Discovery of Dipeptide‐Derived Catalysts for the Enantioselective Addition of Dimethylzinc to Aldehydes

Asymmetric Catalysis Mediated by Synthetic Peptides, Version 2.0: Expansion of Scope and Mechanisms

“…Building off of this body of work, Park and coworkers reported a peptide catalyzed method for the enantioselective alkylation of aldehydes with dimethylzinc. 217 Their strategy was to optimize a dipeptide scaffold without an N-terminal Schiff base that is able to chelate to and activate dimethylzinc for addition to prochiral aldehydes, such as 5.8, providing access to enantioenriched secondary alcohols 5.9 (Figure 84). All of the peptides examined adhered to the general sequence R 2 -Xaa-Pro-OMe (5.10), in which the N-terminus was either mono-or dialkylated.…”

Stereodivergent Catalysis

“…39 Further examples have been described such as the addition of dimethylzinc to aldehydes in the presence of proline derived dipeptides 22 (Figure 1) bearing different substituents in the N-terminus with low values of enantioselectivity. 42 The addition of diethylzinc to benzaldehyde catalyzed by (1S)ketopinic acid derived amides 23a and 23b (Figure 1) gave (R)-1-phenyl-1-propanol with ee up to 78% and the (S)-alcohol with ee up to 66%, respectively. 43 Another case of enantiodivergence in the addition of diorganozinc compounds to aldehydes has been described using diastereomeric aziridine diols as chiral ligands 24a and 24b 44 (Figure 1).…”

New advances in dual stereocontrol for asymmetric reactions

“…52,53 Kang and Park have reported in 2012 a chirality switching for the enantioselective addition of dimethylzinc to aldehydes catalysed by modular chiral catalysts derived from various amino acid-L-proline dipeptides. 54 The steric bulk of the N-substituents (R, see Scheme 19) played an important role in determining the enantioselectivity in such a way that both enantiomers of the product could be obtained by their appropriate tuning.…”