The Catalyst Review December 2015 - 9

SPECIAL FEATURE
When the implications of these results are considered, in terms of catalytic cycle
(Figure 5), it suggests that neither the bromoalkyne nor the terminal alkyne is
involved in rate limiting steps. This then leaves two positions in the catalytic cycle
where the rate limiting step is to be found - the condensation of intermediates 4
and 5 to give 6, or the reductive elimination yielding the final product 3.

Figure 5. Catalytic cycle highlighting the
two possible rate limiting steps.

This publication delivers great insight regarding the mecha-nistic nature of this
particular cross-coupling reaction, the data for which is collected using in situ
IR spectroscopy and well planned investigation of reaction conditions. After an
additional set of experiments, it was found that the rate of the reductive elimination
step was limiting and enhanced by the presence of ligand L1.
Source: Shi, et al. 2008

Case Study 2: Unexpected Formation of a Cyclopentadienylruthenium
Alk-oxycarbonyl Complex with a Coordinated C=C Bond
A Dynamic Kinetic Resolution Catalyzed by Ruthenium Complexes
Even though ruthenium catalysts have been successfully used in combination with lipases to convert racemic second-ary alcohols 2
into enantiopure acetates 3, referred to as dynamic kinetic resolution (DKR), the same reaction is not as effective when using olefinic
alcohol 4 (Åberg et al. 2009). It appears that alco-hol 4 racemizes very slowly, potentially due to coordination of its double bond to
ruthenium. This publication describes the use of NMR spectroscopy and in situ IR spectroscopy to show evidence for a Ru-olefin
complex (Scheme 2).
When reacting allylic alcohol and ruthe-nium complex, two IR bands at 2021 cm-1 and 1964 cm-1 can be seen reducing over time.
These bands correspond to ruthenium complex 1. A new band forming at 982 cm-1 in the CO region can also be seen, as well as a new
peak in the acyl region at 1644 cm-1 Figure 6.
Trending these peaks (Figure 7) allowed Bäckvall and colleagues to observe that the rates of disappearance and for-mation were the
same, which supports the hypothesis that diastereomers 10a and 10b are formed (Figure 8).
This work provides a great example of the power of combining the structural information offered by the functional specificity of midIR with the kinetic information gained from in situ reac-tion rate monitoring. As a result, in situ IR used in conjunction with 1H and 13C
NMR spectroscopy enabled the researchers to identify the formation of diastereomeric ruthenium complexes 10a and 10b. This in
turn helped them explain the slow rate of racemization of 4, which makes 4 a poor substrate for dynamic kinetic resolution.

Case Study 3: Preparation of Grignard Reagents: FTIR and Calorimetric
Investigation for Safe Scale-Up
Even though this paper was published years ago (am Ende, et al. 1999), Grignard reactions are still widely used throughout industry
for carbon-carbon bond formation, and the application of in situ IR spectroscopy still holds the same real-time value. When
considering the appropriate PAT to track Grignard reactions, one should consider whether the PAT technique:
* Is impervious to the presence of solid Mg turnings
* Detects the presence of water in solvent
* Operates robustly under reflux conditions
* Detects low concentrations of all critical components
In a typical Grignard reaction, the strategy is to charge the reactor with Mg and THF, add <10 % organic halide (R-X), raise
temperature to reflux conditions, wait for onset of reaction initiation (by detecting an exothermic temperature rise) and then feed
the remaining R-X. However, detection of the exotherm is difficult under reflux conditions at large scale. Therefore, the authors
developed a real-time method to detect the reaction onset and subsequent progress by applying in situ mid-IR (ReactIR) to monitor
the organic halide concentration and the formation of the Grignard reagent.
The first step of this reaction scheme is shown in Scheme 3. In situ IR spectra measuring solvent, aryl halide and Grignard reagent are
shown in Figure 9. It is possible to follow each of these reaction components via isolated peaks in their spectra.
Figure 10 shows profiles of these peaks along with the reaction mass, trended over time. The point of reaction initiation and the
subsequent formation of the Grignard reagent (1556 cm-1) are clearly observed at time = 0.24 hours. The relative R-X concentration
trend shows the initial addition of 5% of the aryl halide (1590 cm-1) at time = 0.
The Catalyst Review

December 2015

The Catalyst Review December 2015

Table of Contents for the Digital Edition of The Catalyst Review December 2015