Tailor‐Made Ruthenium‐Triphos Catalysts for the Selective Homogeneous Hydrogenation of Lactams

Abstract

The development of at ailored tridentate ligand enabled the synthesis of am olecular ruthenium-triphos catalyst, eliminating dimerization as the major deactivation pathway.T he novel catalyst design showed strongly increased performance and facilitated the hydrogenation of highly challenging lactam substrates with unprecedented activity and selectivity.Catalytic hydrogenation using molecular catalysts based on defined organometallic complexes has been advanced to be an essential tool for the chemical synthesis in research laboratories as well as on the industrial scale.[1] Very effective catalysts could be tailored for the addition of hydrogen to complex organic substrates,l argely based on fundamental mechanistic insight on am olecular level. Moreover,r ecent research efforts have illustrated that ruthenium complexes of the multidentate triphos (1,1,1-tri(diphenylphosphinomethyl)ethane) ligand demonstrate potential for the development of highly active and stable homogeneous species.[2] Especially for the reduction of challenging functionalities, the ruthenium-triphos systems could be established as important molecular catalyst, [2b,c] finding increasing application in numerous research groups.[3] This important advancement moved these molecular catalysts into the spotlight for novel transformations and in special cases closer to processing conditions of heterogeneous catalyst systems.[4] Nevertheless,t he hydrogenation of non-activated aliphatic amides remains an enormous challenge for molecular catalysts and especially the reductive cleavage of lactams requires novel dedicated catalysts.T he group of Bergens introduced the catalyst [Ru(Ph 2 P(CH 2 ) 2 NH 2 ) 2 (m 3 -C 3 H 5 )]BF 4 for the hydrogenation of N-phenylpyrrolidin-2-one,e nabling the formation of the respective amino alcohol with CÀNc leavage with high turnover number (TON).[5] Most recently the group of Milstein presented N,N,P-pincer ruthenium complexes for the conversion of glycine anhydride into ethanolamine in high yield.[6] Ther eduction of lactams to cyclic amines is still demanding,b ut the groups of Mashima and Saito could already use ab is-bidentate (P,N) 2 -Ru system to accomplish this transformation and obtained the cyclic products in low to moderate yield.[7] Therefore,effective homogeneous catalysts for the hydrogenolysis of lactams towards cyclic amines remain largely elusive and the development of novel transition-metal compounds for this challenging catalytic transformation needs to be established. Herein we describe arationally developed novel triphos-type ligand that enables this transformation in hitherto unprecedented efficacy.In our recent effort we could establish the highly versatile and stable ruthenium complex [Ru(triphos)(tmm)] (1a, tmm = trimethylenemethane)a sa ctive catalysts system. [2c,8] Initial mechanistic evaluation of the active hydride species 1b revealed two reaction pathways as important targets for tailoring an improved catalyst (Scheme 1).[ [2a] Them ajor pathway results in deactivation and is b...

Multifaceted catalytic hydrogenation of amides via diverse activation of a sterically confined bipyridine–ruthenium framework

“…The hydrogenation of 3h to azepane proceeded under much milder conditions ( P H2 = 2 MPa), compared with a very recent example in which catalytic (triphos)Ru derivatives were used ( P H2 = ca. 10 MPa) 14 . Although 3h and inter - h might be in an equilibrium even under H 2 40 , the net reaction would proceed via either one of (or both of) the following two pathways involving the same reaction intermediate, N , O -hemiacetal inter - h , which undergoes (Fig.…”

Homogeneous and heterogeneous catalytic reduction of amides and related compounds using molecular hydrogen

“…3d) 60 . This novel complex, in combination with MSA as additive, showed enhanced activity in lactam hydrogenations (at 160°C and 100 bar of H 2 ) to the corresponding cyclic amines 60 . In the same year, our group presented the combination of [Ru(acac) 3 /Triphos/Yb(OTf) 3 ] as an improved catalyst system for the deoxygenative hydrogenation of >25 amides under milder conditions (150°C and 5 bar of H 2 ) ( Fig.…”

“…In 2016, to understand the peculiar ligand behavior, Klankermayer and co-workers synthetized the related well-defined complex [Ru(Triphos-xyl)(tmm)] featuring a 3,5-dimethylphenyl-substituted Triphos ligand (Fig. 3d ) 60 . This novel complex, in combination with MSA as additive, showed enhanced activity in lactam hydrogenations (at 160 °C and 100 bar of H 2 ) to the corresponding cyclic amines 60 .…”

Missing Link in the Homologous Series of Lactams: The X-ray Structure of Valerolactam

“…10 Moreover, 1 is a valuable precursor for the total synthesis of different natural products [11][12][13][14] and is frequently employed in the development of chemical methodologies. [15][16][17] Additionally, several bioactive compounds are valerolactam derivatives. [18][19][20][21][22] Only recently, the biotechnological production of valerolactam (1) 23 and a lactam biosensor 24 have been introduced.…”