Organocatalytic Enantioselective [4+3]-Cycloadditions of Azaoxyallyl Cations with 2-Aminophenyl Enones

The first organocatalytic asymmetric [4+3]-cycloaddition of 2-aminophenyl alpha,beta-unsaturated carbonyls with in situ generated azaoxyallyl cations was developed, and enantioenriched functionalized seven-membered 1,4-benzodiazepine-3-ones were obtained in good yields and with excellent enantioselectivities. This approach was also extended to the first asymmetric [4+3]-cycloaddition of delta-hydroxy alpha,beta-unsaturated carbonyls, affording 1,4-oxazepanes in one step under mild conditions. Several of the novel adducts demonstrated promising bioactivity in the prevention of peripheral nerve degeneration.

Automated summary

The first organocatalytic asymmetric [4+3]-cycloaddition of 2-aminophenyl alpha,beta-unsaturated carbonyls with in situ generated azaoxyallyl cations was successfully developed, leading to the synthesis of enantioenriched functionalized seven-membered 1,4-benzodiazepine-3-ones. This method was also extended to the first asymmetric [4+3]-cycloaddition of delta-hydroxy alpha,beta-unsaturated carbonyls, providing 1,4-oxazepanes in one step under mild conditions. Some of the novel adducts showed promising bioactivity in preventing peripheral nerve degeneration.