Síntesis y estudio de nuevos derivados ciclometalados del ferroceno / Synthesis and study of new cyclometallated derivatives of ferrocene

Abstract

The present Doctoral Thesis focuses in two main fields: alkyne-dicobaltcarbonyl complexes (PART I) and chiral ferrocene derivatives (PART II). Therefore, the obtained results can be summarized as follow: <br/><br/>1. The methodology designed for the synthesis of enantiomerically pure phosphane-substituted carbonyl complexes of propargyl aldehyde was not successful. The steric hindrance at position C-4 of the oxazolidin-2-one and oxazolidin-2-thione appears to difficult the removal of the auxiliary in the corresponding N-(2-alkynoyl) dicobaltcarbonyl complexes.<br/><br/>2. The general catalytic behavior of octacarbonyl dicobalt in the opening of cyclic ethers, such as tetrahydrofuran, by acid chlorides, leading to 4-chlorobutyl esters, has been demonstrated.<br/><br/>3. A pathway to access 1'-substituted and 2-substituted beta-ferrocenyl beta-amino alcohols has been developed. In this way, the synthesis with a high level of enantiomeric purity of (S)-2-amino-2-(1'-methyl)ferrocenylethanol, (pS,R)-2-amino-2-(1-trimethylsilyl)-ferrocenyl ethanol and (pR,R)-2-amino-2-(1-methyl) ferrocenyl ethanol has been achieved via their corresponding diols.<br/><br/>4. A general methodology which gives easy access to mono and disubstituted (1,1'- and 1,2-) 4-ferrocenyl-1,3-oxazolines has been developed.<br/><br/>5. A new type of interannular cyclopalladation of ferrocene has been established. The reaction seems to be quite general for 4-ferrocenyl-1,3-oxazolines with different degrees of substitution of the ferrocene moiety, provided that the C2-oxazoline substituent bears no á-hydrogens. The reaction of 4-ferrocenyl-1,3-oxazolines with palladium acetate in benzene leads to the formation of C2-symmetric complexes with two ferrocene moieties cycloplalladated at the 1' position, connected by a central palladium and four acetate bridges. When the cyclopalladation is performed by disodium tetrachloropalladate, a similar complex, but with two chloride bridges, is obtained. The 3-palladium acetate complexes can be converted into the 2-palladium chloride ones by treatment with lithium chloride in methanol. The structures of both types of complexes have been thoroughly studied by spectroscopy and by X-ray diffraction.<br/><br/>6. Cyclic voltammetric studies of these novel interannular palladacycles have been performed.<br/><br/>7. The µ-chloro bridged dipalladium complex (S)-84 undergoes bridge-splitting with triphenylphosphine leading in nearly quantitative yield to the monomer complex (S)-95. On the other hand, the reaction of (S)-84 with iodine affords 1'-iodo-2-tert-butyl-4-ferrocenyl oxazoline (S)-100. This compound has been converted into 1'-phenyl-2-tert-butyl-4-ferrocenyloxazoline (S)-101 by Suzuki coupling with phenylboronic acid. Finally, (S)-84 leads in good yields to the 1'-diphenylphosphinyl- and 1'-diphenylphosphinothioyl ferrocenes (S)-103 and (S)-104. <br/><br/>8. Interannularly palladated 4-ferrocenyl-1,3-oxazolines behave as active promoters of the Heck olefination, allowing the reaction to be performed at lower temperatures than previously known CN-palladacycle pre-catalysts derived from ferrocene. In the reaction medium, the olefin partner couples with the 1'-position of the ferrocene, leading to the formation of soluble palladium(0) catalytic species. For the first time, the ligand-olefin adduct has been isolated and unequivocally characterized, and further evidence favoring the involvement of a Pd(0)/Pd(II) catalytic cycle has been obtained.<br/><br/>9. The new interannular cyclopalladated ferrocenes have been found to be good catalysts for the asymmetric aza-Claisen rearrangement. Thus, the rearrangement of (E)-cinnamyl N-aryl benzimidates 129-131 takes place with moderate yields (40-49%) and with excellent enantioselectivity (up to 90% ee of the rearranged amide 138). Interestingly enough, the acetate-bridged 3Pd complexes lead to the (S) enantiomer of the rearranged allylic amide, while the chloride bridged 2Pd complexes (from the same (S)-enantiomer of the chiral 4-ferrocenyl-1,3-oxazoline) lead to the opposite (R) enantiomer of the amide.<br/><br/>10. New and outstanding catalysts for the aza-Claisen rearrangement of (E)- and (Z)-allylic trichloroacetimidates have been found. The rearrangement of both (E)- and (Z)-hexenyl trichloroacetimidates, performed in chloroform solution at 38oC with a molar 5% of the chloride bridged 1'-cyclopalladated complex, takes place with quantitative conversion and with outstanding enantioselectivity (>98% ee), according to 1H-NMR and HPLC analyses. Intriguingly, both diastereomers of the starting imidate lead to the same enantiomer (S) of the rearranged amide 142.