SPANamine derivatives in the catalytic asymmetric α-fluorination of β-keto esters

The use of C2-symmetric enantiopure nitrogen ligands in the asymmetric catalytic α-fluorination of β-ketoesters is described. SPANamine 1 in the presence of nickel salts gives up to 63% ee in the fluorination of tert-butyl 2-oxocyclopentanecarboxylate with N-fluorosuccinimide (NFSI). The same enantioselectivity is obtained when SPANamine 1 is used as an organocatalyst, although the reaction is much slower.

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(−)-(R)-Diethyl-4,4,4′,4′,6,6′-hexamethyl-2,2′-spirobi[chroman]-8,8′-dicarboxylateC29H36O6[α]D24=-49.0 (c 0.12, CH2Cl2)Source of chirality: Enantiomer resolution by semi-preparative chiral hplcAbsolute configuration: (R)

(4S,4′S)-2,2′-((R)-4,4,4′,4′,6,6′-Hexamethyl-2,2′-spirobi[chroman]-8,8′-diyl)bis(4-phenyl-4,5-dihydrooxazole)C41H42N2O4[α]D24=-20.0 (c 0.11, CH2Cl2)Source of chirality: precursor + diastereoisomer resolution by semi-preparative chiral hplcAbsolute configuration: (4S,4′S)(R)

(4S,4′S)-2,2′-((S)-4,4,4′,4′,6,6′-Hexamethyl-2,2′-spirobi[chroman]-8,8′-diyl)bis(4-phenyl-4,5-dihydrooxazole)C41H42N2O4[α]D24=-61.0 (c 0.103, CH2Cl2)Source of chirality: precursor + diastereoisomer resolution by semi-preparative chiral hplcAbsolute configuration: (4S,4′S)(S)

(4S,4′S)-2,2′-((R)-4,4,4′,4′,6,6′-Hexamethyl-2,2′-spirobi[chroman]-8,8′-diyl)bis(4-isopropyl-4,5-dihydrooxazole)C35H46N2O4[α]D24=-16.0 (c 0.104, CH2Cl2)Source of chirality: precursor + diastereoisomer resolution by semi-preparative chiral hplcAbsolute configuration: (4S,4′S)(R)

(4S,4′S)-2,2′-((S)-4,4,4′,4′,6,6′-Hexamethyl-2,2′-spirobi[chroman]-8,8′-diyl)bis(4-isopropyl-4,5-dihydrooxazole)C35H46N2O4[α]D24=-31.0 (c 0.101, CH2Cl2)Source of chirality: precursor + diastereoisomer resolution by semi-preparative chiral hplcAbsolute configuration: (4S,4′S)(S)