Applications of the β-azidonation reaction to organic synthesis.: α,β-enones, conjugate addition, and γ-lactam annulation

The P-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant beta-elimination to give 3. Table 1 lists a number of examples of the direct conversion of a TIPS enol ether into the corresponding alpha,beta-enone via a beta-azido TIPS enol ether. The beta-azido group can be ionized with Me3Al or Me2AlCl and the intermediate enonium ion trapped by a variety of nucleophiles such as an allylstannane, electron-rich aromatics, TMS enol ethers, Et2AlCN, Me2AlCCR, Me4AlLi, and vinylaluminum reagents to give the products listed in Table 2. The diastereoselectivity of the reaction of a 4-substituted enonium ion with indole shows an unusual increase of selectivity with increasing temperature. Reduction of the azide 2 provides access to beta-amino TIPS enol ethers 5, which, for example, can be converted into a cinnamide derivative and cyclized via a putative "ene" process into a gamma-lactam.