Enantioselective addition of diethylzinc to aldehydes catalyzed by γ-amino alcohols derived from (+)- and (−)-α-pinene

Primary, secondary and tertiary γ-amino alcohols 4, 5, 7 and 9 and 1,3-diamine 6 were synthesized from (+)- and (−)-α-pinene 1 via chiral N-Boc β-amino ester 3a and carboxamide 3b. The amino alcohols and diamine obtained were applied as chiral catalysts in the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in chiral 1-aryl-1-propanols. The first evidence of the substituent-dependent enantioselectivity of 1,3-amino alcohol catalysts was observed, and the phenomenon interpreted by using molecular modelling at the ab initio level.

Graphical abstractPrimary, secondary and tertiary γ-amino alcohols and 1,3-diamine derived from (+)- and (−)-α-pinene were applied as chiral catalysts in the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in chiral 1-aryl-1-propanols.Figure optionsDownload full-size imageDownload as PowerPoint slide

(1R,2R,3S,5R)-(2-Benzylamino-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)methanol hydrochlorideC18H28ClNO[α]D20=-14.1 (c 0.5, MeOH)Source of chirality: (1S,5S)-(−)-α-pineneAbsolute configuration: 1R,2R,3S,5R

(1R,2R,3R,5R)-Methyl-(2,6,6-trimethyl-3-methylaminomethylbicyclo[3.1.1]hept-2-yl)amine hydrochlorideC13H27ClN2[α]D20=-11.7 (c 0.5, MeOH)Source of chirality: (1S,5S)-(−)-α-pineneAbsolute configuration: 1R,2R,3R,5R

(1R,2R,3S,5R)-(2-Dimethylamino-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)methanol hydrochlorideC13H26ClNO[α]D20=-31.8 (c 0.5, MeOH)Source of chirality: (1S,5S)-(−)-α-pineneAbsolute configuration: 1R,2R,3S,5R