Annuloselectivity in Reactions of Diacyl Dichlorides and Imines: Combined Experimental and Theoretical Studies.

Abstract

The annuloselectivity defined as the annulation selectivity between [2 + 2] and cascade annulations of diacyl dichlorides and imines in the presence of organic bases to afford bis-β-lactams and 2,3-dihydro-1,3-oxazin-4-ones has been studied extensively with a combination of experiments and density functional theory (DFT) calculations. The present results indicate that it is the preference of diacyl dichlorides in the formation of cyclic α-oxoketenes in the presence of organic bases that controls the annuloselectivity. The cascade annulations of hexanedioyl and heptanedioyl dichlorides undergo the chloride-assisted cyclization of the corresponding ω-chlorocarbonylalkylketenes as the rate-determining step in the presence of triethylamine, rather than the generation of bisketenes followed by dimerization, affording five- and six-membered cyclic α-oxoketenes followed by the [4 + 2] annulations with imines to furnish 2,3-dihydro-1,3-oxazin-4-ones. This is an energetically competitive pathway to the normal Staudinger cycloaddition. Further decreasing (pentanedioyl dichloride) or increasing the linker length (octanedioyl and nonanedioyl dichlorides) results in the enhanced energetic barriers for the cyclization, which is less competitive to the direct Staudinger cycloaddition to afford bis-trans-β-lactams as the sole products. The current results provide an insight into the annuloselective control in the reactions of diacyl dichlorides and imines.