Periselectivity in the aza-Diels-Alder Cycloaddition between α-Oxoketenes and N-(5-Pyrazolyl)imines: A Combined Experimental and Theoretical Study

The thermal 6 pi aza-Diels-Alder cycloadditions between alpha-oxoketenes, in situ derived from a thermally induced Wolff rearrangement of 2-diazo-1,3-diketones, and N-(5-pyrazolyl)imines as prototypical electron-rich 2-azadienes lead to two distinct sets of products, essentially as a function of the nature of the alpha-oxoketenes involved. For instance, cyclic five-membered alpha-oxoketenes lead preferentially to spiro hydropyridin-4-ones, which involves the alpha-oxoketenes as the 2 pi partners at their C=C double bond and the N-(5-pyrazolyl)imines as the 4ir partners at their 2-azadiene moiety. In contrast, other cyclic and acyclic alpha-oxoketenes lead preferentially to 1,3-oxazin-4-ones, which now involves the alpha-oxoketenes as the 4R - partners at their 1-oxadiene moiety and the N-(5-pyrazolyl)imines as the 2 pi partners at their C=N double bond. A computational modeling study using DFT methods allowed rationalizing this change of periselectivity: the formation of spiro hydropyridin-4-ones is under thermodynamic control while the formation of 1,3-oxazin-4-ones is kinetically controlled, and slightly thermodynamically disfavored in the five-membered ring series. The competing cyclodimerization of the alpha-oxoketenes is also studied in detail.