Build/couple/pair strategy: From nonchiral molecules to unbiased scaffolds, a methodological approach for the optimization of microwave-assisted intra-molecular Diels-Alder reaction of furans

Build/Couple/Pair strategy is a systematic, short and efficient chem. approach which leads to stereochem. and skeletally diverse small mols.  The products of this process bear chem. orthogonal handles promoting further template optimization.  The three phases are: Build Phase: building block chem.; Couple Phase joining building blocks (stereochem. diversity); Pair Phase: functional group pairing reactions (skeletal diversity).  During the couple phase organo-catalyzed multicomponent reactions achieved every possible stereoisomeric outcome.  These stereogenic centers provided the complete stereochem. control during the pairing phase in which intramol. Diels-Alder reaction of furans (IMDAF) leaded to highly functionalized endo adducts (as documented by X-ray anal.) with appealing degree of structural diversity.  To improve the [4 + 2]-cycloaddn. reaction, we investigated the effect of Lewis acid catalysts, high-pressure, mixt. of solvents/ionic liqs. and microwave technol.  The attractive template 6 could be easily biased towards enzymes through functional group-pairing reactions of strategically positioned chem. handles.