Proline catalyzed direct diastereoselective 6-enolexo aldolization: toward the synthesis of the imino sugar DNJ

A l-proline catalyzed direct diastereoselective 6-enolexo aldolization reaction of differentiating dialdehydes derived from tartaric acid is presented. This organocatalytic approach provides high levels of syn-selectivity (dr >10:1) with the stereocontrolled C–C bond formation between C4 and C5 intramolecularly, which can serve to synthesize imino-sugar skeleton quickly.

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Benzyl ((4S,5S)-5-((tert-butyldimethylsilyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl(2-hydroxyethyl)carbamateC23H39N4O6Si[α]D25=-16.2 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

(3aS,8aS)-7-(2-Hydroxyethyl)-2,2-dimethyltetrahydro-[1,3]dioxolo[4,5-e][1,3]oxazepin-6(7H)-oneC10H17NO5[α]D25=-17.8 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3aS,8aS)

N-(((4S,5S)-5-((tert-Butyldimethylsiloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-N-(2-hydroxyethyl)-4-methylbenzenesulfonamideC22H39NO6SSi[α]D25=-22.2 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

N-(2-Hydroxyethyl)-N-(((4S,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl-4-methylbenzenesulfonamideC16H25NO6S[α]D25=-32.0 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

(3aS,6S,7R,7aS)-6-(Hydroxymethyl)-2,2-dimethyl-5-tosylhexahydro-[1,3]dioxolo[4,5-c]pyridine-7-olC16H23NO6S[α]D25=+9.3 (c 0.5, MeOH)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3aS,6S,7R,7aS)

((3aS,7aS)-2,2-Dimethyl-5-tosyl-3a,4,5,7a-tetrahydro-[1,3]dioxolo[4,5-c]pyridine-6-yl)methanolC16H21NO5S[α]D25=+291.4 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3aS,7aS)

((3aS,6S,7R,7aR)-7-Acetoxy-2,2-dimethyl-5-tosylhexahydro-[1,3]dioxolo[4,5-c]pyridine-6-yl)methyl acetateC20H27NO8S[α]D25=+13.95 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3aS,6S,7R,7aR)

((3aS,7aS)-2,2-Dimethyl-5tosyl-3a,4,5,7a-tetrahydro-[1,3]dioxolo[4,5-c]pyridine-6-yl)methyl acetateC18H23NO6S[α]D25=+187.68 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3aS,7aS)