Amines from transfer hydrogenation

Based on the above activation mechanism we wondered whether it would be possible to develop a biomimetic, organocatalytic reductive amination or transfer hydrogenation of ketimines. We reasoned that the activation of the imine by catalytic protonation through the Brpnsted acid should enable the hydrogen transfer from a suitable NADH mimic to yield the corresponding amine (Fig. 2). Hence, initial experiments focused on the examination of various Brpnsted acids in combination with different hydride sources (Rueping et al. 2005a). 

Recent theoretical [98, 99] and experimental [4, 100] work strongly suggests that, when the catalyst contains a primary or secondary amine ligand, transfer hydrogenation involves transfer to/from a Ru-amide bond. (Buchwald... 

A chiral amine-catalyzed transfer hydrogenation was recently employed successfully by Lear and co-workers to obtain a key intermediate for die total synthesis of (—)-platensimycin (245) (213). (—)-Platensimycin (245) was identified from Streptomyces platensis in 2006 (214, 215). Due to its impressive antibacterial properties, it has generated considerable interest within the scientific and medical communities as a potential powerful new therapy against dmg-resistant bacteria (214, 215). Accordingly, several (formal) total synthesis approaches have been... 

The first experimental data for a reaction involving proton transfer from a hydrogen-bonded acid to a series of bases which were chosen to give ApK-values each side of ApK=0 are given in Fig. 15 (Hibbert and Awwal, 1976, 1978 Hibbert, 1981). The results were obtained for proton transfer from 4-(3-nitrophenylazo)salicylate ion to a series of tertiary aliphatic amines in aqueous solution, as in (64) with R = 3-nitrophenylazo. Kinetic measurements were made using the temperature-jump technique with spectrophoto-metric detection to follow reactions with half-lives down to 5 x 10"6s. The reciprocal relaxation time (t ), which is the time constant of the exponential... 

Noyori and coworkers reported well-defined ruthenium(II) catalyst systems of the type RuH( 76-arene)(NH2CHPhCHPhNTs) for the asymmetric transfer hydrogenation of ketones and imines [94]. These also act via an outer-sphere hydride transfer mechanism shown in Scheme 3.12. The hydride transfer from ruthenium and proton transfer from the amino group to the C=0 bond of a ketone or C=N bond of an imine produces the alcohol or amine product, respectively. The amido complex that is produced is unreactive to H2 (except at high pressures), but readily reacts with iPrOH or formate to regenerate the hydride catalyst. 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

Scheme 6.24 Amines obtained from the transfer hydrogenation of aldimines in the presence of catalyst 9 and Hantzsch ester 19.

Roszkowski et have described a method for the enantioselective preparation of Praziquantel (PZQ) a pharmaceutical for the treatment of schistosomiasis and soil-transmitted helminthiasis. Starting with the imine (P) (readily available from phenylethyl amine, phthalyl anhydride and glycine) an asymmetric transfer hydrogenation yielded the chiral intermediate in 62 % ee, and the crude product was easily crystallized to the required high ee and converted into the Praziquantel as shown in Figure 1.34. 

From these studies it was concluded that the main secondary reactions for TX/amine systems are hydrogen abstraction from the surrounding polymer and decomposition of peroxides through energy transfer. 

Photoinduced electron transfer from the amine to C6o to yield a radical ion pair is suggested to be the initial step for the formation of 54a-b. This is followed by deprotonation of the amine cation by the fullerene anion to give an a-aminoalkyl and HC6o radical pain [134], Subsequent combination of the radical pair leads to the final product. Formation of 55 is likely to be initiated by PET from 54b to C6o. This is then followed by successive intermolecular proton transfer, hydrogen abstraction, and ring closure to give l,2-H2C6o and 55 (Scheme 21). 

Asymmetric hydrogen transfer from 2-propanol to aromatic ketones such as acetophenone (99) has been achieved by using the same chiral Ru complex in 2-propanol containing KOH at room temperature, and (S)-1 -phenylethanol (100) with 98% ee was obtained [68,69]. Similarly, efficient Ru-catalysed transfer hydrogenation of aromatic ketones using the cyclic amino alcohol [(I. S, 3R,4i )-2-azanorbomylmetha-nol] (110) [70] and bis(oxazolinylmethyl) amine (111) [71] was reported. 

Transfer hydrogenation of the imine bond in 146 from HCO2H, catalysed by the Ru chiral amine complex 114, afforded salsolidine (147) [86],... 

The nitropyridines can be reduced to the corresponding aminopyridine and several new methods have been developed to achieve this transformation. 3-Nitropyridine is reduced in excellent yield by the mixed borohydride prepared from 1 equiv of ZrCU and 4 equiv of NaBFLi in THF under reflux <2000SL683>. 3-Nitropyridines may be reduced to the aminopyridine using sodium hydrosulfite in THF/H20 at room temperature <2005JME5104>. 2-Nitropyridine can be reduced to the amine in near quantitative yield by transfer hydrogenation in the presence of 10% Pd/C and recyclable polymer-supported formate, prepared from aminomethylpolystyrene resin and ammonium formate <2005SC223> (Equation 64). The resin is easily recovered by filtration and may be used up to 10 times. 

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