Formic-acid-triethylamine

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>. 

This system is very selective towards the reduction of C-C double bonds, and the oxygen of the acid group that coordinates to the metal is important for good catalytic properties. In the reaction mixture, triethylamine is added in a ratio of formic acid triethylamine of 5 2, which is the commercially available azeotropic mixture of these compounds. 

With the rhodium catalyst, and using TEAF in organic media, the situation is more complex. An example in which a series of formic acid triethylamine ratios... 

As can be seen from the data in Table 35.1, the maximum reaction rate is achieved at the 5 2 formic acid triethylamine ratio that is the commonly used azeotropic mixture known as TEAF. When more acid is present, the catalyst may be less active, but equally there may be less formate anion (i.e., the active reagent). The concentration of the latter also depends upon the solvent being used. When there is more triethylamine present the reaction rate also decreases, and there are some indications that triethylamine may deactivate the catalyst. However, the use of formic acid mixtures with ammonia, ethylamine or diethy-lamine is less effective than triethylamine. 

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. 

Some commonly used buffers, such as sodium and potassium phosphate, are incompatible with ELSD, but there are ready alternatives. For example, ammonium acetate has similar buffering properties to potassium phosphate, and ammonium carbonate, ammonium formate, pyridinium acetate, and pyridinium formate are options for different pH ranges. Typical mobile phase modifiers that do not meet the volatility criteria can be replaced by a wide variety of more volatile alternates. For example, phosphoric acid, commonly used as an acid modifier fo control pH and ionization, can be replaced by trifluoroacetic acid other acids that are sufficiently volatile for use with FLSD include, acetic, carbonic, and formic acids. Triethylamine, commonly used as a base modifier, is compatible with FLSD other base modifiers that can be used are ethylamine, methylamine, and ammonium hydroxide [78]. 

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. 

The highly enantioselective reduction of benzils was achieved by the use of the chiral Ru complex (S,S)-28 with an S/C of 1,000 in a formic acid-triethylamine mixture to give the R,R diol in >99% ee (Scheme 34) [108]. The sense of enan-tioselection was the same as that of the reduction of simple aromatic ketones, suggesting that the adjacent oxygen atom does not participate in the stereoregulation. Introduction of electron-accepting functions at the 4 and 4 positions increased the reaction rate, while the enantioselectivity was not affected by the electronic properties of the substituents. Use of 2-propanol as a hydride source caused both the rate and enantioselectivity to decrease. An unsymmetrical 1,2-... 

When the unsymmetrical 1,2-diketone A was reduced with (S,S)-28 and a formic acid-triethylamine mixture at 10 °C, a-hydroxy ketones, (S)-B in up to >99% ee and C, were obtained selectively (Scheme 36) [ 109]. The selectivity between B and C was highly dependent on the character of the aromatic ring of... 

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. 

An Rh(III)-tetramethylcyclopentadienyl complex containing a tethered functionality is found to give excellent results in the asymmetric transfer hydrogenation of ketones in both aqueous, using sodium formate, and formic acid-triethylamine media. Quantitative yields and almost 100% ees are obtained.374... 

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). 

Bianchini, C., Glendenning, L. Ruthenium(ll)-catalyzed asymmetric transfer hydrogenation of ketones using a formic acid-triethylamine mixture. Asymmetric transfer hydrogenation of imines. Chemtracts 1997, 10, 333-338. 

As the transfer hydrogenation reactions using Ru-TsDPEN catalyst could take place in aqueous solution [108-111], the next stage was to develop a polymeric catalyst suitable for the aqueous conditions. One such example was the use of PEG as a polymer support, as reported by Xiao [112]. The PEG-supported TsDPEN 176 (Scheme 3.54) was highly effective in the Ru(II)-catalyzed transfer hydrogenation of simple ketones by sodium formate in water. The same polymeric catalyst was also effective for the same reaction by using a formic acid-triethylamine azeotrope [113]. 

Anion-exchange HPLC (Nucleosil 5SB column) with 50 mmol formic acid-triethylamine in methanol-water (5 95) mobile phase at pH 2.6 and 30 °C cation-exchange separation (Nucleosil 5SA column) with triethylamine in acetonitrile-water-acetic acid (12.5 82.5 5) mobile phase at pH 3.9 and 6 °C on-line ESI-MS analysis of the column effluents... 

For enantioselective transfer hydrogenations using formic acid/triethylamine and ruthenium diphosphine catalysts see J. M. Brown, H. 

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. 

Table 5.3-6 Recycling of 1 and 2-Ru (Fig. 5.3-10) in the asymmetric transfer hydrogenation of acetophenone using the formic acid-triethylamine azeotropic mixture in the ionic liquids [BMIM][PF6].

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... 

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