Upon hydrogenation of alkynes, two possible products can be formed: a cis- or a trans- olefin. In literature many example of homo- and heterogeneous hydrogenation catalysts are known, that enable a cis-hydrogenation.[89] The most commonly used catalysts for these transformations are poisoned heterogeneous catalysts, as for instance the Lindlar catalyst,[90] that stops at the alkene stage and does not overreduce the product to the unwanted alkane. Catalytic reductions to trans-alkenes are more challenging and just a few examples were reported in literature, using rhodium[91,92] or iridium[93] based metal catalysts.[91–93] These systems do not have good turnover numbers, are restricted to diarylalkynes or are not functional group tolerant. In 2001, the group of Bargon reported a stereoselective hydrogenation of internal alkynes 22 to (E)-alkenes 23[94] using [Cp*Ru(sorb)]OTf 24[95] as catalyst (Scheme 2.9).
Scheme 2.9: A stereoselective trans-hydrogenation of alkynes.
The reaction was studied by PHIP-NMR in order to get a deeper understanding of the mechanism and answer the question whether the transferred hydrogen comes from a single or from multiple hydrogen molecules. Indeed, they observed hyperpolarized signals on several products from different substrates. This shows that the transfer must take place rapidly with the same H2 so that no loss of the pair correlation of the hydrogen atoms can occur. Additionally, the temperature dependence of the reaction was investigated. When the reaction was conducted in the magnet between 10 °C and 30 °C, exclusively or mainly the (E)-product was observed. A further increase of the temperature up to 50 °C generated mostly the (Z)-product. This behavior was explained by a change of a binuclear to a mononuclear ruthenium complex catalyzing the reaction. The authors conjectured that at lower temperatures the trans-product might be formed by a binuclear complex (Scheme 2.10), in accordance with observations with previous results in literature.[91,92] The authors did not observe other additional intermediates. This can be explained in their proposed catalytic cycles, which shows that all the proposed intermediates are highly symmetrical so that no hyperpolarization could be observed (Scheme 2.10). One has to mention that a chiral secondary alcohol substrate is also reported by the authors. In this case the hydrogen substrate complex is asymmetric and potential hyperpolarized signals might be observed. The reaction of terminal alkynes does not yield any product due to the formation of a stable vinylidine complex. However, the influence of hydrogen pressure on this reaction was not investigated and also no yields were reported for this reaction. Overall this was so far the only study of a trans- selective hydrogenation by PHIP and the reaction mechanism is still under debate.
Scheme 2.10: Proposed mechanism for the trans-selective hydrogenation of internal alkynes catalyzed by
Cp*Ru(sorb)OTf.
In 2004, Duckett and his coworkers reported another PHIP NMR study on the hydrogenation reaction of diphenylacetylenes yielding trans- and cis-stilbenes using a cationic palladium (II) diphosphine complex as the catalyst. Interestingly, hyperpolarized signals were observed for the cis olefin, but not for the trans.[96] Additionally, they
observed a covalent palladium intermediate containing three hydrogens. This complex is the precursor of the trans-species as proven by EXSY spectroscopy. In the following years, this group was intensively studying the mechanism of this reaction. [97–99] A palladium hydride turned out to be the active species. The complex with the cis product yields the characterized intermediate. After β-hydride elimination, where two different hydrogens are mixed, the trans-stilbene is formed, resulting in weak enhancement of the olefinic product signals.
Recently, Fürstner et al. reported a hydrogenation protocol for a functional group tolerant and stereoselective trans-hydrogenation of alkynes yielding (E)-alkenes 23 with good E/Z ratios and yields.[100] The authors started their catalyst screening with the conditions reported initially by Bargon[94] and optimized these by changing the solvent to CH2Cl2, using the in situ prepared cationic complex [Cp*Ru(cod)]OTf from [Cp*Ru(cod)]Cl 26 and AgOTf as the catalyst and 10 bar of hydrogen pressure. Initial mechanistic studies showed the formation of several hydride species in the NMR spectrum (H = –4.96, –8.02 and –13.42 ppm) when the sample was kept under hydrogen pressure for one hour. In further experiments it could be shown that [Cp*Ru(H2)(cod)] 27 yields the corresponding alkenes with the same high E/Z ratio as under catalytic hydrogenation conditions, indicating that both species might form similar active intermediates. More recently, Fürstner and his coworkers extended the scope of this catalytic systems with slight modulations on the catalyst to trans-selective hydroborations,[101] hydrostannations,[102] hydrosilylations and hydrogermylations[103] and a generalized mechanism for product formation was proposed (Scheme 2.11, applied to hydrogenations). In contrast to the previously proposed mechanism by Bargon the product formation occurs via a stepwise or concerted formation of a ruthenium metallacycle, which might open and isomerize during the course of the reaction. After hydrogen transfer the catalyst is regenerated through reductive elimination. The concept for this postulated mechanism is inspired by previously conducted computational studies by Trost and Wu on trans-hydrosilylation reactions[104] and on control experiments with the σ-H2 ruthenium hydride complex 27.
Scheme 2.11: Proposed mechanism for the trans-selective hydrogenation of internal alkynes by Fürstner.
The newly proposed mechanism contains several intermediates that could potentially be observable through PHIP investigations, depending on their lifetime. Several observations could not be explained by this mechanism, as for instance overreductions and isomerizations. Therefore a reinvestigation of this mechanism would be of high interest.1