Synthesis and properties of chiral ferrocenylalcohols and diols

Chiral ferrocenyl derivatives find applications in different fields of chemistry, the most important being their use as ligands in asymmetric catalysis. The peculiar chemistry of the metallocene system makes possible a modular and selective modification of the structure of ferrocene-based catalysts in order to achieve a fine tuning of their electronic and steric properties and improve the efficiency and stereoselectivity of the asymmetric reaction. Although the major part of ferrocenyl ligands are P,N- or N,N-ligands, their preparation often uses chiral ferrocenylalcohols or diols as starting material and different protocols can be applied on the basis of the structural pattern of the target ferrocene. A classification of chiral ferrocenylalcohols and diols according to their structure and, consequently, their stereochemical properties, is here proposed and the related preparation methods are reviewed with a main focus on the asymmetric reactions rather than the racemate resolution procedures. The asymmetric reduction of achiral ferrocenylketones has gained much interest since the corresponding optically active ?-ferrocenylalcohols experience nucleophilic substitution of the hydroxyl group with complete retention of configuration giving access to a large number of homochiral derivatives. Asymmetric hydrogenation as well as reduction with borane as hydride source have been found effective in the preparation of alpha-ferrocenylalcohols and have been applied to a variety of ferrocenylketones and diketones. Asymmetric Sharpless' dihydroxylation of ferrocenylalkenes has been exploited for the synthesis of some ferrocenyldiols whereas a number of difunctionalised alcohols have been obtained by reaction of ferrocenecarboxaldehydes with chiral reagents. The large group of planar chiral ferrocenylalcohols is mainly characterized by the 1,2-substitution pattern and they are usually prepared in enantiopure form through diastereoselective metalation of some suitable chiral ferrocenes followed by electrophilic quenching of the intermediate ferrocenyl carbanion. A short survey of the properties of ferrocenylalcohols, including their chemical behavior and methods useful for their characterization is also presented, together with the more recently reported application of O,N- or O,O-ferrocene ligands in asymmetric catalysis.