Synthesis of chiral alcohols containing the 1,3-diferrocenylpropane structural motif

The Claisen–Schmidt condensation of ferrocenecarboxaldehyde with acetylferrocene under microwave irradiation was applied as a simple route to gain access to 1,3-diferrocenyl-1-oxo-prop-2-ene 2, whereas the analogous reaction with 1,1′-diacetylferrocene afforded the 1,1′-disubstituted α,β-enone 13 with three ferrocene units and/or 1,5-dioxo-3-ferrocenyl[5]ferrocenophane 14, depending on the experimental conditions. Michael addition of acetylferrocene enolate to 2 afforded 1,3,5-triferrocenyl-1,5-dioxopentane 7, whose formation was also evidenced during the double bond hydrogenation of 2 on Pd/C as a result of an unusual reaction.The study of the asymmetric reduction of 2 in the presence of CBS/borane system revealed that this enone was not a suitable substrate for the reaction, with it mainly being converted into the corresponding alkene. On the other hand, the reduction of the saturated ketones proceeded with high stereoselectivity affording novel chiral ferrocenylalcohols possessing multiple ferrocene units.

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(S)-1,3-Diferrocenyl-1-hydroxypropaneC23H24Fe2OEe = 97% (by chiral HPLC)[α]D = +18.2 (c 0.7, CHCl3)Source of chirality:asymmetric reduction of 1,3-diferrocenyl-propan-l-oneAbsolute configuration:(S)

(1S,5S)-1,3,5-Triferrocenyl-1,5-dihydroxypentaneC35H36Fe3O2Ee = 97% (by chiral HPLC)[α]D = +2.6 (c 0.6, CHC13)Source of chirality:asymmetric reduction of 1,3,5-triferrocenyl-1,5-pentanedioneAbsolute configuration:(S,S)

(S,S)-2,4,6-TriferrocenyltetrahydropyraneC35H34Fe3OEe = 97%[α]D = +7.6 (c 0.4, CHCl3)Source of chirality:chiral diolAbsolute configuration:(S,S)

(S,S)-1,5-Dihydroxy-3-ferrocenyl[5]ferrocenophaneC25H26Fe2O2Ee = >98% (by chiral HPLC)[α]D = −11.6 (c 0.6, CHCl3)Source of chirality:asymmetric reduction of l,5-dioxo-3-ferrocenyl[5]ferrocenophaneAbsolute configuration:(S,S)

(S,S)-1,1′-Bis(3-ferrocenyl-1-hydroxypropyl)ferroceneC36H38Fe3O2Ee = 98% (by chiral HPLC of corresponding methoxy derivative)[α]D = −2.7 (c 0.3, CHCl3)Source of chirality:asymmetric reduction of 1,1′-bis(3-ferrocenyl-propanoyl)ferroceneAbsolute configuration:(S,S)

(S)-1,3-Diferrocenyl-1-dimethylaminopropaneC25H29Fe2NEe = 97%[α]D = +2.3 (c 0.6, CHCl3)Source of chirality: chiral precursorAbsolute configuration: (S)

(S)-1,3-Diferrocenyl-1-azidopropaneC23H23Fe2N3Ee = 97%[α]D = +27.0 (c 0.4, CHCl3)Source of chirality: chiral precursorAbsolute configuration: (S)