L. L. Troitskaya

Asymmetric cyclopalladation in the ferrocene series as a tool for enantioselective synthesis. Preparation of some analogues of natural products

Abstract The previously described asymmetric cyclopalladation has been applied to the esters of 7-dimethylamino-7-ferrocenylenanthic acid, I, to afford the optically active palladium derivative, II. The absolute configuration of the chiral plane is determined by the configuration of the inductor: the acylamino acid salt. The palladium atom in II was then substituted by a σ-ketovinyl group using the reaction with pentyl vinyl ketone, to yield III. The latter substance undergoes full reduction when treated with Et 3 SiH + CF 3 COOH (the ionic hydrogenation reaction) resulting in the optically active prostanoic acid analogue, IV. On the other hand, III in the form of the methiodide is reduced by NaBH 4 with the elimination of the amine group and the and the formation of allyl alcohol V. This kind of side chain is characteristic of many prostaglandins. Bromination of II followed by the repeated cyclopalladation opens the way to trisubstitute derivatives. The pathway outlined provides a rapid synthesis of optically active compounds which are the ferrocene analogues of natural prostaglandins.

Enantioselectivity in Enzyme-Catalyzed Electron Transfer to and from Planar Chiral Organometallic Compounds

Asymmetric cyclopalladation of dimethylaminomethylferrocene in the presence of N-acetyl-(R)- or (S)- leucine afforded enantiomerically en- riched palladacycles (S)- and (R)- (Pd{C5H3(CH2NMe2)FeC5H5}(m-Cl))2, respectively. Carbonylation of each enantiomer followed by iodomethyla- tion and reduction by sodium amalgam gave (S)- and (R)-2-methylferrocene carboxylic acid (1) with an optical purity of 80 and 93 %, respectively. (S)- and (R)-1 readily undergo one-electron (1e) oxidation to form the corresponding ferricenium cations by hydrogen perox- ide, catalyzed by horseradish peroxidase (HRP) and chloroperoxidase (CLP) from Caldariomyces fumago (258C, pH 5 - 8 and 2.75, respectively). In the case of HRP, the reaction is strictly first- order with respect to (S)- and (R)-1 (ratea k(HRP)(1)), whereas Michae- lis - Menten kinetics are observed for CLP. The strongly pH-dependent kinetic enantioselectivity is, however, only ob- served in the case of HRP. HRP-gener- ated cations (S)-1 a and (R)-1 a have been used to demonstrate that their enzymat- ic reduction by reduced glucose oxidase (GO) is also enantioselective; the (S)-1 a enantiomer is more reactive than (R)-1 a by a factor of 1.54. The existence of the planar chiral enantioselectivity in the GO catalysis was also confirmed by the cyclic voltammetry study of (S)-1 and (R)-1 in the presence of GO and b-d- glucose with glassy carbon and pyrolytic graphite electrodes. The corresponding enantioselectivity factors k(S)-1 a /k(R)- 1 a are 1.7 and 1.6, respectively. Based on the known X-ray structural data for the active site of GO, it has been tentatively suggested that the enantioselectivity originates from the hydrophobic contact between the enzyme tyr-68 residue and the h 5 -C5H5 ring of 1 a , and a hydrogen bond network formed by his-516 and/or his-559 residues and the carboxylic group of the ferrocene derivative. The findings reported confirm the existence of enantioselective electron transfer be- tween oxidoreductases and organome- tallic compounds with a planar chirality. The lack of kinetic enantioselectivity may be a result of i) the incorrect rate- limiting step, ii) unfavorable pH region, and iii) the deficit of charged groups attached to ferrocenes.

Optically active (2-aminomethylferrocenyl) phosphines with the phosphorus chiral center

The reaction of an enantiomeric planar-chiral palladium derivative of dimethyl-aminomethylferrocene with PhMePLi in THF at room temperature afforded a 1.5∶1.0 mixture of diastereomeric aminophosphines containing the phosphorus asymmetrical center along with a chiral plane. The absolute configuration of the phosphorus atom was determined based on the X-ray diffraction data for the complex of the minor diastereomer with PdI2. The presence of the (S)-chiral plane in the initial palladium compound favors the predominant formation of the product with the (S)-configuration of the phosphorus center.

Hydroxyferrocene as a prochiral analog of phenols: cyclopalladation of a mixed phosphite ester of hydroxyferrocene

Hydroxyferrocene (ferrocenol), a metallocene analog of phenol, has been converted into a phosphite ester with chiral (racemic) butane-1,3-diol which undergoes cyclopalladation similarly to hydroxyarene phosphites. In this case, a planar chirality emerges but no diastereoselectivity has been observed. The molecular structure of the cyclopalladated product as pyridine adduct has been established by the X-ray study of a single crystal.

Cyclopalladation of Schiff's bases in the ruthenocene series. The possibility of application of the asymmetric version of the reaction to metalloceneimines

Abstractp-Tolyliminoalkylruthenocenes—Schiffs bases of the ruthenocene series—react with sodium tetrachloropalladate in the presence of carboxylate anion similarly to their ferrocenyl analogs to give cyclopalladation products. The optical rotation values of the products resulting from carbonylation of palladated ferrocene and ruthenocene aldimines, prepared under conditions of asymmetric catalysis, followed by liberation of the aldehyde group were used to determine the stereochemistry and enantiomeric purity of the cyclopalladation products.

Synthetic approaches to trialkyl(ferrocenylmethyl)ammonium salts as cationic templates for the preparation of ferromagnets on the basis of bimetal oxalates

Trialkyl(ferrocenylmethyl)ammonium salts and their 2-substituted analogs designed for the preparation of molecular ferromagnetics based on bimetallic oxalates were synthesized using classical alkylation of dialkylaminomethylferrocenes by alkyl halides and nucleophilic substitution reaction of 2-substituted dimethylaminomethylferrocene methiodides with trialkylamines. In the case of salts with electron-donating substituents in position 2, only the latter of the two proposed routes is applicable because N-alkylation with alkyl halides is accompanied by competing ferrocenylmethylation of the starting amine. On the contrary, the salts with electron-withdrawing 2-substituents should be prepared preferably by the reaction of amines with alkyl halides, while nucleophilic trialkylamination of methiodides is complicated by deprotonation induced by bases.

Diastereoselectivity of the formation of planar chiral ruthenocenol in reactions of chiral tertiary phosphines with the (η4-cyclopentadienone)(η5-cyclopentadienyl)ruthenium cation

The reactions of chiral benzyl- and ethyl(phenyl)ferrocenylphosphines with (acetonitrile)(η4-cyclopentadienone)(η5-cyclopentadienyl)ruthenium trifluoromethylsulfonate proceed diastereoselectively through the attack on the cyclopentadienone ring to form planar chiral 2-phosphonioruthenocenols as mixtures of two diastereomers in ratios of 1.7 : 1 and 2 : 1, respectively.

Diatomic phenols as nucleophilic components in the carbonylation of the chelated C,N-palladacycle of the ferrocene series

The carbonylation of the chelated palladium derivative of dimethylaminoferrocene in the presence of diatomic phenols affords mixtures of the corresponding mono- and diacylated dihydroxybenzenes containing a 2-dimethylaminomethylferrocenyl fragment in the acyl moiety.

Stereochemical control in reactions of chiral ketone with 2-lithiated substituted ferrocene derivatives

The formation of a new chiral center in the reactions of ketone 4-MeOC6H4CH(Et)C(O)Et with planar-chiral 2-lithio-1-methyl- and 1-chloro-2-lithioferrocenes proceeded stereoselectively to give two diastereomers in a ratio of ∼3 : 2 or a single diastereomer, respectively, out of four possible diastereomeric 4-aryl-3-ferrocenylhexan-3-ols. The replacement of the hydroxy group in the resulting compounds by hydrogen under the conditions of ionic hydrogenation was studied. The configurations of the reaction products were established by X-ray diffraction analysis and 1H NMR spectroscopy.