Synthesis Of The Ferrocene-based Squaramide-phosphine Organocatalysts And Their Application In Asymmetric Intramolecular MBH Reaction

Asymmetric organocatalysis has emerged in the past decade as a powerful tool incontemporary organic synthesis and grown into three pillars of asymmetric catalysistogether with biocatalysis and metal catalysis. However, compared with the transitionmetal complex catalysts, the ratio of chiral organocatalyst is still high, the scope of thesubstrate is also limited, and the enantioselectivities need to be further improved in someasymmetric organocatalytic reactions. Currently, very few efficient catalysts were appliedin the industrial production. Therefore, development of the novel high efficient chiralorganocatalysts is a hot topic in the symmetric organocatalysis. So far, numerousorganocatalysts, developed in the past decade, have been rooted in several core structures,such as amino acids,1,2-diamines, β-amino alcohols, cinchona alkaloids, binaphthyl, etc.Very strangely, ferrocene, a “privileged framework” for the construction of effective chiralligands in metal catalysis has not been exploited as a backbone of organocatalysts.Ferrocene derivatives, with planar chirality, rigidity, special electronic and steric properties, are expected to be efficient catalysts in asymmetric organocatalysis, and wehave achieved encouraging results in the past two years. On this basis, we have carried outthe following work in this this paper:1. The novel ferrocene-based squaramide-phosphine chiral bifunctionalorganocatalysts I-IV were designed. These catalysts contained both Lewis base functionalgroup (tertiary phosphine) and Br nsted acid hydrogen bond donor (squaramide), which isin favor of the formation of the enolates intermediates. On the other hand, these catalystscontained planar chirality and C-chirality for studying the effect of stereo genes on thestereoselectivity.2. Catalysts I-IV were easily prepared from Uig’s amine. The total yields were47.9%-50.0%respectively, and the structure of these catalysts were characterized by1HNMR、31P NMR、13C NMR、HRMS spectrum.3. We found that the novel ferrocene-based squaramide-phosphine organocatalystsexit as a mixture of two conformational isomers through the NMR spectra and speculatedthe causes of the phenomenon.4. Catalysts I-IV were applied in the asymmetric intramolecular MBH reaction. Theprocess afforded the cyclic hydroxyl enones with up to85%yield and96%ee under mildconditions.5. The mechanism of the asymmetric intramolecular MBH reactions catalyzed by thenovel ferrocene-based squaramide-phosphine organocatalysts was proposed and thepossible transition state was speculated.This study was beneficial exploration for the development of ferrocene-basedorganocatalysts, and provided more types of “privileged framework” and ideal models forthe construction of effective chiral organocatalysts.