■ INTRODUCTION

Developing new chemodivergent catalytic syntheses with high regio-and chemoselectivity is important for the efficient generation of high-value products while imparting structural diversity from common starting materials. 1 Many successful chemodivergent strategies rely on the variation of additives, solvents, catalysts, slight substrate modifications, and other tactics to achieve these ends. In regard to modifying the catalyst, it is well-documented that changing the metal, especially within a transition-metal series, will significantly modify catalytic selectivity. 2 However, the common heurism associated with lanthanide/rare-earth catalytic chemistry is that incremental variation in the ionic radius affects only small monotonic variations in activity. 3 While this knowledge is vital in optimizing reaction rates, having new selectivity pathways accessible within the lanthanide series could be an effective tool in synthesizing various critical molecular targets and expanding the fundamental understanding of rare-earth catalysis.

Regarding specific target families, pyridines are pervasive as ligands and directing groups, 3 ubiquitous moieties in pharmaceuticals, and natural products 4 and are the second most common ring system in small-molecule pharmaceuticals (Figure 1a), 5 with monosubstituted pyridines predominantly having functionality at the difficultly accessed α-position. 6 Therefore, more efficient and selective means of pyridine and related azine α-functionalization would be an important advance in synthetic methodology. 4 To date, the principal methods to achieve α-selection have been via N-activation, 7 deprotonative metalation, 8 S n Ar, 9 radicals, 10 and transition metal-based catalysis. 5,[11][12][13][14][15][16][17] Despite significant advances, many of these α-selective transformations require activated substrates and/or achieve high selectivity only with synthetically restrictive sterically blocking or directing groups. 5,[18][19][20][21][22] Furthermore, effective processes such as Minisci-and Chichibabin-type radical substitutions require electron-poor substrates and precious metals in catalytic and/or stoichiometric quantities. [23][24][25] Therefore, a catalyst utilizing earthabundant lanthanide metals 26,27 which could selectively functionalize pyridine and related azine α-C-H bonds and be readily altered to afford another chemodivergent reactivity modality would be a valuable tool.

Organoboranes are versatile reagents for diverse coupling reactions, such as Suzuki-Miyuara cross-coupling, [28][29][30][31][32][33] with pinacolborane (HBpin)-based synthons especially useful in such reactions (Figure 1b). [34][35][36][37][38] However, while pyridine borylation at the βand γ-positions can be achieved with efficiency, [39][40][41][42][43] C-H borylation at the α-position remains challenging. 44,45 This reflects the inherent reactivity-depressing electron deficiency of pyridines, the susceptibility of αborylated products to protodeboronation, and the nitrogen lone-pair steric impediment, as well as deactivating coordination to catalytic metal centers. 46,47 In contrast, the high coordination numbers, kinetic lability, and polar metal-ligand bonding of electrophilic lanthanide-organic catalysts have been proven effective in diverse hydroelementation, [48][49][50] C-H activation, 51,52 and polymerization processes. 49,53 These characteristics evidence that lanthanide catalysts can operate by entirely different mechanisms than d-block catalysts, [54][55][56] raising the intriguing question of whether they might activate pyridines via unusual and potentially useful reactivity modalities.

To date, the majority of documented organolanthanidemediated α-pyridine activation has come at the expense of synthetically restrictive blocking groups and/or additives to assist turnover. [57][58][59][60][61] After the initial disclosure of this work 62 and while this full account was nearing completion, a synthetically focused communication by Xu et al. appeared, reporting an analogous pyridine α-borylation methodology using primarily organo-Y catalysts and additional late-stage functionalizations. 63 This laboratory previously reported the highly 1,2-selective and atom-efficient B-N bond-forming pyridine dearomatization using an organolanthanum (Cp* 2 La-) catalyst (Figure 1c). 64 Considering the already sterically encumbered La 3+ ligation (ionic radius = 1.250 Å), we hypothesized that smaller lanthanides such as Lu 3+ (ionic radius = 0.995 Å) with similar ligation and demonstrated C-H activation capacity 65,66 might direct pyridine activation along an alternative and useful pathway. Here, we report the organolanthanide-catalyzed α-mono-borylation of a diverse pyridine series (Figure 1c) using medium-to-small ionic radius (1.175 → 0.995 Å) Cp* 2 Ln-catalysts. It will be seen that this process can be regio-and chemo-selective, especially for electron-rich pyridines, and can tolerate diverse functional groups. To clarify the origin of this intriguing selectivity, detailed kinetic/mechanistic studies supported by solid-state X-ray diffraction and density functional theory (DFT) analyses are carried out. In doing so, we reveal what is, to our knowledge, the origin of the first examples of chemodivergent organolanthanide catalytic selectivity.

■ RESULTS AND DISCUSSION

In this section, the experimental design and characterization methods used in the Cp* 2 LnCH(TMS) 2 , Ln = La, Nd, Sm, Lu, and Y-catalyzed C-H α-mono-borylation of pyridines are outlined. The unique effects various lanthanides have on the selectivity are then discussed, followed by the effects that steric constraints and substrate substituents have on the reaction pathway. Next, the reaction mechanism is analyzed both experimentally and theoretically via DFT, demonstrating good agreement. This information is then applied to probing and elucidating the origin of the observed organolanthanide chemodivergence and substituent effects. Finally, a conclusion to discuss the findings and their potential impact is presented.

Exploratory Catalytic Transformations and Product Characterization. Organolanthanide [Cp* 2 LnCH(TMS) 2 ]catalyzed pyridine functionalizations with HBpin were investigated under anhydrous/anaerobic conditions to exclude possible impurities. Cp* 2 LuCH(TMS) 2 was selected to first explore pyridine substituent effects and the reaction mechanism. Separately, the hydride analogue [Cp 2 *LuH] 2 was also surveyed and found to afford similar reactivity patterns (Pages S113 and S114). However, due to ease of synthesis and lack of deleterious side reactions with HBpin, Cp* 2 LuCH(TMS) 2 was selected for extensive studies (see Experimental Section for details).

Table 1 summarizes substituent effects on the relative rates and α-C-H-borylated/1,2-dearomatized product ratio over fixed reaction times for a series of variously substituted pyridines, revealing that selective α-mono-borylation is readily achieved with a 1:1 pyridine/HBpin ratio and 1-6 mol % Cp* 2 LuCH(TMS) 2 precatalyst at 80-120 °C in toluene solution. The α-borylated and 1,2-dearomatized products were characterized by 1 H, 11 B, 13 C, COSY, and HSQC NMR spectroscopy, focusing on established, structurally diagnostic fingerprints, [16][17][18]53 high-resolution mass spectrometry (HRMS), and in two cases, by single-crystal X-ray diffraction (vide infra and Supporting Information Pages S130 and S131). Preparative scale borylations were also carried out, and the products were isolated, characterized as described above, and then subjected to later stage derivatization by both Suzuki cross-coupling and classical proto(deutero)-deboranation. The 2 H-labeled products were characterized by multinuclear NMR spectroscopy (see Supporting Information Pages S115-S128), and all products had the expected exclusive α-borylation regiochemistry.

Lanthanide Ion Effects. A broad series of trivalent Cp* 2 LnCH(TMS) 2 precatalysts where Ln = La, Nd, Sm, Lu, and Y were surveyed under mild, straightforward reaction conditions (see Experimental Section for details). Strikingly, for identical pyridines, it is found that contracting the Ln 3+ size incrementally shifts selectivity as shown in Figure 2: large La 3+ yields exclusive 1,2-dearomatization, Nd 3+ affords nearly equal amounts of dearomatized and borylated products, Sm 3+ creates primarily borylated products, and small Y 3+ and Lu 3+ affect exclusive α-C-H borylation. The origin of the metal ion effects is further discussed in the theory section below.

Borylation Scope. Regarding substrate specifics (Table 1 and Pages S4-S63), dimethylaminopyridine (DMAP) is found Reaction conditions: 0.083 mmol of pyridine and HBpin unless stated otherwise in 0.5 mL of tol-d 8 ; all yields for 6 h at 100 °C unless stated otherwise. Yields by 1 H NMR with the mesitylene internal standard. b 24 h, 80 °C with 3.30 mmol of pyridine and 1.65 mmol of HBpin. Preparative isolated yield. c 24 h. d 80 °C. e 0.065 mmol of pyridine and HBpin. f 0.165 mmol pyridine and HBpin. g 2.0 equiv HBpin. h 120 °C. See Supporting Information for additional information. to undergo rapid α-borylation at 1 mol % catalyst loading, yielding the isolated borylated product 4a, the structure of which was confirmed by NMR, HRMS, and single-crystal X-ray diffraction (Figure 3). Note that 4a has a dimeric structure with α-borylation regiochemistry confirmed as proposed. Similarly, additional heterocyclic Lewis base-substituted pyridines are found to undergo α-borylation in high yields without the need for protecting groups, yielding the corresponding borylated products 4b, 4c, and 4d, with negligible competing 1,2-dearomatization (Table 1). The dimeric molecular structure of 4b was also confirmed by single X-ray diffraction (Figure 3), again verifying borylation in the pyridine α-position, and obtained in good isolated yield. Note also that the solid-state structures of 4a and 4b reveal that they both crystallize with the α-Bpin moieties in a cis arrangement and have similar bond lengths and angles (Figure 3).

Regarding other pyridines, note that the N-H moiety of a secondary amine substituent is well-tolerated without protection, affording 4e in reasonable selectivity (Table 1). Pyridines with other oxygen-containing substituents also afford α-borylated products 4f and 4i in reasonable selectivity despite the oxophilic nature of the lanthanide centers. Additionally, pyridine and various alkylated pyridines generate monofunctionalized α-borylated products 4j, 4k, 4n, and 4o with minimal competing dearomatization or functional group borylation. 64 Electron-deficient functional groups such as 4,4′-bipyridine (4l) and 4-CF 3 (4m) are also tolerated and produce α-borylated products with good selectivity. Interestingly, however, functionalities at the pyridine β-positions (4p) afford approximately equimolar amounts of α-borylated and 1,2-dearomatized products, while electron-deficient azines such as 4q and 4r yield exclusively 1,2-dearomatized products. In all cases in this study, when both pyridine α-positions are vacant and 1:1 pyridine/HBpin ratios are employed, only monoborylation products are observed, indicating that the second borylation process is significantly slower and/or Bpin functionalization is deactivating. As noted above, both 4a and 4b were also obtained in preparative scale reactions, and the isolated products were purified and characterized spectroscopically by the techniques described above (see Materials and Methods Section). Finally, to further verify the pyridine α-borylation regioselectivity of the present process and to verify the late-stage functionalization reactivity of the isolated α-borylated pyridine products, 4a and 4b were subjected to proto(deutero)deboranation and Suzuki crosscoupling conditions (Scheme 1). Both were found to undergo quantitative conversion to the corresponding α-deuterated products, as established by NMR spectroscopy and good yields with a 2-iodothiophene (Scheme 1); Supporting Information Pages S115-S124, Figures S108-S121).

Substituent Effects. The sterics and electronics of the substrates have a significant effect on the reaction pathway. Electroneutral/donating substituents (e.g., tertiary amines and alkoxy groups) at the γ-position accommodate α-borylation with high selectivity and acceptable to excellent yields. Furthermore, bulky groups at the γ-position (e.g. t-butyl and phenyl) do not seem to affect the selectivity toward αborylation. Electron-withdrawing substituents at γ-position and bulky groups at either the βor other α-positions (e.g., halogens or alcohols) significantly depress borylation activity and, often times, lead to the 1,2-dearomatized product. Similarly, other azine heterocycles, which are electrondeficient, yield the 1,2-dearomatized product selectively. The substituent effects are further discussed in the theory section below.

Experimental Investigation of the Reaction Mechanism. Detailed 1 H NMR spectroscopic kinetic studies (Pages S64-S82) indicate a rate law which is first-order in Cp* 2 Luconcentrations, half-order in pyridine concentrations, and inverse half-order in HBpin concentrations (eq 1 and Figure 4a-c). Note also that the NMR reveals a DMAP-HBpin adduct formation, 67 the molecular structure of which was confirmed by single-crystal X-ray diffraction (Figure 5a and Page S132), suggesting that HBpin acts as an inhibitor, 68 competing with pyridine in binding to the electrophilic Cp* 2 Lu-center. Such "off-cycle" kinetic phenomena were also observed in our earlier study of lanthanocene-mediated pyridine 1,2-dearomatization, along with a similar but not identical rate law. 64 In addition to pyridine-HBpin adduct formation, other factors may be at play such as deactivation of the catalyst. 64 In the present case, C-H activation of pyridine proceeds with an experimental kinetic isotope effect (KIE) of 2.8 ± 0.2, and variable-temperature kinetic measurements with standard Eyring kinetic analyses yield activation parameters ΔH ‡ = 14.2(0.7) kcal mol -1 , ΔS ‡ = -28.7(2.9) kcal mol -1 K -1 , and E a = 14.9(0.7) kcal mol -1 (Figure 4d-f and S80-S81) in good agreement with theory (vide infra). Large negative ΔS ‡ implies a highly organized transition state, a hallmark of many d 0 , f n metal-centered catalytic processes involving Lewis basic heteroatom substrates. 43,64 Additional DFT-based mechanistic analysis is presented below.

DFT and Energetic Span Analysis. To further probe the reaction mechanism, DFT calculations were undertaken to quantitatively investigate the C-H borylation pathway using DMAP (4a) as a model substrate (Figure 6). In the first step, DMAP coordinates to the Cp* 2 LuCH(TMS) 2 precatalyst, which is slightly exergonic (ΔG = -0.9 kcal mol -1 ). Here and beyond, the experimental half-order kinetics reflects a dissociative equilibration of the azine-HBpin adduct to the reactive monomeric precursors, which by DFT is slightly endergonic and strongly exothermic (ΔG dissoc = 2.3 kcal mol -1 , ΔH = -9.4 kcal mol -1 ) (Figure 6). 68 Next, a concerted fourcenter σ-bond metathesis H transfer from the DMAP αposition cleaves the Lu-CH(TMS) 2 bond to yield η 2 -complex III, which is structurally confirmed by NMR and X-ray crystallography (Figure 5b and Page S133), in a highly exergonic ΔG = -20.5 kcal mol -1 step with a barrier of ΔG ‡ = 28.5 kcal mol -1 (TS1) (see Supporting Information). Note that complex III has principal bond lengths and angles similar to the only other solid-state structure determination for an activated pyridine by an organolanthanide scaffold (Figure 5b) and has the shortest Ln-C(aromatic) bond distance reported to date. 69 Note also that a stoichiometric Cp* 2 LuCH(TMS) 2 + DMAP 6 h/80 °C reaction quantitatively yields complex III, which was characterized crystallographically with pyridine (Figure 5b), and supports the proposed reaction sequence.

Once complex III is formed, HBpin associates and undergoes σ-bond metathesis, forming a new B-C bond at the DMAP α-position (IV). This step is computed to be exergonic by -11.9 kcal mol -1 with a barrier of ΔG ‡ = 12.1 kcal mol -1 (TS2) to yield the lowest energy intermediate on the reaction coordinate, which is the TOF-determining

intermediate (TDI)

. 70 Although we cannot conclude whether complex IV is present in the experimental reaction mixtures because of the complexity and quadrupole-induced broadening of the NMR spectra, similar structures have been reported before and are likely stabilized in part by μ 2 -M-H-B bonding. 71 Next, an equilibrium is established between complexes IV and V with an additional DMAP coordinating to the catalytic center (ΔG = 3.3 kcal mol -1 ). This triggers the slightly endergonic (ΔG = 4.6 kcal mol -1 ) release of the C-H borylated product from V via H̅ transfer to the Cp* 2 Lu-center, yielding intermediate VI. From there, the catalytic transformation is driven by product dimerization that is both exothermic and exergonic, with ΔH = -30.3 kcal mol -1 and ΔG = -8.4 kcal mol -1 , respectively, affording complex (VI). S18.

Figure 9. DFT-derived ΔΔG ‡ (ΔG ‡ 1,2-dearomatization-ΔG ‡ C-H borylation) energetics as a function of substrate substitution. For more information, see Figure S123 and Table S19.

Note that the greater electron density of the DMAP borylated product favors stable dimers more than the corresponding pyridine dimer by ΔΔH = -6.6 kcal mol -1 and ΔΔG = -5.0 kcal mol -1 and the corresponding 4-(trifluoromethyl)pyridine dimer by ΔΔH = -9.1 kcal mol -1 and ΔΔG = -6.7 kcal mol -1 , consistent with the yield trends in Table 1 and Figure S123. From Figure 6, note that complex VI undergoes H 2 elimination, which is detectable by 1 H NMR, to restore III for a new cycle. This step is slightly exergonic with a barrier of ΔG ‡ = 24.5 kcal mol -1 (TS3) and is the TOF-determining transition state (TDTS) 70 with a calculated KIE of 2.8, in excellent agreement with the experimental KIE of 2.8 ± 0.2. The overall energetic span is 28.2 kcal mol -1 when considering IV as the TDI species and TS3 as the TDTS species.

Discussion�Origin of Chemodivergence. The origin of the intriguing regioselective sensitivity to Cp 2 *Ln-catalytic center was next analyzed by DFT, noting that C-H functionalization and 1,2-dearomatization share a common entry point (I in Figure 7). It is found that Cp 2 *Luhas the greatest barrier for 1,2-dearomatization, with ΔG ‡ = 33.4 kcal mol -1 (Figure S124), which is 1.6 kcal mol -1 greater than La (Figure S125) and in agreement with the experiment (Figure 2). Furthermore, ΔΔG ‡

(1,2dearo-CHboryl) = +5.2 and -4.5 kcal mol -1 for Cp 2 *Lu-and Cp 2 *La-, respectively, were again in agreement with the experiment (Figure 2). Ligand-ligand and ligand-substrate non-bonded repulsions likely play a significant role as the Ln 3+ ionic radius contracts from La 3+ (1.250 Å) to Lu 3+ (0.995 Å). Note that the 1,2-dearomatization pathway (Figure 7, left) requires binding a second pyridine molecule, which should be less favorable as the ligand sphere contracts. This is also supported by the crystal structures of the complexes and the steric effects quantified in free volume contours (Figure 8a,b). 72 C-H borylation may also be promoted by the more electrophilic Cp 2 *Lu-3+ having a less hydridic hydride (Figure 8c,d, and Table S18). Interestingly, Cp 2 *Luselectively catalyzes both azine α-mono-C-H borylation and 1,2-dearomatization, depending on the substrate substituents, while Cp 2 *Laexclusively catalyzes azine 1,2-dearomatization. Additionally, DFT analysis of substituent effects on the chemodivergence (Figure 9 and Table S19) reveals that ΔΔG ‡

(1,2dearo-CHboryl) falls from the most electron-rich substrate DMAP (+5.2 kcal mol -1 ) to pyridine (+2.6 kcal mol -1 ) and to the least electron-rich 4-(trifluoromethyl)pyridine (+0.3 kcal mol -1 ) in good agreement with the experimental TOFs and presumably from the increased electron density at the α-carbon, which stabilizes the bond between the electropositive-Bpin moiety (Figure 9). Moreover, substituent π-donation stabilizes more electron-rich α-borylated dimers (Figure 9), while electron-poor pyridines are likely more susceptible to α-position nucleophilic attack by proximate Cp 2 *Ln-H moieties (I in Figure 7), yielding 1,2dearomatized products.

Conclusions. We report marked chemodivergence in an organolanthanide-mediated catalytic reaction involving a broad class of pyridinoid substrates: a cross-over with the lanthanide identity from highly selective HBpin-delivering B-N bondforming dearomatization to highly selective α-C-H functionalization/borylation with HBpin. Regarding the latter pathway, experimental and theoretical mechanistic data support the formation of a C-H activated η 2 -lanthanide-azine complex, followed by intermolecular α-mono-borylation via σ-bond metathesis. Varying the lanthanide identity and substrate substitution promotes chemodivergence of the catalytic selectivity: smaller/more electrophilic Cp 2 *Ln-3+ ions and electron-rich substrates favor selective α-C-H functionalization, whereas larger/less electrophilic Cp 2 *Lnions and electron-poor substrates favor selective B-N bond-forming 1,2-dearomatization. Such organolanthanide series' catalytic chemodivergence is, to our knowledge, unprecedented and relevant to the placement of early lanthanides in the periodic table. 73,74 These results should inform the design of future organolanthanide catalysts and their selective transformations.

■ EXPERIMENTAL SECTION

Materials and Methods. Due to the air-and moisture-sensitivity of organolanthanide complex 1, all manipulations of air-sensitive materials for this mechanistically oriented study were carried out with rigorous exclusion of O 2 and moisture in flame-or oven-dried Schlenk-type glassware on either a dual-manifold Schlenk line, interfaced to a high-vacuum manifold (10 -6 Torr), or in a N 2 -filled MBraun glovebox with a high-capacity recirculator (<1 ppm O 2 ). Argon (airgas) was purified by a passage through a MnO column to remove O 2 and a column of Davison 4A molecular sieves to remove water immediately before use. Toluene-d 8 (Cambridge Isotope Laboratories, 99+ atom % D) for NMR reactions and kinetic measurements was stored over Na/K alloy in vacuo and vacuum transferred before use. Pyridines were purchased from Sigma-Aldrich, TCI America, or Acros Organics, distilled from CaH 2 , and stored under an inert atmosphere in a glovebox. Liquid substrates and substrate solutions were degassed by freeze-pump-thaw methods. Solid substrates were purified by sublimation under high vacuum and were stored in a glovebox. Pinacolborane (HBpin) was purchased from TCI America, distilled, and stored at -35 °C in a glovebox. The hexmathylbenzene and mesitylene internal integration standard for kinetic NMR studies was purchased from Strem and Sigma-Aldrich, sublimed under high vacuum or dried over CaH 2 , and stored in the glove box.

Physical and Analytical Measurements. NMR spectra were recorded on Bruker Avance III HD (BBFO Smart Probe, FT, 400 MHz, 1 H; 400 MHz, 13 13 C spectra were referenced using internal solvent resonances and are reported relative to tetramethylsilane (TMS). BF 3 •OEt 2 was used as an external reference for 11 B NMR spectra. NMR experiments on air-sensitive samples were conducted in Teflonvalve-sealed sample tubes (J. Young). High-resolution mass spectra (HRMS) were acquired on an Agilent 6210 LC-TOF (ESI, APCI, APPI) mass spectrometer with acetonitrile as the solvent in the positive ion mode or on a Bruker Impact-II (ESI, APPI, APCI) mass spectrometer with water, methanol, or acetonitrile as the solvent in the positive ion mode.

Improved Synthesis of Cp* 2 LuCH(TMS) 2 (1). The precatalyst Cp* 2 LuCH(TMS) 2 1 was prepared in accordance with the following procedure: a suspension of 1.15 g (4.09 mmol) of anhydrous LuCl 3 (Sigma-Aldrich) in 150 mL of THF was transferred to a flask containing LiCp* in a -78 °C dry ice/acetone bath. The reaction mixture was gradually heated and then allowed to reflux for 12 h. The solvent was then removed in vacuo, and the residue was stirred overnight with 200 mL of diethyl ether. The mixture was then filtered, the filtrate was reduced in volume to 30 mL, and the remaining solution was transferred to another flask to be cooled to -40 °C. The off-white crystalline solid obtained after decanting the supernatant was dried under high vacuum, affording 1.5 g of Cp* 2 LuCl 2 Li(ether) 2 in 55% yield (Page S131). For similar structures with Ce 75 and Sm 76 rather than Lu, see references. The corresponding Cp* 2 LuCl 2 Na-(ether) 2 can be obtained by using NaCp* instead of LiCp* (Page S132). Once isolated, 2.0 g of Cp* 2 LuCl 2 Li(ether) 2 was suspended in a solution of toluene and cooled to -78 °C. A solution of LiCH(TMS) 2 in toluene was then added dropwise to the solution of Cp* 2 LuCl 2 Li(ether) 2 , stirred, and allowed to warm to room temperature. The toluene was removed in vacuo, and the resulting 0.4 g of Cp* 2 LuCH(TMS) 2 was recrystallized from pentane (Supporting Information Page S125). In addition, the NMR spectra of these known complexes are in good accordance with the literature data. 77 The synthesis of Cp* 2 LnCH(TMS) 2 complexes with Ln = La, Nd, Sm, and Y was carried out based on previous literature, and the NMR spectra of these known complexes were in good accordance with the literature data. 77,78 Procedure for Typical NMR-Scale Catalytic Reactions. In a glovebox, 3-6 mg of the catalyst Cp* 2 LuCH(TMS) 2 (1) was weighed into a 4 mL vial; 500 μL of toluene-d 8 was added, thoroughly mixed, and transferred to a J. Young NMR tube. Pyridine was syringed or weighed into a 4 mL vial and mixed with the solution, while mesitylene (5 mL) was syringed into the NMR tube. HBpin was then added to the J-Young NMR tube. The sealed NMR tube was removed from the glovebox, placed in an oil bath at 80-100 °C, and left there for the indicated reaction times. The resulting mixture was analyzed in situ by 1 H, 13 C, and 11 B NMR spectroscopies. Pyridine-2-boronic acid pinacol ester products are air-and moisture-sensitive.

Computational Details. Geometry optimizations of all reactants, products, intermediates, and transition states were carried out along the entire catalytic cycle. Calculations were performed by adopting the M06 hybrid meta-GGA functional. The quasi-relativistic effective core potential of Stuttgart/Dresden, which explicitly treats 5s, 5p, 6s, and 5d electrons, was employed for the lanthanide atoms. The standard all-electron 6-31G** basis was used for all remaining atoms. Molecular geometry optimization of stationary points was carried out without symmetry constraints and used analytical gradient techniques. The transition states were searched with the synchronous, transitguided quasi-Newton (STQN) method. Frequency analysis was performed in order to verify stationary and saddle points and to obtain thermochemical information under standard conditions (298.15 K and 1 atm). The force constants were determined analytically upon harmonic approximation. For the analysis of the substituent effect, enthalpic and entropic corrections were evaluated only for the DMAP case and appended to all the other profiles obtained by substitution of the pyridine-derived substrate. In order to evaluate ΔG of solvation, the SMD variation of the polarized continuum formalism was adopted. For the analysis of the metal effect, solvation contribution was evaluated only for the lutetium + DMAP case and then appended for other cases. All calculations were performed using G16 code on Linux cluster systems. Molecular graphics were produced using the Chemcraft graphical package.

■ ASSOCIATED CONTENT

* sı Supporting Information

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.2c06844.

Experimental procedures, characterization data, spectra for all new compounds, crystallographic data, and Cartesian coordinates of all computed structures (PDF)