Asymmetric Synthesis of Metallocenes through Enantioselective Addition of Organolithium Reagents to 6-(Dimethylamino)fulvene

Abstract

Enantioselective addition of aryllithiums 2a-d (Ar = Ph (a), 2-MeC(6)H(4) (b), 2-MeOC(6)H(4) (c), 1-naphthyl (d)) to 6-(dimethylamino)fulvene (1) in the presence of (-)-sparteine in toluene at -78 degrees C generated chiral cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)methyl group, where the enantioselectivities are 51, 91, 90, and 83% for 4a, 4b, 4c, and 4d, respectively. Treatment of the chiral cyclopentadienides 4 with FeCl(2) or Fe(acac)(2) gave ferrocenes, which contain an N,N-dimethylamino(aryl)methyl side chain on both of the cyclopentadienyl rings. The enantiomeric purity of the chiral ferrocenes 7 thus obtained is 99% ee or higher for those containing a 2-MeC(6)H(4) (7b) or a 2-MeOC(6)H(4) (7c) group.

An Efficient Approach to Chiral Ferrocene‐Based Secondary Alcohols via Asymmetric Hydrogenation of Ferrocenyl Ketones

“…[11] A similar approach was introduced by Hayashi et al using chiral cyclopentadienyllithium generated from 6-(dimethylamino)fulvene in the presence (À)-sparteine. [12] Given that nucleophilic substitution at the chiral acarbon attached directly to the ferrocene proceeds with stereoretention, [10] some catalytic methods under non-reducing conditions such as asymmetric arylation of ferrocenecarboxaldehyde, [13] (À)-sparteine/Pd-mediated aerobic oxidative kinetic resolution [14,15] and stereoselective enzymatic acylation of racemic 2 [16] have been explored in attempts to synthesize optically pure 2, a precursor to Ugis amine. However, acquisition of both enantiomers of 2 is often difficult using these methods due to the unavailability of the antipodic catalyst.…”

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and indolyl-substituted titanocene anti-cancer drugs

“…Synthesis 6-N,N-Dimethylamino fulvene (3a) was synthesised according to the already published procedure [24], and its structure is shown in Scheme 1.…”

Novel zirconocene anticancer drugs?

“…Fulvenes 1a-c were synthesised according to published procedures [22][23][24] and their structures are shown in Fig. 2.…”