Synthesis of (3S,3S′,4S,4S′)-1,1′-ethylenedipyrrolidine-3,3′,4,4′-tetraol and related diamino diols: donor–acceptor hydrogen-bonding motifs of the C2 symmetric 3,4-dihydroxypyrrolidine unit

Enantiopure 1,1′-ethylenedipyrrolidines possessing 3,4-disubstitution have been prepared from esters of l-(+)-tartaric acid. Although diacylation routes via the diacetoxypyrrolidin-2,5-diones were problematic, N,N-dialkylation protocols proved to be reliable and led to the synthesis of (3S,3S′,4S,4S′)-1,1′-ethylenedipyrrolidine-3,3′,4,4′-tetraol, (3R,3′S,4R,4′S)-3,4-diamino-1,1′-ethylenedipyrrolidine-3′,4′-diol and (3R,3′R,4S,4′S)-3,3′-diamino-1,1′-ethylenedipyrrolidine-4,4′-diol. The tetraol possesses a crystal structure that exhibits an unusual zig-zag intermolecular pattern comprising a network of hydrogen bonds involving the terminal hydroxyl groups and a nitrogen atom of one of the pyrrolidine rings.

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(3S,3′S′,4S,4′S′)-3,3′,4,4′-Tetrakis(methoxymethyloxy)-1,1′-ethylenedipyrrolidineC18H36N2O8Ee = 100%[α]D30=-10.6 (c 0.15, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,3′S′,4S,4′S′)

(3S,3S′,4S,4S′)-1,1′-Ethylenedipyrrolidine-3,3′,4,4′-tetraolC10H20N2O4Ee = 100%[α]D30=+15.4 (c 0.35, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,3′S′,4S,4′S′)

(3R,3′S,4R,4′S)-3,4-Diazido-3′,4′-bis(methoxymethyloxy)-1,1′-ethylenedipyrrolidineC14H26N8O4Ee = 100%[α]D34=-6.0 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,3′S′,4S,4′S′)

(3R,3′S,4R,4′S)-3,4-Diamino-3′,4′-bis(methoxymethyloxy)-1,1′-ethylenedipyrrolidineC10H30N4O4Ee = 100%[α]D33=-9.7 (c 1.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,3′S′,4S,4′S′)

(2S,3R)-3-Azido-1,4-bis(methanesulfonyloxy)butane-2-olC6H13N3O7S2Ee = 100%[α]D30=-35.4 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(3R,3′R,4S,4′S)-3,3′-Diazido-1,1′-ethylenedipyrrolidine-4,4′-diolC10H18N8O2Ee = 100%[α]D28=+44.7 (c 1.2, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3′R,4S,4′S)

(3R,3′R,4S,4′S)-3,3′-Diamino-1,1′-ethylenedipyrrolidine-4,4′-diolC10H22N4O2Ee = 100%[α]D32=+36.3 (c 1.3, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,3′R,4S,4′S)