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Transannular Diels-Alder Reaction Catalyzed by Chiral OxazaborolidineContributor(s):Hisashi Yamamoto, Joshua N. Payette
Harvard University, Cambridge, USA
Asymmetric Catalysis of the Transannular Diels-Alder Reaction
Science 2007, 317: 1736-1740
22 November 2007 (online)
transannular Diels-Alder reaction - oxazaborolidines - macrocycles
While catalytic, asymmetric intermolecular and intramolecular Diels-Alder reactions are well established, the present paper provides the first report of the corresponding transannular Diels-Alder (TADA) reaction. A survey of various Lewis and Brønsted acid catalysts revealed that oxazaborolidine 1 was the only catalyst able to promote cyclization of macrolactone 2 (n, m = 1). Subsequently, various-sized macrocycles containing α,β-unsaturated lactone or ketone dienophilic moieties were cyclized to furnish tricyclic endo products containing medium-to-large-sized rings in good to excellent diastereo- and enantioselectivities.
This is a creative application of Corey’s proline-derived oxazaborolidine system into a hitherto unexplored area of asymmetric catalysis. While catalyst 1 is often seen with an o-tolyl boron substituent, it was found that substitution with 2-FC6H4 provided TADA products in significantly higher ee values (10% vs. 90%). Also, chiral macrocyclic substrates could undergo cycloaddition to give products with significantly higher diastereomeric ratios than those obtained under thermal or conventional Lewis acid catalysis. To illustrate the utility of this process in natural product synthesis, 2 was cyclized to give 3, which was eventually transformed into 11,12-diacetoxydrimane.