonyl-ene reactions catalyzed by Cu((S,S)-tert-Bu-box)2 generating chiral α-functionalized-α-hydroxy-β-ketoesters in up to 94% yield and 97% ee. The suggested mode of activation is bi-dentate coordination between copper and the oxygen atoms of the two keto-carbonyl groups. The 2,3-diketoesters are conveniently accessed from the corresponding α-diazo-β-ketoester, and catalyst loading as low as 1.0 mol % is achieved.