Synthesis and use of an asymmetric transfer hydrogenation catalyst based on iron(II) for the synthesis of enantioenriched alcohols and amines

Abstract

The catalytic hydrogenation of prochiral ketones and imines is an advantageous approach to the synthesis of enantioenriched alcohols and amines, respectively, which are two classes of compounds that are highly prized in pharmaceutical, fragrance and flavoring chemistry. This hydrogenation reaction is generally carried out using ruthenium-based catalysts. Our group has developed an alternative synthetic route that is based on the environmentally friendlier iron-based catalysis. This protocol describes the three-part synthesis of trans-[amine(imine)diphosphine]chlorocarbonyliron(II) tetrafluoroborate templated by iron salts and starting from commercially available chemicals, which provides the precatalyst for the efficient asymmetric transfer hydrogenation of ketones and imines. The use of the enantiopure (S,S) catalyst to reduce prochiral ketones to the (R)-alcohol in good to excellent yields and enantioenrichment is also detailed, as well as the reduction to the amine in very high yield and enantiopurity of imines substituted at the nitrogen with the N-(diphenylphosphinoyl) group (-P(O)Ph2). Although the best ruthenium catalysts provide alcohols in higher enantiomeric excess (ee) than the iron complex catalyst used in this protocol, they do so on much longer time scales or at higher catalyst loadings. This protocol can be completed in 2 weeks.

The Golden Age of Transfer Hydrogenation

“…Iron-catalyzed TH has kept growing in the last 5 years, and great progress has been achieved. 275 After their pioneering study on TH based on iron catalysts containing PNNP backbones, in 2010 Morris' group 276,277 prepared a series of new iron (II) precatalysts trans-[Fe(Br)-(CO)(PPh 2 CH 2 CHNCHRCHRNCHCH 2 PPh 2 )][BPh 4 ] with diamines containing various substituents through a onepot synthetic route. These authors found that all of them showed excellent catalytic properties in the ATH of acetophenone with 2-PrOH and KO t Bu under mild conditions.…”

Evaluation of techniques for performing cellular isolation and preservation during microgravity conditions

“…To counteract this assumed outcome, we utilized a completely closed system known as a cannula transfer (Supplementary Figure 1) commonly used in chemical synthesis protocols. 1 In order to transfer liquids from one tube to another, the tubes have septum lids that can be punctured by long needles connected to each other via Tygon tubing. Injection of air into the liquid-containing tube increases the pressure in the tube causing the liquid to move up through the needle and tubing into the empty tube.…”

Asymmetric Transfer and Pressure Hydrogenation with Earth‐Abundant Transition Metal Catalysts

“…The above mechanism was validated by preparing amine-(imine)diphosphine (P-NH-N-P type) ligands, to show that they activate iron for the catalysis of ketones. [39][40][41] The catalyst precursors C5a-C5c showed excellent reactivity for the reduction of several ketones. Acetophenone (S1), in the presence of 0.016-0.05 mol% of complex C5c bearing large 3,5-xylyl substituents, 0.033-0.40 mol% t-BuOK, in i-PrOH as the solvent and hydrogen donor, was reduced with 90% ee and with a TOF of 100 000 h -1 at 28 o C. Complex C5a was an effective precatalyst for other more challenging substrates such as naphthyl and heteroaryl ketones.…”