Contribution of the anomeric effect to the solution and crystal structure of [1S,2S,6S,7S]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane, a condensation product of l-serine methyl ester with formaldehyde Original Research Article

The reaction of l-serine methyl ester hydrochloride (1) with paraformaldehyde (2) in dichloromethane in the presence of triethylamine afforded a novel compound: [1S,2S,6S,7S]-1,6-diaza-4,9-dioxa-2,7-dimethoxycarbonylbicyclo[4.4.1]undecane (4) as a 2:3 adduct of 1 with 2. 1H and 13C NMR spectroscopy were unable to discriminate between two possible symmetrical structures. The latter was unambiguously proved by X-ray crystallography. The crystal structure established: (i) the existence of two identical seven-membered rings each containing a NCO grouping; (ii) the existence of a long COCNCNCOC sequence in which each nitrogen belongs simultaneously to a NCO (oxazolidine) and to a NCN (aminal) motifs; (iii) the existence of a chair-like conformation for both seven-membered rings; (iv) the antiperiplanar geometry of pNCO and consequently the manifestation of a strong anomeric effect in both NCO groupings, whereas anomeric effect was virtually absent in the NCN sequence, as corroborated by bond distances and bond angles. Chemical shifts, coupling constants and NOE effects confirm that the conformational features of 4 are preserved in solution.