Enantioselective ethylation of aldehydes with 1,3-N-donor ligands derived from (+)-camphoric acid

Derivatives of (+)-camphoric acid were prepared by a short and simple synthetic sequence and proved to be excellent ligands for the enantioselective ethylation of benzaldehyde with diethylzinc, with ees of up to 96% being obtained. The most efficient ligand was tested with several aromatic aldehydes and ees of up to 99% were observed. Structural features of the ligands are determinant for achieving high enantioselectivities.

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N-((1S,3R)-3-Amino-2,2,3-trimethylcyclopentyl)-4-methylbenzenesulfonamideC15H25N2O2SEe = 100%[α]D25=+15 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1S,3R)

N-((1S,3R)-3-Amino-2,2,3-trimethylcyclopentyl)-1-((1S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonamideC18H33N2O3SEe = 100%[α]D25=+45 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acid and (+)-10-camphorsulfonyl chlorideAbsolute configuration: (1S,3R) [(1S)]

N,N′-((1R,3S)-1,2,2-Trimethylcyclopentane-1,3-diyl)-bis(4-methylbenzenesulfonamide)C22H30N2O2S4Ee = 100%[α]D25=+30 (c 0.5, CHCl3)Source of chirality: (+)-camphoric acidAbsolute configuration: (1R,3S)

N,N′-((1R,3S)-1,2,2-Trimethylcyclopentan-1,3-diyl)-bis-(1S)-(7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonamideC28H46N2O6S2Ee = 100%[α]D25=+40 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acid and (+)-10-camphorsulfonyl chlorideAbsolute configuration: (1R,3S) [(1S)]

N-((1S,3R)-3-(Dimethylamino)-2,2,3-trimethylcyclopentyl)-4-methylbenzenesulfonamideC17H28N2O2SEe = 100%[α]D25=+20 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1S,3R)

Benzyl (1S,3R)-3-(dimethylamino)-2,2,3-trimethylcyclopentylcarbamateC18H28N2O2Ee = 100%[α]D25=+20 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1S,3R)

N-((1S,3R)-3-(Ethylamino)-2,2,3-trimethylcyclopentyl)benzamideC17H26N2OEe = 100%[α]D25=+60 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1S,3R)

N-((1S,3R)-3-(Diethylamino)-2,2,3-trimethylcyclopentyl)benzamideC19H30N2OEe = 100%[α]D25=+70 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acidAbsolute configuration: (1S,3R)

N,N′-((1R,3S)-1,2,2-Trimethylcyclopentan-1,3-diyl)-bis(1S,2R)-(7,7-dimethyl-2-hydroxybicyclo[2.2.1]heptan-1-yl)methanesulfonamideC28H50N2O6S2Ee = 100%[α]D25=+5 (c 2.0, CH2Cl2)Source of chirality: (+)-camphoric acid and (+)-10-camphorsulfonyl chlorideAbsolute configuration: (1S,3R) [(1S,2R)]

N-((1S,3R)-3-(Ethylamino)-2,2,3-trimethylcyclopentyl)-1-((1S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonamideC20H36N2O3SEe = 100%[α]D25=+55 (c 1.0, CH2Cl2)Source of chirality: (+)-camphoric acid and (+)-10-camphorsulfonyl chlorideAbsolute configuration: (1S,3R) [(1S)]