| Natural cinchona alkaloids and their derivatives have a rich and successful history of catalyzing a wide range of organic reactions in a highly efficient and stereoselective fashion. Specifically, our group has shown that several derivatives of these natural products are excellent catalysts for asymmetric Diels-Alder reactions and [4+2] additions. A particularly noteworthy feature of these catalysts, however, is that they are able to engage relatively unreactive dienes, such as 2-pyrones, and dienophiles, such as simple enones and beta-aliphatic nitroalkenes, in these cycloaddition reactions. This makes them an important tool for any synthetic chemist to have at their disposal.;We have developed the first highly enantioselective Diels-Alder reaction of 3- hydroxy-2-pyrones with simple alpha,beta-unsaturated ketones via catalysis by an easily accessible bifunctional cinchona alkaloid with an acid cocatalyst. The methodology allows facile access to a wide range of highly enantioenriched aliphatic and aromatic substituted bicyclic compounds, which are useful synthetic building blocks. The synthetic utility of these products was further demonstrated by their transformation into chiral dihydrophenols via a simple decarboxylative retro-Diels-Alder reaction.;We have also developed the first asymmetric [4+2] addition reaction of 3- hydroxy-2-pyrones with beta-aliphatic nitroalkenes. beta-aliphatic nitroalkenes are much less reactive compared to their aromatic counterparts, however, under the catalysis of a novel bifunctional cinchona alkaloid, they readily reacted to produce a wide variety of highly enantioenriched aliphatic substituted bicyclic compounds. Furthermore, mechanistic studies performed through the analysis of 13C kinetic isotope effects proved that the cycloaddition proceeds through a stepwise mechanism rather than a traditional concerted Diels-Alder process. |
