CO₂ is abundant, inexpensive, nontoxic, and environmentally benign; thus, its chemical fixation and transformation into valuable chemicals that involve new carbon-carbon bond formation has attracted considerable attention [1-6]. In general, strong nucleophilic organometallic reagents (i.e., metal = lithium [7], magnesium [8], aluminum [9, 10], or zinc [11-14]) directly undergo a reaction with CO₂ to produce carboxyl-containing organic compounds. However, current methods for these reactions are limited with respect to functional group tolerance and substrate stability. In contrast to strong nucleophilic organometallic reagents, weak nucleophilic organometallic reagents (i.e., metal = tin [15], silicon [16], or boron [17]) cannot undergo a direct reaction with CO₂ and require the presence of transition-metal catalysts for carboxylation. Among these organometallic reagents, organoboranes are frequently utilized because of their commercial availability, relatively low toxicity, and high tolerance to functional groups. Recently, Hazari et al. [18] reported a type of monodentate carboxylate [(η³-allyl)Pd(L)(carboxylate) (L = NHC)], which is an efficient catalyst for the carboxylation of allylboranes with CO₂. Then, they developed an N-heterocyclic carbene-supported dimer as an active and stable catalyst for the carboxylation of allylboranes with CO₂ (Eq. (1)) [19]. Duong et al. [20] also studied the carboxylative reaction of allylboronates with CO₂ in the presence of a Cu(I)/NHC catalyst (Eq. (2)). The abovementioned Pd- or Cu-catalyzed carboxylation reactions of allylboranes involved the use of N-heterocyclic carbene ligands. The use of carbene ligands is typically disadvantageous because it often leads to air/moisture sensitivity, tedious work-up procedures, and high work-up costs [21-27]. Therefore, the development of a simple and robust catalyst system that allows for the efficient carboxylation of allylboranes with CO₂ without any additional ligands is desirable.

(1)

(2)

(3)

Recently, our group reported palladium nanoparticles-catalyzed carbonylative and carboxylative reactions of (chloromethyl)arenes with allyltributylstannane [28-30]. We found that palladium nanoparticles can form in situ, and π-benzyl-π-allyl could be used as the carbon-based ligand for palladium nanoparticles [31-33]. Based on our previous study, we hypothesized that the π-allyl involving allylboranes may also be used as a carbon-based ligand for the palladium-catalyzed chemical fixation of CO₂. As expected, the carboxylative Suzuki coupling reaction of benzyl chlorides with allyl pinacolborate occurred in the presence of palladium nanoparticles (PdNPs) (Eq. (3)). The results are reported in the current work.

All reactions were carried out under a nitrogen atmosphere, unless otherwise noted. The solvents used were purified by standard techniques without special instructions. ¹H and ¹³C NMR spectra were recorded on either a Varian Inova-400 spectrometer (400 MHz for ¹H and 100 MHz for ¹³C) or a Bruker Avance II-400 spectrometer (400 MHz for ¹H and 100 MHz for ¹³C). CDCl₃ and tetramethylsilane were used as a solvent and internal standard, respectively. Infrared spectra were recorded on a NEXUS Fourier transform-infrared spectrometer. High-resolution mass spectra were recorded through gas chromatography-time-of-flight mass spectrometry. All starting materials are commercially available.

In the initial study, the reaction of benzyl chloride (1a) with allyl pinacolborate in the presence of CO₂ was selected as a model for the optimization of reaction conditions (Table 1). A series of palladium precatalysts, including PdCl₂, Pd₂(dba)₃, Pd(OAc)₂, and Pd(acac)₂, were initially tested in tetrahydrofuran (THF) at 50 ℃ by using TBAB and KF as a stabilizer and an activator, respectively (Table 1 entries 1-4). Among the palladium precatalysts tested, Pd(acac)₂ exhibited the highest catalytic activity, affording the benzyl but-3-enoate (2a) in 81% yield (Table 1 entry 4). These results indicated that PdNPs generated in situ from newly formed Pd(0) species possessed higher catalytic activity than those generated from Pd₂(dba)₃. No reaction was observed when TBAB was used as a stabilizer in the absence of KF, suggesting that the target reaction was unable to proceed in the absence of an activator (Table 1 entry 5) [34]. Thus, we screened several fluorides (KF, TBAF, and CsF) to determine a suitable activator (Table 1 entries 4, 6, and 7). The mixed products of 2a and 2a′ were obtained in 53% yield when TBAF was used as the activator for the reaction (Table 1 entry 6), and only a 13% yield of 2a was obtained when CsF was used as the activator (Table 1 entry 7). These results indicated that KF is the most suitable activator for the carboxylative Suzuki coupling of benzyl chlorides with allyl pinacolborate. Nonpolar (toluene) and polar [THF, dioxane, and N, N-dimethyl formamide (DMF)] solvents were then examined (Table 1 entries 4 vs. 8-10). THF was the best solvent. The yield of 2a decreased to 33% when the reaction was performed for 12 h (Table 1 entry 11). Further studies revealed that no product was generated when the reaction was performed at room temperature (Table 1 entry 12). A similar yield of product 2a was obtained when the reaction temperature was enhanced to 70 ℃, and a slightly decreased yield was obtained when the reaction was performed at 3.0 MPa CO₂ (Table 1 entries 13 and 14). Therefore, the subsequent palladium-catalyzed carboxylative Suzuki coupling reactions of various benzyl chlorides with allyl pinacolborate were performed in the presence of Pd(acac)₂ as a precatalyst, TBAB as a stabilizer, and KF as an activator at 50 ℃ and at 2.0 MPa of CO₂ pressure in THF for 24 h.

The carboxylative Suzuki coupling reactions of benzyl chlorides 1a-1m with allyl pinacolborate were conducted under optimum conditions, and the results are summarized in Table 2. Good yields similar to that of 2a were observed when the 1-(chloromethyl)-4-fluorobenzene (1b) bearing a fluorine atom on the para position of the benzene ring was employed under optimized reaction conditions. The desired product, 4-fluorobenzyl but-3-enoate (2b), was obtained in 76% yield (Table 2 entry 2). Ortho-chloro-substituted benzyl chloride (1c) also underwent target carboxylative coupling and provided the desired product, 2-chlorobenzyl but-3-enoate (2c), in 57% yield (Table 2 entry 3). However, only 49% yield of 2, 4-dichlorobenzyl but-3-enoate (2d) was obtained when 2, 4-dichloro-1-(chloromethyl) benzene (1d) bearing two chlorine atoms on the ortho and para positions of the benzene ring was employed under optimized reaction conditions (Table 2 entry 4). Notably, halogen atoms (F and Cl) linked to the benzene rings of the substrates were maintained in the structures of the products (2b-2d), suggesting that further manipulation may produce useful compounds. Reactions of benzyl chlorides 1e-1g bearing methyl, methoxyl, and propargyloxy on the para positions generated comparatively good yields of products 3e to 3g (73%, 71%, and 63%, respectively). Furthermore, 1-(chloromethyl)naphthalene (1h) and o-methyl-substituted 1-(chloromethyl)naphthalene 1i were utilized in this type of a carboxylative coupling reaction (Table 2 entries 8 and 9). Products 2h and 2i were obtained in moderate yields (60% and 71%, respectively).

The success in the carboxylative coupling of benzyl chlorides and 1-(chloromethyl)naphthalene substrates encouraged us to examine the carboxylative coupling reactions of five-membered heteroarene substrates (Table 2 entries 10 and 11). The reactions of 2-(chloromethyl) thiophene (1j) and 5-bromo-2-(chloromethyl)thiophene (1k) proceeded smoothly to furnish the corresponding β, γ-unsaturated ester products 2j and 2k in satisfatory yields (68% and 74%, respectively). Finally, 1-(bromomethyl)naphthalene (1l) and (E)-(3- chloroprop-1-en-1-yl)benzene (1m) were utilized in this type of carboxylative coupling reaction (Scheme 1). The desired products 2h and 2m were obtained in 58% and 44% yields, respectively. The relatively low yields were considered to be due to the low reactivities of 1l and 1m; incomplete conversion of the starting materials was observed.

A plausible mechanism for the palladium nanoparticles-catalyzed carboxylative Suzuki coupling reaction of benzyl chlorides with allyl pinacolborate is illustrated in Scheme 2. The precatalyst Pd(acac)₂ reacted with allyl pinacolborate in the presence of the stabilizer TBAB and the activator KF to generate PdNPs. The oxidative addition of benzyl chloride to PdNPs then occurred to produce a π-benzylpalladium chloride intermediate A, which underwent transmetalation with allyl pinacolborate in the presence of the activator KF to generate the π-benzyl-π-allylpalladium intermediate B. The π-allyl carbon-based ligands in intermediate B facilitate the coordination of CO₂ to form intermediate C. The nucleophilic addition of the σ-allyl group to CO₂ produced intermediate D, which underwent reductive elimination to produce the target product 2a and regenerate PdNPs.

We developed a novel palladium nanoparticles-based catalyst system for carboxylative Suzuki coupling of benzyl chlorides with allyl pinacolborate in the absence of phosphine ligands. Notably, the catalytic system is generated in situ; thus, cumbersome processes for the preparation of metal nanoparticles can be prevented when this system is used. The mild reaction conditions (low CO₂ pressure and temperature), experimental simplicity, and the broad substrate scope are features of the novel and general catalytic method proposed in this study. Further reactions and mechanistic studies are underway in our laboratory and will be reported in due course.