Chiral (cyclopentadienone)iron complexes with a stereogenic plane as pre-catalysts for the asymmetric hydrogenation of polar double bonds

Abstract

In this paper, we describe a small library of easy-to-prepare chiral (cyclopentadienone)iron precatalysts for enantioselective C=O and C=N hydrogenations. Starting from readily accessible achiral materials, six chiral (cyclopentadienone)iron complexes (1a-f) possessing a stereogenic plane were synthesized in racemic form. Based on the screening of pre-catalysts (±)-1a-f in the hydrogenation of ketones and ketimines, we selected two complexes (1a and 1d) for resolution by semipreparative enantioselective HPLC. The absolute configuration of the separated enantiomers of 1a and 1d was assigned by XRD analysis (1a) and by comparison between experimental and DFT-calculated ECD and ORD spectra (1d). The enantiopure pre-catalysts (S)-1a and (R)-1d were tested in the asymmetric hydrogenation of several ketones and ketimines and showed good activity and modest enantioselectivity, the e.e. values ranging from very low to moderate (54%).

Recent Catalytic Applications of (Cyclopentadienone)iron Complexes

“…In the attempt to bring the stereochemical information as close as possible to the CIC's functional groups involved in HT, we recently developed several chiral CICs endowed with a stereogenic plane due to the presence of different substituents at position 2 and 5 of the cyclopentadienone ring (Scheme ) , . We surmised that a large difference in size between these substituents could lead to effective stereodiscrimination between the substrate's enantiofaces.…”

“…The chiral CICs with stereogenic plane developed by our group and their applications in ketone and ketimine AH . PMP = p ‐methoxyphenyl.…”

Bifunctional homogeneous catalysts based on first row transition metals in asymmetric hydrogenation

“…Furthermore, the dissociation of the phosphoramidite ligand prior to H2 uptake led to the formation of a minor achiral hydride. (27) and (28) starting from readily accessible achiral materials and separeting the enantiomers by preparative CSP HPLC (Scheme 35) [110]. The pre-catalysts (27) and (28) were applied to the AH of ketones and ketimines and the resulting alcohols and amines were obtained in fair to high yields (33-99%) with low to average enantioselectivities (up to 54% ee for amines and up to 45% ee for alcohols).…”

Synthesis and Catalytic Application of Knölker-Type Iron Complexes with a Novel Asymmetric Cyclopentadienone Ligand Design

“…As such, higher catalytic enantioselectivities could be achieved [42,43], with the best example featuring BINOLderived cyclopentadienone ligand provided by Gajewski et al [44][45][46]. Alternatively, racemic mixtures of asymmetric ruthenium [47] and iron catalysts [48] with different 2,5-substituents were separated using preparative chiral HPLC chromatography, yielding batches of both pure enantiomers. These catalyst versions achieved appreciable enantioselectivities for certain substrates, however, they was not high enough to make them industrially relevant.…”

“…Alternatively, racemic mixtures of asymmetric ruthenium [47] and iron catalysts [48] with different 2,5-substituents were separated using preparative chiral HPLC chromatography, yielding batches of both pure enantiomers. These catalyst versions achieved appreciable enantioselectivities for certain substrates, however, they was not high enough to make them industrially relevant.…”