Highly enantioselective catalytic Friedel–Crafts reactions of cyclic α-alkylidene β-oxo imides

Highly enantioselective catalytic Friedel–Crafts reactions of cyclic α-alkylidene β-oxo imides with indole, pyrrole, and furan derivatives at relatively low temperatures are described. The X-ray crystallographic analysis of the product revealed that the sense of enantioselectivity of the Friedel–Crafts reactions could be well explained by the proposed chelate model. The model was stabilized by an intramolecular hydrogen bond, wherein the cyclic α-alkylidene β-oxo imide coordinates with Cu(II) through the two imide carbonyls.

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Methyl ((3S,4S)-4-(1-methyl-1H-indol-3-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC17H18N2O597% ee[α]D24 = +31 (c 0.33, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(1-Methyl-1H-indol-3-yl)tetrahydro-2H-pyran-2-oneC14H15NO297% ee[α]D25 = +11 (c 0.18, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(1H-indol-3-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC16H16N2O568% ee[α]D24 = +22 (c 0.44, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(1H-Indol-3-yl)tetrahydro-2H-pyran-2-oneC13H13NO268% ee[α]D25 = +27 (c 0.28, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(1-benzyl-1H-indol-3-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC23H22N2O593% ee[α]D26 = +36 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(1-Benzyl-1H-indol-3-yl)tetrahydro-2H-pyran-2-oneC20H19NO293% ee[α]D26 = +17 (c 0.24, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(5-methoxy-1-methyl-1H-indol-3-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC18H20N2O695% ee[α]D21 = +25 (c 0.21, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(5-Methoxy-1-methyl-1H-indol-3-yl)tetrahydro-2H-pyran-2-oneC15H17NO395% ee[α]D22 = +8.6 (c 0.32, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl 3-((3S,4S)-3-((methoxycarbonyl)carbamoyl)-2-oxotetrahydro-2H-pyran-4-yl)-1-methyl-1H-indole-5-carboxylateC19H20N2O793% ee[α]D26 = +16 (c 0.17, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

Methyl (S)-1-methyl-3-(2-oxotetrahydro-2H-pyran-4-yl)-1H-indole-5-carboxylateC16H17NO493% ee[α]D26 = +12 (c 0.095, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(5-chloro-1-methyl-1H-indol-3-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC17H17N2O5Cl93% ee[α]D22 = +27 (c 0.15, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(5-Chloro-1-methyl-1H-indol-3-yl)tetrahydro-2H-pyran-2-oneC14H14NO2Cl93% ee[α]D23 = +31 (c 0.33, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(1,5-dimethyl-1H-pyrrol-2-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC14H18N2O567% ee[α]D23 = +7.6 (c 0.19, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(1,5-Dimethyl-1H-pyrrol-2-yl)tetrahydro-2H-pyran-2-oneC11H15NO267% ee[α]D24 = +4.2 (c 0.17, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-2-oxo-4-(1,2,5-trimethyl-1H-pyrrol-3-yl)tetrahydro-2H-pyran-3-carbonyl)carbamateC15H20N2O584% ee[α]D22 = +16 (c 0.28, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(1,2,5-Trimethyl-1H-pyrrol-3-yl)tetrahydro-2H-pyran-2-oneC12H17NO284% ee[α]D21 = −5.3 (c 0.075, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl ((3S,4S)-4-(5-methylfuran-2-yl)-2-oxotetrahydro-2H-pyran-3-carbonyl)carbamateC13H15NO675% ee[α]D21 = +5.3 (c 0.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3S,4S)

(S)-4-(5-Methylfuran-2-yl)tetrahydro-2H-pyran-2-oneC10H12O375% ee[α]D20 = +17 (c 0.035, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-5-(1-Methyl-1H-indol-3-yl)-5,6,7,8-tetrahydro-2H-benzo[e][1,3]oxazine-2,4(3H)-dioneC17H16N2O397% ee[α]D26 = +29 (c 0.035, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Methyl ((1R,2S)-2-(1-methyl-1H-indol-3-yl)-5-oxocyclopentane-1-carbonyl)carbamateC17H18N2O492% ee[α]D25 = +16 (c 0.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(S)-3-(1-Methyl-1H-indol-3-yl)cyclopentan-1-oneC14H15NO97% ee[α]D25 = +12 (c 0.25, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)