Diastereoselective trimolecular condensation between indole, Meldrum’s acid and chiral sugar-derived aldehydes

The trimolecular condensation of indole, Meldrum’s acid and chiral, sugar-derived aldehydes took place in good yield and high diastereoselectivity. The absolute configuration of the α-carbon of the chiral aldehydes ensured a predictable diastereocontrol of the newly created stereogenic centre except for (3aR,5S,6S,6aR)-6-benzyloxy-2,2-dimethyl-tetrahydrofuro[3,2-d][1,3]dioxole-5-carbaldehyde 3i. In this case, the opposite stereochemistry may be explained by a less congested conformer of the Knoevenagel-adduct intermediate.

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(1′S,2′S,3′R,4′S)-5-[2′,3′,4′,5′-Tetrahydroxy-1′-(1H-indol-3-yl)-(2,3:4,5)-di-O-isopropylidene-pentan-1′-yl]-2,2-dimethyl-1,3-dioxane-4,6-dioneC25H31NO8[α]D23=-58 (c 0.35, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (1S,2S,3R,4S)

(1′S,2′S,3′R)-5-[4′,4′-Bis(ethylsulfanyl)-2′,3′-dihydroxy-1′-(1H-indol-3-yl)-2′,3′-di-O-isopropylidene-butan-1′-yl]-2,2-dimethyl-1,3-dioxane-4,6-dioneC25H33NO6S2[α]D22=-50 (c 1.0, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (1S,2S,3R)

(1′S,2′S,3′R,4′S)-5-[2′,3′-Bis(benzyloxy)-4′,5′-dihydroxy-1′-(1H-indol-3-yl)-4′,5′-di-O-isopropylidene-pentan-1′-yl]-2,2-dimethyl-1,3-dioxane-4,6-dioneC34H39NO8[α]D22=-144 (c 0.31, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (1S,2S,3R,4S)

(1′S,2′S,3′R,4′S)-5-[2′-Benzyloxy-3′-tert-butyldimethylsilyloxy-4′,5′-dihydroxy-1′-(1H-indol-3-yl)-4′,5′-di-O-isopropylidene-pentan-1′-yl]-2,2-dimethyl-1,3-dioxane-4,6-dioneC35H47NO8Si[α]D22=-57.1 (c 0.3, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (1S,2S,3R,4S)

5-{(S)-[(3a′R,5′R,6′S,6a′R)-6′-Benzyloxy-2′,2′-dimethyl-dihydro-5H-furo[3,2-d][1,3]dioxol-5′-yl](1H-indol-3-yl)methyl}-2,2-dimethyl-1,3-dioxane-4,6-dioneC29H31NO8[α]D24=+22.2 (c 0.4, CHCl3)Source of chirality: reaction substrateAbsolute configuration: S,(3aR,5R,6S,6aR)

(3S,4S,5S)-4-(1H-Indol-3-yl)-2-oxo-5-[(1′S,2′S)-1′,2′,3′-trihydroxypropan-1′-yl]-tetrahydrofuran-3-carboxylic acid methyl esterC17H19NO7[α]D23=+134.6 (c 0.23, MeOH)Source of chirality: reaction substrateAbsolute configuration: (3S,4S,5S) (1′S,2′S)

(3S,4S,5S)-5-[2′,2′-Bis(ethylsulfanyl)-(1′R)-1′-hydroxyethyl]-4-(1H-indol-3-yl)-2-oxo-tetrahydrofuran-3-carboxylic acidC19H23NO5S2[α]D24=+189.5 (c 0.4, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (3S,4S,5S)) (1′R)

(3S,4S,5S)-4-(1H-Indol-3-yl)-2-oxo-5-[(1′S,2′S)-1′,2′,3′-trihydroxypropan-1′-yl]-tetrahydrofuran-3-carboxylic acidC16H17NO6[α]D24=+139.3 (c 0.22, acetone)Source of chirality: reaction substrateAbsolute configuration: (3S,4S,5S) (1′S,2′S)

(3S,4S,5S)-4-(1H-Indol-3-yl)-2-oxo-5-[(1′R,2′S)-1′-tert-butyldimethylsilyloxy-2′,3′-dihydroxy-2′,3′-di-O-isopropylidene-propan-1′-yl]-tetrahydrofuran-3-carboxylic acidC25H35NO7Si[α]D25=+70 (c 0.13, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (3S,4S,5S) (1′R,2′S)

(2S,3R,3aR,6S,7S,7aR)-2,3-Dihydroxy-2,3-di-O-isopropylidene-7-(1H-indol-3-yl)-5-oxo-hexahydro-2H-furo[3,2-b]pyran-6-carboxylic acidC19H19NO7[α]D24=-12 (c 0.88, acetone)Source of chirality: reaction substrateAbsolute configuration: (2S,3R,3aR,6S,7S,7aR)

(2S,3R,3aR,7S,7aR)-2,3-Dihydroxy-2,3-di-O-isopropylidene-7-(1H-indol-3-yl)-hexahydro-2H-furo[3,2-b]pyran-5-oneC18H19NO5[α]D24=-213 (c 0.29, CHCl3)Source of chirality: reaction substrateAbsolute configuration: (2S,3R,3aR,7S,7aR)