Chiral Ferrocene Derivatives. An Introduction

Abstract

Soon after its discovery, it was found, that ferrocene behaves in many respects like an aromatic electron-rich organic compound, which is activated towards electrophilic reactions almost like phenol. As a consequence, a rich organic chemistry of ferrocene was developed, in which the organometallic moiety is treated like a simple phenyl group. Thus, Friedel -Crafts acylation leads to ferrocenyl ketones, which can be reduced to secondary ferrocenyl alcohols containing an asymmetric carbon atom. Compounds of this type can be resolved into the enantiomers by standard resolution techniques [l] and do not provide any problems with respect to chemistry and nomenclature. However, ferrocene is different from phenyl with respect to stereochemistry : a derivative with at least two different substituents in the same ring cannot be superimposed with its mirror image, i.e., it is chiral. The first compound of this type to be prepared was 3,1'-dimethyl-ferrocenecarboxylic acid, in which both enantiomers were obtained by resolution of the racemate with cinchonidine and quinidine ( Fig. 4-1) [2]. Crystals of one enantiomer suitable for X-ray structure analysis could be grown; this result confirmed unequivocally the correlation with the true configuration of the molecule [3].Schlogl has investigated the problem systematically and suggested this isomerism to be an example of planar chirality fl, 41. A simple rule was developed to assign chirality descriptors to homoannular di-or polysubstituted ferrocenes: The observer regards the molecule from the side of the ring to be assigned (called the "upper" ring). The substituents are then analyzed for priority according to the Cahn -Ingold -Prelog (CIP) rules. If the shortest path from the substituent with highest priority to that following in hierarchy is clockwise, the chirality descriptor is (R), otherwise it is (S) [5]. If both rings bear at least two different substituents, the process is started with the ring containing the substituent of highest priority, the molecule is then turned upside down and the second ring subsequently assigned. In order to show clearly that the chirality descriptor belongs to a planar element of chirality, it is often written as (,R) or ($), respectively. Another convention exists, which states that in ferrocene derivatives with both central and planar chirality, the descriptor of the central chirality is written first. Thus, (R, S) should mean that the compound contains an element of central chirality with ( R ) configuration and an element of planar chirality with (S) configuration. This order is used in this book. However, the opposite order of the descriptors was suggested in a recent monograph 174

Diastereoselective Addition of Organometallics to Chiral Amino Formyl- and Acylferrocenes: Synthesis of A Chiral 1,2-Homo Disubstituted Ferrocene

“…The same stereochemical outcome was observed in the reduction of the carbonyl group of 1(R)-(dimethylamino)ethyl-2(Sp)analogue (8) with DIBAH and LiAlH 4 ; DIBAH and LiAlH 4 produced the R (9a) and S (9b) configuration alcohols, respectively, as the major isomers (runs 4-5). Table 2 Diastereoselective Reduction of 7-8 with Metal Hydrides a a 7-8 (0.5 mmol), metal hydride (0.6 mmol), THF (5.0 mL): 0°C, 1-3 h. b Determined by 1 H NMR (400 MHz). C The reaction was carried out at rt for 24 h in ethanol (5.0 mL).…”

“…Well-designed chiral ferrocenes may produce high stereoselectivities to asymmetric organic reactions such as asymmetric hydrogenation, asymmetric allyl substitution, and asymmetric coupling reactions. 1 Recent successes in the synthesis of a variety of chiral ferrocenes without optical resolution now have attracted considerable attention in asymmetric synthesis. 2 We have reported that the addition of organometallic reagents to 1(R)-(dimethylamino)ethyl-2(Sp)-formylferrocene (1) proceeded with high diastereoselection to give the corresponding (1R,2S;2Sp)-amino alcohol (2) as a major isomer (70-90% de): especially with dialkylzinc, the single isomer of the amino alcohol (2) was obtained.…”

“…Table 1 Diastereoselective Addition of Organometallics to 4 a a 4 (0.5 mmol), organometallic reagent (0.6 mmol), THF (5.0 mL: -78°C, 15 min then rt, 2 h. b Determined by 1 H NMR (400 MHz). c CeCl 3 (0.6 mmol) was added.…”

The preparation and characterization of some novel ferocenil derivatives

“…In order to get a more comprehensive insight into the role of α-ferrocenyl carbocation, we discussed the reaction mechanism. As demonstrated in Scheme 3, the beginning of the reaction is marked by the protonation of β-hydroxy ureas 6a-c by acetic acid and dehydration of the resulting oxonium ions II, eventually giving α-ferrocenyl carbocations III (Wagner, G., & Herrmann, R., 1995). Finally, a nucleophilic attack of the carbamide nitrogen on the positive centre of α-ferrocenyl carbocations III forms cations IV, which yielded the target 1-aryl-4-ferrocenyl-3-phenyltetrahydropyrimidin-2(1H)-ones after deprotonations (5a-c).…”

Enantiopure Ruthenocenes Cp*Ru(1,2‐C5H3R1R2) with a Planar Chiral Cyclopentadienyl Ligand and a Pentamethylcyclopentadienyl Spectator Ligand

“…In all cases an admixture of starting material was present as impurity; for more details see below and Experimental Section. Scheme 6. The stereochemistry of complexes 1 may be specified in one of two ways: [29] either by specifying the planar chirality of the C 5 H 3 R 1 R 2 ring as originally proposed by Schlögl, [30] or by specifying the central chirality of the ring carbon bearing the highest ranking substituent with the help of the CIP rules. [31] As we shall prove below, the SMP-CH 2 group of the complexes 10a-i has the role of R 1 in the illustration of complex 1, and E occupies the position of R 2 .…”