Salicylaldehyde Schiff bases derived from 2-ferrocenyl-2-amino alcohols. Part 1: New chiral ligands for the titanium-catalyzed enantioselective cyanation of aldehydes

The condensation of a set of diversely substituted (S)-2-amino-2-ferrocenyl ethanol derivatives 1a–e with the salicylaldehydes 5A–C resulted in the generation of a small library of new chiral Schiff base-ligands, whose titanium isopropoxide complexes have been tested as catalysts in the asymmetric addition of trimethylsilyl cyanide to aldehydes. The enantioselectivity of the reaction is strongly influenced (a) by the substitution pattern of the 2-amino-2-ferrocenyl ethanol moiety, and (b) by the nature of the C3′ substituent in the salicylaldehyde. Computational modelling of the intermediate transition state complexes (based on the Schiff base, benzaldehyde, isopropoxide and cyanide bonded to titanium) show that the experimental results can be accommodated by a careful analysis of the steric interactions between the 2-aminoethanol and salicylaldehyde moieties, and the metal-coordinated aldehyde.

Chiral Schiff base–alkoxytitanium complexes derived from salicylaldehydes and from a set of diversely substituted (S)-2-amino-2-ferrocenylethanols have been prepared and tested as catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes.Figure optionsDownload as PowerPoint slide

(1S,2R)-1-Azido-1-ferrocenyl-2-propyl acetateC15H17FeN3O2Er = 98:2[α]D23=+91.3 (c 0.560, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2R)-1-Amino-1-ferrocenyl-2-propanolC13H17FeNOEr = 98:2[α]D23=+70.1 (c 0.510, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1R,2S)-2-Amino-2-ferrocenyl-1-phenylethanolC18H19FeNOEr = 99.5:0.5[α]D23=-11.5 (c 0.260, CH2Cl2)Source of chirality:asymmetric synthesisAbsolute configuration:(1R,2S)

2-[((S)-1-Ferrocenyl-2-hydroxyethylimino)methyl]phenolC19H19FeNO2Er = 99:1[α]D23=+203.0 (c 0.280, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-[((1S,2R)-1-Ferrocenyl-2-hydroxypropylimino)methyl]phenolC20H21FeNO2Er = 98:2[α]D23=+481.0 (c 0.570, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2R)

2-[((S)-1-Ferrocenyl-2-hydroxy-2-methylpropylimino)methyl]phenolC21H23FeNO2Er = 97:3[α]D23=+443.0 (c 0.290, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-tert-Butyl-6-[((S)-1-ferrocenyl-2-hydroxyethylimino)methyl]phenolC23H27FeNO2Er = 99:1[α]D23=+240.0 (c 0.290, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-tert-Butyl-6-[((1S,2R)-1-ferrocenyl-2-hydroxypropylimino)methyl]phenolC24H29FeNO2Er = 98:2[α]D23=+469.0 (c 0.210, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2R)

2-tert-Butyl-6-[((S)-1-ferrocenyl-2-hydroxy-2-methylpropylimino)methyl]phenolC24H29FeNO2Er = 97:3[α]D23=+419.2 (c 0.230, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-tert-Butyl-6-[((S)-1-ferrocenyl-2-hydroxy-1-methylethylimino)methyl]phenolC24H29FeNO2Er = 96:4[α]D23=+139.2 (c 0.80, CHCl3)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-Adamantyl-5-methyl-6-[((S)-1-ferrocenyl-2-hydroxyethylimino)methyl]phenolC30H35FeNO2Er = 99:1[α]D23=+204.2 (c 0.360, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(S)

2-Adamantyl-5-methyl-6-[((1S,2R)-1-ferrocenyl-2-hydroxypropylimino)methyl]phenolC31H37FeNO2Er = 98:2[α]D23=+408.3 (c 0.570, EtOH)Source of chirality:asymmetric synthesisAbsolute configuration:(1S,2R)

2-Adamantyl-5-methyl-6-[((S)-1-ferrocenyl-2-hydroxy-1-methylethylimino)methyl]phenolC31H37FeNO2Er = 96:4[α]D23=+137.6 (c 0.50, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

2-[((S)-1-Ferrocenyl-2-hydroxy-2-methylpropylamino)methyl]phenolC21H25FeNO2Er = 97:3[α]D23=+61.9 (c 1.350, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

2-tert-Butyl-6-[((S)-1-ferrocenyl-2-hydroxyethylamino)methyl]phenolC23H29FeNO2Er = 99:1[α]D23=+13.4 (c 0.400, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

2-tert-Butyl-6-[((1S,2R)-1-ferrocenyl-2-hydroxypropylamino)methyl]phenolC24H31FeNO2Er = 98:2[α]D23=+180.8 (c 0.520, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)