Transfer hydrogenation process

The low induction for the acetoacetates was attributed to a transfer hydrogenation process within an enol form of the substrate, coordinated through the carbon-carbon double bond, CH3C(OH)=CH—C02R, rather than hydrosilylation of the carbonyl moiety (285). 

Numerous enantioselective transfer hydrogenation processes have now been developed and operated at commercial scale to give consistent, high-quality products, economically. These include variously substituted aryl alcohols, styrene oxides and alicyclic and aliphatic amines. Those discussed in the public domain include (S)-3-trifluoromethylphenylethanol [48], (f )-3,5-bistrifluorophenylethanol [64], 3-nitrophenylethanol [92], (S)-4-fluorophenylethanol [lc], (f )-l-tetralol [lc], and (T)-l-methylnaphthylamine [lc]. 

The highest ttn published to our knowledge so far for chemzymes (in the sense of polymer-enlarged chemical catalysts) is found in the transfer hydrogenation process catalyzed by Gao-Noyori s catalyst bound to a siloxane polymer (Fig. 3.1.3, 4) [13, 14]. In this transfer hydrogenation acetophenone is reduced to (S)-phenyl-ethanol using isopropanol as hydrogen donor. The product is produced in a CMR with 91% ee at a space-time yield of 578 g L d the ttn for the catalyst is 2633. 

Both the IP A and TEAF transfer hydrogenation processes have been successfully scaled-up on a number of occasions to make tens of kilograms of high quality products. Studies are currently underway to scale-up the process to the multiton scale. 

Interestingly, Suzuki and coworkers demonstrated that Ir(III) catalysts could promote formal ketone hydroacylation of 1,5-ketoaldehydes, yielding either isocou-marins or 3,4-dihydroisocoumarins (Scheme 2.43). The presence of pivaldehyde as an oxidant favors the formation of isocoumarins. The mechanism of this transformation involves a transfer hydrogenation process (see Section 2.5.1) [88]. 

Yet another interesting application of complex 51 [109] was described by us in the context of transfer hydrogenation processes. Compound 51 was found to be active in the reduction of CO2 to formate using isopropanol as the hydrogen source (Equation 10.1) [110]. This unprecedented reaction is interesting because it uses an inexpensive and environmentally friendly hydrogen source and provides an easy access to formic acid and sodium formate. 

This catalytic system also performed effectively under solvent-free conditions, where it afforded the desired C-alkylated products in high yields. Moreover, the same authors reported that the analogous benzothienyl-iridium complexes afforded high levels of catalytic activity in the C-alkylation reactions of primary and secondary alcohols, as well as the reaction of ketones and primary alcohols through transfer hydrogen processes [107-109]. 

Since no reaction occurred at all in the absence of either the aldehyde catalyst or the base or both of them, as well as other proofs such as control reactions using high purity bases (>99.99 % purity), the authors concluded that the reaction is a true TM-free transformation. In addition to the aldehydes catalytic effect, the authors proved that imine intermediates and other TM-free oxidants could also be employed to initiate the reaction, which is consistent with, and further supports, the TM-free N-aUcylation mechanism (Scheme 39). Along with other results of mechanistic studies, the authors proposed a mechanism for the aldehyde-catalyzed A -alkylation reaction (Scheme 41). Firstly, the external aldehydes condense with amines/amides to give imine intermediates, which were then reduced by alcohols via a TM-free MPV-0 transfer hydrogenation process to give product amines and regenerate byproduct aldehydes as the new alkyl source in next reaction cycle. In the key TM-ffee transfer... 

For the mechanistically more simple transfer hydrogenation process with 2 in particular, the charge-separated nature of this transition state persuasively explains the experimentally observed increase in the initial reaction rate and the average activity as a function of reaction medium polarity by Xiao and Liu as well as Tanis. Indeed such an observation is characteristic for so-called dipolar transition state reactions,where activated complexes differ considerably in charge separation or charge distribution from the initial reactants, contrary to pericyclic reactions in... 

An interesting case in which sol-gel-entrapped and non-entrapped fert-butyldi-methylsilyltriflic acid catalyze different transformations of methyl 1-cyclopenteneacetate in -xylene. While the ceramic catalyst gives 3-methylbenzaldehyde (as the result of a transfer hydrogenation process coupled with intramolecular alkylation, the soluble acid forms only 2- and 3-substituted methyl cyclopenetaneacetates (Parvulescu, 2001). 

Almost at the same time, Liu and Che published a cascade intermolecular hydroamination/asymmetric reduction sequence, which included achiral Au complex-catalyzed hydroamination of aryl amines and chiral phosphoric acid-promoted Hantzsch ester reduction to afford secondary aryl amines [70], More recently, the same group reported a tandem one-pot assembly of functionalized tetrahydroquino-lines from amino aldehyde and alkynes by combining Au and chiral phosphoric acid catalysis [71], The reaction was initiated by Au-promotedquinololine 210 generation, followed by an enantioselective HEH-incorporated transfer hydrogenation process (Scheme 9.67). 

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