Quinoline homogeneous hydrogenation

Several heteroaromatic compounds can be hydrogenated by [Rh(COD) (PPh3)2]+ species. Thus, this cationic complex has been reported to be a catalyst precursor for the homogeneous hydrogenation of heteroaromatic compounds such as quinoline [32] or benzothiophene [33]. Detailed mechanistic cycles have been proposed by Sanchez-Delgado and coworkers. The mechanism of hydrogenation of benzothiophene by the cationic rhodium(III) complex, [Rh(C5Me5) (MeCN)3]2+, has been elucidated by Fish and coworkers [34]. 

Cuprous Salts in Quinoline and Other Amines. The first homogeneous hydrogenation reaction to be recognized and studied was the reduction of cupric acetate in quinoline solution. Following Calvin s pioneering work in 1938 (4, 5), this and related systems have been examined by a number of other workers including, Weller et al. 89, 30) and Wilmarth et al. (31-33). 

Only a few years ago it appeared that only one case of homogeneous hydrogenation catalysis was known—the cuprous-acetate-in-quinoline system. The uniqueness of this system appeared to define a very special set of chemical and physical circumstances. However, recent searching for this type of catalyst has disclosed a number of active catalysts. It appears possible that many more will be found in the future and that the chemical reactivity of hydrogen at low temperatures has not been fully appreciated. As new and old systems become better defined, there is high hope that this scientific approach to hydrogenation catalysis will continue to provide critical information of theoretical and, ultimately, of great practical importance. 

Homogeneous hydrogenation of Q to THQ is also catalyzed by Os3(CO)j2 and its derivatives. These studies, together with the synthesis of osmium cluster complexes of quinoline, have led to another mechanism for quinoline hydrogenation which involves more than one metal center. It is likely that reactions catalyzed by Cp Rh(NCMe)3 and Os3(CO)i2 proceed by different mechanisms. Whether either of these mechanisms is consistent with the heterogeneously catalyzed conversion of Q to THQ is unknown. 

Scheme 16 General mechanisms of the homogeneous hydrogenation of quinoline.

Table III. Hydrogenation of Quinoline to 1,2,3,4-Tetrahydro-quinoline in homogeneous solution at 300°C...

Several homogeneous systems have been reported to catalyze the hydrogenation of polynuclear N-heterocycles efficiently the regioselective reduction of the N-containing ring in quinoline, isoquinoline, indole, benzoquinolines, acridine and other related molecules can be achieved with relative ease and under moderate conditions of temperature and pressure. A number of metals are known to be active (Cr, Mo, W, Mn, Fe, Ru, Os, Co, Rh, Ir) but most of the published work has concentrated on ruthenium and rhodium precursors [95-100] as shown in Table 3.3. 

A recent development is the transfer hydrogenation of heterocyclic systems such as pyrrole, pyridinium, and quinoline systems. Whilst the yields and enan-tioselectivities are modest at the moment, further development may improve this. For example, 1-methyl-isoquinoline has been reduced to the tetrahydro species and 1-picoline has been reduced to 1-methylpiperidine. Hydrogenation of alkenes has been reported [16], but in the CATHy -catalyzed reaction alkene reduction has only been observed after extended reaction times. Whilst heterogeneous transfer hydrogenation of nitro groups is well known, homogeneous systems do not reduce these groups. 

Several approaches have been followed for the generation of optically active heteroarenes by homogeneous asymmetric hydrogenation. One approach involves direct asymmetric hydrogenation of the unactivated heteroarene. This approach has been most successful for heteroarenes that are polycyclic, like quinolines, isoquinolines, or quinoxa-lines (benzopyrazines). Less success has been achieved on the direct asymmetric hydrogenation of pyridines. To address this limitation, the hydrogenation of modified pyridines has been conducted. In one set of examples, pyridines and related benzo-fused heteroarenes were modified at tfie nitrogen by acylation or the installation of another auxiliary to make the pyridine more electron poor and to dock the catalyst. In a second set of examples, a chiral auxiliary was placed on the pyridine, and the product was formed diastereoselectively by an achiral catalyst. 

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