Nickel-accelerated addition of dialkylzinc reagents to aldehydes. Application to enantioselective synthesis

Abstract

The reaction of several dialkylzinc reagents with aromatic aldehydes 1 in the presence of a catalytic amount of nickel(II) acetylacetonate (5 mol%) at 0 ºC gave the expected addition products 2 in 1 h in very good yields. Aliphatic aldehydes 1 required stirring at room temperature for 24 h to afford the addition products in good yields. In comparison with non-catalyzed reactions this process represents a great improvement in reaction rate and selectivity for the formation of addition products. The enantioselective addition of diethylzinc to benzaldehyde 1a in the presence of the nickel catalyst and chiral aziridino alcohols 3 results in an interesting switch of the sense of the asymmetric induction in comparison with the nickel-free process.

Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands

“…Under the optimized conditions, all of the catalysts afforded excellent yields and the enantioselectivities towards (S)-1-phenyl-1-propanol displayed a clear dependence on the amino acid substituent (Table 5). As predicted, and as observed for related systems, 7,18 higher values of enantioselectivities were achieved for bulky substituents.…”

“…17 Only in the last decade nickel complexes, more suitable in terms of cost and environmental impacts, have been described as efficient catalysts for related reactions. 7,18 On the other hand, bis(amino amides) 2 containing aliphatic spacers have been prepared by our group as precursors of macrocyclic pseudopeptides being able to act as chiral solvating agents for enantiomeric excess determination of α-hydroxy acids, 19 in enantioselective catalytic processes, 20 forming a nanoporous architectures, 21 and chelating transition metals. 22 Bis(imino amide) derivatives 3 containing an ortho-substituted aromatic spacer derived from 1,2-diaminobenzene have also been reported to form a catalytic tetradentate complex with zinc in the presence of ZnR 2 species, affording excellent enantioselectivities in the addition to aldehydes.…”