Formic acid-triethylamine reduction with

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-... 

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. 

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... 

Soni, R. Hall, T. H. Mitchell, B. P. Owen, M. R. Wills, M. Asymmetric reduction of electron-rich ketones with tethered Ru(II)/TsDPEN catalysts using formic acid/triethylamine or aqueous sodium formate. /. Org. Chem. 2015,80,6784-6793. 

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

A different dimerization takes place in formic acid (33. 34). Unlike other carboxylic acids which behave as nucleophiles, formic acid behaves as a reductant and the dimerization proceeds with partial reduction. By carrying out the reaction in a mixture of formic acid and triethylamine at 59°C using Pd(OAc)2, 1,6-octadiene (24) was obtained. 

Heck tried the reductive dimerization of isoprene in formic acid in the presence of triethylamine at room temperature using 1% palladium phosphine catalysts to give dimers in up to 79% yield (95). Better selectivity to the head-to-tail dimer was obtained by using Pd(OAc)2 with 1 1 ratio of arylphosphines. THF as solvent showed a favorable effect. In a scaled-up reaction with 0.5 mole of isoprene using 7r-allylpalladium acetate and o-tolyphosphine, the isolated yield of the dimers was 87%. The dimers contained 71% of the head-to-tail isomers. The mixture was converted into easily separable products by treatment with concentrated hydro-... 

Oeavage of esters to acids and hydrocarbons mentioned above was achieved not only with hydrides but also by catalytic hydrogenation and reduction with metals. For example the acetate of mandelic acid was converted to mandelic acid and acetic acid by hydrogenation at 20° and 1 atm over palladium on barium sulfate in ethanol in the presence of triethylamine in 10 minutes [1035], and a,a-diphenylphthalide was reduced by refluxing for 5 hours with zinc in formic acid to a,a-diphenyl-o-toluic acid in 92% yield [1036]. Such reductions are of immense importance in esters of benzyl-type alcohols where the yields of the acids are almost quantitative. 

Selective reduction of aldehydes.2 This reduction can be effected with formic acid (1.25 equiv.) and triethylamine (1 equiv.) and a catalytic amount of RuC12[P(C6H5)3]3 at 25° in THF. Under these conditions nitro, keto, ester, and t-amide groups are not reduced. The reduction of aldehydes, however, is sensitive to steric hindrance. Thus mesitaldehyde is reduced very slowly. 

A RhCp complex (S,S)-6 (Cp =pentamethylcyclopentadienyl), which is iso-lobal with Ru(rj6-arene) complex (S,S)-5 (Scheme 13), effected the transfer hydrogenation of a cyclic imine substituted by an isopropyl group with an S/C of 200 in the presence of a 5 2 mixture of formic acid and triethylamine to give the R amine in 99% ee (Scheme 13) [31]. When the reaction was performed with an S/C of 1,000, the optical yield decreased to 93%. The methyl imine was reduced with a 91% optical yield. Reduction of a cyclic sulfonimide resulted in the R sul-tam in 81% ee. 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

Reduction of quaternary pyridinium halides (or, more precisely, formates) with formic acid in the presence of potassium formate at about 150°C is usually referred to as the Lukes reduction.80-95 Instead of potassium formate, triethylamine may be used, especially with quaternary pyridinium iodides.85,86 Mixtures of l-alkyl-3-piperideines (77) and 1-alkylpiperidines (78) are usually obtained. Formation of piperideines (77) might be explained by analogy with the Ladenburg reduction of pyridine bases the double bond at position 3 is resistant toward further reduction by formic acid or by... 

This reaction type has also been used for the diastereoselective reduction of a variety of structurally related o -amino-/3-keto esters (equations 9 and 10). Treatment of rac-73 with a substoichiometric amount of chiral mediator 72, using formic acid and triethylamine as the hydrogen source, gave the enantiomerically pure a-amino-/ -hydroxy ester (R,S)-syn-74 in 100% yield with 95 5 dr and 99% ee (equation 9), via the diastereoselective reduction of (S)-73. The unreacted R)-73 efficiently racemizes through tautomerization under these reaction conditions. 

Semihydrogenation of alkynes. Formic acid is a hydrogen source for the Pd(0)-catalyzed transfer reduction of the triple bond to afford the (Z)-alkene with a selectivity of 89-98%. The reducing system also contains triethylamine. 

A more universal method of SpAs preparation is based on reduction of IcP bases (e.g., 2, 327 and 330) instead of the IcP quaternary salts mentioned above. The reduction was performed with nickel aluminium alloy or, better still, with a mixture of formic acid and triethylamine. In the latter case, reaction results in the formation of isolable 5-formyl SpAs derivatives (e.g., 554 and 555) readily hydrolyzed in hot hydrochloric acid to SpAs in 85-95% yield, unsubstituted (493) or substituted (556 and 557) at the ring nitrogen atoms. By this method, the previously unknown 2-aza-SpA 558 were prepared from l,2,3-triazolo[4,5-c]pyridine (2002ZOR440). 

Irradiation of iron and cobalt porphyrins (13 Fe(TPP), 14 Co(TPP), H2TPP = 5,10,15,20-tetraphenyl-21/f,23/f-porphyrin) in the presence of triethylamine (TEA) using > 320-nm tight caused the photocatalytic reduction of CO2 [15, 16, 27-31]. When 13 was used as a photocatalyst, CO was detected with TNco = 70 after 180-h irradiation [15]. Formic acid was the main product when 14 was employed as a photocatalyst [16]. The reaction mechanism proposed on the basis of UV-vis absorption changes during photolysis and radiolysis, and electrochemical measurements are shown in Scheme 3. M (TPP) is reduced to M (TPP) by photoinduced electron transfer from TEA, which subsequently disproportionates to M°(TPP), the proposed catalyticaUy-active species. 

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. 

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