Hydrogenation of Indole by Phosphine-Modified Rhodium and Ruthenium Catalysts

Abstract

The selective hydrogenation of indole (IN) to indoline (INE) by rhodium and ruthenium catalysts modified with the tripodal polyphosphine ligand MeC(CH 2 PPh 2 ) 3 (triphos) has been investigated in the homogeneous phase. Both [Rh(DMAD)(triphos)]PF 6 (DMAD ) dimethyl acetylenedicarboxylate) and [Ru(MeCN) 3 (triphos)](SO 3 CF 3 ) 2 have been found to generate effective catalysts for the conversion of IN to INE in THF in the presence of triflic acid. The protic acid is required to generate the 3H-indolium cation, which contains a localized CdN bond. The rhodium precursor was more efficient than the ruthenium species and allowed for hydrogenation of the substrate even at 60 °C with turnover frequencies as high as 100. Catalytic experiments in autoclaves and in high-pressure sapphire NMR tubes have provided valuable information on the hydrogenation mechanism of IN.

Mechanistic analysis of the transition metal-catalyzed hydrogenation of imines and functionalized enamines

“…These reports by James [24][25][26][27][28][29][30][31][32][33], Bianchini [34,35], Oro [36][37][38][39] …”

Hydrogenation of Arenes and Heteroaromatics

“…Consistently, the hydrogenation of indole is generally inhibited when the reaction mixture contains basic substrates such as quinoline, THQ, and pyridine. The only catalysts that have proved able to regioselectively hydrogenate indole to indoline with an acceptable TOF are [Rh(DMAD)(triphos)]PF 6 and [Ru(NCMe) 3 (triphos)] (SO 3 CF 3 ) 2 , though on condition that a protic acid is added to the catalytic mixture [74,76]. The rhodium catalyst was more efficient than the ruthenium catalyst, and allowed for hydrogenation of the substrate even at 60 8C and 30 bar H 2 , with TOFs as high as 100.…”

8.17 Homogeneous Catalytic Hydrogenation of CåC and CåC

“…104 Pyridine can be reduced to piperidine in the presence of the nickel Ziegler catalyst, 111 2 ]H 2 (PPh 3 ) 2 } − amongst other ruthenium complexes to give the products where the heterocycle is reduced but benzene nuclei are not. 120,[150][151][152][153] For the reduction of quinolone, the cationic rhodium complex [Rh(PPh 3 ) 2 (COD)] + gave the most active catalytic system. 154 Sulfur heteroaromatics, such as thiophene and benzothiophenes, can be reduced by a number of homogeneous catalytic systems including [RuCl 2 (PPh 3 ) 3 ], 154 150,159,160 Many of the recent catalytic systems that have been developed for the hydrogenation of heteroaromatic compounds not only reduce the unsaturation, but also provide asymmetric induction (see Section 8.17.5.2.2.1).…”