Structurally constrained C1-1,1′-bisisoquinoline-based chiral ligands: geometrical implications on enantioinduction in the addition of diethylzinc to aldehydes

New highly constrained chiral C1-1,1′-bisisoquinoline ligands have been synthesized. X-ray crystallographic analysis of these ligands showed peculiar structural differences between the parent 1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline and its alkyl, acyl and sulfonyl derivatives. The consequences of their geometrical conformations on enantioinduction were examined by employing the enantioselective addition of diethylzinc to aldehydes. Such conformations greatly affected the catalytic efficiency of these ligands.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(+)-1′,2′,3′,4′-Tetrahydro-1,1′-bisisoquinolineC18H16N2[α]D25=+202.0 (c 0.90, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate

(+)-N′-Methyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC19H18N2[α]D25=+159.7 (c 1.13, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate

(+)-N′-(2-Hydro-5-nitro-benzyl)-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC25H21N3O3[α]D25=+62.5 (c 0.77, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate

(+)-N′-Ethanoyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC20H18N2O[α]D25=+399.4 (c 0.65, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate

(+)-N′-Tosyl-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolineC25H22N2O2S[α]D25=+243.5 (c 1.0, CH2Cl2)Source of chirality: diastereomeric resolution with (S)-(−)-α-methylbenzyl isocyanate