Formic acid-triethylamine hydrogenation with

Tietze adopted a somewhat more indirect route to enantiopure tetrahydro-p-carbolines 166. This approach begins with P-S reaction of tryptamine with aldehydes or a-keto acids to yield the carbolines 163, which upon oxidation to the corresponding imines 164 subsequently undergo enantioselective hydrogenation with the catalyst 165 in a 5 2 formic acid/triethylamine mixture in acetonitrile <00EJO2247>. 

Ionic liquids have also been applied in transfer hydrogenation. Ohta et al. [110] examined the transfer hydrogenation of acetophenone derivatives with a formic acid-triethylamine azeotropic mixture in the ionic liquids [BMIM][PF6] and [BMIM][BF4]. These authors compared the TsDPEN-coordinated Ru(II) complexes (9, Fig. 41.11) with the ionic catalyst synthesized with the task-specific ionic liquid (10, Fig. 41.11) as ligand in the presence of [RuCl2(benzene)]2. The enantioselectivities of the catalyst immobilized by the task-specific ionic liquid 10 in [BMIM][PF6] were comparable with those of the TsDPEN-coordinated Ru(II) catalyst 9, and the loss of activities occurred one cycle later than with catalyst 9. 

The procedure for getting the polymer-bound ligands is very easy to reproduce. Three jS-functionalized aromatic ketones were successfully reduced to the corresponding alcohols by heterogeneous asymmetric hydrogen transfer reaction with formic acid-triethylamine azeotrope as the hydrogen donor. One of the product alcohols (19c) is an intermediate for the synthesis of optically active fluoxetine. 

Racemic benzoin was reduced with (S,S)-28 in a formic acid-triethylamine mixture to give the R,R diol (dl meso=98.2 1.8) quantitatively in >99% ee via dynamic resolution, revealing that racemization at the benzylic carbon atom occurs rapidly under transfer hydrogenation conditions (Scheme 37) [108]. The reduction rate of (R)-benzoin was calculated to be 55 times faster than the S isomer. 

Hydrogenation of dienes with up to 20 1.0 diastereoselectivity and 99% ee is mediated by carbene complexes. The scope and limitations of these reactions were investigated.288 Asymmetric transfer hydrogenation to prochiral ketones, catalysed by a Ru(II) complex (10) or its dimer, with formic acid-triethylamine has been reported, (0 The protocol leads to high yields and enantioselectivity up to 96%. It has been suggested that 16-electron Ru(II) and the Ru-H intermediates are involved in this reaction.289... 

A ruthenium complex containing a novel imidazolium salt moiety catalyses the asymmetric transfer hydrogenation of acetophenone derivatives, with a formic acid- triethylamine azeotropic mixture in an ionic liquid, [bmim][PF6]. The yields and ee are excellent.308... 

Asymmetric hydrogenation of cyclic imine 8 using two mol % of chiral Ru-complex 9 in a formic acid-triethylamine mixture, as developed by Noyori and co-workers, results in the desired stereoisomer 10 with an excellent optical purity of 97 %... 

A example, typically enantioselective, is the transfer hydrogenation of itaconic acid, which is reduced to methylsuccinic acid with the formic acid/triethylamine azeotrope (Scheme 1). 

We therefore quickly turned our attention to the ruthenium-catalyzed asymmetric transfer hydrogenation recently reported by Noyori. Without any optimization, 95% yield and 96% e.e. were obtained with 0.25 mol% catalyst and formic acid-triethylamine 5 2 azeotropic mixture (2.5 mL/g) in CH2CI2 at room temperature for 8 h (Scheme 6.17). - Apart from the high yield, enantiomeric excess, and turnover, this procedure is particularly simple to carry out. It also allows an easy recovery of the optically active amine by filtration, as its formiate salt at the end of the reaction, if needed, would offer an additional improvement in optical purity. 

RuGl2(G6H6)]2 is an efficient, recyclable catalyst for the asymmetric transfer hydrogenation of acetophenone derivatives with a formic acid-triethylamine azeotropic mixture in [G4GiIm]PF6 (Figure... 

Ruthenium complexes of 31, 32 and 33 using the azeotrope triethylamine/formic acid as hydrogen doimor permitted the reduction of P-keto ester, amide and nitrile with high conversion (> 95%) and ee (> 90%) (Scheme 18). The electronic character and the spacer length between the polystyrene part and the benzene ring had very little effect on the reduction outcome, for a same substrate conversion and ee are similar. Here also, it has been shown that the catalyst formed with ligand 32 could be reused at least three times without loss of activity and enantioselectivity. 

Similarly, a dimeric ruthenium complex (Fig. 78) catalyzes the reduction of cyclohexyl methyl ketone in quantitative yield with 69% ee, using a formic acid/triethylamine (5 2) azeotrope mixture as the hydrogen donor (336). 

The most efficient systems are based on arene Ru(II) or pentamethyl-cyclopentadienyl Rh(HI) complexes with the chiral ligands depicted in Figure 90. Sodium formate is used as the hydrogen source (355-357). In the reduction of AT-sulfonylimines (HI), higher reactivity was observed when formic acid-triethylamine azeotrope was used as the hydrogen donor, probably due to the... 

The hydrogen sources typically used for these reactions are IPA and a base, or formic acid-triethylamine. The IPA system is reversible, which can lead to erosion of enantioselectivity over time. One way to counter this is to operate at high dilution so there is a large excess of IPA however, this would not be desirable on an industrial scale where throughput is key. This problem can be overcome by removal of acetone during the reaction, which can be achieved in a variety of ways. The formic acid-triethylamine system is irreversible and therefore does not suffer from this issue. However, other factors have been shown to be important in achieving an efficient process, such as the ratio of formic acid to triethylamine and effective removal of the carbon dioxide generated, which reacts reversibly with the hydride complex formed. ... 

Formic acid, anhydrous (M.W. 46.03, m.p. 8.5°, b.p. 100.8°, density 1.22), or a 90% aqueous solution, is an excellent hydrogen donor in catalytic hydrogen transfer carried out by heating in the presence of copper [77] or nickel [77]. Also its salt with triethylamine is used for the same purpose in the presence of palladium [72, 73], Conjugated double bonds, triple bonds, aromatic rings and nitro compounds are hydrogenated in this way. 

---