Transannular Diels-Alder Reaction Catalyzed by Chiral Oxazaborolidine

Key words

transannular Diels-Alder reaction - oxazaborolidines - macrocycles

Significance

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.

Comment

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.