Kinetic Analysis of Domino Catalysis: A Case Study on Gold-Catalyzed Arylation

Abstract

Domino catalysis is a well-explored route to increasing the efficiency of multistep reactions. However, the kinetic features required for efficient turnover of a process where "multiple transformations are effected by a single catalytic mechanism" have not been explored in any detail. The kinetics of a nominally simple two-stage domino catalytic reaction have been analyzed by way of a gold-catalyzed coupling of two electron-deficient arylsilanes to generate an arylated fluorene. A combination of in situ interleaved 1 H and 19 F NMR spectroscopic kinetic measurements, kinetic simulations, and variations in substitution reveal how the catalyst partitioning between the two different cycles impacts both the rate and the selectivity of the process. The insight enables identification that sequential catalyst speciation and accumulation of the domino intermediate are general kinetic criteria for efficient domino catalysis.

Stopped‐Flow 19F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

“…[15,16] However, monitoring rapid irreversible reactions by NMR spectroscopy poses a considerably different challenge, especially when such processes are initiated by mixing, rather than by a readily controlled external stimulus such as light. [17] Over the last decade we have investigated a wide range of anion-mediated processes involving organoboron [18][19][20][21] and organosilicon [22][23][24][25][26] reagents, including hydrolytic activation and degradation of boronic acids, [18,21] and their derivatives. [19,20] In the majority of examples we were able to employ standard 1 H, 11 B, 19 F, and 29 Si NMR spectroscopic techniques to analyze the reaction kinetics.…”

“…Over the last decade we have investigated a wide range of anion‐mediated processes involving organoboron [18–21] and organosilicon [22–26] reagents, including hydrolytic activation and degradation of boronic acids, [18,21] and their derivatives [19,20] . In the majority of examples we were able to employ standard 1 H, 11 B, 19 F, and 29 Si NMR spectroscopic techniques to analyze the reaction kinetics.…”

Requiem for the Rate-Determining Step in Complex Heterogeneous Catalytic Reactions?

“…There are cases when the rate equation for linear sequences with a small number of steps was not derived and a system of differential equations was solved even if the rate equation for the steady -state system can be readily derived. This was done, for example in [48], when a solver of differential equations was used for a four step sequence of the Fujiwara-Moritani reaction (Figure 4), unfortunately not reporting how the balance equation for catalytic species was taken into account, For a particular case of the mechanism in Figure 4, the rate equation can be easily derived as this mechanism is a special case of Equations ( 11) and (12) with irreversible steps 2 and 3 simply resulting in Or, after introducing the explicit expressions for the frequencies of steps For a particular case of the mechanism in Figure 4, the rate equation can be easily derived as this mechanism is a special case of Equations ( 11) and (12) with irreversible steps 2 and 3 simply resulting in r = ω +1 ω +2 ω +3 ω +4 C cat ω 2 ω 3 ω 4 + ω −1 ω 3 ω 4 + ω 1 ω 2 ω 3 + ω −4 ω 2 ω 3 + ω −4 ω −1 ω 3 + +ω 4 ω 1 ω 2 + ω 3 ω 4 ω 1 (25) Or, after introducing the explicit expressions for the frequencies of steps (26) In a more general case, when the reaction mechanisms comprise linear and nonlinear steps without any rate-limiting ones, derivation of an explicit rate equation can be too tedious. Instead, a comparison between the experimental and calculations should be done in an implicit form using a system of differential equations considering also an algebraic balance equation for the catalytic species.…”

“…Kinetic analysis was applied for decades to assist reactor design and scaling up of various reactions relevant for oil refining and synthesis of basis and specialty chemicals. More recently, because of a widespread application of so-called flow chemistry to streamline pharmaceutical research and products, kinetic analysis also started to be more widely utilized in the field of fine chemicals [11][12][13]. It was argued [11] that the framework of a mechanistically based rate equation combined with in situ experimental data is useful for the interpretation of complex reaction networks.…”

In Situ Studies of Arylboronic Acids/Esters and R3SiCF3 Reagents: Kinetics, Speciation, and Dysfunction at the Carbanion–Ate Interface

“…After detailed investigation, we elucidated that CH 2 N 2 is generated transiently in situ , which is another example of a benefit of “slow-release”. These investigations led us to develop an interest in the role of anions as initiators for nucleophilic transfer of organic fragments from organosilanes to electrophiles, including from Ar-TMS to Au, and eventually to detailed studies of TMSCF 3 . ,, …”