Structure and Reactivity of Five‐ and Six‐Ring N, N‐, N, O‐, and O, O‐acetals: A lesson in allylic 1, 3‐strain (A^{1, 3}strain)

Abstract The X‐ray structures of fifteen 1, 3‐imidazolidine, 1, 3‐oxazolidine, 1, 3‐dioxan‐4‐one, and hydropyrimidine‐4(1 H )‐one derivatives are described ( Table 2 ) and compared with known structures of similar compounds ( Figs. 1–20 ). The differences between structures containing exocyclic N ‐acyl groups and those lacking this structural element arise from the A 1,3 effect of the amide moieties. Even t ‐Bu groups are forced into axial positions of six‐ring half‐chair or into flag‐pole positions of six‐ring twist‐boat conformers by this effect ( Figs. 16–20 ). In the N ‐acylated five‐membered heterocycles, a combination of ring strain and A 1, 3 strain leads to strong pyramidalizations of the amide N‐atoms ( Table 1 ) such that the acyl groups wind up on one side and the other substituents on the opposite side of the rings ( Figs. 4–9 and Scheme 3 ). Thus, the acyl (protecting!) groups strongly contribute to the steric bias between the two faces of the rings. Observed, at first glance surprizing stereoselectivities of reactions of these heterocycles ( Schemes 1 and 2 ) are interpreted ( Scheme 3 ) as an indirect consequence of the amide A 1, 3 strain effect. The conclusions drawn are considered relvant for a better understanding of the ever increasing role which amide groups play in stereoselective syntheses.