Pd-Catalyzed [3+2]-Dehydrogenative Annulation Reactions

The significance of cross dehydrogenative couplings has increased considerably in recent years. This article revisits the [3+2] C-C/N-C, C-C/O-C and C-C/C-C annulation strategy, recently reported by our group, according to a Pd(II) catalyzed dehydrogenative variant. Our original report relied on Pd(0) catalysis, using & alpha;,& beta;-unsaturated-& gamma;-oxy carbonyls as bis-electrophiles and resonance-stabilized acetamides or 3-oxoglutarates as C/N and O/C or C/C bis-nucleophiles, respectively. In this more modern and straightforward Pd(II)-catalyzed dehydrogenative approach, & beta;,& gamma;-unsaturated carbonyl derivatives replace & alpha;,& beta;-unsaturated-& gamma;-oxy carbonyls as bis-electrophiles. Our study includes experimental optimization and showcases the synthetic versatility in the formation of diverse heterocyclic structures, such as bicyclic lactams, furo-cycloalkanones and bicycloalkane-diones. Furthermore, a mechanism is proposed to elucidate the underlying processes involved in these reactions. Pd-catalyzed [3+2] annulations go dehydrogenative: a new protocol enables the Pd(II)-catalyzed [3+2] annulation between resonance-stabilized acetamides (or 3-oxoglutarates) and & beta;,& gamma;-unsaturated cyclic carbonyl derivatives. This dehydrogenative strategy represents a more atom- and step- economical version than the corresponding Pd(0)-catalyzed redox-neutral couplings previously studied by our group, enabling the straightforward construction of a number of heteropolycyclic structures.image