(1R,6R,13R,18R)-(Z,Z)-1,18-Bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3,16-dimethylene-8,20-diazadispiro[5.6.5.6]tetracosa-7,19-diene

The crystal structure of the title compound, C34H54N2O4, has been solved in order to prove the relative and absolute chirality of the newly-formed stereocentres which were established using an asymmetric Diels–Alder reaction at an earlier stage in the synthesis. This unprecedented stable dialdimine contains a 14-membered ring and was obtained as the minor diastereoisomer in the Diels–Alder reaction. The absolute stereochemistry of the stereocentres of the acetal functionality was known to be R based on the use of a chiral (R)-trisubstituted dienophile derived from enantiopure (S)-glyceraldehyde. The assignment of the configuration in the dienophile and the title di-aldimine differs from (S)-glyceraldehyde due to a change in the priority order of the substituents. The crystal structure establishes the presence of six stereocentres all attributed to be R. The 14-membered ring contains two aldimine bonds [C—N = 1.258 (2) and 1.259 (2) Å]. It adopts a similar conformation to that proposed for trans–trans-cyclotetradeca-1,8-dienes.

The crystal structure of the title compound, C 34 H 54 N 2 O 4 , has been solved in order to prove the relative and absolute chirality of the newly-formed stereocentres which were established using an asymmetric Diels-Alder reaction at an earlier stage in the synthesis. This unprecedented stable dialdimine contains a 14-membered ring and was obtained as the minor diastereoisomer in the Diels-Alder reaction. The absolute stereochemistry of the stereocentres of the acetal functionality was known to be R based on the use of a chiral (R)-trisubstituted dienophile derived from enantiopure (S)glyceraldehyde. The assignment of the configuration in the dienophile and the title di-aldimine differs from (S)-glyceraldehyde due to a change in the priority order of the substituents. The crystal structure establishes the presence of six stereocentres all attributed to be R. The 14-membered ring contains two aldimine bonds [C-N = 1.258 (2) and 1.259 (2) Å ]. It adopts a similar conformation to that proposed for trans-trans-cyclotetradeca-1,8-dienes.

Comment
The title spiro-di-aldimine was obtained as part of a synthetic program directed towards the synthesis of the spiroimine unit of the spirolides AD. This family of marine toxins were isolated from the digestive glands of contaminated mussels, scallops and toxic plankton from the East coast of Nova Scotia in Canada and are considered as fast-acting toxins (Hu et al., 1995;Hu et al., 2001;Gill et al., 2003;Guéret & Brimble, 2010). The work demonstrates a new method to access an enantiopure spiro-di-aldimine and an enantiopure bicyclic ketimine in good overall yield. The synthesis of the spiroimine is a synthetic challenge and to date the synthesis of the 7,6-spiroimine moiety of the spirolides has not been achieved. By reaction of a chiral (R)-trisubstituted dienophile derived from (S)-glyceraldehyde with Danishefsky's diene (Asano et al., 2006;Danishefsky et al., 1990;Petrzilka & Grayson, 1981), the resultant Diels-Alder adducts were afforded as a mixture of 3 diastereoisomers in a 5:2:1 ratio. The undesired minor diastereoisomer was used to develop the synthetic route to the desired spiroaldimine. The Diels-Alder adduct was converted to the spiroimine precursor in several steps. Reaction of this advanced azido-aldehyde intermediate with triphenylphosphine surprisingly afforded the stable title dimer instead of the expected 7,6-bicyclic aldimine. The stability of the title dimer is unexpected compared to the known instability of aldimines in general.
Given that the stereochemistry at C26 and C32 is known to be R (based on using enantiopure (S)-glyceraldehyde as the starting material), the absolute configuration at C1, C6, C13 and C20 has therefore also been assigned as R. The assignment of configuration of the trisubstituted dienophile and the title di-aldimine differs from the starting (S)-glyceraldehyde due to a change in the priority order of substituents.

Refinement
In the absence of significant anomalous scattering, the absolute configuration could not be reliably determined from the X-ray analyses and then the Friedel pairs were merged and any references to the Flack parameter were removed.
Atoms were placed in calculated positions and a riding model (C-H = 0.93 or 0.97 Å), with U iso (H) = 1.2 or 1.5 times U eq (C) was used during refinement.
Figures Fig. 1. The molecular view of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii.