Metal-Ligand Cooperation with Thiols as Transient Cooperative Ligands: Acceleration and Inhibition Effects in (De)Hydrogenation Reactions

Abstract

ConspectusOver the past two decades, we have developed a series of pincer-type transition metal complexes capable of activating strong covalent bonds through a mode of reactivity known as metal-ligand cooperation (MLC). In such systems, an incoming substrate molecule simultaneously interacts with both the metal center and ligand backbone, with one part of the molecule reacting at the metal center and another part at the ligand. The majority of these complexes feature pincer ligands with a pyridine core, and undergo MLC through reversible dearomatization/aromatization of this pyridine moiety. This MLC platform has enabled us to perform a variety of catalytic dehydrogenation, hydrogenation, and related reactions, with high efficiency and selectivity under relatively mild conditions.In a typical catalytic complex that operates through MLC, the cooperative ligand remains coordinated to the metal center throughout the entire catalytic process, and this complex is the only catalytic species involved in the reaction. As part of our ongoing efforts to develop new catalytic systems featuring MLC, we have recently introduced the concept of transient cooperative ligand (TCL), i.e., a ligand that is capable of MLC when coordinated to a metal center, but the coordination of which is reversible rather than permanent. We have thus far employed thiol(ate)s as TCLs, in conjunction with an acridanide-based ruthenium(II)-pincer catalyst, and this has resulted in remarkable acceleration and inhibition effects in various hydrogenation and dehydrogenation reactions. A cooperative thiol(ate) ligand can be installed in situ by the simple addition of an appropriate thiol in an amount equivalent to the catalyst, and this has been repeatedly shown to enable efficient bond activation by MLC without the need for other additives, such as base. The use of an ancillary thiol ligand that is not fixed to the pincer backbone allows the catalytic system to benefit from a high degree of tunability, easily implemented by varying the added thiol. Importantly, thiols are coordinatively labile enough under typical catalytic conditions to leave a meaningful portion of the catalyst in its original unsaturated form, thereby allowing it to carry out its own characteristic catalytic activity. This generates two coexisting catalyst populations─one that contains a thiol(ate) ligand and another that does not─and this may lead to different catalytic outcomes, namely, enhancement of the original catalytic activity, inhibition of this activity, or the occurrence of diverging reactivities within the same catalytic reaction mixture. These thiol effects have enabled us to achieve a series of unique transformations, such as thiol-accelerated base-free aqueous methanol reforming, controlled stereodivergent semihydrogenation of alkynes using thiol as a reversible catalyst inhibitor, and hydrogenative perdeuteration of C═C bonds without using D₂, enabled by a combination of thiol-induced acceleration and inhibition. We have also successfully realized the unprecedented formation of thioesters through dehydrogenative coupling of alcohols and thiols, as well as the hydrogenation of organosulfur compounds, wherein the cooperative thiol serves as a reactant or product. In this Account, we present an overview of the TCL concept and its various applications using thiols.

Scheme 1. Conventional Metal–Ligand Cooperation through Dearomatization/Aromatization and Metal–Ligand Cooperation with Thiol(ate)s as Transient Cooperative Ligands

Scheme 2. Reversible Activation of H₂ with Thiol(ate) as a Transient Cooperative Ligand and Related Reactions

Figure 1

X-ray crystal structures of Ru-3 and Ru-4.

Scheme 3. Thiol-Accelerated Methanol Reforming

Figure 2

Proposed mechanism of aqueous methanol reforming by Ru-1 in the presence of thiol.

Scheme 4. Dehydrogenation of Formic Acid by Ru-1

Figure 3

Effect of different additives on the methanol reforming activity of Ru-1.

Scheme 5. Alkyne Semihydrogenation with Thiol-Controlled Switchable Stereoselectivity

Figure 4

Control experiments for Z/E isomerization by Ru-1 in the absence and presence of thiol (NACET, N-acetylcysteine ethyl ester).

Figure 5

Representative selection of substrates investigated for thiol-controlled alkyne semihydrogenation.

Scheme 6. Amine-Controled Isomerization of an Alkene by Ru-1

Figure 6

Proposed catalytic cycle for alkyne semihydrogenation by Ru-1 with thiol as catalyst inhibitor.

Figure 7

Screening of additives for alkyne semihydrogenation catalyzed by Ru-1. EDT, ethanedithiol; 2-MAA, N-decyl 2-mercaptoacetamide; 3-MPA, 3-mercaptopropionic acid.

Scheme 7. Acceleration Effect of Thiol in H/D Exchange between H₂ and D₂O Catalyzed by Ru-1

Figure 8

Elementary steps of H/D exchange between H₂ and D₂O catalyzed by Ru-1 in the presence and absence of thiol, and respective calculated reaction energies.

Figure 9

Effect of the amount of thiol on styrene C=C bond perdeuteration catalyzed by Ru-1, as reflected in D atom incorporation and perdeuterated product yield.

Figure 10

Acceleration and inhibition effects of thiol in the hydrogenative alkene perdeuteration catalyzed by Ru-1.

Figure 11

Representative examples of alkene substrates investigated for hydrogenative perdeuteration.

Scheme 8. Stoichiometric Experiments toward Hydrogenation of Thioesters

Figure 12

Proposed mechanism of thioester hydrogenation by Ru-1.

Figure 13

Hydrogenation of various thioesters.

Figure 14

Hydrogenation of thiocarbamates and thioamides.

Figure 15

Formation of thioesters by dehydrogenative coupling of alcohols and HexSH.