1-Amino-1-ferrocenyl-2-methyl-2-propanol: a case study on the conformational control of asymmetric induction

Abstract

Evidence gathered both from X-ray diffraction data and from molecular modelling studies suggests that the introduction of a gem-dimethyl moiety at C1 in 2-amino-2-ferrocenylethanol should exert strong conformational control on the ferrocenyl group when this compound is incorporated into a heterocyclic ring. In order to test this hypothesis, we have developed an efficient, enantioselective and enantiodivergent route to 1-amino-1-ferrocenyl-2-methylpropan-2-ol. According to our expectations, the corresponding 1,3-oxazolidin-2-one (Fc-‘SuperQuat’) exhibited excellent diastereofacial selectivity in the Diels–Alder reaction of its N-crotonyl derivative with cyclopentadiene, in sharp contrast to the lack of diastereoselectivity observed when using the unsubstituted 4-ferrocenyl-1,3-oxazolidin-2-one. In a similar way, the presence of a gem-dimethyl group at C5 in a 2-(2-diphenylphosphinophenyl)-4-ferrocenyl-1,3-oxazoline (Fc-PHOX) ligand brings about a major change in the enantioselectivity of the palladium-catalyzed asymmetric allylic substitution by dimethyl malonate anion, and leads to unprecedented (for PHOX ligands derived from acyclic 2-amino alcohols) levels of asymmetric induction in substrates such as ( E)-1,3-dimethyl-2-propenyl and 2-cyclohexenyl acetates.