Ferrocenes lithiation

Sulphoxide removal using sulphoxide-lithium exchange is also effective. It was employed in tandem with a sulphoxide-directed stereoselective ortholithiation of the ferrocene 105 in the synthesis of the phosphine ligand 106 (Scheme 45). Ferrocene lithiation is discussed further in Section III. 

Stannylated ferrocenes can be prepared by the reaction of a lithiated ferrocene with an organotin chloride, or of a lithiated stannylcyclopentadiene with FeCl2, for example, Scheme 10.305 The products can be described by the shorthand FcSn.. . where x and y indicate the number of stannyl substituents in each of the two rings. 

The ligands discussed so far all contained C2 symmetry. An important new class of ligands having Ci symmetry was introduced by Togni [22] (see Figure 4.19). They can be easily made from an enantiomeric amine as the precursor in a few steps. Different substituents can be introduced at the phosphorus atoms. In addition to the chiral carbon atom the molecule has planar chirality as well. The chiral carbon atom is used to introduce the planar chirality, i.e. lithiation of the ferrocenyl amine takes place at a specific side of the amine at the ferrocene moiety. 

Mono- and bis-tellurenyl ferrocenes are achieved respectively by treatment of lithiated fer-rocenes with butyltellurenyl bromide (route a) or with dibutyl ditelluride (route b). Mono tellurenyl ferrocene is also obtained in a two-step procedure by treating lithiated ferrocene with Te to give the ditelluride followed by reductive alkylation (route c). - ... 

Butyltelluroferrocene A solution of BuTeBr (freshly prepared from 8 mmol of BuTeTeBu and 8 mmol of Brj) was added to a THF solution of lithiated ferrocene (prepared from 10 mmol of ferrocene) at 0°C. The reaction mixture was stirred at room... 

By coordinating to arenes, transition metals can facilitate ring lithiation by decreasing the electron density in the ring and acidifying the ring protons. We shall consider briefly the two most important metal-arene complexes in this regard—arenechromium tricarbonyls and ferrocenes. 

Ferrocene is best deprotonated by f-BuLi/f-BuOK in THF at 0 since BuLi alone will not lithiate ferrocene in the absence of TMEDA and leads to multiple lithiation in the presence of TMEDA. In the example in Scheme 134, a sulphur electrophile and a Kagan-Sharpless epoxidation lead to the enantiomerically pure sulphinyl ferrocene 278. The sulphinyl group directs stereoselective ortholithiation (see Section I.B.2), allowing the formation of products such as 279. Nucleophilic attack at sulphur is avoided by using triisopropylphenyllithium for this lithiation. 

Despite the resolution which was required to produce the enantiomerically pure starting materials (which fortunately is highly efficient—recrystalhzation of the mother liquors allows isolation of both enantiomers) , Ugi s lithiation provided the basis for a rapid growth in the use of enantiomerically pure, planar chiral ferrocenes which has continued since. Several reviews have covered applications of enantiomerically pure ferrocenes as chiral ligands, which until the 1990 s were all made using Ugi s method... 

Attempts to make C2-symmetric ferrocenes by double lithiation of a bis-acetal met with only limited success . A second lithiation of the ferrocenylacetal 298 leads to functionalization of the lower ring of the ferrocene, in contrast with the second adjacent lithiation of the oxazolines described below. This can be used to advantage if, for example, the first-formed aldehyde 301 is protected in situ by addition of the lithiopiperazine 53 °, directing f-BuLi to the lower ring (Scheme 139) °. The same strategy can be used to introduce further functionalization to products related to 302. For example, silane 303, produced in enantiomerically pure form by the method of Scheme 138, may be converted to the ferrocenophane 304 by lithiopiperazine protection, lithiation and functionalization (Scheme 140) . 

A ferrocenyloxazoline with only one adjacent position available for deprotonation will lithiate at that position irrespective of stereochemistry. This means that the same oxazoline can be used to form ferrocenes with either sense of planar chirality. The synthesis of the diastereoisomeric ligands 311 and 313 illustrates the strategy (Scheme 143), which is now commonly used with other substrates to control planar chirality by lithiation (see below). Ferrocene 311 is available by lithiation of 305 directly, but diastereoselective silylation followed by a second lithiation (best carried out in situ in a single pot) gives the diastereoisomeric phosphine 313 after deprotection by protodesilylation ". ... 

Some success has been achieved by a method which bridges the gap between the use of a chiral base and the use of an auxiliary to functionalize ferrocenes stereoselectively. Double protection of the dialdehyde 340 by addition of the chiral amine 341, and lithiation with t-BuLi, gives a mixture of Uthiated species which lead to 342 and 343, in proportions dependent on the amount of f-BuLi employed (Scheme 151). Though the yields of each are not high, both products 342 and 343 are obtained in very high enantiomeric excess . ... 

Contemporaneously with Snieckus, Uemura and coworkers showed that ferrocene 369 bearing an aminomethyl group may also be lithiated enantioselectively by alkyllithi-ums to give 370 in these cases, better results are obtained with the C2-symmetric amine 368 than with (—)-sparteine (Scheme 157). 

Some headway has been made using sulphoxides to direct the lithiation of arenechromium tricarbonyls in the manner of Kagan s work with ferrocenes . Diastereoselectiv-ities in the lithiation-quench of 392 are excellent, though yields are poor with most electrophiles. Diastereoselectivity reverses on double lithiation, because the last-formed anionic site in 394 is the most reactive (Scheme 163). 

The malic acid-derived auxiliary which gives good results in the ferrocene series also looks promising among the chromium complexes, and the six-membered acetal of 400 is much more easily hydrolysed than the tartrate-derived acetals of Scheme 164 . Lithiation and bromination of 400 gives, after hydrolysis of the acetal, the complex 401 in 90% ee, increasing to >99% after recrystallization (Scheme 165). 401 is an intermediate in a formal synthesis of (—)-steganone (Scheme 182, Section III.B.2.b). 

A lithiated chiral ferrocene was also converted to the bis(ferrocenyl)cyano cuprate and aminated with 5h to yield an aminoferrocene (Scheme 50) °. 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

The synthesis of ferrocene 9 relied on chemistry introduced by Sammakia, Uemura, and Richards [18]. They had shown that 2-ferrocenyl oxazoline 10 derived from t-leucine could be selectively deprotonated and trapped with electrophiles to afford ortho-functionalized planar-chiral products 11 with excellent diastereoselectivities (Scheme 2.1.2.3). Following this strategy, 9 became accessible in a highly straightforward manner by trapping the lithiated intermediate derived from 10 with benzophenone [10, 11],... 

The method has the advantage that it ensures formation of pure monosubstituted ferrocene, free of the disilylated products. This procedure has been used also for lithiation of a cyclopentadienylcobalt derivative, which showed ferrocene-like behavior (R = Ph) (128, 129) ... 

Carbonation and subsequent hydrolysis of either lithiated or sodiated metallocenes lead to the corresponding carboxylic acids. Ferrocenecarboxylic acid and ferrocene-1,1 -dicarboxylic acid are readily produced in this manner and can be conveniently separated by extraction of the former with ethyl ether or benzene. The reaction of metalated ferrocenes with various chlorosilanes has led to a variety of triaryl- or trialkvlsilylferrocenes (3, 28, 90). 

Metalated ferrocenes have served as valuable intermediates for the synthesis of a number of other derivatives. Treatment of lithiated ferrocenes with tributyl borate followed by hydrolysis leads to ferroceneboronic acid (XXXIII) as well as the diboronic acid (73). Ferroceneboronic acid, like benzeneboronic acid, is readily cleaved by cupric bromide or cupric chloride to form the corresponding halo derivatives (XXXIV). Ferrocene-l,l -diboronic acid reacts in the same manner, and either one or two carbon-boron bonds can be cleaved. Further reactions of this type have led to a variety of mixed dihaloferrocenes (73, 75). 

During studies relating to the synthesis of certain trialkylsilylferrocenes from lithiated ferrocenes and trialkylchlorosilanes, Rausch and coworkers detected minute amounts of a dark orange crystalline substance which was subsequently shown to be biferrocenyl on the basis of analytical evidence (27, 92). To provide an unequivocal synthesis and a more satisfactory route to this compound, several alternative routes were investigated. 

Ferrocenes substituted with silicon-silicon groupings are prepared by (1) the reaction of lithiated ferrocenes with an appropriate chloropolysilane and/ or (2) lithiation of a cyclopentadienyldisilane followed by treatment with ferrous chloride. The following give examples (116,117) ... 

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