Structure and Reactivity of Five- and Six-Ring N,N-, N,O-, and O,O-acetals: A lesson in allylic 1, 3-strain (A1, 3 strain)

The X-ray structures of fifteen 1, 3-imidazolidine, 1, 3-oxazolidine, 1, 3-dioxan-4-one, and hydropyrimidine-4(1H)-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.