Synthesis of Substituted Benzaldehydes via a Two-Step, One-Pot Reduction/Cross-Coupling Procedure

The synthesis of functionalized (benz)aldehydes, via a two-step, one-pot procedure, is presented. The method employs a stable aluminum hemiaminal as a tetrahedral intermediate, protecting a latent aldehyde, making it suitable for subsequent cross-coupling with (strong nucleophilic) organometallic reagents, leading to a variety of alkyl and aryl substituted benzaldehydes. This very fast methodology also facilitates the effective synthesis of a C-11 radiolabeled aldehyde. Aluminum-ate complexes enable transmetalation alkyl fragments onto palladium and subsequent cross-coupling.