Phosphanes ferrocenes

Ferrocene-bridged phosphole-phosphane ligands and their activity in palladium-catalyzed allylic substitution <2006EIJC5148>. 

We will now turn our attention towards the synthesis and application of phosphane functionalised carbenes. A very interesting class of ligands is based on the ferrocene [265-267] scaffold. Cp functionahsed carbenes will be discussed in Section 4.3 and we will find our ferrocene functionalised carbenes there as well. However, the synthesis of the ligands involves a strategy to introduce the phosphane and carbene moieties onto the ferrocene scaffold in a way that optimises results despite the fact that both groups are best introduced last. 

The prototype for Cp-modified NHC ligands comes, as usual for functionalised carbene ligands, from phosphane chemistry, in this case from the well known l,l -bis(diphenylphos phino)ferrocene (dppf) [163,164]. A recent example was introduced by Coleman et al. [165] using a synthetic route that is very similar to the protocol used for the formation of ferrocene... 

When coordinated to a gold centre, the Fc functionalised NHC ligand devised by Horvath et al. shows cytotoxic properties [144]. It is not quite clear what the role of the ferrocene substituent is since the ferrocene is in the para position of the phenyl wingtip group. One might think that such an architecture would render the Fc group sterically irrelevant and electronically somewhat of lesser importance. However, gold(I) phosphane and NHC complexes are known for their antitumour activity [184]. 

We are already well accustomed with the historical relationship seen in the development of NHC ligands with special features. They often follow the example of successful phosphane ligands. Chiral NHC are no exception, although in key areas the very difference in shape between NHC and phosphanes prevents the development of NHC ligands as structural phosphane mimics. The axial (atropisomers with binaphthyl backbone [6,7]) and planar (ferrocene derivatives [8,9], [2,2]-paracyclophanes [10,11]) chiral examples, however, are styled on their phosphane predecessors [12-15]. We will first look at the unique options for NHC ligands before we turn to the more familiar phosphane mimics. 

Naturally, it is possible to synthesise a similar ligand system without central chirality and in fact without the unnecessary methylene linker unit. A suitable synthesis starts with planar chiral ferrocenyl aldehyde acetal (see Figure 5.30). Hydrolysis and oxidation of the acetal yields the corresponding carboxylic acid that is transformed into the azide and subsequently turned into the respective primary amine functionalised planar chiral ferrocene. A rather complex reaction sequence involving 5-triazine, bromoacetal-dehyde diethylacetal and boron trifluoride etherate eventually yields the desired doubly ferrocenyl substituted imidazolium salt that can be deprotonated with the usual potassium tert-butylate to the free carbene. The ligand was used to form a variety of palladium(II) carbene complexes with pyridine or a phosphane as coligand. 

A similar but chiral ligand system 110 was developed by Hidai by treatment of the known ferrocene 109 with hydrogen peroxide followed by methyl-ation with Mel and subsequent treatment of the ammonium salt with sodium cyclopentadienide and reduction of the phosphane oxide with LiAlH4 (Scheme 17). 

Sondenecker A, Cvengros J, Aardoom R, Togni A (2011) P-stereogenic ferrocene-based (trifluoromethyl)phosphanes synthesis, structure, coordination properties and catalysis. Eur J Org Chem 2011 78-87. doi 10.1002/ejoc.201001162... 

The pro-ligands 16-R (Scheme 5.10) led to (carbene)rhodium(I) complexes upon deprotonation in the presence of potassium ferf-butoxide and [RhCl(COD)]2 in THF (Scheme 5.12), followed by chloride abstraction, which could also be carried out with AgBF4/CH2Cl2 without oxidization of the ferrocene unit. While the selectivity for 20-Mes was almost total, complex 20-Me was obtained along with another carbene/phosphane complex in a 85 15 ratio, the minor species... 

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