Studies on the structure–enantioselectivity relationships in the catalytic asymmetric intramolecular cyclopropanation reaction of α-diazo-β-keto sulfones possessing a methyl-substituted phenyl group

This manuscript describes studies on structure–enantioselectivity relationships in the catalytic asymmetric intramolecular cyclopropanation (IMCP) reaction of α-diazo-β-keto sulfones possessing a methyl-substituted phenyl group. Enantioselectivity of the IMCP reaction of the α-diazo-β-keto sulfones was varied by the position of a methyl group on the phenyl group in the substrate, and the 2,3-dimethylphenyl sulfone 11h provided the product 12h in 95% yield with 93% ee. This yield is superior to that of the substrate with a mesityl sulfone 11b, and the product 12h is useful because alkylation of its cyclopropane-opened β-keto sulfone derivative 15h provides the C-alkylated product as a major product.

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(1R,5R)-1-(2-Methylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC13H14O3SEe = 86%[α]D25 = −35.4 (c 1.00, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(3-Methylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC13H14O3SEe = 77%[α]D26 = −35.8 (c 1.50, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(4-Methylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC13H14O3SEe = 69%[α]D28 = −25.2 (c 0.75, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(2,3-Dimethylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC14H16O3SEe = >99%[α]D26 = −37.2 (c 1.02, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(2,5-Dimethylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC14H16O3SEe = 82%[α]D28 = −43.0 (c 1.05, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(2,6- Dimethylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC14H16O3SEe = 91%[α]D28 = −50.0 (c 1.25, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(3,4-Dimethylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC14H16O3SEe = 72%[α]D28 = −42.3 (c 1.09, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,5R)-1-(3,5-Dimethylphenylsulfonyl)bicyclo[3.1.0]hexan-2-oneC14H16O3SEe = 62%[α]D28 = −41.0 (c 1.37, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,5R)

(1R,2R)-[2-(2,3-Dimethylbenzenesulfonyl)-3-oxocyclopentyl]acetonitrileC15H17NO3SEe = 93%[α]D25 = −33.0 (c 1.15, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (1R,2R)

(R)-(3-Oxocyclopentyl)acetonitrileC7H9NOEe = >99%[α]D24 = −70.1 (c 1.20, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (R)

(R)-[2-(2,3-Dimethylbenzenesulfonyl)-3-methoxy-2-cyclopentenyl]acetonitrileC16H19NO3SEe = 93%[α]D25 = −17.9 (c 0.72, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (R)

(R)-[2-(2,3-Dimethylbenzenesulfonyl)-3-(2-propynyloxy)-2-cyclopentenyl]acetonitrileC18H19NO3SEe = 93%[α]D25 = −11.2 (c 0.94, CHCl3)Source of chirality: catalytic asymmetric intramolecular cyclopropanationAbsolute configuration: (R)