Synfacts 2007(12): 1269-1269  
DOI: 10.1055/s-2007-991343
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Transannular Diels-Alder Reaction Catalyzed by Chiral Oxazaborolidine

Contributor(s):Hisashi Yamamoto, Joshua N. Payette
E. P. Balskus, E. N. Jacobsen*
Harvard University, Cambridge, USA
Asymmetric Catalysis of the Transannular Diels-Alder Reaction
Science  2007,  317:  1736-1740  
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Publication History

Publication Date:
22 November 2007 (online)


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.