transannular Diels-Alder reaction - oxazaborolidines - macrocycles
Significance
<P>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.</P>
Comment
<P>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-FC
6H
4 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.</P>
