Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

Abstract

SummaryIn the hydrogenation of sluggish unactivated enamine substrates, Rh complexes of electron-deficient phosphines are demonstrated to be far more reactive catalysts than those derived from triphenylphosphine. These operate at low catalyst loadings (down to 0.01 mol %) and are able to reduce tetrasubstituted enamines. The use of the sustainable and environmentally benign solvent (R)-limonene for the reaction is also reported with the amine isolated by acid extraction.

Glycerol Boosted Rh‐Catalyzed Hydroaminomethylation Reaction: A Mechanistic Insight

“…Taking into account the remarkable effect of glycerol and given the fact that hydrogenation of the imine‐, iminium‐ or enamine‐type intermediates is generally accepted as the rate‐determining step for Rh‐catalyzed HAM, we considered that a hydrogen transfer (glycerol as reducing agent) could be operative in addition to the hydrogenation reaction, enabling low‐pressure conditions while overriding the need for a metal‐based co‐catalyst . Thus, the nature of the hydrogen donor was further assessed with glycerol and butan‐1‐ol at 80 °C, revealing that enamine reduction was faster in the latter, albeit with moderate 1 a selectivity (Table , entries 1 and 2).…”

C–F Bond Activation of P(C6F5)3by Ruthenium Dihydride Complexes: Isolation and Reactivity of the “Missing” Ru(PPh3)3H(halide) Complex, Ru(PPh3)3HF

“…The presence of P­(C 6 F 5 ) groups appeared to be mandatory for the bond activation steps described above. Neither P­(C 6 H 4 - p -F) 3 nor P­(3,4,5-C 6 F 3 H 2 ) 3 exhibited reactivity comparable to that of PCF with 1 (Figures S9 and S10). Thus, the addition of 2 equiv of P­(C 6 H 4 - p -F) 3 to a C 6 D 6 solution of 1 resulted in the slow (3 days) formation of two new triplet hydride resonances at slightly lower frequency (δ −6.71 and −6.89, both with 2 J HP = 20.6 Hz) from that of 1 , which we propose arises from the substitution of one or two PPh 3 ligands by the fluorinated phosphine (Scheme ).…”

“…In an attempt to broaden the scope of these substitution reactions, we turned our attention to more electronically diverse phosphines, in particular, the perfluorinated phosphine P­(C 6 F 5 ) 3 (abbreviated as PCF). While the chemistry of PCF (as well as its derivatives) with transition-metal centers has been probed quite extensively, predominantly with catalytic applications in mind, − there are a small number of reports that show that PCF (or derivatives thereof) are susceptible to C–F activation by nucleophilic ligands on metal centers. − To the best of our knowledge, these nucleophilic ligands have not included hydrides.…”

A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase

“…In a previous study, we identified cofactor 1 (Figure a) as a promising cofactor for the transfer hydrogenation using wild-type hCAII (hCAII WT ) as a protein scaffold . Enantiopure amines represent attractive targets both as pharmaceutical ingredients and agrochemicals. − Following a seminal report in 2011, imine reductases have firmly highlighted their versatility for the production of enantiopure amines. − These complement homogeneous catalysts for the reduction of prochiral enamines and imines. − Capitalizing on our previous efforts in ATHases, we set out to introduce a covalent anchor between the IrCp* cofactor and hCAII. We hypothesized that the resulting firm localization of the cofactor may positively affect both the turnover numbers (TONs) and the stereoselectivity of the resulting ATHase.…”