Periselectivity in the Aza-Diels–Alder Reaction of 1-Azadienes with α-Oxoketenes: A Combined Experimental and Theoretical Study

Marc Presset,Guillaume Dauvergne,Jean Rodriguez,Yoann Coquerel,Michel Rajzmann

doi:10.3390/molecules25204811

Marc Presset, Guillaume Dauvergne + Show 3 more

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https://doi.org/10.3390/molecules25204811

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Abstract

Inversions in the periselectivity of formal aza-Diels–Alder cycloadditions between α-oxoketenes generated by a thermally-induced Wolff rearrangement and 1-azadienes were observed experimentally as a function of the α-oxoketene and the 1-azadiene, as well as the reaction temperature and time. Some unexpected inversion in the diastereoselectivity was observed, too. These variations in selectivities were fully rationalized by computational modeling using density functional theory (DFT) methods.

Highlights

Introduction αOxoketenes [1,2,3,4,5,6] were first employed in organic synthesis in 1902 with the pioneering work of Ludwig Wolff on 2-diazo-1,3-dicarbonyl compounds [7]
2-diazo-1,3-dicarbonyl compounds extruding nitrogen gas [13,14]. α-Oxoketenes 1 are electrophilic species that most commonly react with imines through formal aza-Diels–Alder cycloadditions involving the α-oxoketenes as 4π reaction partners (1-oxadienes) and the imines as the 2π reaction partners to give 1,3-oxazin-4-ones of type 4 (Scheme 1) [1,2,3,4,5,6,15]
We previously reported the formal aza-Diels–Alder cycloaddition between the α,β-unsaturated imine the five-membered cyclic α-oxoketene

Summary

Results and Discussion

We previously reported the formal aza-Diels–Alder cycloaddition between the α,β-unsaturated. The same reaction conducted with azadiene 2f provided only the 1,3-oxazin-4The influence the nature of the α-oxoketene on periselectivity was evaluated experimentally. It was shown that α-oxoketene 1d derived from the Wolff rearrangement of methyl 2-diazoacetylacetate reacted with the 1-azadiene 2i at 160 ◦ C to give the 1,3-oxazin-4-one 4i in 43% yield, and no reaction at higher temperature was attempted. The six-membered cyclic α-oxoketene 1b derived from the thermal Wolff rearrangement of 2-diazocycloheptan-1,3-dione was reacted with 1-azadiene 2g at 160 °C to afford cleanly the 1,3-oxazin-4-one 4g, while the same reaction mixture at 200 °C for a prolonged time previously afforded the spiro hydropyridin-2-one 3g in 53% yield (Scheme 3a) [16]. Free Gibbs generally computed at 298 Kto corresponding to of isolation of the of products, and at the temperature kinetically meaningful the temperature isolation of the products, andreaction at the for reaction temperature for steps

Free the α-oxoketene

Free at at

Experimental Section

Conclusions