Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis

Abstract

This Article describes the development of a decarbonylative Pd-catalyzed aryl–fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [R_FC(O)X] with aryl organometallics (Ar-M’). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between R_FC(O)X and Ar–M’ can be avoided by using M’ = boronate ester. Second, carbonyl de-insertion and Ar–R_F reductive elimination are the two slowest steps of the catalytic cycle when R_F = CF₃. Both steps are dramatically accelerated upon changing to R_F = CHF₂. Computational studies reveal that a favorable F₂C–H----X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoromethyl acetyl fluoride.

Graphical Abstract

INTRODUCTION

Due to the prevalence of fluoroalkyl (R_F) substituents in bio-active molecules, there is a high demand for reagents and synthetic methods for the formation of (heteroaryl)aryl–R_F bonds.^1,2 The prevailing approach involves transition metal-catalyzed cross-coupling of aryl halide electrophiles (ArX) with fluoroalkyl nucleophiles (R_F–M).^3,4 Despite extensive work in this area, the scope and broad utility of these transformations remain limited, largely due to challenges associated with the fluoroalkyl nucleophiles.⁴ The most common fluoroalkyl nucleophiles, R₃SiR_F, have limited availability for diverse R_F substituents, undergo sluggish transmetalation in the absence of bases, and exhibit poor stability in the presence of the basic additives required for transmetalation.^4,5 While some designer Ag and Zn-based fluoroalkyl nucleophiles have been developed to address these challenges, these reagents still have limitations with respect to synthetic accessibility and/or broad availability, particularly for diverse R_F groups.^4,6,7

A complementary cross-coupling approach to form (hetero)aryl–R_F bonds would involve the reaction of fluoroalkyl carboxylic acid-derived electrophiles (R_FC(O)X) with (hetero)aryl nucleophiles (Ar–M’, Scheme 1).^8–13 This strategy eliminates the challenges associated with transmetalation from a weakly nucleophilic R_F reagent.^4,5 Furthermore, it leverages the abundance, low cost, and stability of fluoroalkyl carboxylic acid derivatives.¹³

Scheme 1.

(A) Traditional fluoroalkylative cross-coupling using fluoroalkyl nucleophiles; (B) This work: decarbonylative fluoroalkylation with fluoroalkyl carboxylic acid-derived electrophiles.

A putative catalytic cycle for this transformation is shown in Scheme 2 and involves (i) oxidative addition of R_FC(O)X to form [M]–acyl complex I, (ii) carbonyl de-insertion to generate [M]–R_F intermediate II, (iii) transmetalation of the aryl nucleophile (Ar–M’) to form complex III, and (iv) aryl–R_F bond-forming reductive elimination to release the product. An early study from our group established the feasibility of each of these individual steps using trifluoroacetic anhydride and diphenyl zinc as the coupling partners, and Pd[P(o-Tol)₃]₂/RuPhos as [M].^13a However, catalytic turnover was not viable in this system due to a rapid uncatalyzed background reaction between the reagents to form trifluoromethyl ketones (Scheme 2, uncatalyzed acylation, v).

Scheme 2.

(A) General reaction scheme for decarbonylative fluoroalkylation and (B) proposed catalytic cycle with undesired acylation shown.

In addition to the competing background reaction, our early work identified several other limitations associated with individual steps of the catalytic cycle.^13a For instance, direct oxidative addition of trifluoroacetic anhydride at (RuPhos)Pd⁰ (step i) proved challenging. As such, a two-step sequence involving initial oxidative addition at Pd(P(o-Tol)₃)₂ followed by a separate ligand exchange between P(o-Tol)₃ and RuPhos is required. Furthermore, both carbonyl de-insertion (step ii) and aryl–CF₃ bond-forming reductive elimination (step iv) were slow and/or low yielding. Finally, transmetalation (step iii) was limited to strongly nucleophilic organometallic reagents like diphenyl zinc.^13a

We hypothesized that these challenges could be addressed via a mechanistic-based redesign of the catalyst and coupling partners for this reaction. In this report, we initially identify fluoroalkyl anhydrides and aryl boronate esters as compatible R_FC(O)X and Ar–M’ coupling partners. We then use this pair to interrogate each step of the cycle in Scheme 2 with (SPhos)Pd⁰ as the catalyst. These stoichiometric organometallic studies provide key insights into the impact of R_F, X, and M’ on each step, ultimately informing the development of a Pd-catalyzed method for the difluoromethylation of aryl boronate esters.

RESULTS AND DISCUSSION

Identifying Compatible Coupling Partners.

Our original attempts at Pd-catalyzed decarbonylative aryl fluoroalkylation were hampered by the uncatalyzed background addition of the diphenyl zinc nucleophile to the trifluoroacetic anhydride electrophile (TFAAn) to form phenyl trifluoromethyl ketone (A).^13a This background reaction proceeds in 77% yield within 1 h at 25 °C (Table 1, entry 1), as determined by ¹⁹F NMR spectroscopic analysis. Our initial studies focused on identifying more compatible coupling partners for the proposed catalytic transformation. We hypothesized that aryl boron reagents, which are significantly less nucleophilic than their zinc counterparts,^13a,14,22e would minimize ketone formation. Indeed, none of the ketone A was formed upon stirring a CDCl₃ solution of trifluoroacetic anhydride (TFAAn) with phenyl boronic acid over 1 h at 25 °C. However, under these conditions a different undesired reaction, hydrolysis of the anhydride, proceeded to form trifluoroacetic acid (TFA, B) in quantitative yield (Table 1, entry 2). We next examined phenylboronic acid neopentylglycol ester (PhBneo) as the nucleophile, reasoning that it should minimize this hydrolysis process. Indeed, no detectable side product formation was observed upon stirring stirring a CDCl₃ solution of TFAAn with PhBneo over 1 or 3 h at 25 °C (Table 1, entries 3 and 4). Compatibility was also observed when using phenylboronic acid pinacol ester (PhBpin) under otherwise identical conditions (entry 5). Furthermore, compatibility with PhBneo was maintained when moving to other fluoroalkyl anhydrides (e.g., difluoroacetic anhydride) was well as other fluoroalkyl carboxylic acid derivatives (e.g., difluoroacetyl fluoride; see Supporting Information for complete details).

Table 1.

Compatibility of TFAAn with different aryl nucleophiles.

entry	PhM’	yield A	yield B
1	Ph2Zn	77%	0%
2	PhB(OH)2	<1%	>95%
3	PhBneo	<1%	<1%
4a	PhBneo	<1%	<1%
5	PhBpin	<1%	<1%

^a25 °C for 3 h.

Catalytic Cycle: Oxidative Addition and Carbonyl De-insertion.

With a pair of compatible reagents in hand, we next focused on challenges associated with the individual steps of the catalytic cycle. As described above, previous studies with RuPhos as the ligand accessed the TFAAn oxidative addition product in two discrete steps. First, Pd(P(o-Tol)₃)₂, was treated with TFAAn, and this was followed by a separate ligand exchange with RuPhos.^13a We hypothesized that replacing the large isopropoxy-substituents of RuPhos with smaller methoxy groups (of SPhos) could accelerate oxidative addition and ligand substitution and facilitate the single-pot formation of SPhos-ligated trifluoroacetyl intermediate I-COCF₃ (Figure 1). Indeed, the reaction of a THF solution of Pd[P(o-Tol)₃]₂/SPhos with TFAAn yielded I-COCF₃ in 98% yield within 15 min at 25 °C (Figure 1B). Complex I-COCF₃ was characterized in situ by ¹⁹F and ³¹P NMR spectroscopy, and the data are in excellent agreement with those for the reported RuPhos analogue.^13a In particular, this complex can be clearly identified as a trifluoroacyl Pd intermediate (rather than a Pd–CF₃ complex) based on the diagnostic chemical shift of the CF₃ group (approximately −75 ppm Pd–C(O)CF₃ versus −12 ppm for Pd–CF₃).^3a,13a,14

Figure 1.

Oxidative addition and carbonyl de-insertion of TFAAn at SPhos/Pd⁰ in THF. ¹⁹F NMR spectra of (A) TFAAn; (B) Reaction of TFAAn with SPhos/Pd⁰ in THF after 0.25 h at room temperature; (C) Reaction of TFAAn with SPhos/Pd⁰ in THF after 4 h at room temperature; (D) Reaction heated to 90°C for 0.5 h. Spectra are referenced to 4-fluorotoluene (−119.85 ppm).

While Pd(P(o-Tol)₃)₂/SPhos proved highly reactive for oxidative addition of TFAAn at room temperature (Scheme 2, step i), carbonyl de-insertion (Scheme 2, step ii) at I-COCF₃ remained slow in this system. After 4 h at 25 °C, no change in the ¹⁹F NMR spectrum was observed, and the decarbonylated intermediate, II-CF₃, was not detected. CO de-insertion was only observed upon heating the reaction. After 30 min at 90 °C, I-COCF₃ was nearly fully consumed with concomitant formation of II-CF₃ in 91% yield (Figure 1C). Complex II-CF₃ was characterized in situ (by analogy to the RuPhos analogue) based on its distinct broad Pd–CF₃ ¹⁹F NMR resonance at −11.6 ppm.^3a,13a,15,16

We hypothesized that the rate of carbonyl de-insertion would be impacted by the nature of the migrating fluoroalkyl substituent.^17a Thus we next explored the difluoromethyl analogue, in which a single fluorine atom is replaced by a hydrogen. This dramatically alters the size, nucleophilicity, dipole moment, and H-bond donor ability of the fluoroalkyl group,^2a–d and all of these factors could potentially impact the carbonyl de-insertion step.¹⁷ Furthermore, it is well-documented that Ar–CHF₂ bond-forming reductive elimination at Pd^II centers occurs under much milder conditions than analogous Ar–CF₃ couplings.^3,4,9a As such, this modification should accelerate this other challenging elementary step (iv) of the catalytic cycle in Scheme 2.

The reaction of a THF solution of Pd[P(o-Tol)₃]₂/SPhos with 1 equiv of difluoroacetic anhydride (DFAAn, Figure 2A) under otherwise identical conditions afforded >99% conversion of DFAAn within 15 min at room temperature. As shown in Figure 2B, the oxidative addition product I-COCHF₂ was formed in 85% yield and characterized in situ via ¹⁹F NMR spectroscopy. This result demonstrates that oxidative addition remains fast in this system, despite the lower electrophilicity of DFAAn relative to that of TFAAn.

Figure 2.

Oxidative addition and carbonyl de-insertion of DFAAn at SPhos/Pd⁰ in THF. ¹⁹F NMR spectrum of (A) DFAAn; (B) Reaction of DFAAn with SPhos/Pd⁰ in THF after 15 min at room temperature; (C) Reaction of DFAAn with SPhos/Pd⁰ in THF after 10 h at room temperature. Black star represents 4-fluorotoluene (−119.85 ppm, internal standard).

Interestingly, in marked contrast to the trifluoromethyl analogue, carbonyl de-insertion at I-COCHF₂ also proceeded at room temperature. II-CHF₂ was formed in 13% yield after 0.25 h, and the reaction was nearly complete within 10 h at 25 °C, affording II-CHF₂ in 91% yield as determined by ¹⁹F NMR spectroscopy (Figure 2C). Complex II-CHF₂ was isolated in 61% yield and was structurally characterized by X-ray crystal-lography. An ORTEP diagram of II-CHF₂, along with representative bond distances and bond angles, are shown in Figure 3. A noteworthy feature of this structure is a short (2.38 Å) distance between H29 (from the CHF₂ group) and O3 (of the difluoroacetate ligand). A significantly longer distance (3.60 Å) is observed between H29 and O4. The short (2.38 Å) distance as well as the C29-H29-O3 angle of 96.9° are consistent with the existence of an attractive interaction between H29 and O3.¹⁸

Figure 3.

ORTEP diagram of II-CHF₂. Select hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angle (deg): O3–Pd1 2.11, O4–Pd1 3.09, C29–Pd1 1.99, C1–Pd1 2.46; H29---O3 2.38, H29---O4 3.60; C29–Pd1–O3 81.7, C29–H29---O3 96.9.

Density functional theory (DFT) calculations¹⁹ (M06/LANL2DZ/6–311G**) were performed to interrogate the origin of the large rate enhancement for carbonyl de-insertion at I-COCHF₂ relative to I-COCF₃. This difference is counter to commonly accepted trends, where the rate is typically inversely proportional to the nucleophilicity of the migrating R group.^17a Figure 4 shows an energy profile for 1,1-CO de-insertion at I-COR_F proceeding through TS1-R_F to initially form CO-bound complex (CO)Pd–R_F. CO dissociation then generates the experimentally observed product II-R_F. Consistent with the experimental observations, the calculations show a large (~16 kcal/mol) difference between the barrier for 1,1-de-insertion at I-COCHF₂ versus I-COCF₃. In addition, the overall thermodynamics associated with conversion of I-COCHF₂ to II-CHF₂ + CO (DG = −18.4 kcal/mol) is significantly more favorable than for the CF₃ analogue (DG = −3.2 kcal/mol).

Figure 4.

Energetics (the preferred binding mode highlighted as conformer A, see SI for details) for the carbonyl de-insertion process at (A) I-COCF₃ and (B) I-COCHF₂ with selected key angles α, β, γ, and δ for I-COR_F and TS1-R_F.

The computed structures show the presence of an attractive interaction with electrostatic character between H29 (of the CHF₂ group) and O3 (of the carboxylate ligand). This interaction appears to contribute significantly to both the kinetic and thermodynamic preference for carbonyl de-insertion at the CHF₂ versus CF₃ analogue²⁰. In the ground state starting material, I-COCHF₂, a weak H(d+)---O(d^–) electrostatic contact (3.59 Å) contributes to a distortion of the coordination geometry at Pd away from square planar. For instance, the angle between the acyl and carboxylate ligands (β in Figure 4) is 97.5° in I-COCF₃ (which cannot engage in this weak contact) versus 154.9° in I-COCHF₂. Given that carbonyl de-insertion transition states involve a three-coordinate metal center,^17b this distortion makes the geometry of I-COCHF₂ much closer to that of the transition state, TS1-CHF₂ than in the CF₃ analogue. The H---O bond distance becomes significantly shorter moving from I-COCHF₂ (3.59 Å) to TS1-CHF₂ (2.69 Å) to II-CHF₂ (2.37 Å). Notably, the latter closely matches that observed experimentally in the X-ray crystal structure of II-CHF₂ (2.38 Å).

Further analysis of the electrostatic potential surfaces (EPSs) of I-COCHF_2, TS1-CHF₂, and II-CHF₂ and of non-covalent interaction (NCI) maps of the II-R_F adducts reveal the key role of various attractive interactions (Figure 5).^20n–p Specifically, orbital donor-acceptor interactions, electrostatic interactions, and a series of weakly attractive non-covalent bonds (dipole-induced dipole) were all observed in the -CHF₂ containing structures, most prominently in TS1-CHF₂ (see Supporting Information for complete details). In contrast, the electrostatic potential surfaces of the CF₃-analogues show more diffuse dispersive repulsive interactions between the highly electronegative trifluoromethyl groups. These repulsive interactions are most pronounced in TS1-CF₃, providing further insights into the relatively high barrier to carbonyl de-insertion at I-COCF₃.

Figure 5.

Electrostatic potential surfaces (for the optimal conformer A, see SI for details) generated for (A) I-COCF₃, TS1-CF₃, and II-CF₃; (B) I-COCHF₂, TS1-CHF₂, and II-CHF_2. Energies are in represented in kcal/mol.

Catalytic Cycle: Transmetalation and Reductive Elimination.

We next used complex II-CHF₂ to interrogate the final two steps of the catalytic cycle: transmetalation and aryl–R_F bond-forming reductive elimination (Figure 6). With boronic acid 1a as the nucleophile, 55% conversion of II-CHF₂ was observed over 0.25 h at room temperature, with concomitant formation of the difluoromethylated organic product 1 in 40% yield. None of the Pd^II σ-aryl intermediate III-CHF₂ was detected, indicating that Ar–CHF₂ bond-forming reductive elimination is facile at room temperature.

Figure 6.

Transmetalation/reductive elimination sequence between II-CHF₂ and aryl boron nucleophiles 1a-c.

In contrast, the boronate ester nucleophiles 1b and 1c showed low reactivity towards transmetalation with II-CHF₂. In both cases, >99% of II-CHF₂ remained after 0.25 h at 25 °C, and only traces of 1 were detected. These results indicate that transmetalation between the Pd^II–difluoroacetate intermediate II-CHF₂ and aryl boronate esters is likely to be a key bottleneck in catalysis.

We hypothesized that this issue could be addressed by changing the X-type ligand on Pd^II from trifluoroacetate to a more reactive fluoride.^21,22 Previous work^23,24 has demonstrated that transition metal fluoride complexes exhibit high transmetalation activity towards various aryl boron nucleophiles. To generate a Pd^II–F intermediate, we treated a THF solution of II-CHF₂ with anhydrous tetramethylammonium fluoride (Me₄NF) for 0.5 h at 25 °C (Figure 7). This resulted in complete consumption of II-CHF₂ and the appearance of a broad ¹⁹F NMR resonance at −349.5 ppm, which is diagnostic for a metal-fluo-ride.²¹ While this intermediate could not be isolated cleanly, the addition of boronate ester 1b resulted in consumption of the Pd–F signal within 15 min at 25 °C and formation of the reductive elimination product 1 in 27% yield (Figure 7). Again, the putative intermediate III-CHF₂ was not detected. Overall, this sequence demonstrates that a fluoride ligand enables the targeted transmetalation/reductive elimination sequence with 1b, thus closing the formal catalytic cycle in this system.

Figure 7.

Generation of a Pd–F intermediate facilitates transmetalation with organoboron reagent 1b and subsequent reductive elimination (steps iii and iv in Scheme 2).

Development of Catalytic Reaction.

The organometallic studies described above demonstrate that each individual step of the catalytic cycle in Scheme 2 can proceed at room temperature. As such, our initial catalysis attempts focused on the room temperature SPhos/Pd[P(o-Tol)₃]₂-catalyzed decarbonylative coupling of DFAAn with boronate ester 1b in the presence of metal fluoride (MF) sources. As summarized in Figure 8, none of these reactions (with Me₄NF, Bu₄NF, or CsF) yielded the target difluoromethylated product 1. However, in the crude ¹⁹F NMR spectra of reactions that used CsF as the fluoride source, difluoroacetyl fluoride (DFAF) observed as a major byproduct.

Figure 8.

Initial attempts at catalysis using DFAAn and fluoride salts.

We noted that acid fluorides are significantly less electrophilic than their anhydride counterparts^8j, which could result in slower oxidative addition. To address this potential issue, we next explored elevated temperatures. Gratifyingly, at 130 °C using excess CsF relative to DFAAn, the coupling product 1 was observed, albeit in modest (22%) yield (Figure 8). The stoichiometric studies suggest that at 130 °C carbonyl de-insertion should also be feasible for the −CF₃ and −CF₂CF₃ analogues. As such, we explored the analogous catalytic reactions using TFAAn and pentafluoropropionic anhydride (PFPAn) at 130 °C. As shown in Figure 8, 4-trifluoromethylbenzonitrile and 4-pentafluoroethylbenzonitrile were formed in these transformations, in modest yields of 5% and 4%, respectively. In all three decarbonylative fluoroalkylation reactions a significant amount of the corresponding fluoroalkyl acid was observed in the crude mixture, consistent with competing decomposition of the anhydrides with traces of water in the fluoride salts.

Moving forward, we focused on optimizing catalytic decarbonylative difluoromethylation, since this was the highest yielding reaction among those in Figure 8. To eliminate the need for the hygroscopic fluoride additives, we independently synthesized anhydrous DFAF as a concentrated solution in THF (see SI for full details) and deployed it directly as the electrophile for cross-coupling.^23,24 As shown in Table 2, entry 1, none of product 1 was detected at room temperature with DFAF as the electrophile, consistent with slow oxidative addition. However, upon heating this reaction to 130 °C, 1 was formed in 51% yield (entry 3). The reaction was further optimized with respect to reagent stoichiometry, temperature, solvent, and reaction time.²⁵ Under the optimized conditions (10 mol % Pd[P(o-Tol)₃]₂, 20 mol % of SPhos, 5 equiv of DFAF, and 1 equiv of 1b in a mixture of THF:toluene at 150 °C for 5 h), 1 was formed in 92–93% yield as determined by ¹⁹F NMR spectroscopic analysis and was isolated in 77% yield (see SI for details).

Table 2.

Optimization of difluoromethylation of 1a with DFAF.

entry	X	T (°C)	solvent	yield (%)a
1	1	25	THF	<1
2	1	100	THF	29
3	1	130	THF:toluene (1:1)	51
4	3	130	THF:toluene (1:1)	58
5	5	130	THF:toluene (1:1)	67
6	5	150	THF:toluene (1:1)	86
7	5	150	THF:dioxane (1:1)	72
8b	5	150	THF:toluene (1:1)	93
9b	5	150	THF:toluene (1:2)	92

^aYields determined by ¹⁹F NMR with 4-fluorotoluene internal standard.

^bReaction was run for 5 h.

We next evaluated the scope of arene nucleophiles for this transformation. As summarized in Table 3, a variety of neopentylglycol boronate esters bearing electron withdrawing substituents (1–13) reacted to afford modest to excellent yields of difluoromethylarene products.²⁶ Nitriles (1, 2), ketones (3–5), esters (6–8), sulfoxides (11), sulfonamides (12, 13) were well-tolerated under the reaction conditions. In addition, azole derivatives (9, 10) reacted in low to modest yields. Boronate esters bearing fluorinated substituents also underwent difluoromethylation in good to excellent yields but proved too volatile for isolation (see SI). Interestingly, boronate ester derivatives bearing electron donating substituents, such as methyl, phenyl, or benzyl ethers, showed low reactivity²⁷ under these conditions (typically <5% yield). ¹⁹F NMR spectroscopic analysis of these low yielding reactions showed significant quantities of unreacted DFAF and no identifiable organic by-products. Ongoing efforts are focused on interrogating the mechanistic origin of this limitation and developing second generation catalysts to overcome it.

Table 3.

Scope of aryl boronate esters for the catalytic electrophilic decarbonylative difluoromethylation using difluoroacetyl fluoride.

^a15 mol% Pd[P(o-tol)₃]₂/30 mol% SPhos used for catalysis. See Supporting Information for details.

CONCLUSIONS

In summary, this Article presents a detailed investigation of decarbonylative cross-couplings between fluoroalkyl carboxylic acid-derived electrophiles and aryl boron nucleophiles. The combination of stoichiometric organometallic and computational studies unveiled several key findings that ultimately enabled the development of a catalytic difluoromethylation reaction. First, unusually low barriers are observed for the key carbonyl de-insertion step at (SPhos)Pd^II(C(O)CHF₂)(X) complexes relative to their trifluoromethyl analogues. Several attractive non-covalent interactions involving the acidic CHF₂ hydrogen appear to play a crucial role in lowering this barrier, a finding that could prove more broadly useful in the future development of decarbonylative couplings with these electrophiles.

The generation of a Pd–fluoride intermediate proved critical for promoting the challenging transmetalation step of the sequence. This finding led to the use of difluoroacetyl fluoride as the electrophile in catalysis to directly access a ‘transmetalation-active’ Pd-fluoride intermediate in situ and enable base-free transmetalation. While similar effects have been observed at nickel centers, this report is rare example of base-free cross-coupling of an acid fluoride derivative at Pd.²⁴ⁱ Overall, we expect this study to engender interest in the unique properties of fluoroalkyl groups and the reactivity of metal–fluoroalkyl complexes in the context of catalytic reaction development.

ABBREVIATIONS

THF

Tetrahydrofuran

DCM

dichloromethane

Et₂O

diethyl ether

DFAF

difluoroacetyl fluoride

DFAAn

difluoroacetic anhydride

TFAAn

trifluoroacetic anhydride

DFA

difluoroacetic acid

TFA

trifluoroacetic acid

PFPAn

pentafluoropropionic anhydride

PFPA

pentafluoropropionic acid

TMAF

tetramethyl ammonium fluoride

TBAF

tetrabutylammonium fluoride

RT

room temperature

SPhos

2-dicylcohexylphosphino-2’,6’-dimethoxybiphenyl