The kinetics and mechanism of the organo-iridium catalysed racemisation of amines

Abstract

The dimeric iodo-iridium complex [IrCp*I 2 ] 2 (Cp*=pentamethylcyclopentadiene) is an efficient catalyst for the racemisation of secondary and tertiary amines at ambient and higher temperatures with a low catalyst loading. The racemisation occurs with pseudo-first-order kinetics and the corresponding four rate constants were obtained by monitoring the time dependence of the concentrations of the (R) and (S) enantiomers starting with either pure (R) or (S) and show a first-order dependence on catalyst concentration. Low temperature 1 H NMR data is consistent with the formation of a 1:1 complex with the amine coordinated to the iridium and with both iodide anions still bound to the metal-ion, but at the higher temperatures used for kinetic studies binding is weak and so no saturation zero-order kinetics are observed. A cross-over experiment with isotopically labelled amines demonstrates the intermediate formation of an imine which can dissociate from the iridium complex. Replacing the iodides in the catalyst by other ligands or having an amide substituent in Cp* results in a much less effective catalysts for the racemisation of amines. The rate constants for a deuterated amine yield a significant primary kinetic isotope effect k H /k D = 3.24 indicating that hydride transfer is involved in the rate-limiting step.

Deactivation mechanisms of iodo-iridium catalysts in chiral amine racemization

“…Figure 5 shows the effect of adding 20%(v/v) alcohols to the racemization of (S)-( 2) in ethyl acetate. The racemization half-life (t1/2) with ethyl acetate is 66 minutes corresponding to second order rate constant of kcat of 1.77x10-2 M -1 .s -1 (compared to 2.16x10 -2 M -1 .s -1 in toluene at the same temperature) 22 and complete racemization is observed. Whereas, the addition of iso-propanol and ethanol slightly increase the kcat to 1.83x10 -2 M -1 .s -1 , with end points of 6% and 13% e.e.…”

“…Their steric size may prevent multiple coordination and, as previously reported, the secondary imine dissociates readily enabling high catalyst turnover. 22 Having determined the cause of catalyst deactivation as hydrolysis of the intermediate imine, the obvious remedy is to exclude water. A control reaction, with N-methyl-2phenethylimine in wet toluene but without catalyst, showed little hydrolysis, however the addition of catalyst (1) resulted in rapid formation of acetophenone.…”

“…Previous work on the [IrCp*I2]2 catalyst, reports the kinetics and mechanism of chiral amine racemization and shows amine coordination to the iridium followed by hydride transfer. 22 With N-substituted amines it was shown that the racemization occurs by release of the imine/iminium into the bulk solvent prior to non-selective reduction by a hydridoiridium species. A similar system has been reported by Yamaguchi et al, in which IrCp*(NH3)3I2 catalyst carries out alkylation of aqueous ammonia with a range of alcohols.…”

Catalytic racemization of secondary alcohols with new (arene)Ru(II)-NHC and (arene)Ru(II)-NHC-tertiary phosphine complexes

“…Since the groundbreaking discovery of Shvo's catalyst [42][43] several Ru(II), Rh(I) and Ir(I) complexes were found capable for racemization of secondary alcohols under relatively mild conditions [12][13][14][15][44][45][46][47][48][49][50][51][52][53][54][55][56][57], although ruthenium catalysts are the most abundant. The reaction may proceed with formation of M-H monohydride intermediates (Rh, Ir) or with M(H) 2 dihydride species (Ru) [55].…”

Enzyme-catalyzed kinetic resolution and heterogeneous metal-catalyzed racemization of 1-substituted tetrahydroisoquinoline and tetrahydro-ß-carboline derivatives

“…Stirling and his co-workers have investigated the DKR of 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (±)-1 by [IrCp*I2]2 and Candida rugosa in toluene in the presence of 3-methoxyphenyl propyl carbonate at 40 °C. 118,119 90% conversion was observed and 96% ee characterized the formation of the (R)-carbamate (82% yield, 23 h) (Scheme 18).…”