Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

作者: A. N. Thadani , A. R. Stankovic , V. H. Rawal

DOI: 10.1073/PNAS.0308545101

关键词: Enantioselective synthesisEnantiomeric excessCatalytic cycleHydrogen bond catalysisChemistryEnantiomerChemical synthesisDieneOrganic chemistryCatalysis

摘要: Like molecules of life (e.g., proteins and DNA), many pharmaceutical drugs are also asymmetric (chiral); they not superimposable on their mirror images. One image form (enantiomer) a drug can have desirable activity, the other not. Consequently, development methods for selective synthesis one enantiomer is great scientific economic importance. We report here that simple, commercially available chiral alcohol, α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), catalyzes all-carbon Diels–Alder reactions aminosiloxydienes substituted acroleins to afford products in good yields high enantioselectivities (up 92% enantiomeric excess). It remarkable promoted by hydrogen bonding, ubiquitous “glue” helps keep water together holds up 3D structures proteins. Hydrogen bond catalysis little used chemical synthesis, wherein most complexes Lewis acidic metal salts coordinated ligands. As it does enzymes, bonding only organizes TADDOL into well defined conformation, but, functioning as Bronsted acid catalyst, activates dienophile toward reaction with diene. The gross structure has been found profound influence both rate enantioselectivity cycloadditions. These structure–function effects rationalized evaluating conformation adopted TADDOLs crystal state. suggested π,π-stacking plays an central role overall catalytic cycle, particular, enantioselective step.

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