The kinetics and mechanism of the organo-iridium-catalysed enantioselective reduction of imines

Abstract

The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N ′ -tosylethane-1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5:2 ratio of formic acid: triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90% ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)-enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds -the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)-enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer.

Asymmetric Transfer Hydrogenation of 1‐Aryl‐3,4‐Dihydroisoquinolines Using a Cp*Ir(TsDPEN) Complex

“…Remarkably, using this catalytic system, substrates 2b, 2e and 2f (79-86 % ee) were hydrogenated with higher ees than using the Ru-based complex 1b, where only 29-39 % ee was achieved. [28] We observed the same behavior with 4 and 1e′ under optimized conditions, although the effect was even more pronounced in some cases (Figure 3). [28] We observed the same behavior with 4 and 1e′ under optimized conditions, although the effect was even more pronounced in some cases (Figure 3).…”

“…The authors explain this unusual phenomenon by different kinetics of formation of each enantiomer -while the (R) isomer is formed in a first-order reaction with reaction rates decreasing exponen- tially, the formation of the opposite (S) enantiomer follows a zero order kinetics. [28] We observed the same behavior with 4 and 1e′ under optimized conditions, although the effect was even more pronounced in some cases (Figure 3). In fact, the other isomer of the product 5 can be formed depending on the reaction conditions.…”

“…orthophosphoric acid - Table S2, entries 5-15), the 85 % aq. Therefore, orthophosphoric acid was investigated further, including the anhydrous phosphoric acid (APA) [11] prepared by mixing the 85 % H 3 PO 4 with stoichiometric amounts of phosphorus pentoxide (Table S2, entries [16][17][18][19][20][21][22][23][24][25][26][27][28]. Therefore, orthophosphoric acid was investigated further, including the anhydrous phosphoric acid (APA) [11] prepared by mixing the 85 % H 3 PO 4 with stoichiometric amounts of phosphorus pentoxide (Table S2, entries [16][17][18][19][20][21][22][23][24][25][26][27][28].…”

“…solution of orthophosphoric acid helped increase the ee to 82 % (Table S2, entry 14). Therefore, orthophosphoric acid was investigated further, including the anhydrous phosphoric acid (APA) [11] prepared by mixing the 85 % H 3 PO 4 with stoichiometric amounts of phosphorus pentoxide (Table S2, entries [16][17][18][19][20][21][22][23][24][25][26][27][28]. With this additive and anhydrous iPrOH as a solvent, the ee was increased to 86 % at full conversion (Table S2, entry 26 and Table 2, entry 1).…”

Reversible and Selective CO2 to HCO2− Electrocatalysis near the Thermodynamic Potential

“…A few sources of error are possible with the previously estimated thermodynamic potential. The latter relies on an estimate of the p K a of formic acid in acetonitrile, which has not been experimentally measured . The calculation also relies on the accuracy of the p K a of the CH 2 (TBD) 2 ⋅H + in acetonitrile and the absence of any effects (such as homoconjugation), in which the p K a would not precisely represent the proton activity of the solution.…”