The Asymmetric Self-Replicative Alkylation of N-Arylaldimines Using Organolithium Reagents

Among the possible explanations for the origin of homochirality on Earth, the propagation of a minute chiral imbalance by asymmetric amplification in chemical reactions, that is, asymmetric autocatalysis, has been widely studied since the 1950s. Despite significant efforts by the chemical community, only one experimental asymmetric autocatalytic system has been reported to date: the enantioselective addition of diisopropyl zinc to pyrimidyl aldehydes, the Soai reaction. Here, we present the rational design of a new transformation that exhibits asymmetric autoinductive behavior: the reaction of organolithium reagents with N-arylaldimines toward the formation of chiral lithium amides. Although our investigations into a variety of reaction systems did not result in chiral amplification, we achieved chiral replication in the alkylation of (E)-1-(2-methoxyphenyl)-N-phenylmethanimine. The addition of ⁿBuLi this imine in the presence of a 20% enantiomeric excess (ee) solution of N-(1-(2-methoxyphenyl)pentyl)aniline afforded the desired butylated product in 20% ee, for both the (S)-and (R)-enantiomers, representing the first example of organolithium reagents being used in asymmetric autoinductive reactions.