Chiral-at-Rhodium Catalyst Containing Two Different Cyclometalating

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Chiral-at-Rhodium Catalyst Containing Two Different Cyclometalating Ligands Yvonne Grell,† Yubiao Hong,† Xiaoqiang Huang,† Takuya Mochizuki,†,‡ Xiulan Xie,† Klaus Harms,† and Eric Meggers*,† †

Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan

‡

Organometallics Downloaded from pubs.acs.org by IDAHO STATE UNIV on 04/26/19. For personal use only.

S Supporting Information *

ABSTRACT: A method for the synthesis of a bis-cyclometalated rhodium complex containing two different cyclometalating ligands is reported and applied to asymmetric catalysis. The preparation of this previously inaccessible class of tris-heteroleptic bis-cyclometalated rhodium(III) complexes was achieved by a stepwise protocol that relies on the formation of an isolable mono-cyclometalated rhodium(III) species in the first step, providing the opportunity to introduce a different second ligand in a subsequent additional cyclometalation step. The obtained racemic complex was resolved into its single enantiomers using an established chiral auxiliary ligand approach. The final Λ- and Δconfigured chiral-at-metal rhodium complexes contain a cyclometalated 5-tert-butyl-1-methyl-2-phenylbenzimidazole, a cyclometalated 5-tert-butyl-2-phenylbenzothiazole, and two acetonitrile ligands, complemented by a hexafluorophosphate counterion, and proved to be highly efficient for asymmetric [2 + 2] photocycloadditions.

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INTRODUCTION Chiral Lewis acids serve as highly versatile catalysts for the asymmetric synthesis of chiral compounds.1 Recently, we introduced a new class of chiral Lewis acids based on biscyclometalated iridium(III)2 and rhodium(III)3 complexes.4 Two substitutionally and configurationally inert cyclometalating achiral ligands create a C2-symmetrical helical geometry with a stereogenic metal center (metal-centered chirality5,6), whereas two substitutionally labile acetonitrile ligands provide the reactive sites of the catalyst, allowing for substrate or reagent coordination. We and others demonstrated that these chiral-at-metal complexes catalyze a large variety of asymmetric transformations, including unique visible-light-induced asymmetric reactions.7 Whereas our initial work focused on biscyclometalated iridium catalysts, we later realized that the analogous rhodium complexes are for many catalytic applications superior, in large part due to their much more favorable ligand exchange kinetics, which is supposed to be the rate-limiting step in most heat- and light-induced catalytic cycles.8 The design of structurally modified bis-cyclometalated rhodium(III) complexes is therefore of significant interest for the development of bis-cyclometalated chiral-at-rhodium catalysts with novel properties. The synthesis of bis-cyclometalated complexes of iridium(III) goes back to a method first reported by Nonoyama more than 40 years ago involving heating iridium trichloride hydrate with the ligand of choice in 2-ethoxyethanol to obtain biscyclometalated iridium(III) μ-chloro-bridged dimers as single diastereomers, which then serve as versatile intermediates for subsequent conversions.9 The same procedure can be applied © XXXX American Chemical Society

to the analogous rhodium complexes. Although this chemistry is very convenient, one apparent limitation exists: namely, it provides bis-cyclometalated complexes in which both cyclometalating ligands are identical (Figure 1). However, for

Figure 1. Comparison of bis-cyclometalated rhodium(III) complexes with two identical and different cyclometalating ligands.

modification of photophysical and catalytic applications the synthesis of bis-cyclometalated complexes of iridium(III) and rhodium(III) with two different cyclometalating ligands is desirable. The majority of the reported methods for the preparation of bis-cyclometalated iridium complexes bearing two different cyclometalating ligands use statistical methods which have the disadvantage of leading to mixtures of complexes.10 Whereas recently a few reports have been published on strategies that circumvent such a combinatorial Special Issue: Asymmetric Synthesis Enabled by Organometallic Complexes Received: February 15, 2019

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DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX

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Scheme 1. Auxiliary-Mediated Synthesis of Λ- and Δ-RhNS via Mono-Cyclometalated Rhodium(III) Species 2a

approach,11−13 no method exists for the controlled synthesis of related bis-cyclometalated rhodium(III) complexes. Here, we disclose the first method for the stepwise preparation of an enantiomerically pure bis-cyclometalated rhodium(III) complex containing two different cyclometalating ligands and demonstrate its high performance in asymmetric [2 + 2] photocycloadditions.

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RESULTS AND DISCUSSION The stepwise synthesis introduced here of rhodium(III) complexes with two different cyclometalating ligands is based on a serendipitous finding. Previous bis-cyclometalated rhodium complexes used as chiral catalysts typically contained two 5-tert-butyl-2-phenylbenzoxazoles3 or the analogous benzothiazole14 ligand. When we attempted to expand this family of bis-cyclometalated rhodium catalysts to related benzimidazole complexes, we found that the reaction stopped after the first cyclometalation. Scheme 1 shows the optimized reaction conditions. Accordingly, the reaction of rhodium trichloride hydrate with 1.10 equiv of 5-tert-butyl-1-methyl-2phenylbenzimidazole (1) and subsequent treatment with AgPF6 in acetonitrile provided mono-cyclometalated rhodium(III) species 2, whose structure was confirmed by X-ray crystallography (Figure 2). Initially, 2 equiv of ligand 1 were used in order to obtain the corresponding rhodium bisbenzimidazole complex (further referred to as RhN). However, the bis-cyclometalated complex was only ever formed in less than 10% yield under various reaction conditions (see the Supporting Information), whereas mono-cyclometalation to 2 occurred predominantly. Optimization of the initial reaction conditions led to 2 being formed as the sole product of the first cyclometalation step in high yield (86%). Encouraged by these results, we sought out to test the incorporation of a different second ligand, thereby providing the opportunity to further expand the scope of bis-cyclometalated chiral-at-metal rhodium(III) catalysts. To this end, 5-tert-butyl-2-phenylbenzothiazole (3) was selected as an appropriate ligand.13 Gratifyingly, the addition of ligand 3 to a suspension of 2 in 3/ 1 2-ethoxyethanol/water led to the formation of the desired tris-heteroleptic complex rac-RhNS. However, under the initial reflux conditions we observed in addition to the desired product also the formation of complexes with two of the same cyclometalating ligands, namely [Rh(3-H)2(MeCN)2]PF6 (RhS) and to a smaller extent [Rh(1-H)2(MeCN)2]PF6 (RhN), in addition to product formation (Table 1, entry 1). Since all of these bis-cyclometalated complexes did not differ in Rf values, they were isolated as a mixture by standard silica gel chromatography. The overall yields given in Table 1 were calculated with the molar mass of rac-RhNS, as this also represents the average molar mass of all three complexes. Further 1H NMR analysis of the isolated mixture allowed determination of the relative amount of each complex via integration of the signals. As the corresponding signals of RhS and RhN were not baseline separated, only ratios of the target complex to both bis-heteroleptic complexes are reported. For entry 1, the ratio of 1.7:1 corresponds to an approximate byproduct yield of 22%. In order to optimize the yield of the second cyclometalation step with respect to the desired biscyclometalated complex with two different cyclometalating ligands, different reaction conditions were attempted. Lowering the reaction temperature to 80 °C led to a significant improvement in the product to byproduct ratio (entries 2−4), providing rac-RhNS in a reasonable yield after prolonging the

a

Abbreviations: n.i. = not isolated.

reaction time (entry 4). Notably, rac-RhNS was always formed as the major product (entries 1−4). The preparation of racRhNS in a one-pot procedure via a sequential addition of ligands 1 and 3 was also investigated, in an attempt to shorten the reaction sequence by one step (entry 5). Unexpectedly, this completely abolished the formation of the desired product. Instead, only RhS was obtained in 21% yield, revealing the necessity of a stepwise introduction of ligands starting from RhCl3. B

DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX

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Figure 2. Crystal structure of mono-cyclometalated rhodium(III) complex 2 as an ORTEP drawing with 50% probability thermal ellipsoids. The hexafluorophosphate counterion and solvent molecules are omitted for clarity.

With rac-RhNS in hand, we next engaged in the synthesis of single enantiomers using a previously established chiral auxiliary ligand approach.15−19 Accordingly, a mixture of four diastereomers was prepared by employing the chiral salicyloxazoline (S)-4.14,19b,20 Due to the unsymmetrical nature of the chiral auxiliary, in theory four diastereomers can form: namely, Λ-(S)-5a, Λ-(S)-5b, Δ-(S)-5a, and Δ-(S)-5b. Indeed, the complexes Λ-(S)-5a, Λ-(S)-5b, and Δ-(S)-5a could be resolved by regular silica gel chromatography to afford the pure diastereomers, while Δ-(S)-5b was not isolated most likely due to the formation of only trace amounts. Importantly, the corresponding auxiliary complexes formed from RhS and RhN could be easily separated at this stage from the desired tris-heteroleptic complexes. Absolute configurations were assigned on the basis of the crystal structure of Δ-(S)-5a, as shown in Figure 3. The structure of Δ-(S)-5a, having the oxazoline nitrogen of (S)-4 trans to the phenyl moiety of phenylbenzimidazole 1 and the oxygen of (S)-4 trans to the phenyl moiety of phenylbenzothiazole 3, was also confirmed in solution by

Figure 3. Crystal structure of auxiliary complex Δ-(S)-5a as an ORTEP drawing with 50% probability thermal ellipsoids. Solvent molecules are omitted for clarity. 1

H−1H 2D NOESY (see the Supporting Information). Analogous NMR measurements showed that the more stable stereoisomer Λ-(S)-5a possesses the same connectivity. A similar experiment for Λ-(S)-5b could not be performed, as it almost completely isomerized to Λ-(S)-5a within 24 h in CD2Cl2, indicating a dynamic equilibrium of the two species (see the Supporting Information). This is consistent with the obtained CD spectra of purely separated Λ-(S)-5a and Λ-(S)5b after each was subjected to an acidic cleavage of the auxiliary, since they show that both complexes contain the same metal-centered configuration (see the Supporting Information). Accordingly, Λ-(S)-5a and Λ-(S)-5b do not have to be separated from each other and can be isolated as a mixture, thereby simplifying the resolution of the diastereomers significantly. Acid-induced substitution of the coordi-

Table 1. Optimization of the Reaction Conditions of the Second Cyclometalationa

conditions (1st step) entry

T (°C)

t (h)

overall yield (%)b

rac-RhNS to RhS/RhN ratioc

1 2 3 4 5d

125 80 80 80 80

5 23 48 72 48

60 29 44 56 21

1.7:1 4.6:1 5.3:1 5.6:1 0:1

Reaction conditions first step: 2 and 3 (1.00 equiv) were stirred in 2-ethoxyethanol/water (3/1) (0.05 M) at the indicated temperature for the indicated time under an atmosphere of nitrogen. bIsolated yield after second step. The product was isolated as a mixture of rac-RhNS and the bisheteroleptic complexes RhS and RhN. cRatios were determined by 1H NMR. dSequential addition of ligands. After RhCl3 was stirred with ligand 1 for 7 h at 150 °C (see Scheme 1), benzothiazole 3 was added. The corresponding reaction mixture was further stirred at the indicated temperature for the indicated time. Exclusive formation of RhS. a

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Scheme 2. Comparison of Catalytic Activities of Δ-RhNS and Δ-RhS for the Intermolecular [2 + 2] Photocycloaddition of α,β-Unsaturated N-Acyl Pyrazoles with Alkenes

nated chiral auxiliary with two acetonitrile ligands and subsequent counterion exchange with NH4PF6 afforded the single enantiomers Λ-RhNS (93%) and Δ-RhNS (>99%) with retention of configuration. The CD spectra of Λ- and Δ-RhNS are shown in Figure 4 and confirm their mirror-image

Figure 4. Circular dichroism spectra of Λ- and Δ-RhNS (0.2 mM in CH3OH).

structures. HPLC on a chiral stationary phase exhibited the high enantiopurity (>99% ee) of the tris-heteroleptic rhodium complexes (see the Supporting Information). Furthermore, a crystal structure of Δ-RhNS could be obtained and is presented in Figure 5.

rhodium complexes Λ- and Δ-RhS.21 We also performed a reaction that has not been reported before in which Δ-RhNS catalyzes the asymmetric [2 + 2] photocycloaddition between the α,β-unsaturated N-acyl pyrazole 9 and the aliphatic internal alkene cycloheptene (10) to provide the desired cycloaddition product 11 in high yields, with satisfactory diastereoselectivity and with excellent enantioselectivity. The relative and absolute configuration of cyclobutane 11 was assigned by X-ray crystallography (see the Supporting Information).

Figure 5. Crystal structure of Δ-RhNS as an ORTEP drawing with 50% probability thermal ellipsoids. The hexafluorophosphate counterion and solvent molecules are omitted for clarity.

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CONCLUSIONS In conclusion, we developed the first method for the synthesis of a bis-cyclometalated rhodium(III) complex containing two different cyclometalating ligands. The synthetic strategy for this new class of chiral-at-rhodium catalysts relies on a stepwise introduction of ligands, which is enabled by the formation of a stable mono-cyclometalated rhodium(III) intermediate instead of the expected bis-cyclometalated complex when a phenylbenzimidazole ligand is used. This allows introduction of a different second bidentate ligand in a subsequent second cyclometalation step, thereby giving access to previously elusive tris-heteroleptic bis-cyclometalated rhodium complexes

Finally, the application of Δ-RhNS for asymmetric [2 + 2] photocycloadditions between α,β-unsaturated N-acyl pyrazoles and alkenes was investigated (Scheme 2).21−23 The reaction of α,β-unsaturated N-acyl pyrazole 6 with 2-phenylpropene (7) under irradiation with blue LEDs and catalysis by Λ-RhNS provided the [2 + 2] photocycloaddition product 8 as a single diastereomer in a yield of 94% and with 99% ee. As an important control, employing Δ-RhNS instead afforded the opposite enantiomer with an identical ee of 99%. These results are comparable with reported results using the established D

DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX

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(w), 2332 (w), 1621 (w), 1584 (w), 1523 (w), 1485 (w), 1428 (w), 1366 (w), 1335 (w), 1295 (w), 1262 (w), 1161 (w), 1027 (w), 831 (s), 769 (w), 733 (w), 695 (w), 651 (w), 556 (m), 453 (w) cm−1. HRMS (APCI) m/z calcd. for C24H27N5Rh [M-HCl]+: 488.1316, found: 488.1329. HRMS (APCI): m/z calcd for C22H25ClN4Rh [M − MeCN]+ 483.0817, found 483.0830. Mp: 214 °C dec (CH2Cl2). Synthesis of rac-RhNS. A suspension of complex 2 (100 mg, 0.15 mmol, 1.00 equiv) and 5-tert-butyl-2-phenylbenzothiazole (3; 40.0 mg, 0.15 mmol, 1.00 equiv) in 2-ethoxyethanol (2.25 mL) and H2O (0.75 mL) was stirred at 80 °C for 72 h in the dark. The reaction mixture was cooled to room temperature, and the solvent was removed thoroughly under reduced pressure (water bath of rotary evaporator set to 60 °C). AgPF6 (68 mg, 0.27 mmol, 1.80 equiv) and MeCN (3.00 mL) were added, successively, and the resulting suspension was stirred at 60 °C for 14 h in the dark. The mixture was cooled to room temperature, and then it was filtered over a short plug of Celite and rinsed with MeCN. The solvent was removed under reduced pressure, and the obtained residue was purified by column chromatography (CH2Cl2/MeCN 60/1 → 40/1 → 20/1) to afford rac-RhNS (72 mg, 0.08 mmol, 56%, ratio of rac-RhNS to RhS/RhN 5.6:1) as a pale yellow solid. TLC (CH2Cl2/MeCN 20/1): Rf = 0.40. 1 H NMR (300 MHz, CD2Cl2): δ 8.52 (d, J = 1.6 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.99 (d, J = 1.1 Hz, 1H), 7.82 (dd, J = 7.8, 1.1 Hz, 1H), 7.72 (dd, J = 8.6, 1.8 Hz, 1H), 7.68−7.64 (m, 2H), 7.61 (d, J = 8.7 Hz, 1H), 7.05 (dt, J = 7.6, 1.0 Hz, 1H), 7.00 (dt, J = 7.5, 1.0 Hz, 1H), 6.84−6.78 (m, 2H), 6.27 (d, J = 7.8 Hz, 1H), 6.15 (d, J = 7.8 Hz, 1H), 4.29 (s, 3H), 2.18 (brs, 6H), 1.47 (s, 9H), 1.46 (s, 9H) ppm. 13C NMR (126 MHz, CD2Cl2): δ 176.6, 161.7, 158.3, 158.2, 152.5, 150.5, 148.5, 140.4, 139.7, 135.1, 134.1, 134.0, 133.5, 131.0, 129.9, 129.3, 126.1, 125.3, 125.0, 124.1, 124.0, 123.1, 122.8, 121.4 (2C), 117.1, 112.6, 110.4, 35.6, 35.4, 32.8, 31.8 (3C), 31.6 (3C), 3.64 (2C) ppm. 19 F NMR (282 MHz, CD2Cl2): δ −74.0 (d, JP−F = 711 Hz, 6F) ppm. IR (neat): ν̃ 2957 (w), 2868 (w), 2282 (w), 1580 (w), 1555 (w), 1513 (w), 1480 (w), 1440 (w), 1419 (w), 1364 (w), 1330 (w), 1294 (w), 1257 (w), 1160 (w), 1122 (w), 1026 (w), 993 (w), 933 (w), 835 (s), 760 (w), 729 (w), 699 (w), 671 (w), 651 (w), 611 (w), 555 (m), 458 (w) cm−1. HRMS (APCI): m/z calcd for C39H41N5RhS [M]+ 714.2132, found 714.2135. Mp: 213 °C (CH2Cl2). Synthesis of Λ- and Δ-(S)-5. rac-RhNS (93 mg, 0.11 mmol, 1.00 equiv), K2CO3 (45 mg, 0.33 mg, 3.00 equiv), and chiral auxiliary (S)4 (31 mg, 0.12 mmol, 1.10 equiv) were dissolved in EtOH (4.60 mL, absolute) and stirred for 5 h at 70 °C. The reaction mixture was cooled to room temperature, diluted with CH2Cl2, and filtered over a short plug of Celite. The solvent was removed under reduced pressure, and the mixture of four diastereomers was purified by column chromatography (n-pentane/EtOAc + 1% Et3N 10/1 → 8/1 → 6/1 → 5/1 → 4/1 → 3/1) to give Λ-(S)-5a (25 mg, 0.03 mmol, 26%), Λ-(S)-5b (12 mg, 0.01 mmol, 13%), and Δ-(S)-5a (42 mg, 0.05 mmol, 43%) as yellow solids. Complex Δ-(S)-5b could not be isolated, most likely due to formation only in trace amounts. If necessary, the individual diastereomers have to be purified again by column chromatography to provide the final catalysts Λ- and Δ-RhNS with high enantiomeric purities. For precise assignments of 1H and 13 C signals see Figures S2−S17 in the Supporting Information. Λ-(S)-5a. TLC (n-pentane/EtOAc 2/1 + 1% Et3N): Rf = 0.38. 1H NMR (600 MHz, CD2Cl2): δ 8.98 (d, J = 1.6 Hz, 1H), 7.73 (dd, J = 7.8, 1.1 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 1.3 Hz, 1H), 7.48−7.46 (m, 2H), 7.39 (d, J = 8.8 Hz, 1H), 7.34 (dd, J = 7.6, 1.1 Hz, 1H), 6.95−6.92 (m, 2H), 6.89−6.85 (m, 1H), 6.82−6.79 (m, 1H), 6.78 (dt, J = 7.4, 1.4 Hz, 1H), 6.72 (dt, J = 7.5, 1.3 Hz, 1H), 6.55 (d, J = 7.8 Hz, 1H), 6.43 (d, J = 8.7 Hz, 1H), 6.28 (d, J = 7.4 Hz, 2H), 6.60 (d, J = 7.9 Hz, 1H), 5.87 (ddd, J = 13.0, 7.8, 1.1 Hz, 1H), 4.84− 4.80 (m, 2H), 4.10 (s, 3H), 4.01 (dd, J = 6.7, 2.3 Hz, 1H), 1.45 (s, 9H), 1.30 (s, 9H) ppm. 13C NMR (126 MHz, CD2Cl2): δ 175.5 (d, JC,Rh = 3.3 Hz), 174.9 (d, JC,F = 3.4 Hz), 171.1 (d, JC,Rh = 30.6 Hz), 169.6 (d, JC,Rh = 32.4 Hz), 165.8 (d, JC,F = 3.4 Hz), 164.0 (d, JC,F = 257.2 Hz), 159.6 (d, JC,Rh = 3.3 Hz), 151.7, 151.6, 147.5, 141.9, 141.5, 140.6, 136.2, 134.9, 134.1, 134.0, 132.6 (d, JC,F = 14.1 Hz), 129.7, 129.5, 128.9, 128.0 (2C), 127.5 (2C), 125.8, 124.6, 123.7, 122.5, 122.2, 121.7, 121.3, 121.1 (d, JC,F = 2.4 Hz), 119.8, 112.6, 109.7,

and providing the opportunity to expand the structural diversity of chiral-at-metal catalysts. Through an established auxiliary-mediated approach, the final catalyst can be obtained conveniently in a nonracemic fashion with high enantiomeric purities (>99% ee for each enantiomer). A high catalytic performance was demonstrated for asymmetric [2 + 2] photocycloadditions. Further applications of the newly synthesized catalyst and the development of bifunctional versions thereof are currently under investigation in our laboratory.

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EXPERIMENTAL SECTION

General Methods and Materials. All reactions were carried out under a nitrogen atmosphere in oven-dried glassware unless noted otherwise. Solvents were distilled under nitrogen from calcium hydride (MeCN, CH2Cl2), sodium/benzophenone (THF), or sodium (toluene) prior to use. Reagents that were purchased from commercial suppliers were used without further purification. Flash column chromatography was performed with silica gel 60 M from Macherey-Nagel (irregularly shaped, 230−400 mesh, pH 6.8, pore volume 0.81 mL × g−1, mean pore size 66 Å, specific surface 492 m2 × g−1, particle size distribution 0.5% < 25 μm and 1.7% > 71 μm, water content 1.6%). 1H NMR, 13C{1H} NMR, and 19F{1H} NMR spectra were recorded on a Bruker AV II 300 MHz, AV III HD 250 MHz, AV III 500 MHz, AV III HD 500 MHz, or AV II 600 MHz spectrometer at ambient temperature. Chemical shift values δ are reported in ppm with the solvent resonance as internal standard. All 13C NMR signals are singlets unless noted otherwise. IR spectra were recorded on a Bruker Alpha FT-IR spectrometer. CD spectra were aquired with a JASCO J-810 CD spectropolarimeter (600−200 nm, data pitch 0.5 nm, bandwidth 1 nm, response 1 s, sensitivity standard, scanning speed 50 nm/min, accumulation of three scans). High-resolution mass spectrometry was performed on a Finnigan LTQ-FT Ultra mass spectrometer (Thermo Fischer Scientific) using ESI or APCI as the ionization source. EI mass spectra were recorded on an AccuTOF GCv instrument (JEOL). Melting points were determined on a Mettler Toledo MP70 apparatus using capillary tubes closed on one end. Chiral HPLC was performed on an Agilent 1200 or 1260 instrument or on an Agilent 1200 instrument with an Agilent 6120 Series Quadrupole LC/MS System with multimode source. Synthesis of Complex 2. The synthesis was related to a procedure reported by our group but was performed with modifications.20 A suspension of RhCl3 hydrate (100 mg, 0.39 mmol, 1.00 equiv) and 5-tert-butyl-1-methyl-2-phenylbenzimidazole (1; 113 mg, 0.43 mmol, 1.10 equiv) in 2-ethoxyethanol (5.85 mL) and H2O (1.95 mL) was stirred at 150 °C for 7 h. The reaction mixture was cooled to room temperature, and the solvent was removed thoroughly under reduced pressure (water bath of rotary evaporator set to 60 °C). AgPF6 (177 mg, 0.70 mmol, 1.80 equiv) and MeCN (7.80 mL) were added, successively, and the resulting suspension was stirred at 60 °C for 15 h in the dark. The mixture was cooled to room temperature, and then it was filtered over a short plug of Celite and rinsed with MeCN. The solvent was removed under reduced pressure, and then the residue was filtered again over a short silica pad (ca. 1 cm) using CH2Cl2/MeCN 50/1 as eluent to remove the excess AgPF6. Purification of the obtained yellow oil by column chromatography (CH2Cl2/MeCN 20/1 → 10/1 → 5/1) afforded complex 2 (223 mg, 0.33 mmol, 86%) as a yellow solid. TLC (CH2Cl2/MeCN 5/1): Rf = 0.33. 1H NMR (500 MHz, CD3CN): δ 8.13 (dd, J = 1.7, 0.6 Hz, 1H), 8.01 (dd, J = 7.7, 1.5 Hz, 1H), 7.97 (dd, J = 7.8, 1.1 Hz, 1H), 7.61 (dd, J = 8.8, 1.8 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.40 (dt, J = 7.6, 1.6 Hz, 1H), 7.35 (dt, J = 7.5, 1.2 Hz, 1H), 4.21 (s, 3H), 2.63 (s, 3H), 2.10 (s, 3H), 1.47 (s, 9H) ppm. 13C NMR (126 MHz, CD3CN): δ 157.9 (d, JC,Rh = 2.5 Hz), 157.1 (d, JC,Rh = 25.2 Hz), 148.8, 140.0, 136.7, 135.7, 134.2, 131.1, 126.6, 125.9, 123.6, 123.5 (d, JC,Rh = 5.9 Hz), 123.0 (d, JC,Rh = 6.2 Hz), 112.6, 111.8, 35.7, 33.2, 31.9 (3C), 4.49, 3.92 ppm. 19F NMR (282 MHz, CD3CN): δ −72.9 (d, JP−F = 707 Hz, 6F) ppm. IR (neat): ν̃ 2958 E

DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 100.9 (d, JC,F = 6.2 Hz), 98.4 (d, JC,F = 24.1 Hz), 75.3, 69.5, 60.7, 35.4, 35.3, 32.7, 31.9 (3C), 31.8 (3C) ppm. 19F NMR (235 MHz, CD2Cl2): δ −105.3 (s, 1F) ppm. IR (neat): ν̃ 3048 (w), 2952 (w), 2865 (w), 2328 (w), 1617 (s), 1579 (w), 1528 (w), 1510 (w), 1476 (w), 1445 (s), 1364 (w), 1321 (w), 1280 (w), 1250 (w), 1216 (m), 1156 (w), 1093 (w), 1031 (m), 989 (w), 951 (w), 925 (w), 864 (w), 817 (w), 792 (w), 754 (w), 729 (m), 696 (m), 672 (w), 651 (w), 612 (w), 579 (w), 530 (w), 461 (w) cm−1. HRMS (APCI): m/z calcd for C50H47FN4O2RhS [M + H]+ 889.2453, found 889.2460. Mp: 305 °C dec (EtOAc). CD (CH3OH): γ, nm (Δε, M−1 cm−1) 397 (−10), 347 (+38), 300 (−36), 242 (+32), 228 (−16), 216 (+7), 203 (+28). Λ-(S)-5b. TLC (n-pentane/EtOAc 2/1 + 1% Et3N): Rf = 0.50. 1H NMR (250 MHz, CD2Cl2): δ 8.15 (s, 1H), 8.03 (s, 1H), 7.83 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.42− 7.37 (m, 2H), 7.15 (d, J = 8.6 Hz, 1H), 6.97−6.88 (m, 5H), 6.80− 6.68 (m, 4H), 6.46 (d, J = 8.7 Hz, 1H), 6.16 (d, J = 6.0 Hz, 2H), 5.90−5.82 (m, 2H), 4.93−4.79 (m, 2H), 3.98−3.95 (m, 1H), 3.74 (s, 3H), 1.45 (s, 9H), 1.28 (s, 9H) ppm. 13C NMR could not be measured due to rapid isomerization to Λ-(S)-5a. 19F NMR (235 MHz, CD2Cl2): δ −105.5 (s, 1F) ppm. IR (neat): ν̃ 3052 (w), 2954 (w), 2922 (s), 2853 (w), 1616 (s), 1579 (m), 1528 (m), 1509 (w), 1477 (w), 1444 (s), 1378 (w), 1364 (w), 1323 (w), 1280 (w), 1250 (w), 1216 (m), 1157 (w), 1095 (m), 1026 (s), 988 (w), 950 (w), 927 (w), 866 (w), 791 (m), 755 (w), 728 (s), 695 (m), 670 (w), 651 (w), 612 (w), 580 (w), 531 (m), 461 (m) cm−1. HRMS (APCI): m/z calcd for C50H47FN4O2RhS [M + H]+ 889.2453, found 889.2474. Mp: 254 °C dec (CH2Cl2). Δ-(S)-5a. TLC (n-pentane/EtOAc 2/1 + 1% Et3N): Rf = 0.23. 1H NMR (600 MHz, CD2Cl2): δ 9.11 (d, J = 1.6 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.83 (d, J = 1.4 Hz, 1H), 7.71 (dd, J = 7.8, 1.1 Hz, 1H), 7.56 (dd, J = 8.6, 1.9 Hz, 1H), 7.42 (dd, J = 8.8, 1.7 Hz, 1H), 7.38 (dd, J = 7.6, 1.1 Hz, 1H), 8.76 (d, J = 8.8 Hz, 1H), 6.95 (dt, J = 7.5, 1.2 Hz, 1H), 6.92−6.89 (m, 1H), 6.86−6.82 (m, 4H), 6.79−6.75 (m, 2H), 6.62 (dt, J = 7.4, 1.1 Hz, 1H), 6.40 (d, J = 7.7 Hz, 1H), 6.29− 6.25 (m, 2H), 5.91 (d, J = 7.8 Hz, 1H), 5.87 (ddd, J = 11.7, 7.9, 1.0 Hz, 1H), 4.22 (dd, J = 8.9, 7.7 Hz, 1H), 4.12 (s, 3H), 4.07−4.00 (m, 2H), 1.39 (s, 9H), 1.23 (s, 9H) ppm. 13C NMR (126 MHz, CD2Cl2): δ 176.1 (d, JC,Rh = 3.7 Hz), 174.4 (d, JC,F = 3.6 Hz), 170.7 (d, JC,Rh = 32.5 Hz), 169.7 (d, JC,Rh = 31.5 Hz), 166.0, 163.2 (d, JC,F = 253.9 Hz), 159.1 (d, JC,Rh = 3.1 Hz), 152.3, 151.4, 147.0, 140.6, 140.5, 140.4, 135.8, 135.4, 134.1, 133.6, 132.3 (d, JC,F = 13.4 Hz), 129.3, 129.0, 128.9, 128.3 (2C), 127.4, 127.4 (2C), 125.8, 124.5, 124.2, 122.5, 121.9, 121.8, 121.7, 119.7 (d, JC,F = 1.9 Hz), 119.2, 113.6, 109.4, 103.3 (d, JC,F = 7.8 Hz), 98.3 (d, JC,F = 22.7 Hz), 75.3, 70.0, 35.4, 35.3, 32.5, 31.9 (3C), 31.4 (3C) ppm. 19F NMR (282 MHz, CD2Cl2): δ −107.5 (s, 1F) ppm. IR (neat): ν̃ 3049 (w), 2954 (m), 2864 (w), 1733 (w), 1618 (s), 1579 (m), 1530 (w), 1508 (w), 1476 (w), 1446 (s), 1418 (w), 1361 (m), 1327 (w), 1281 (w), 1261 (w), 1220 (s), 1156 (w), 1118 (w), 1093 (w), 1027 (s), 988 (w), 952 (w), 867 (w), 842 (w), 788 (m), 753 (w), 725 (m), 695 (s), 672 (w), 650 (w), 613 (w), 582 (w), 529 (m), 460 (m) cm−1. HRMS (APCI): m/z calcd for C50H47FN4O2RhS [M + H]+ 889.2464, found 889.2476. Mp: 267 °C (EtOAc). CD (CH3OH): λ, nm (Δε, M−1 cm−1) 390 (+10), 359 (−9), 351 (−6), 333 (−19), 300 (+26), 268 (−8), 246 (−23), 230 (+12), 219 (−7), 215 (−1), 205 (−54). Synthesis of Λ-RhNS. To a solution of Λ-(S)-5a (20 mg, 0.02 mmol, 1.00 equiv) in MeCN (0.55 mL) was added trifluoroacetic acid (TFA; 17 μL, 0.22 mmol, 10.0 equiv) in one portion, and the reaction mixture was stirred for 7 h at 50 °C. The mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained yellow oil was transferred to a column with CH2Cl2, and CH2Cl2/MeCN 100/1 + 0.1% TFA was used as the first eluent to prevent the auxiliary from recoordinating to the metal center. By using CH2Cl2/MeCN 20/1 → 10/1 residual TFA and the auxiliary ligand (dark purple band) were eluted, before excess NH4PF6 (20.0 equiv) was added atop of the sea sand. The residual pale yellow band was then eluted with CH2Cl2/MeCN 1/1. After removal of the solvent, the obtained yellow solid was subjected to a short silica pad (ca. 1 cm) using CH2Cl2/MeCN 50/1 as eluent to remove the excess NH4PF6 to yield Λ-RhNS (18 mg, 0.02 mmol, 93%) as a pale yellow

solid. Enantiomeric excess was established by HPLC analysis using a Daicel Chiralpak IB-N5 column, ee = 99.6% (HPLC: 254 nm, H2O + 0.1% TFA/MeCN = 40/60 to 50/50 in 180 min, 50/50 until 240 min, flow rate 0.6 mL/min, 25 °C, tR(Δ-RhNS) = 193.7 min, tR(ΛRhNS) = 205.3 min). CD (CH3OH): λ, nm (Δε, M−1 cm−1) 390 (−15), 354 (+45), 297 (−48), 244 (+33), 230 (+7), 220 (+16), 213 (−3), 205 (+33). All other spectroscopic data are in agreement with rac-RhNS. Synthesis of Δ-RhNS. To a solution of Δ-(S)-5a (43 mg, 0.05 mmol, 1.00 equiv) in MeCN (1.20 mL) was added TFA (37 μL, 0.48 mmol, 10.0 equiv) in one portion, and the reaction mixture was stirred for 6 h at 40 °C. Workup was performed as described above. Δ-RhNS (42 mg, 0.05 mmol, >99%) was obtained as a pale yellow solid. Enantiomeric excess was established by HPLC analysis using a Daicel Chiralpak IB-N5 column, ee = 99.4% (HPLC: 254 nm, H2O + 0.1% TFA/MeCN = 40/60 to 50/50 in 180 min, 50/50 until 240 min, flow rate 0.6 mL/min, 25 °C, tR(Δ-RhNS) = 193.7 min, tR(ΛRhNS) = 205.3 min). CD (CH3OH): λ, nm (Δε, M−1 cm−1) 390 (+15), 354 (−45), 297 (+48), 244 (−33), 230 (−7), 220 (−16), 213 (+3), 205 (−33). All other spectroscopic data are in agreement with rac-RhNS.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.9b00105. Synthesis of ligands, catalysis experiments, NMR studies, NMR spectra, HPLC traces, and crystallographic data (PDF) Accession Codes

CCDC 1892281−1892284 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail for E.M.: [email protected]. ORCID

Xiaoqiang Huang: 0000-0002-0927-4812 Eric Meggers: 0000-0002-8851-7623 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge funding from the Deutsche Forschungsgemeinschaft (ME 1805/13-1). T.M. thanks the Ishihara laboratory (Nagoya University) for extramural funding.

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REFERENCES

(1) Walsh, P. J.; Kozlowski, M. C. Fundamentals of Asymmetric Catalysis; University Science Books: Sausalito, CA, 2009. (2) For our initial publication on chiral-at-iridium Lewis acid catalysis, see: Huo, H.; Fu, C.; Harms, K.; Meggers, E. Asymmetric catalysis with substitutionally labile yet stereochemically stable chiralat-metal iridium(III) complex. J. Am. Chem. Soc. 2014, 136, 2990− 2993. (3) For our initial publication on chiral-at-rhodium Lewis acid catalysis, see: Wang, C.; Chen, L.-A.; Huo, H.; Shen, X.; Harms, K.; F

DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Gong, L.; Meggers, E. Asymmetric Lewis acid catalysis directed by octahedral rhodium centrochirality. Chem. Sci. 2015, 6, 1094−1100. (4) Zhang, L.; Meggers, E. Steering asymmetric Lewis acid catalysis exclusively with octahedral metal-centered chirality. Acc. Chem. Res. 2017, 50, 320−330. (5) (a) Brunner, H. Optically active organometallic compounds of transition elements with chiral metal atoms. Angew. Chem., Int. Ed. 1999, 38, 1194−1208. (b) Knof, U.; von Zelewsky, A. Predetermined chirality at metal centers. Angew. Chem., Int. Ed. 1999, 38, 302−322. (c) Amouri, H.; Gruselle, M. Chirality in Transition Metal Chemistry; Wiley: Chichester, U.K., 2008. (d) Meggers, E. Asymmetric synthesis of octahedral coordination complexes. Eur. J. Inorg. Chem. 2011, 2011, 2911−2926. (6) Zhang, L.; Meggers, E. Stereogenic-only-at-metal asymmetric catalysts. Chem. - Asian J. 2017, 12, 2335−2342. (7) For asymmetric photocatalysis with chiral-at-metal iridium(III) or rhodium(III) complexes, see for example: (a) Huo, H.; Shen, X.; Wang, C.; Zhang, L.; Röse, P.; Chen, L.-A.; Harms, K.; Marsch, M.; Hilt, G.; Meggers, E. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 2014, 515, 100−103. (b) Lin, S.-X.; Sun, G.-J.; Kang, Q. A visible-light-activated rhodium complex in enantioselective conjugate addition of α-amino radicals with Michael acceptors. Chem. Commun. 2017, 53, 7665−7668. (c) Liang, H.; Xu, G.-Q.; Feng, Z.-T.; Wang, Z.-Y.; Xu, P.-F. Dual catalytic switchable divergent synthesis: An asymmetric visible-light photocatalytic approach to fluorine-containing γ-keto acid frameworks. J. Org. Chem. 2019, 84, 60−72. (8) (a) Shen, X.; Harms, K.; Marsch, M.; Meggers, E. A rhodium catalyst superior to iridium congeners for enantioselective radical amination activated by visible light. Chem. - Eur. J. 2016, 22, 9102− 9105. (b) Huo, H.; Harms, K.; Meggers, E. Catalytic, enantioselective addition of alkyl radicals to alkenes via visible-light-activated photoredox catalysis with a chiral rhodium complex. J. Am. Chem. Soc. 2016, 138, 6936−6939. (c) Huang, X.; Webster, R. D.; Harms, K.; Meggers, E. Asymmetric catalysis with organic azides and diazo compounds initiated by photoinduced electron transfer. J. Am. Chem. Soc. 2016, 138, 12636−12642. (d) Huang, X.; Lin, J.; Shen, T.; Harms, K.; Marchini, M.; Ceroni, P.; Meggers, E. Asymmetric [3 + 2] photocycloadditions of cyclopropanes with alkenes or alkynes through visible-light excitation of catalyst-bound substrates. Angew. Chem., Int. Ed. 2018, 57, 5454−5458. For a recent account, see: (e) Huang, X.; Meggers, E. Asymmetric photocatalysis with bis-cyclometalated rhodium complexes. Acc. Chem. Res. 2019, 52, 833−847. (9) Nonoyama, N. Benzo[h]quinolin-10-yl-N iridium(III) complexes. Bull. Chem. Soc. Jpn. 1974, 47, 767−768. (10) (a) Felici, M.; Contreras-Carballad, P.; Smits, J. M. M.; Nolte, R. J. M.; Williams, R. M.; De Cola, L.; Feiters, M. C. Cationic heteroleptic cyclometalated iridiumIII complexes containing phenyltriazole and triazole-pyridine clicked ligands. Molecules 2010, 15, 2039−2059. (b) Edkins, R. M.; Wriglesworth, A.; Fucke, K.; Beeby, A. The synthesis and photophysics of tris-heteroleptic cyclometalated iridium complexes. Dalton Trans. 2011, 40, 9672−9678. (c) Baranoff, E.; Curchod, B. F. E.; Frey, J.; Scopelliti, R.; Kessler, F.; Tavernelli, I.; Rothlisberger, U.; Grätzel, M.; Nazeeruddin, Md. K. Acid-induced degradation of phosphorescent dopants for OLEDs and its application to the synthesis of tris-heteroleptic iridium(III) bis-cyclometalated complexes. Inorg. Chem. 2012, 51, 215−224. (d) Xu, X.; Yang, X.; Dang, J.; Zhou, G.; Wu, Y.; Li, H.; Wong, W.-Y. Trifunctional IrIII ppy-type asymmetric phosphorescent emitters with ambipolar features for highly efficient electroluminescent devices. Chem. Commun. 2014, 50, 2473−2476. (e) Lepeltier, M.; Dumur, F.; Graff, B.; Xiao, P.; Gigmes, D.; Lalevee, J.; Mayer, C. R. Tris-cyclometalated iridium(III) complexes with three different ligands: A new example with 2-(2,4difluorophenyl)pyridine-based complex. Helv. Chim. Acta 2014, 97, 939−956. (f) Xu, X.; Yang, X.; Wu, Y.; Zhou, G.; Wu, C.; Wong, W.Y. Tris-heteroleptic cyclometalated iridium(III) complexes with ambipolar or electron injection/transport features for highly efficient electrophosphorescent devices. Chem. - Asian J. 2015, 10, 252−262. (g) Cudre, Y.; de Carvalho, F. F.; Burgess, G. R.; Male, L.; Pope, S. J.

A.; Tavernelli, I.; Baranoff, E. Tris-heteroleptic iridium complexes based on cyclometalated ligands with different cores. Inorg. Chem. 2017, 56, 11565−11576. (11) Tamura, Y.; Hisamatsu, Y.; Kumar, S.; Itoh, T.; Sato, K.; Kuroda, R.; Aoki, S. Efficient synthesis of tris-heteroleptic iridium(III) complexes based on the Zn2+-promoted degradation of tris-cyclometalated iridium(III) complexes and their photophysical properties. Inorg. Chem. 2017, 56, 812−833. (12) Hisamatsu, Y.; Kumar, S.; Aoki, S. Design and synthesis of trisheteroleptic cyclometalated iridium(III) complexes consisting of three different nonsymmetric ligands based on ligand-selective electrophilic reactions via interligand HOMO hopping phenomena. Inorg. Chem. 2017, 56, 886−899. (13) Adamovich, V.; Bajo, S.; Boudreault, P.-L. T.; Esteruelas, M. A.; Lopez, A. M.; Martín, J.; Olivan, M.; Oñate, E.; Palacios, A. U.; SanTorcuato, A.; Tsai, J.-Y.; Xia, C. Preparation of tris-heteroleptic iridium(III) complexes containing a cyclometalated aryl-N-heterocyclic carbene ligand. Inorg. Chem. 2018, 57, 10744−10760. (14) Ma, J.; Shen, X.; Harms, K.; Meggers, E. Expanding the family of bis-cyclometalated chiral-at-metal rhodium(III) catalysts with a benzothiazole derivative. Dalton Trans. 2016, 45, 8320−8323. (15) Meggers, E. Chiral auxiliaries as emerging tools for the asymmetric synthesis of octahedral metal complexes. Chem. - Eur. J. 2010, 16, 752−758. (16) Gong, L.; Wenzel, M.; Meggers, E. Chiral-auxiliary-mediated asymmetric synthesis of ruthenium polypyridyl complexes. Acc. Chem. Res. 2013, 46, 2635−2644. (17) Helms, M.; Lin, Z.; Gong, L.; Harms, K.; Meggers, E. Method for the preparation of non-racemic bis-cyclometalated iridium(III) complexes. Eur. J. Inorg. Chem. 2013, 2013, 4164−4172. (18) Chen, L.-A.; Xu, W.; Huang, B.; Ma, J.; Wang, L.; Xi, J.; Harms, K.; Gong, L.; Meggers, E. Asymmetric catalysis with an inert chiral-atmetal iridium complex. J. Am. Chem. Soc. 2013, 135, 10598−10601. (19) See also: (a) Chepelin, O.; Ujma, J.; Wu, X.; Slawin, A. M. Z.; Pitak, M. B.; Coles, S. J.; Michel, J.; Jones, A. C.; Barran, P. E.; Lusby, P. J. Luminescent, enantiopure, phenylatopyridine iridium-based coordination capsules. J. Am. Chem. Soc. 2012, 134, 19334−19337. (b) Marchi, E.; Sinisi, R.; Bergamini, G.; Tragni, M.; Monari, M.; Bandini, M.; Ceroni, P. Easy separation of Δ and Λ isomers of highly luminescent [IrIII]-cyclometalated complexes based on chiral phenoloxazoline ancillary ligands. Chem. - Eur. J. 2012, 18, 8765−8773. (c) Davies, D. L.; Singh, K.; Singh, S.; Villa-Marcos, B. Preparation of single enantiomers of chiral at metal bis-cyclometallated iridium complexes. Chem. Commun. 2013, 49, 6546−6548. (20) Ma, J.; Zhang, X.; Huang, X.; Luo, S.; Meggers, E. Preparation of chiral-at-metal catalysts and their use in asymmetric photoredox chemistry. Nat. Protoc. 2018, 13, 605−632. (21) Huang, X.; Quinn, T. R.; Harms, K.; Webster, R. D.; Zhang, L.; Wiest, O.; Meggers, E. Direct visible-light-excited asymmetric Lewis acid catalysis of intermolecular [2 + 2] photocycloadditions. J. Am. Chem. Soc. 2017, 139, 9120−9123. (22) Huang, X.; Li, X.; Xie, X.; Riedel, R.; Meggers, E. Catalytic asymmetric synthesis of a nitrogen heterocycle through stereocontrolled direct photoreaction from electronically excited state. Nat. Commun. 2017, 8, 2245. (23) Hu, N.; Jung, H.; Zheng, Y.; Lee, J.; Zhang, L.; Ullah, Z.; Xie, X.; Harms, K.; Baik, M.-H.; Meggers, E. Catalytic asymmetric dearomatization by visible-light-activated [2 + 2] photocycloaddition. Angew. Chem., Int. Ed. 2018, 57, 6242−6246.

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DOI: 10.1021/acs.organomet.9b00105 Organometallics XXXX, XXX, XXX−XXX