Aldehyde ferrocenyl

Since electron-donating substituents at the phosphorus atom favor addition reactions over olefination reactions, addition of 9 to aldehydes leads to the exclusive formation of the silyl-pro-tected allylic alcohols 10. No reaction products arising from Wittig alkenylation could be detected. The ylides (R,S)-9 and (S.S)-9 and their enantiomers were prepared from the corresponding optically pure l-[2-(diphenylphosphino)ferrocenyl]-A,A -dimethylethanamine diastereomers 7 via the phosphonium salts 8. 

The gold complex, generated in situ from bis(4-isocyanocyclohexyl)gold(I) tetrafluoroborate and (A)-A-methyl-,V-[2-(dialkylamino)ethyl]-l-[(5)-r,2-bis(diphenylphosphino)ferrocenyl]eth-ylamine, is an effective catalyst for the aldol reaction of various aldehydes with methyl iso-cyanoacetate to give the trans- and cw-4,5-dihydro-l,3-oxazoles. Depending on the aldehyde, the transjeis product ratio ranges from 84 16 to 100 0, and the ee of the main diastereomer is between 72 and 97%26. 

Scheme 10.39 Ferrocenyl sulfide-catalysed epoxidations of aldehydes.

Chinese researchers reported a synthetic route to photochrome 16 (Scheme 7), in which the aldehyde functions are then transformed into cyclic acetals and thioacetals, methylol and dicyanoethylene groups (07T5437, 08T2576). Scheme 7 also gives (at the bottom) symmetrical photochrome 17 (where R are ferrocenyl substituents), which does not exhibit fluorescence in the initial state, but shows fluorescence in the cyclic form and which is also synthesized starting from dialdehyde 16 (08AFM302). 

The homochiral ferrocenyl 1,4-thiazepines 72 were used for the asymmetric transformation of aldehydes into epoxides 74. The reaction involved the formation of an intermediate sulfur ylide 73. The ee s were up to 94%, although the diastereoselectivity remains to be controlled, being 60 40-82 18 in favor of the trans-oxirane 74 (Scheme 8) <2004TA3275>. 

The direct strong steric interaction between substrate substituents and ligand substituents has been demonstrated in asymmetric addition of diethylzinc to aldehydes catalysed by sterically congested ferrocenyl aziridino alcohol derivatives.114 In addi- tion, this non-bonded steric repulsion influenced enantioselectivities significantly, and even led to inversion of the absolute configuration. This fact was further confirmed by theoretical calculations and the design of a new chiral ferrocenyl aziridino alcohol ligand. 

Roberts et al. have observed the unusual fragmentation of loss of formaldehyde in methyl esters of ortho-substituted ferrocenyl-benzenes 172). This novel fragmentation of loss of aldehyde has also been observed by Lupin et al. for methyl, ethyl, and n-propyl esters of ortho-substituted ferrocenyl benzenes as well as for methyl esters of alkenyl ferrocenes 134). The ortho effect, in a rearrangement depicting a six-membered transition state, has been proposed by Bursey et al. to explain this fragmentation, but it is more likely that the metal atom plays an important role, possibly with the migration of the methoxyl group to the metal 134). 

Ferrocenyl-substituted aldehydes have also been prepared by a Suzuki reaction [46]. 

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. 

On the other hand, some experimental results are in agreement with the predominance of path b (Fig. 24) they arc due in particular to the aptitude of a very large number of substrates to react readily with aldehydes (see references reported for 12 and Ref. 274). Indeed, several successful syntheses of Mannich bases have been carried out starting from the hydroxymethyl derivative of the substrate, as reported for C-Mannich bases obtained from ferrocenyl derivatives,- nitroalkanes. - and hydrogen cyanide as well as for N-, S-, P-Mannich bases of benzimidazoles, sulfonic acids,- phosphines, etc. 

Ferrocene derivatives coupled with heterocyclic systems have attracted special attention in recent years because of their interesting organic and inorganic properties. Recently, an efficient and rapid route for the synthesis of 4-aryl-2-ferrocenyl-quinolines 70 has been described by Tu and co-workers [116] through a microwave-assisted MCR of acetylferrocene with an aromatic aldehyde and dimedone in the presence of ammonium acetate in DMF. This novel procedure provides the target hetero-metallic compounds in excellent yields without the need of any purification (Scheme 54). 

Ferrocenyl ketones (287) and ferrocenyl aldehyde (288) readily undergo a number of classic organic transformations, such as aldol, Knoevenagel, and Wittig reactions. Conversion of (288) into the dimethylaminoacetonitrile (317)... 

Table 4. Asymmetric addition of diethylzinc to aldehydes in the presence of chiral ferrocenyl compounds...

For the stereoselective formation of diastereomeric products, it was recognized at an early stage that the U-4CR can proceed stereoselectively if chiral primary amines and aldehydes are employed as the reactive components. The peptide derivatives 17 can only be formed if the amino component 14 contains an alkyl group that can be replaced by a proton in 16 producing 17 (Scheme 3).P l The essential problems were first solved separately by a variety of experimental investigations.It was found that chiral, a-ferrocenyl-substituted alkyl-amines 18 are able to fulfill all the requirements of peptide synthesis by stereoselective U-4CRs (Scheme 4).hi New, efficient methods were developed for the preparation of alkyl-amines in order to investigate their role in the synthesis of peptide derivatives by the... 

Enantioselective Addition of Dialkylzinc to Aldehydes Catalyzed by Chiral Ferrocenyl Aminoalcohols... 

Fig. 3-2. Chiral ferrocenyl amino alcohol catalysts employed in alkylation of aldehydes with dialkylzincs.

Disubstituted ferrocenyl amino alcohols 20a—u were derived from 3, 21 — 23, and 25 by treatment with n-butyllithium followed by reaction with a carbonyl compound. When aldehydes were used as carbonyl component, two chromatogra-phically separable diastereomers (20a—b, 20c—d, 20i—j, 201—m, 20q—r) were obtained. In the cases of 20h, 20k, and 20u, the diastereomeric mixtures were isomerized to single diastereomers without separation by treatment with aqueous phosphoric acid. The yields and the properties of 20 are summarized in Table 3-4. The absolute configuration of the two diastereomers was tentatively assigned on the basis of their NMR spectra, their stability to aqueous phosphoric acid, and spectral comparison with 20n, absolute configuration of which was confirmed by single-crystal X-ray analysis [35]. 

In Section 3.5.2 we described the highly enantioselective addition of dialkylzinc to achiral aldehydes catalyzed by chiral 1,2-disubstituted ferrocenyl amino alcohols, which shows high stereoselectivity even in the alkylation of a-branched aliphatic aldehydes. In order to further develop the characteristics of our catalysts, the ethylation of aldehydes substituted with an a-thio- and seleno group was investigated. 

Optically active ferrocene derivatives, particularly ferrocenyl phosphines, have hitherto been utilized as chiral ligands for a wide range of asymmetric synthesis. We have now revealed that the ferrocene moiety can easily be incorporated in amino alcohol ligands instead of phosphinic ligands. The preparative methods for several types of ferrocenylamino alcohols were developed and they were successfully used to catalyze enantioselective addition of dialkylzinc to aldehydes with high enantio-selectivity. In particular, 1,2-disubstituted ferrocenyl amino alcohols with planar... 

If an achiral ferrocene derivative is converted to a chiral one by chiral reagents or catalysts, this may be called an asymmetric synthesis. All asymmetric syntheses of ferrocene derivatives known so far are reductions of ferrocenyl ketones or aldehydes to chiral secondary alcohols. Early attempts to reduce benzoylferrocene by the Clemmensen procedure in (5)-l-methoxy-2-methylbutane as chiral solvent led to complex mixtures of products with low enantiomeric excess [65]. With (25, 3R)-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol as chiral modifier for the LiAlH4 reducing agent, the desired alcohol was formed with 53% ee (Fig. 4-9 a) [66]. An even better chiral ligand for LiAlH4 is natural quinine, which allows enantioselective reduction of several ferrocenyl ketones with up to 80% ee [67]. Inclusion complexes of ferrocenyl ketones with cyclodextrins can be reduced by NaBH4 with up to 84% enantioselectivity (Fig. 4-9 b) [68 — 70]. 

The synthesis of the required acids was effected as outlined below. Condensation of the cyclic ketone (XXVI) with- dimethylsulfonium methylide 10 ) afforded a mixture of exo and endo aldehydes (XXVIII and XIX) on acid work-up of the reaction. The very great ease with which the intermediate epoxide (XXVII) undergoes acid catalyzed isomerization is not surprising in view of the very great stability of a-ferrocenyl carbonium ions previously noted. 

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