Base-free Asymmetric Transfer Hydrogenation of 1,2-Di- and Monoketones Catalyzed by a Chiral Iron(II) Hydride

Abstract

The chiral iron(II) hydride complex [FeH(CNCEt3)(1a)](BF4) (3, 1a is a chiral macrocycle with an (NH)2P2 donor set) catalyzes the base-free transfer hydrogenation (ATH) of prochiral ketones and the hemireduction of benzils to the corresponding benzoins using iPrOH as hydrogen donor. Ketones give the same excellent enantio-selectivity (up to 99% ee) as the parent catalyst [Fe(CNCEt3)2(1a)](BF4)2 (2), which is only active upon treatment with NaOtBu. Benzoins, whose labile stereocenter is known to undergo racemization under basic conditions, are formed in up to 83% isolated yield with enantioselectivity as high as 95%.

Chiral Iron Complexes in Asymmetric Organic Transformations

“…A bifunctional catalysis mechanism was proposed, in which iron acts as a hydride source and one of the amines as proton source (Scheme 9). [35] tBuONa deprotonates one amine ligand, causing the decoordination of one isonitrile and the formation of amido complex 16 b-I; isopropanol transfers both H + and H À to the complex, then the ketone approaches the complex through a NÀ HÀ O hydrogen bond and the hydride is transferred to the ketone in the enantiodetermining step, as confirmed by DFT studies; H + is finally transferred, yielding the product and the regeneration of intermediate 16 b-I. [35b] The overall mechanism and the active hydride species are similar to the ones reported by Morris (Figure 3), but the topology of the complexes and the helicity here play a predominant role on the selectivity: the rigidity of ligand L5 and the Δ-cis-β geometry of complex 16 b, along with the use of bulky isonitriles, resulted in discriminating the approach of the ketone enantioface to the complex and thus the enantioselectivity.…”

Chiral Benzoins via Asymmetric Transfer Hemihydrogenation of Benzils: The Detail that Matters

“…35 Therefore, we prepared 3 and used it as a base-free ATH catalyst for ketones and benzils (4). 29,30,35 In the presence of hydride 3, benzil (4a) was reduced to benzoin (5a) in good yield (70%) and excellent enantioselectivity (95% ee). However, more sterically demanding substrates (i.e., o-substituted benzils) gave only moderate enantioselectivity (40−49% ee).…”

“…In a preliminary report, we have described a transfer hydrogenation catalyst that operates under base-free conditions and produces highly enantioenriched benzoins. , The catalyst exploits the chiral N 2 P 2 macrocyclic ligands ( S P , S P , S C, S C )- 1 (Chart ) − and was evolved from the bis­(isonitrile) iron­(II) complexes [Fe­(CNR) 2 ( 1 )]­(BF 4 ) 2 ( 2 ). Upon activation with base (NaO t Bu, 10 equiv), precatalysts 2 are highly active (TOF up to 6650 h –1 ) in the asymmetric transfer hydrogenation of a broad scope of ketones with excellent enantioselectivity. , A mechanistic study revealed that the activation with base in 2-propanol converts the bis­(isonitrile) complex 2 to the hydride [FeH­(CNR)­( 1 )]­BF 4 ( 3 ), which is the catalytically active species .…”

“…Upon activation with base (NaO t Bu, 10 equiv), precatalysts 2 are highly active (TOF up to 6650 h –1 ) in the asymmetric transfer hydrogenation of a broad scope of ketones with excellent enantioselectivity. , A mechanistic study revealed that the activation with base in 2-propanol converts the bis­(isonitrile) complex 2 to the hydride [FeH­(CNR)­( 1 )]­BF 4 ( 3 ), which is the catalytically active species . Therefore, we prepared 3 and used it as a base-free ATH catalyst for ketones and benzils ( 4 ). ,, In the presence of hydride 3 , benzil ( 4a ) was reduced to benzoin ( 5a ) in good yield (70%) and excellent enantioselectivity (95% ee). However, more sterically demanding substrates (i.e., o -substituted benzils) gave only moderate enantioselectivity (40–49% ee).…”

Cobalt‐Catalyzed Chemoselective Transfer Hydrogenation of C=C and C=O Bonds with Alkanols

“…Iron complex was developed by the Morris [6] and Knölker groups, respectively, and exhibited high efficiency in the transfer hydrogenation, which was unambiguously proposed to react by an outer‐sphere pathway involving metal‐ligand cooperativity . Other iron complexes with either NH or pyridine‐type moiety in the ligand were also developed by the Beller and Mezzetti groups,, parts of them were rendered chiral property for enantioselective transformation. Besides, both of Ni(0) and Ni(II) complexes were employed in the transfer hydrogenation of aldehydes, ketones and enones, but the reaction condition was relatively harsh, and the substrate tolerance was limited ,.…”