ChemInform Abstract: 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).

Abstract

~~~~The X-ray structures of fifteen 1,3-imidazolidine, 1,3-oxazolidine, 1,3-dioxan-4-one, and hydropyrimidine-4( I 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',' effect of the amide moieties. Even I-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',3 strain leads to strong pyramidalizations of the amide N-atoms (Table I ) 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 I and 2 ) are interpreted (Scheme 3 ) as an indirect consequence of the amide A's3 strain effect. The conclusions drawn are considered relevant for a better understanding of the ever increasing role which amide groups play in stereoselective syntheses.

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin–Anh and Chelation-Control Models

“…520 The allyl group attacked from the face opposite the two alkyl groups, which could adopt pseudoaxial orientations to minimize allylic strain with the carbamoyl group. 521 Attack on the carbon−nitrogen double bond from the more exposed face, as shown in 930, would form the observed product.…”

“…531 It is likely that the Lewis acid−base complex adopts a conformation resembling 989 (Scheme 398) to minimize allylic strain, as has been observed for other nitrogen-containing five-memberedring species. 521 Stereoelectronically favored attack from inside the envelope 530,532−534 would lead to the observed product. Additions of allylmagnesium reagents to complexes of imines with boron Lewis acids are also stereoselective with multicyclic imines (Scheme 399).…”

‘100 years of peptide synthesis’: ligation methods for peptide and protein synthesis with applications to β‐peptide assemblies*

“… Model reactions for the determination of the stereochemical course of the pseudo‐proline‐ligation. The preferred formation of the 2,4‐ cis ‐substituted heterocycles is rationalized in papers by the Seebach group (76,77). …”