Efficient asymmetric addition of diethylzinc to aldehydes using C₂‐novel chiral pyridine β‐amino alcohols as chiral ligands

Abstract

A series of novel C 2 -symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1 H NMR, 13 C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)-2,2′-((pyridine-2,6-diylbis(methylene)) bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)-2,2′-((1,3-phenylenebis(methylene))bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction.

Deciphering the mechanism behind efficient enantioselective ethylation with thiazolidine‐based amino alcohols

“…[ 12,13 ] Although the study of this particular reaction is the subject of extended bibliography, focused on the synthesis of several classes of ligands and evaluation of their catalytic performances, they are often associated with long and expensive synthetic sequences and a narrow range of aromatic aldehydes as substrates. [ 14–38 ] Additionally, the conceptualization and interpretation of the observed enantioselectivities is still scarcely explored. Since Noyori's pioneering investigation on the mechanism of enantioselective alkylation, [ 39,40 ] mostly supported by electronic structure calculations, other authors have resorted to this approach for insight on the features of their ligands, as well as the type of interaction with the remaining reagents, that allow them to exhibit a certain type of chiral induction.…”

d-Penicillamine and l-cysteine derived thiazolidine catalysts: an efficient approach to both enantiomers of secondary alcohols

“…Besides creating a new chiral center from the carbonyl carbon, the reaction allows for the elongation of the carbon chain in the alcohol relatively to the parent aldehyde. [1][2][3][4][5][6][7] Many types of chiral ligands have been used in this process, namely, diamines and their derivatives, diols and amino alcohols, among others giving products with high enantiomeric excesses. 8,9 Ligands with cyclic or bicyclic structures are especially good candidates as chiral ligands due to their rigid backbone structures.…”

Enantioselective Conjugate Addition of Catalytically Generated Zinc Homoenolate

“…(S)-2-(Dimethylamino)-3-methyl-1,1-diphenylbutan-1-ol (L2): 29 Prepared according to the literature procedure. 30 A 25-mL round bottom flask equipped with a magnetic stir bar was charged with (S)-2-amino-3-methyl-1,1-diphenylbutan-1-ol 31 (255 mg, 1.00 mmol), paraformaldehyde (300 mg, 10.0 mmol), methanol (6 mL), and acetic acid (0.1 mL), followed by the addition of NaBH3CN (189 mg, 3.00 mmol). The resultant black suspension was stirred at 23 °C for 48 h and then filtered through a pad of Celite.…”

“…The organic solution was concentrated under reduced pressure, and the residue was purified by flash chromatography to afford the product as a pale yellow solid (222 mg, 78%); procedure. 20 A 25-mL round bottom flask equipped with a magnetic stir bar was charged with (S)-2-amino-1,1-diphenylpropan-1-ol 31 (1.00 g, 4.40 mmol), NaHCO3 (0.81 g, 9.68 mmol), and toluene (12 mL), followed by the addition of 1,3-dibromopropane (0.98 g, 4.84 mmol). After 48 h of reflux, the mixture was filtered through a pad of Celite.…”