Kinetic Studies of the Ni-catalyzed Cross-coupling of Alkyl Halides and a Tosylate with Butyl Grignard Reagent in the Presence of 1,3-Butadiene

Abstract

Kinetic studies of the nickel-catalyzed cross-coupling reaction of alkyl bromides, iodides, and tosylates with butyl Grignard reagents in the presence of butadiene were performed. The reaction rate was first order with respect to the halides and the nickel catalyst. The butyl Grignard reagent, at concentrations of ca. 0.4 M or higher, had little effect on the reaction rate. The relative reactivities and activation parameters were determined for these alkyl halides and a tosylate.Cross-coupling reactions are useful and powerful tools for connecting two different organic moieties via a single bond and have been widely employed in organic synthesis.1 During the past decade, the scope of this cross-coupling has been expanded to the use of alkyl halides as a coupling partner.2 In a previous study, we reported that nickel as well as palladium and copper showed unique catalytic activities for cross-coupling reactions in which alkyl halides were used in the presence of a ³-carbon ligand such as 1,3-butadiene or an alkyne.3 The Ni/butadiene system (eq 1) showed particularly high performance, allowing the selective alkylalkyl cross-coupling of alkyl halides with a Grignard reagent 4 in the presence of various functional groups. 5 Furthermore, the turn-over number can reach the order of 10 7 . 6 In order to probe this reaction in more detail, we performed kinetic studies and report on the results obtained.We first examined the time course for the reaction of nonyl bromide (1a) with excess butyl Grignard reagent using various Ni salts and 1,3-butadiene in THF at 0°C. As shown in Figure 1, all of the Ni salts afforded tridecane (3a) exclusively in quantitative yield based on the bromide within 15 min, but an induction period was observed for several salts probably due to their low solubilities in THF. NiBr 2 /dme (dme: dimethoxyethane) and [Ni(acac) 2 ] did not show any apparent induction period. Therefore, we used NiBr 2 /dme as the source of the Ni catalyst throughout this kinetic study.We then examined order of the rate for each reagent. A reaction using NiBr 2 /dme, similar to that of Figure 1 was performed using different concentrations of nonyl bromide (1a) at ¹35°C and the reaction was quenched with 1 M HCl(aq) after stirring for 90 s. These results were plotted in Figure 2 and a good straight line was obtained, indicating that this reaction obeys first-order kinetics with respect to nonyl bromide with a pseudofirst-order rate constant k obs = 1.76 © 10 ¹3 s ¹1 for r = k obs [n-C 9 H 19 Br].The effect of the catalyst and Grignard reagent on the reaction rate was examined using heptyl tosylate (1b) at 1°C for 150 s. In a similar manner, the yield of undecane (3b) was plotted against the concentration of the Ni catalyst employed, and the results are shown in Figure 3. These data clearly indicate that the reaction rate is first order with respect to the catalyst concentration.When we ran the same reaction using different concentrations of n-BuMgCl, an interesting result was obtained (Figure 4). The reaction was accelerat...

Nickel‐Catalyzed Dimerization and Alkylarylation of 1,3‐Dienes with Alkyl Fluorides and Aryl Grignard Reagents

“…Although complex B has four potent nucleophilic centers, namely the a-a nd g-carbon atoms of the s-allyl group,t he ipso carbon atom of the aryl group,and the Ni center, [19] alkyl fluorides react selectively at the g-carbon atom of the s-allyl group in B to give intermediate C by an S N 2m echanism in aprocess that is probably assisted by the coordination of MgX cations to the eliminating Fanion. Substituent(s) at the ortho position(s) of the aryl group block the approach of alkyl halides towards the Ni center and the ipso carbon atom.…”

Nickel-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents in the presence of 1,3-butadiene: mechanistic studies of four-component coupling and competing cross-coupling reactions

“…Alternatively, the Ni center in complex B can react with alkyl fluorides to give the cross-coupling product 4 through complex D (steps E and F). 25 Therefore, the reaction courses of four-component coupling vs. cross-coupling are determined by the reaction of alkyl fluorides with complex B (step C vs. step E).…”

Nickel‐Catalyzed Coupling of Thiomethyl‐Substituted 1,3‐Benzothiazoles with Secondary Alkyl Grignard Reagents

“…Under similar reaction conditions, alkyl bromides undergo rapid cross‐coupling with alkyl Grignard reagents at 0 °C or even below 11c,j. Then a competitive reaction of 1 a and n NonBr was conducted, and the time course for the reaction, as well as the corresponding independent reactions, are shown in Figure 2, in which the competitive reaction is shown as a solid line and independent reactions are shown as dashed lines.…”

“…It is likely that cross‐coupling with nonyl bromide proceeded via the bis(π‐allyl)metal species 5 as the catalytically active species, which then reacts with alkyl halides as the rate‐determining step, as shown in Scheme , cycle 1 11j. Benzothiazole 1 a traps 5 and/or 6 to suppress cycle 1 and redirects the reaction to cycle 2 and/or cycle 3, which we propose to explain the cross‐coupling of 2‐methylthio‐1,3‐thiazoles with Grignard reagents.…”