Stereochemistry of 2,6‐Diaminoadamantane Salts: Transannular Interactions

A series of bisprimary, bistertiary, and bisquaternary adamantane‐2,6‐diammonium salts were synthesized from adamantane‐2,6‐dione starting material. Conversion of the dione to a dioxime followed by H 2 /PtO 2 hydrogenation afforded 2,6‐diaminoadamantane dihydrochloride 2a . Reductiveamination of 2a with aqueous formaldehyde (H 2 /PtO 2 ) gave rac ‐ N , N , N′ , N′ ‐tetramethyl‐2,6‐diaminoadamantane dihydrochloride salt 3 . Diffusion of acetone into a solution of 3 in methanol gave 2.5 hydrate crystals in a triclinic P $\bar {1}$ cell, which had two molecules of opposite handedness and five water molecules in the asymmetric unit. Diamine 2a with excess CH 3 I yielded rac ‐ N , N , N , N′ , N′ , N′ ‐hexamethyladamantane‐2,6‐diaminium diiodide quaternary salt 4a . Diiodide 4a with molecular bromine gave the corresponding dibromide 4b . Acetone diffusion into a solution of 4a (or 4b ) in methanol gave isostructural monohydrate crystals in orthorhombic Pnma cells. An enantiomeric pair of 4a , 4b (2 RS ,6 RS )‐diaminium ions is disordered about the mirror plane, since chiral cation occupancy of this location requires symmetry that cannot be fulfilled. In solution, all the cations had C 2 symmetry, as detected by NMR spectroscopy, whereas an approximate C 2 symmetry was observed in crystals. RmS(G) quantification of crystallographic pseudo‐symmetry shows high fidelity for pseudo‐inversion symmetry between cations of opposite handedness in crystal 3 , and for pseudo‐ C 2 symmetry within adamantane skeletons of crystals 3 , 4a , and 4b . Axial NMe 3 or NHMe 2 groups on adamantane‐2 (or ‐6‐)‐positions suffer cis ‐1,3‐diaxial repulsion, very similar to that involving axial t Bu or i Pr groups and H(axial) protons on cyclohexane. These transannular steric interactions tilt the NMe 3 units outward by about 19°, while NHMe 2 groups slant outward by a smaller and more usual 7°.