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

ORGN 571

Manuela Rodriquez, manuela@broad.harvard.edu1, Takuya Uchida, tuchida@fas.harvard.edu1, Alan Provost, aprovost@broad.harvard.edu1, and Stuart L. Schreiber2. (1) Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, (2) Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142
Build/Couple/Pair strategy is a systematic, short and efficient chemical approach which leads to stereochemically and skeletally diverse small molecules. The products of this process bear chemically orthogonal handles promoting further template optimization. The three phases are: Build Phase: building block chemistry; Couple Phase joining building blocks (stereochemical 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 stereochemical control during the pairing phase in which intramolecular Diels-Alder reaction of furans (IMDAF) leaded to highly functionalized endo adducts (as documented by X-ray analysis) with appealing degree of structural diversity. To improve the [4 + 2]-cycloaddition reaction, we investigated the effect of Lewis acid catalysts, high-pressure, mixture of solvents/ionic liquids and microwave technology. The attractive template 6 could be easily biased towards enzymes through functional group-pairing reactions of strategically positioned chemical handles.

 

Materials, Devices and Switches, Metal-Mediated Reactions, Asymmetric Reactions, Total Synthesis, Biologically-Related Molecules and Processes
7:00 PM-9:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- La Louisiane, Blrm. C, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008