Stereoelectronic Factors in Iron Catalysis: Synthesis and Characterization of Aryl-Substituted Iron(II) Carbonyl P–N–N–P Complexes and Their Use in the Asymmetric Transfer Hydrogenation of Ketones

Abstract

A series of five (S,S)-trans-[Fe(CO)(Br)(PR2-CH2CHNCH(Ph)CH(Ph)NCHCH2-PR2)][X] compounds (1a–c, X = BPh4; 1d,e, X = BF4) were synthesized and tested for the asymmetric transfer hydrogenation (ATH) of acetophenone. Three of the complexes had methyl-substituted aryl groups (a, R = para-CH3C6H4; b, R = ortho-CH3C6H4; c, R = 3,5-(CH3)2C6H3), and two had trifluoromethyl-substituted aryl groups (d, R = para-CF3C6H4; e, R = 3,5-(CF3)2C6H3). Using both known and new phosphonium dimers, [cyclo-(PR2CH2CH(OH)−)2][Br]2 (2a–c), in a one-pot template reaction, the corresponding (S,S)-trans-[Fe(CH3CN)2(PR2-CH2CHNCH(Ph)CH(Ph)NCHCH2-PR2)][BPh4]2 complexes (3a–c) were generated and then converted to precatalysts 1a–c via CO addition reactions. While investigating compounds 1a–c, an alternative route for synthesizing phosphonium dimers was developed that allowed the facile introduction of tetrafluoroborate counterions. Compounds 1d and 1e could not be synthesized using previously developed methods; phosphinoacetaldehyde diethyl acetal precursors (5d, 5e) were isolated because trifluoromethyl-substituted phosphonium dimers did not form. Precursors 5d and 5e were incompatible with a base-catalyzed template approach, so a new acid-catalyzed template procedure was developed to generate the tetrafluoroborate salts (S,S)-trans-[Fe(CH3CN)2(PR2-CH2CHNCH(Ph)CH(Ph)NCHCH2–PR2)][BF4]2 (3d, 3e). Both 3d and 3e were converted to precatalysts 1d and 1e via CO addition reactions. Complexes 1b, 1d, and 1e were inactive for the ATH of acetophenone, while complexes 1a and 1c were active. Compound 1a showed very high activity, with a turnover frequency of 30 000 h–1 at 28 °C, and is currently the most active iron ATH catalyst. Compound 1c produced more enantiopure (R)-1-phenylethanol, with an ee of 90%, and is the most selective iron catalyst reported to date for the ATH of acetophenone. The activity of complexes 1a–e for ATH was compared to those of known complexes 1f (R = Ph), 1g (R = Et), 1h (R = i-Pr), and 1i (R = Cy), and the most active catalysts were defined by a narrow range of electronic (ν(CO)) as well as steric (Tolman cone angles) parameters.

The Golden Age of Transfer Hydrogenation

“…276 Another report indicated that the steric and electronic properties of these complexes were tunable through change of the substituents of their phosphorus donors, resulting in seeking out more active and selective iron−PNNP catalysts. 278 Along with catalytic examinations, many theoretical studies of the mechanism of TH of ketones using iron(II)−PNNP complexes have been conducted by Morris' group, 279−285 and these investigations led to the rational design of other welldefined iron hydrogenation catalysts. A five-coordinate iron(II) complex 46 was prepared by double deprotonation of the PNNP ligand of the precursor complex 45 by a base.…”

Synthesis of New Late Transition Metal P,P-, P,N-, and P,O- Complexes Using Phosphonium Dimers as Convenient Ligand Precursors

“…Yield: 70% (36 mg). 1 31 A vial was charged with dicyclohexylphosphinoaldehyde chloride dimer (26 mg, 0.047 mmol), KOtBu (10 mg, 0.094 mmol) and toluene (2 mL). The mixture was stirred for 10 minutes, yielding a white suspension.…”

Asymmetric catalysis using iron complexes – ‘Ruthenium Lite’?

“…38 Of these, three were inactive however 29 proved to be the most active of this class of iron catalyst reported to date, with TOFs of up to 30,000 h -1 . Another, complex 31, was found to be the most enantioselective for acetophenone reduction to date, producing 1-phenylethanol in up to 90% ee.…”