Stereoelectronic effects on reactivity. Crystal-structure–reactivity correlations for acetals with synperiplanar lone pairs

Abstract

The synthesis and five crystal structures are reported for a series of tetrahydropyranyl acetals 3, in which the tetrahydropyranyl ring is fixed in the symmetrical boat conformation. The spontaneous hydrolysis of four aryl acetals 3 is a few times faster than that of corresponding compounds in which the tetrahydropyran ring is conformationally mobile and thus free to adopt the chair conformation. There appears to be no stereoelectronic barrier to participation by synperiplanar (sp) as compared with antiperiplanar (ap) lone pairs in the acetal cleavage reaction. However, at least part of this increased reactivity towards hydrolysis must derive from the higher ground state energy of the boat conformation, and a careful examination of a series of compounds 3 reveals intriguing and systematic differences between the two systems. The spontaneous hydrolysis of the synperiplanar series shows extraordinarily high sensitivity to the leaving group (β_LG = 1.4), compared with the already high value known for axial tetrahydropyranyl acetals with antiperiplanar lone pairs. In contrast, bond length correlations show a reduced sensitivity. The results suggest that the n–σ*_C–O interaction (endocyclic anomeric effect) is weaker in the ground state in the sp geometry.