Conformations of Azacyclodeca-3,8-diynes and 1,6-Diazacyclodeca-3,8-diynes and the Generalized Anomeric Effect:  A Test for Current Conformational Models for Azaheterocycles

The conformations of azacyclodeca-3,8-diyne ( 4a ) and its N -methyl ( 4b ) and N -isopropyl ( 4c ) derivatives as well as 1,6-diazacyclodeca-3,8-diyne ( 5a ) and its 1,6-dimethyl ( 5b ), 1,6-diisopropyl ( 5c ), 1,6-di- tert -butyl ( 5d ), and 1,6-ditolyl ( 5e ) derivatives have been investigated by single-crystal X-ray diffraction, in solution by NMR and by theoretical methods. In the solid state, 4a,c and 5a − e adopt a chair conformation with the substituents in the bis-axial positions. In solution 4 and 5 show Δ G ⧧ = 10.4 and 11.0 kcal/mol, respectively, for ring inversion. Trapping of 5c with HCl indicates the presence of bis-axial, axial, and equatorial conformations in solution. The equilibrium between boat and chair conformations in 4 and 5 is ascribed to much reduced torsional strain between the propargylic hydrogens. The preference of the axial orientation of the substituents on the nitrogen atom(s) in 4 and 5 is interpreted in terms of the vicinal interactions of both the NR bond and the lone pair with the adjacent CH and CC bonds, synaxial 1,3-interactions of both the NR bond and the lone pair, and secondary interactions of CH/CC bonds of the alkyl substituent with the endocyclic CH 2 groups as well as with triple bonds ( back and front strain ).