DOI: 10.1002/chem.201503910
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& Reaction Mechanisms
A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R¢I from Alkylpalladium Iodide Complexes with Accessible b-Hydrogens Wei Hao+,[a] Junnian Wei+,[a] Yue Chi,[a] Patrick J. Walsh,[b] and Zhenfeng Xi*[a] Abstract: DFT calculations have been performed on the palladium-catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C¢N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non-polar solvents, thus promoting reductive elimination and preventing b-hydride elimination. The C¢N bond cleavage process was explored and the computations show that PPh3 is not
bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C¢N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover-limiting steps were found to be C¢N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction.
Introduction The discovery of transition-metal-catalyzed reactions remains at the forefront of organic chemistry. Despite the diversity of new transformations reported in recent years, several fundamental and well-established steps reoccur in many of their proposed catalytic cycles. Among these, oxidative addition (OA) and reductive elimination (RE) are ubiquitous.[1]In classic cross-coupling reactions, such as the Mizoroki–Heck, Suzuki– Miyaura, Stille, and Negishi reactions, Pd0 undergoes oxidative addition of aryl or alkyl halides.[2] It was generally accepted that aryl halide complexes, [LnPd(Ar)(X)], which are typically formed through oxidative addition, did not undergo the microscopic reverse, reductive elimination, to form Ar¢X bonds. Although hints that such processes could take place were reported by Echavarren and Stille,[3] seminal studies by Roy and Hartwig clearly demonstrated the direct reductive elimination of aryl palladium halide complexes to form Ar¢X was possible.[4] These breakthroughs inspired a reexamination of reductive elimination processes with aryl halides, including formation of Ar¢F bonds.[5, 6] Subsequently, reductive elimination of alkyl ha[a] W. Hao,+ J. Wei,+ Y. Chi, Prof. Dr. Z. Xi Beijing National Laboratory for Molecular Sciences (BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University Beijing 100871 (P. R. China) E-mail: [email protected]
[b] Prof. Dr. P. J. Walsh Roy and Diana Vagelos Laboratories, Department of Chemistry University of Pennsylvania, 231 South 34th Street, Philadelphia Pennsylvania 19104-6323 (USA) E-mail: [email protected] [+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201503910. Chem. Eur. J. 2016, 22, 3422 – 3429
Scheme 1. Stoichiometric reductive elimination reactions to form C¢X bonds.
lides was realized by the Milstein group (Scheme 1).[7] Soon after these formative works, the groups of Lautens and Tong reported C(sp3)¢X bond formation by reductive elimination under palladium catalysis (Scheme 2).[8–10] To avoid potential problems caused by competing b-hydride elimination pathways, their systems avoided syn-b-hydrogens.[11–12] Overall, the findings in these studies indicate that reductive elimination of C¢X bonds is not only reversible but also synthetically valuable. Very recently, we reported a system that forms C(sp3)¢I bonds by reductive elimination, despite the presence of syn-bhydrogens that might be expected to give olefins through bhydride elimination.[13] The coupling partners for the reaction are alkynes and ortho-iodoaniline derivatives such as 1 a (Scheme 2). The palladium-catalyzed reaction is initiated with
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Full Paper to form the C¢I bond was obtained. We therefore proposed that the role of the base is to promote the reductive elimination step.[15] In our proposed mechanism, the intermediate [LnPd(alkyl)(I)] (I) does not undergo b-hydride elimination to give alkene products. Unlike many Heck reactions, which proceed through b-hydride elimination and afford conjugated alkenes, our system would form an isolated olefin that would not benefit from such conjugation. It is also possible that the intermediate [LnPd(alkyl)(I)] undergoes b-hydride elimination to form the olefin complex, but that dissociation of the olefin has a high barrier and reinsertion occurs, eventually leading to the observed reductive elimination product. Similar mechanistic proposals have been made by Feringa and Tang in recent publications.[16] To shed light on the factors that control the relative barriers leading to alkyl halide reductive elimination versus b-hydride elimination, we have performed computational modeling of the intermediates in our proposed catalytic cycle in Scheme 3. Herein, we describe the results of our study.
Computational Details Scheme 2. Catalytic reactions with reductive eliminations to form C¢X bonds
oxidative addition of the C(sp2)¢I bond followed by alkyne insertion and C¢N bond cleavage, forming the [LnPd(alkyl)(I)] intermediate I.[14] Reductive elimination of I to generate the C(sp3)¢I bond forms the observed product (Scheme 3). It is noteworthy that this is the first example of reductive elimination of alkyl halides from alkylpalladium(II) halide complexes that possess readily accessible b-hydrogens. Interestingly, we found that the reaction requires base (LiOtBu). The base plays a key role: in the absence of LiOtBu no reductive elimination
All calculations were carried out with the GAUSSIAN 09 program package.[17] All the minima and transition states were fully calculated at the B3LYP/LANL2DZ[18a]/6-31 g* level in the gas phase. The single-point energies were calculated at the at M06[18]/SDD (for Pd, I)/6-311 + G** (for other elements) level. The effect of solvent (C6H12) was examined by performing single-point self-consistent reaction field (SCRF) calculations based on the polarizable continuum model (PCM) for gasphase optimized structures.[19] Harmonic frequency calculations were performed at the same level for every structure to confirm they are local minimum or transition states and to derive the thermochemical corrections for enthalpies and free energies. The intrinsic reaction coordinate (IRC) analysis was performed throughout the pathways to confirm that all stationary points are smoothly connected. We found very small differences in the relative energies of the reaction surface in the gas phase and in solution. Therefore, all energies presented here are based on the gas-phase values.
Results and Discussion
Scheme 3. Proposed catalytic cycle for the formation of alkyl iodoindoles from 1 a and alkynes. Chem. Eur. J. 2016, 22, 3422 – 3429
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To gain insight into the mechanism in Scheme 3, we performed DFT studies on the reaction of 1 a with 3-hexyne. The five major steps discussed in the Introduction, that is, oxidative addition, alkyne insertion, C¢N bond cleavage, reductive elimination, and b-hydride elimination, were studied. The results of our study are outlined in Figures 1, 2, and 6–8, where the free energy profile of the preferred reaction pathways are depicted. As outlined below, this data can be used to rationalize why reductive elimination of [LnPd(alkyl)(I)] intermediate I is observed over b-hydride elimination. 3423
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Figure 1. The free energy profile for the oxidative addition, alkyne insertion, and C¢N bond cleavage.
Discussion of catalytic species Experimentally, we observed that PPh3 was the best of the ligands examined in our initial studies. For bulky monodentate phosphine ligands, such as Q-Phos and P(tBu)3, only 32 % and 28 % yield, respectively, of the reductive elimination products were observed. With bidentate phosphine ligands, such as DPPE, DPPP and DPPF, only trace product could be detected.[13b] Triphenylphosphine is a moderately bulky ligand (cone angle = 1458)[21] that usually forms isolable trans-[(Ph3P)2PdXY] complexes (where X and Y are anionic ligands).[22] In contrast to these stable four-coordinate adducts, for electronic reasons it has been proposed that palladium complexes with odd coordination numbers more readily undergo reductive elimination than those with even coordination numbers.[1b] This hypothesis has been supported by the theoretical studies by Norrby, Liu, and other groups,[23] in which the transition state for oxidative addition of aryl halide by palladium(0) is favored when the palladium is bound to only one dative ligand. It is proposed that mono-ligated Pd species undergo oxidative addition more readily than those with two dative ligands, because of the significant distortion energy price paid when oxidative addition takes place with L2Pd0 intermediates.[24] Based on these publications, we employed mono-ligated [Pd(PPh3)] in the oxidative addition and reductive elimination steps. Oxidative addition step Under our reported experimental conditions,[13b] we combined [Pd(allyl)Cp] (Cp = cyclopentadienyl) with 2 equivalents of PPh3. This method is known to efficiently generate [Pd(PPh3)2].[25] We therefore also began our calculations with [Pd(PPh3)2]. Dissociation of one of the triphenylphosphine ligands and coordination of the substrate 1 a through the amino and iodo groups Chem. Eur. J. 2016, 22, 3422 – 3429
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to form I-1 requires 14.1 kcal mol¢1. Next, oxidative addition takes place via transition state TS-1. Here, the amino group dissociates and at the same time Pd moves closer to the C¢I bond, approaching the three-membered ring oxidative addition transition state TS-1. The activation barrier to cleave the C¢I bond is calculated to be only 1.5 kcal mol¢1. To form the intermediate I-2, Pd re-coordinates the nitrogen atom, leading to the tetra-coordinate complex. The small barrier for the oxidative addition of 1.5 kcal mol¢1 is similar to that calculated by Norrby and co-workers in the oxidative addition of Ph¢I to [Pd(PPh3)] from the activated complex [(Ph¢I)Pd(PPh3)].[23a] Alkyne insertion step The next step in the catalytic cycle is proposed to be alkyne insertion. Thus, intermediate I-2 binds the alkyne to generate I-3, which then proceeds to the insertion transition state TS-2. The alkyne insertion leads to intermediate I-4. Thus, from I-2 to TS2 requires 17.0 kcal mol¢1 (Figure 1). Another plausible pathway for the alkyne insertion (Figure 2) involves ligand exchange between PPh3 and 3-hexyne of I-2 to give I-2’ with an energy cost of 5.6 kcal mol¢1. Insertion of the alkyne into the Pd¢C bond is calculated to occur through transition state TS-2’ with a barrier of 19.8 kcal mol¢1. Loss of phosphine occurs to form a six-membered metallacycle I-4. This pathway would cost 25.4 kcal mol¢1. Comparing these two alkyne insertion pathways, loss of phosphine after TS-2 is less energetically costly. It was found that coordination of a second equivalent of PPh3 to I-2 would give 4-coordinate I-2-PPh3, which has much lower energy than I-2. Crystallization of the oxidative addition product in the presence of an equivalent of triphenylphosphine led to the four-coordinate trans-I-2-PPh3 in the solid state (Figure 3). Comparing the bond lengths and angles in the
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Figure 2. The free energy profile for the alkyne insertion without coordinated PPh3.
Figure 4. Calculated structure for the intermediate I-2-PPh3. Hydrogen atoms are omitted for clarity. Selected bond lengths (æ) and angles (8): Pd¢I 2.820, Pd¢C 2.043, Pd¢P(1) 2.471, Pd¢P(2) 2.499; P(1)-Pd-I(1) 90.482, P(1)-PdP(2) 173.903, P(2)-Pd-I(1) 91.897, C(1)-Pd-I(1) 172.185.
Figure 3. ORTEP drawing of I-2-PPh3 with thermal ellipsoids at the 30 % level. Hydrogen atoms are omitted for clarity. Selected bond lengths (æ) and angles (8): Pd(1)¢I(1) 2.6949(3), Pd(1)¢C(1) 2.025(2), Pd(1)¢P(1) 2.3315(6), Pd(1)¢P(2) 2.3510(6); P(1)-Pd(1)-I(1) 91.688(16), P(1)-Pd(1)-P(2) 169.36(3), P(2)Pd(1)-I(1) 93.764(15), C(1)-Pd(1)-I(1) 178.20(7).
crystal structure of I-2-PPh3 with the calculated structure (Figure 4) shows reasonable agreement. C¢N bond cleavage step The next series of steps in the catalytic cycle result in C¢N bond formation and cleavage to generate the indole ring and Chem. Eur. J. 2016, 22, 3422 – 3429
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form the alkylpalladium iodide intermediate I-8. The amino group of intermediate I-4 dissociates from the palladium and attacks the palladium-bound C(sp2) via TS-3 to form the fivemembered ring with a C(sp2)¢N bond length of 1.600 æ in I-6 (Figure 5). The Pd then moves away from the five-membered ring and approaches the C(sp3)¢N bond of the six-membered ring in TS-4 with a C(sp2)¢N bond length of 1.509 æ (Figure 5). In this process, the C(sp3)¢N bond is cleaved via a four-membered-ring transition state (TS-7) to give the Pd p complex I-7 with a coordinated C=C bond. Intermediate I-7 binds a PPh3 to generate the key alkyl halide palladium intermediate I-8. The C¢N bond cleavage step (I-4 to I-7) overcomes an activation barrier of 29.7 kcal mol¢1 (from I-4 to TS-4; Figure 1). We were curious about how the energy of the C¢N bondforming reaction pathway from I-4 would change with coordination of an equivalent of PPh3 to palladium. Coordination of PPh3 to I-5 gives intermediate I-5-PPh3 (Figure 6). The barrier to C¢N bond cleavage via TS-4-PPh3 was calculated to be 35.2 kcal mol¢1 with the bound phosphine, indicating that reaction via intermediate I-5 (Figure 1) is more favorable than that via I-5-PPh3. Experimentally, in our catalytic reaction, addition of excess PPh3 to the reaction mixture resulted in a dramatic decrease in the yield of 2 a. Thus, use of a Pd/PPh3 ratio of 1:2 resulted in 92 % yield of the product whereas a 1:10 ratio resulted in only 15 % yield.[13b] The experimentally observed inhibition by added phosphine is in line with the calculated turnover-limiting step. We next examined the role of LiOtBu. Previous work shows that LiOtBu prefers to be monomeric when interacting with the transition metal in both calculations and experiments.[26] Binding of LiOtBu to the intermediate I-8 to give I-9 was found to be exothermic by 21.3 kcal mol¢1. Starting from intermediate I-9, the reductive elimination and b-hydride elimination pathways were explored.
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Figure 5. Selected transition states and intermediates involved in Figure 1 and Figure 6. Key bond lengths are given in æ.
plex I-9 is energetically costly. The energy required for loss of LiI (I-9 to I-12) is calculated to be 52.9 kcal mol¢1, rendering this path toward b-hydride elimination too high in energy. Thus, from the calculations above, and those from prior reports, we conclude: 1) for the C¢N bond cleavage step, PPh3 dissociates from the Pd center before the C¢N bond is broken; 2) in non-polar solvents, LiOtBu coordination promotes the reductive elimination and the high barrier to LiI elimination prevents the b-hydride elimination; 3) two steps in the catalytic cycle are turnover limiting, that is, the reductive elimination of the alkylpalladium iodide and cleavage of the C¢N bond. Both of these steps are inhibited by phosphine.
Mechanistic considerations Figure 6. The free energy profile for the C¢N bond cleavage with one PPh3 coordinating to Pd.
Reductive elimination versus b-hydride elimination As shown in Figure 7, reductive elimination from the intermediate I-9 via a three-membered-ring transition state (TS-5) requires 35.9 kcal mol¢1 and leads to the complex I-10. In I-10, the iodide of R¢I and the Li atom are weakly coordinated to the palladium. Ligand exchange steps then lead to regeneration of [Pd(PPh3)2] and closing of the catalytic cycle. We also calculated the reductive elimination step without participation of LiOtBu (Figure 8). Starting from intermediate I9, release of LiOtBu to generate I-8 followed by reductive elimination to form the C(sp3)¢I bond via a three-membered ring TS-5’ was examined. The optimized transition state of this reductive elimination was very similar to the work reported by Houk and Lautens et al.[11] This process, however, was calculated to require 44.9 kcal mol¢1 (Figure 8). Comparing these two calculated pathways, we consider that the LiOtBu-mediated reductive elimination is preferred. The mechanism of the competing b-hydride elimination pathway starting from I-9 was then investigated and is shown in Figure 7. For the intermediate I-9, LiI would be formed before b-hydride elimination. In the gas phase and in nonpolar solvent systems, the release of LiI from the neutral comChem. Eur. J. 2016, 22, 3422 – 3429
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To determine if the DFT calculations outlined above are in line with solution chemistry, a series of stoichiometric reactions were conducted. Treatment of ortho-iodoaniline derivative 1 a with in situ generated [Pd(PPh3)2] in cyclohexane at room temperature[25] results in oxidative addition to give I-2-PPh3 in 90 % yield (Scheme 4). This observation indicates that oxidative addition, and the proceeding steps, occurs with low barriers relative to the subsequent steps. The crystal structure of I-2PPh3 shows trans-PPh3 ligands coordinated to the Pd (Figure 3), as is typically observed in related structures. To explore the alkyne insertion and C¢N bond cleavage steps, 3-hexyne was combined with intermediate I-2-PPh3 and heated to 100 8C in cyclohexane, resulting in only 50 % conversion to the alkylpalladium iodide product in 12 h. Heating at
Scheme 4. The formation of intermediate I-2-PPh3 through oxidative addition.
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Figure 7. The free energy profile for reductive elimination versus b-hydride elimination.
insertion and C¢N bond cleavage steps. The observation that the oxidative addition, alkyne insertion, and C¢N bond cleavage proceed in the absence of LiOtBu indicates that LiOtBu is not necessary in these steps. Furthermore, reductive elimination does not take place in the absence of LiOtBu, even at 130 8C. The DFT calculations are in agreement with these experimental results.
Conclusion
Figure 8. The free energy profile for reductive elimination without LiOtBu.
130 8C for 12 h, however, resulted in consumption of the starting I-2-PPh3 and formation of the alkylpalladium iodide intermediate I’, which was isolated in 68 % yield (Scheme 5). These experiments illustrate that high temperature is required for the Chem. Eur. J. 2016, 22, 3422 – 3429
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b-Hydride elimination is, perhaps, the most common decomposition pathway for transition-metal alkyl complexes. In fact, chemists have invested significant effort to circumvent b-hydride elimination, most recently in cross-coupling reactions to form bonds between sp3-hybridized carbon atoms.[7, 8] We recently discovered an unusual reaction of palladium alkyl iodide complexes that preferentially undergo reductive elimination over the expected b-hydride elimination pathway. Inspired by this observation, a DFT study was conducted herein on the reductive elimination pathway. The C(sp3)¢I reductive elimination was compared to the b-hydride elimination pathway to understand the energetics that govern product formation. Our study suggests that b-hydride elimination was not observed because of the high barrier to eliminate LiI from the LiOtBu adduct, [(Ph3P)Pd(alkyl)(I)(LiOtBu)], in non-polar solvents under experimental (cyclohexane) and computational
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Scheme 5. The formation of alkylpalladium iodide I’ by alkyne insertion and C¢N bond cleavage.
(gas-phase) conditions. Thus, reductive elimination of [(Ph3P)Pd(alkyl)(I)(LiOtBu)] is more favorable. As such, LiOtBu plays a key role in the overall catalytic cycle and, specifically, in the reductive elimination step. It will be interesting to determine if the results of this study are generalizable to other palladium catalyzed processes. This is a topic of current research in our laboratories.
Acknowledgements This work was supported by the 973 Program (2012CB821600) and the Natural Science Foundation of China. PJW acknowledges the US NSF (CHE-1464744). We thank Prof. Guosheng Liu (Shanghai Institute of Organic Chemistry), Prof. Zhangjie Shi (Peking University), Prof. Zhixiang Yu (Peking University), and Prof. Zhenyang Lin (The Hong Kong University of Science and Technology) for helpful discussions. Keywords: alkylpalladium iodide complexes · computational chemistry · reaction mechanisms · reductive elimination · synthetic methods [1] a) R. H. Crabtree, The Organometallic Chemistry of the Transition Metals, 4th ed., John Wiley & Sons, New York, 2005; b) J. F. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, University of Science Books, Sausalito, 2010. [2] a) M. Larhed, A. Hallberg, in Handbook of Organopalladium Chemistry for Organic Synthesis (Ed.: E.-I. Negishi), Wiley-Interscience, New York, 2002; b) S. Brse, A. de Meijere, in Metal-Catalyzed Cross-Coupling Reactions (Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004; c) M. Beller, A. Zapf, T. H. Riermeier, in Transition Metals in Organic Synthesis; Building Blocks and Fine Chemicals, Vol. 1 (Eds.: M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004; d) A. C. Frisch, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 674 – 688; Angew. Chem. 2005, 117, 680 – 695. [3] a) R. Ettorre, Inorg. Nucl. Chem. Lett. 1969, 5, 45 – 49; b) A. M. Echavarren, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 5478 – 5486. [4] a) A. H. Roy, J. F. Hartwig, J. Am. Chem. Soc. 2001, 123, 1232 – 1233; b) A. H. Roy, J. F. Hartwig, J. Am. Chem. Soc. 2003, 125, 13944 – 13945; c) A. H. Roy, J. F. Hartwig, Organometallics 2004, 23, 1533 – 1541. [5] For other reductive elimination of aryl halides from aryl palladium(II) halides, see: a) D. V. Yandulov, N. T. Tran, J. Am. Chem. Soc. 2007, 129, 1342 – 1358; b) V. V. Grushin, W. J. Marshall, Organometallics 2007, 26, 4997 – 5002; c) S. G. Newman, M. Lautens, J. Am. Chem. Soc. 2010, 132, 11416 – 11417; d) T. J. Maimone, P. J. Milner, T. Kinzel, Y. Zhang, M. K. Takase, S. L. Buchwald, J. Am. Chem. Soc. 2011, 133, 18106 – 18109; e) H. G. Lee, P. J. Milner, S. L. Buchwald, Org. Lett. 2013, 15, 5602 – 5605; f) C. M. Le, P. J. C. Menzies, D. A. Petrone, M. Lautens, Angew. Chem. Int. Ed. 2015, 54, 254 – 257; Angew. Chem. 2015, 127, 256 – 259. [6] a) D. A. Watson, M. Su, G. Teverovskiy, Y. Zhang, J. Garca-Fortanet, T. Kinzel, S. L. Buchwald, Science 2009, 325, 1661 – 1664; b) X. Shen, A. Hyde, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132, 14076 – 14078; c) J. Pan, X. Wang, Y. Zhang, S. L. Buchwald, Org. Lett. 2011, 13, 4974 – 4976. Chem. Eur. J. 2016, 22, 3422 – 3429
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[7] a) C. M. Frech, D. Milstein, J. Am. Chem. Soc. 2006, 128, 12434 – 12435; b) M. Feller, M. A. Iron, L. J. W. Shimon, Y. Diskin-Posner, G. Leitus, D. Milstein, J. Am. Chem. Soc. 2008, 130, 14374 – 14375; c) M. Feller, Y. DiskinPosner, G. Leitus, L. J. W. Shimon, D. Milstein, J. Am. Chem. Soc. 2013, 135, 11040 – 11047. [8] For reductive elimination of alkyl halides from alkylpalladium(II) halides, see: a) S. G. Newman, M. Lautens, J. Am. Chem. Soc. 2011, 133, 1778 – 1780; b) H. Liu, C. Chen, L. Wang, X. Tong, Org. Lett. 2011, 13, 5072 – 5075; c) H. Liu, C. Li, D. Qiu, X. Tong, J. Am. Chem. Soc. 2011, 133, 6187 – 6193; d) S. G. Newman, J. K. Howell, N. Nicolaus, M. Lautens, J. Am. Chem. Soc. 2011, 133, 14916 – 14919; e) D. A. Petrone, H. A. Malik, A. Clemenceau, M. Lautens, Org. Lett. 2012, 14, 4806 – 4809; f) X. Jia, D. A. Petrone, M. Lautens, Angew. Chem. Int. Ed. 2012, 51, 9870 – 9872; Angew. Chem. 2012, 124, 10008 – 10010; g) D. A. Petrone, M. Lischka, M. Lautens, Angew. Chem. Int. Ed. 2013, 52, 10635 – 10638; Angew. Chem. 2013, 125, 10829 – 10832; h) D. A. Petrone, H. Yoon, H. Weinstabl, M. Lautens, Angew. Chem. Int. Ed. 2014, 53, 7908 – 7913; Angew. Chem. 2014, 126, 8042 – 8046; i) C. Chen, L. Hou, M. Cheng, J. Su, X. Tong, Angew. Chem. Int. Ed. 2015, 54, 3092 – 3096; Angew. Chem. 2015, 127, 3135 – 3139. [9] For reductive elimination from PdIV and PdIII complexes, see: a) S. Ma, X. Lu, J. Org. Chem. 1993, 58, 1245 – 1250; b) R. van Belzen, H. Hoffmann, C. J. Elsevier, Angew. Chem. Int. Ed. Engl. 1997, 36, 1743 – 1745; Angew. Chem. 1997, 109, 1833 – 1835; c) R. van Belzen, C. J. Elsevier, A. Dedieu, N. Veldman, A. L. Spek, Organometallics 2003, 22, 722 – 736; d) G. Yin, G. Liu, Angew. Chem. Int. Ed. 2008, 47, 5442 – 5445; Angew. Chem. 2008, 120, 5522 – 5525; e) T. Furuya, T. Ritter, J. Am. Chem. Soc. 2008, 130, 10060 – 10061; f) D. C. Powers, T. Ritter, Nat. Chem. 2009, 1, 302 – 309; g) N. D. Ball, M. S. Sanford, J. Am. Chem. Soc. 2009, 131, 3796 – 3797; h) T. Wu, G. Yin, G. Liu, J. Am. Chem. Soc. 2009, 131, 16354 – 16355; i) Y. Li, X. Liu, H. Jiang, Z. Feng, Angew. Chem. Int. Ed. 2010, 49, 3338 – 3341; Angew. Chem. 2010, 122, 3410 – 3413; j) T. Furuya, D. Benitez, E. Tkatchouk, A. E. Strom, P. Tang, W. A. Goddard III, T. Ritter, J. Am. Chem. Soc. 2010, 132, 3793 – 3807; k) J. Vicente, A. Arcas, F. Juli-Hernndez, D. Bautista, Chem. Commun. 2010, 46, 7253 – 7255; l) D. C. Powers, D. Benitez, E. Tkatchouk, W. A. Goddard III, T. Ritter, J. Am. Chem. Soc. 2010, 132, 14092 – 14103; m) W. Oloo, P. Y. Zavalij, J. Zhang, E. Khaskin, A. N. Vedernikov, J. Am. Chem. Soc. 2010, 132, 14400 – 14402; n) D. C. Powers, D. Y. Xiao, M. A. L. Geibel, T. Ritter, J. Am. Chem. Soc. 2010, 132, 14530 – 14536; o) Y. Li, X. Liu, H. Jiang, B. Liu, Z. Chen, P. Zhou, Angew. Chem. Int. Ed. 2011, 50, 6341 – 6345; Angew. Chem. 2011, 123, 6465 – 6469; p) K. S. L. Chan, M. Wasa, X. Wang, J.-Q. Yu, Angew. Chem. Int. Ed. 2011, 50, 9081 – 9084; Angew. Chem. 2011, 123, 9247 – 9250; q) J. M. Racowski, J. B. Gary, M. S. Sanford, Angew. Chem. Int. Ed. 2012, 51, 3414 – 3417; Angew. Chem. 2012, 124, 3470 – 3473; r) M. H. P¦rez-Temprano, J. M. Racowski, J. W. Kampf, M. S. Sanford, J. Am. Chem. Soc. 2014, 136, 4097 – 4100; s) E. P. A. Talbot, T. de A. Fernandes, J. M. McKenna, F. D. Toste, J. Am. Chem. Soc. 2014, 136, 4101 – 4104. [10] For reviews on reductive elimination, see: a) A. Vigalok, Chem. Eur. J. 2008, 14, 5102 – 5108; b) V. V. Grushin, Acc. Chem. Res. 2010, 43, 160 – 171; c) T. Furuya, J. E. M. N. Klein, T. Ritter, Synthesis 2010, 1804 – 1821; d) K. M. Engle, T.-S. Mei, X. Wang, J.-Q. Yu, Angew. Chem. Int. Ed. 2011, 50, 1478 – 1491; Angew. Chem. 2011, 123, 1514 – 1528; e) T. Furuya, A. S. Kamlet, T. Ritter, Nature 2011, 473, 470 – 477; f) X. Jiang, H. Liu, Z. Gu, Asian J. Org. Chem. 2012, 1, 16 – 24; g) C. Chen, X. Tong, Org. Chem. Front. 2014, 1, 439 – 446. [11] Y. Lan, P. Liu, S. G. Newman, M. Lautens, K. N. Houk, Chem. Sci. 2012, 3, 1987 – 1995. [12] a) X. Lu, Top. Catal. 2005, 35, 73 – 86; b) A. C. Bissember, A. Levina, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 14232 – 14237. [13] a) W. Hao, J. Wei, W.-X. Zhang, Z. Xi, Angew. Chem. Int. Ed. 2014, 53, 14533 – 14537; Angew. Chem. 2014, 126, 14761 – 14765; b) W. Hao, H. Wang, P. J. Walsh, Z. Xi, Org. Chem. Front. 2015, 2, 1080 – 1084. [14] a) W. Geng, W.-X. Zhang, W. Hao, Z. Xi, J. Am. Chem. Soc. 2012, 134, 20230 – 20233; b) W. Hao, W. Geng, W.-X. Zhang, Z. Xi, Chem. Eur. J. 2014, 20, 2605 – 2612; c) K. Ouyang, W. Hao, W.-X. Zhang, Z. Xi, Chem. Rev. 2015, 115, 12045 – 12090. [15] a) F. Ozawa, A. Kubo, T. Hayashi, Chem. Lett. 1992, 2177 – 2180; b) C. Amatore, A. Jutand, Acc. Chem. Res. 2000, 33, 314 – 321; c) I. D. Hills, G. C. Fu, J. Am. Chem. Soc. 2004, 126, 13178 – 13179; d) K. Ouyang, Z. Xi, Acta Chim. Sinica 2013, 71, 13 – 25.
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Full Paper [16] a) C. Vila, M. Giannerini, V. Hornillos, M. FaÇans-Mastral, B. L. Feringa, Chem. Sci. 2014, 5, 1361 – 1365; b) C. Li, T. Chen, B. Li, G. Xiao, W. Tang, Angew. Chem. Int. Ed. 2015, 54, 3792 – 3796; Angew. Chem. 2015, 127, 3863 – 3867. [17] Gaussian 09, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, ©. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian, Inc. Wallingford CT, 2010. [18] a) P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299 – 310; b) Y. Zhao, D. G. Truhlar, Acc. Chem. Res. 2008, 41, 157 – 167. [19] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999 – 3093. [20] a) S. H. Vosko, L. Wilk, M. Nusair, Can. J. Phys. 1980, 58, 1200 – 1211; b) A. D. Becke, J. Chem. Phys. 1993, 98, 5648 – 5652; c) C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785 – 791. [21] C. A. Tolman, J. Am. Chem. Soc. 1970, 92, 2956 – 2965. [22] a) J. Granell, D. Sainz, J. Sales, X. Solans, M. Font-Altaba, J. Chem. Soc. Dalton Trans. 1986, 1785 – 1790; b) T. Aoki, Y. Ishii, Y. Mizobe, M. Hidai, Chem. Lett. 1991, 615 – 618; c) T. I. Wallow, F. E. Goodson, B. M. Novak, Organometallics 1996, 15, 3708 – 3716; d) V. V. Grushin, Organometallics 2000, 19, 1888 – 1900; e) M. Retbøll, A. J. Edwards, A. D. Rae, A. C. Willis, M. A. Bennett, E. Wenger, J. Am. Chem. Soc. 2002, 124, 8348 – 8360; f) D.
Chem. Eur. J. 2016, 22, 3422 – 3429
www.chemeurj.org
[23]
[24] [25]
[26]
Sol¦, L. Vallverdu, X. Solans, M. Font-Bardia, J. Bonjoch, Organometallics 2004, 23, 1438 – 1447; g) J. Vicente, J.-A. Abad, R.-M. Lûpez-Nicols, P. G. Jones, Organometallics 2004, 23, 4325 – 4327; h) V. V. Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006, 128, 12644 – 12645; i) R. S. Chauhan, C. P. Prabhu, P. P. Phadnis, G. Kedarnath, J. A. Golen, A. L. Rheingold, V. K. Jain, J. Organomet. Chem. 2013, 723, 163 – 170; j) J. Zhang, A. Bellomo, N. Trongsiriwat, T. Jia, P. J. Carroll, S. D. Dreher, M. T. Tudge, H. Yin, J. R. Tobinson, E. J. Schelter, P. J. Walsh, J. Am. Chem. Soc. 2014, 136, 6276 – 6287. a) M. Ahlquist, P. Fristrup, D. Tanner, P.-O. Norrby, Organometallics 2006, 25, 2066 – 2073; b) Z. Li, Y. Fu, Q.-X. Guo, L. Liu, Organometallics 2008, 27, 4043 – 4049; c) A. Ariafard, B. F. Yates, J. Am. Chem. Soc. 2009, 131, 13981 – 13991; d) Z. Li, Y. Fu, S.-L. Zhang, Q.-X. Guo, L. Liu, Chem. Asian J. 2010, 5, 1475 – 1486. F. Schoenebeck, K. N. Houk, J. Am. Chem. Soc. 2010, 132, 2496 – 2497. a) E. A. Mitchell, M. C. Baird, Organometallics 2007, 26, 5230 – 5238; b) D. M. Norton, E. A. Mitchell, N. R. Botros, P. G. Jessop, M. C. Baird, J. Org. Chem. 2009, 74, 6674 – 6680; c) L. Xue, Z. Lin, Chem. Soc. Rev. 2010, 39, 1692 – 1705; d) B. E. Jaksic, J. Jiang, A. W. Fraser, M. C. Baird, Organometallics 2013, 32, 4192 – 4198. a) F. Soki, J.-M. Neudçrfl, B. Goldfuss, J. Organomet. Chem. 2008, 693, 2139 – 2146; b) L. R. Collins, J. P. Lowe, M. F. Mahon, R. C. Poulten, M. K. Whittlesey, Inorg. Chem. 2014, 53, 2699 – 2707; c) J. A. Bellow, M. Yousif, D. Fang, E. G. Kratz, G. A. Cisneros, S. Groysman, Inorg. Chem. 2015, 54, 5624 – 5633. For the aggregate state of salts, see: d) A. B. Charette, C. Molinaro, C. Brochu, J. Am. Chem. Soc. 2001, 123, 12160 – 12167; e) T. Wang, Y. Liang, Z.-X. Yu, J. Am. Chem. Soc. 2011, 133, 9343 – 9353.
Received: September 29, 2015 Published online on January 25, 2016
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& Reaction Mechanisms
A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R¢I from Alkylpalladium Iodide Complexes with Accessible b-Hydrogens Wei Hao+,[a] Junnian Wei+,[a] Yue Chi,[a] Patrick J. Walsh,[b] and Zhenfeng Xi*[a] Abstract: DFT calculations have been performed on the palladium-catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C¢N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non-polar solvents, thus promoting reductive elimination and preventing b-hydride elimination. The C¢N bond cleavage process was explored and the computations show that PPh3 is not
bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C¢N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover-limiting steps were found to be C¢N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction.
Introduction The discovery of transition-metal-catalyzed reactions remains at the forefront of organic chemistry. Despite the diversity of new transformations reported in recent years, several fundamental and well-established steps reoccur in many of their proposed catalytic cycles. Among these, oxidative addition (OA) and reductive elimination (RE) are ubiquitous.[1]In classic cross-coupling reactions, such as the Mizoroki–Heck, Suzuki– Miyaura, Stille, and Negishi reactions, Pd0 undergoes oxidative addition of aryl or alkyl halides.[2] It was generally accepted that aryl halide complexes, [LnPd(Ar)(X)], which are typically formed through oxidative addition, did not undergo the microscopic reverse, reductive elimination, to form Ar¢X bonds. Although hints that such processes could take place were reported by Echavarren and Stille,[3] seminal studies by Roy and Hartwig clearly demonstrated the direct reductive elimination of aryl palladium halide complexes to form Ar¢X was possible.[4] These breakthroughs inspired a reexamination of reductive elimination processes with aryl halides, including formation of Ar¢F bonds.[5, 6] Subsequently, reductive elimination of alkyl ha[a] W. Hao,+ J. Wei,+ Y. Chi, Prof. Dr. Z. Xi Beijing National Laboratory for Molecular Sciences (BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University Beijing 100871 (P. R. China) E-mail: [email protected]
[b] Prof. Dr. P. J. Walsh Roy and Diana Vagelos Laboratories, Department of Chemistry University of Pennsylvania, 231 South 34th Street, Philadelphia Pennsylvania 19104-6323 (USA) E-mail: [email protected] [+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201503910. Chem. Eur. J. 2016, 22, 3422 – 3429
Scheme 1. Stoichiometric reductive elimination reactions to form C¢X bonds.
lides was realized by the Milstein group (Scheme 1).[7] Soon after these formative works, the groups of Lautens and Tong reported C(sp3)¢X bond formation by reductive elimination under palladium catalysis (Scheme 2).[8–10] To avoid potential problems caused by competing b-hydride elimination pathways, their systems avoided syn-b-hydrogens.[11–12] Overall, the findings in these studies indicate that reductive elimination of C¢X bonds is not only reversible but also synthetically valuable. Very recently, we reported a system that forms C(sp3)¢I bonds by reductive elimination, despite the presence of syn-bhydrogens that might be expected to give olefins through bhydride elimination.[13] The coupling partners for the reaction are alkynes and ortho-iodoaniline derivatives such as 1 a (Scheme 2). The palladium-catalyzed reaction is initiated with
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Full Paper to form the C¢I bond was obtained. We therefore proposed that the role of the base is to promote the reductive elimination step.[15] In our proposed mechanism, the intermediate [LnPd(alkyl)(I)] (I) does not undergo b-hydride elimination to give alkene products. Unlike many Heck reactions, which proceed through b-hydride elimination and afford conjugated alkenes, our system would form an isolated olefin that would not benefit from such conjugation. It is also possible that the intermediate [LnPd(alkyl)(I)] undergoes b-hydride elimination to form the olefin complex, but that dissociation of the olefin has a high barrier and reinsertion occurs, eventually leading to the observed reductive elimination product. Similar mechanistic proposals have been made by Feringa and Tang in recent publications.[16] To shed light on the factors that control the relative barriers leading to alkyl halide reductive elimination versus b-hydride elimination, we have performed computational modeling of the intermediates in our proposed catalytic cycle in Scheme 3. Herein, we describe the results of our study.
Computational Details Scheme 2. Catalytic reactions with reductive eliminations to form C¢X bonds
oxidative addition of the C(sp2)¢I bond followed by alkyne insertion and C¢N bond cleavage, forming the [LnPd(alkyl)(I)] intermediate I.[14] Reductive elimination of I to generate the C(sp3)¢I bond forms the observed product (Scheme 3). It is noteworthy that this is the first example of reductive elimination of alkyl halides from alkylpalladium(II) halide complexes that possess readily accessible b-hydrogens. Interestingly, we found that the reaction requires base (LiOtBu). The base plays a key role: in the absence of LiOtBu no reductive elimination
All calculations were carried out with the GAUSSIAN 09 program package.[17] All the minima and transition states were fully calculated at the B3LYP/LANL2DZ[18a]/6-31 g* level in the gas phase. The single-point energies were calculated at the at M06[18]/SDD (for Pd, I)/6-311 + G** (for other elements) level. The effect of solvent (C6H12) was examined by performing single-point self-consistent reaction field (SCRF) calculations based on the polarizable continuum model (PCM) for gasphase optimized structures.[19] Harmonic frequency calculations were performed at the same level for every structure to confirm they are local minimum or transition states and to derive the thermochemical corrections for enthalpies and free energies. The intrinsic reaction coordinate (IRC) analysis was performed throughout the pathways to confirm that all stationary points are smoothly connected. We found very small differences in the relative energies of the reaction surface in the gas phase and in solution. Therefore, all energies presented here are based on the gas-phase values.
Results and Discussion
Scheme 3. Proposed catalytic cycle for the formation of alkyl iodoindoles from 1 a and alkynes. Chem. Eur. J. 2016, 22, 3422 – 3429
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To gain insight into the mechanism in Scheme 3, we performed DFT studies on the reaction of 1 a with 3-hexyne. The five major steps discussed in the Introduction, that is, oxidative addition, alkyne insertion, C¢N bond cleavage, reductive elimination, and b-hydride elimination, were studied. The results of our study are outlined in Figures 1, 2, and 6–8, where the free energy profile of the preferred reaction pathways are depicted. As outlined below, this data can be used to rationalize why reductive elimination of [LnPd(alkyl)(I)] intermediate I is observed over b-hydride elimination. 3423
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Figure 1. The free energy profile for the oxidative addition, alkyne insertion, and C¢N bond cleavage.
Discussion of catalytic species Experimentally, we observed that PPh3 was the best of the ligands examined in our initial studies. For bulky monodentate phosphine ligands, such as Q-Phos and P(tBu)3, only 32 % and 28 % yield, respectively, of the reductive elimination products were observed. With bidentate phosphine ligands, such as DPPE, DPPP and DPPF, only trace product could be detected.[13b] Triphenylphosphine is a moderately bulky ligand (cone angle = 1458)[21] that usually forms isolable trans-[(Ph3P)2PdXY] complexes (where X and Y are anionic ligands).[22] In contrast to these stable four-coordinate adducts, for electronic reasons it has been proposed that palladium complexes with odd coordination numbers more readily undergo reductive elimination than those with even coordination numbers.[1b] This hypothesis has been supported by the theoretical studies by Norrby, Liu, and other groups,[23] in which the transition state for oxidative addition of aryl halide by palladium(0) is favored when the palladium is bound to only one dative ligand. It is proposed that mono-ligated Pd species undergo oxidative addition more readily than those with two dative ligands, because of the significant distortion energy price paid when oxidative addition takes place with L2Pd0 intermediates.[24] Based on these publications, we employed mono-ligated [Pd(PPh3)] in the oxidative addition and reductive elimination steps. Oxidative addition step Under our reported experimental conditions,[13b] we combined [Pd(allyl)Cp] (Cp = cyclopentadienyl) with 2 equivalents of PPh3. This method is known to efficiently generate [Pd(PPh3)2].[25] We therefore also began our calculations with [Pd(PPh3)2]. Dissociation of one of the triphenylphosphine ligands and coordination of the substrate 1 a through the amino and iodo groups Chem. Eur. J. 2016, 22, 3422 – 3429
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to form I-1 requires 14.1 kcal mol¢1. Next, oxidative addition takes place via transition state TS-1. Here, the amino group dissociates and at the same time Pd moves closer to the C¢I bond, approaching the three-membered ring oxidative addition transition state TS-1. The activation barrier to cleave the C¢I bond is calculated to be only 1.5 kcal mol¢1. To form the intermediate I-2, Pd re-coordinates the nitrogen atom, leading to the tetra-coordinate complex. The small barrier for the oxidative addition of 1.5 kcal mol¢1 is similar to that calculated by Norrby and co-workers in the oxidative addition of Ph¢I to [Pd(PPh3)] from the activated complex [(Ph¢I)Pd(PPh3)].[23a] Alkyne insertion step The next step in the catalytic cycle is proposed to be alkyne insertion. Thus, intermediate I-2 binds the alkyne to generate I-3, which then proceeds to the insertion transition state TS-2. The alkyne insertion leads to intermediate I-4. Thus, from I-2 to TS2 requires 17.0 kcal mol¢1 (Figure 1). Another plausible pathway for the alkyne insertion (Figure 2) involves ligand exchange between PPh3 and 3-hexyne of I-2 to give I-2’ with an energy cost of 5.6 kcal mol¢1. Insertion of the alkyne into the Pd¢C bond is calculated to occur through transition state TS-2’ with a barrier of 19.8 kcal mol¢1. Loss of phosphine occurs to form a six-membered metallacycle I-4. This pathway would cost 25.4 kcal mol¢1. Comparing these two alkyne insertion pathways, loss of phosphine after TS-2 is less energetically costly. It was found that coordination of a second equivalent of PPh3 to I-2 would give 4-coordinate I-2-PPh3, which has much lower energy than I-2. Crystallization of the oxidative addition product in the presence of an equivalent of triphenylphosphine led to the four-coordinate trans-I-2-PPh3 in the solid state (Figure 3). Comparing the bond lengths and angles in the
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Figure 2. The free energy profile for the alkyne insertion without coordinated PPh3.
Figure 4. Calculated structure for the intermediate I-2-PPh3. Hydrogen atoms are omitted for clarity. Selected bond lengths (æ) and angles (8): Pd¢I 2.820, Pd¢C 2.043, Pd¢P(1) 2.471, Pd¢P(2) 2.499; P(1)-Pd-I(1) 90.482, P(1)-PdP(2) 173.903, P(2)-Pd-I(1) 91.897, C(1)-Pd-I(1) 172.185.
Figure 3. ORTEP drawing of I-2-PPh3 with thermal ellipsoids at the 30 % level. Hydrogen atoms are omitted for clarity. Selected bond lengths (æ) and angles (8): Pd(1)¢I(1) 2.6949(3), Pd(1)¢C(1) 2.025(2), Pd(1)¢P(1) 2.3315(6), Pd(1)¢P(2) 2.3510(6); P(1)-Pd(1)-I(1) 91.688(16), P(1)-Pd(1)-P(2) 169.36(3), P(2)Pd(1)-I(1) 93.764(15), C(1)-Pd(1)-I(1) 178.20(7).
crystal structure of I-2-PPh3 with the calculated structure (Figure 4) shows reasonable agreement. C¢N bond cleavage step The next series of steps in the catalytic cycle result in C¢N bond formation and cleavage to generate the indole ring and Chem. Eur. J. 2016, 22, 3422 – 3429
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form the alkylpalladium iodide intermediate I-8. The amino group of intermediate I-4 dissociates from the palladium and attacks the palladium-bound C(sp2) via TS-3 to form the fivemembered ring with a C(sp2)¢N bond length of 1.600 æ in I-6 (Figure 5). The Pd then moves away from the five-membered ring and approaches the C(sp3)¢N bond of the six-membered ring in TS-4 with a C(sp2)¢N bond length of 1.509 æ (Figure 5). In this process, the C(sp3)¢N bond is cleaved via a four-membered-ring transition state (TS-7) to give the Pd p complex I-7 with a coordinated C=C bond. Intermediate I-7 binds a PPh3 to generate the key alkyl halide palladium intermediate I-8. The C¢N bond cleavage step (I-4 to I-7) overcomes an activation barrier of 29.7 kcal mol¢1 (from I-4 to TS-4; Figure 1). We were curious about how the energy of the C¢N bondforming reaction pathway from I-4 would change with coordination of an equivalent of PPh3 to palladium. Coordination of PPh3 to I-5 gives intermediate I-5-PPh3 (Figure 6). The barrier to C¢N bond cleavage via TS-4-PPh3 was calculated to be 35.2 kcal mol¢1 with the bound phosphine, indicating that reaction via intermediate I-5 (Figure 1) is more favorable than that via I-5-PPh3. Experimentally, in our catalytic reaction, addition of excess PPh3 to the reaction mixture resulted in a dramatic decrease in the yield of 2 a. Thus, use of a Pd/PPh3 ratio of 1:2 resulted in 92 % yield of the product whereas a 1:10 ratio resulted in only 15 % yield.[13b] The experimentally observed inhibition by added phosphine is in line with the calculated turnover-limiting step. We next examined the role of LiOtBu. Previous work shows that LiOtBu prefers to be monomeric when interacting with the transition metal in both calculations and experiments.[26] Binding of LiOtBu to the intermediate I-8 to give I-9 was found to be exothermic by 21.3 kcal mol¢1. Starting from intermediate I-9, the reductive elimination and b-hydride elimination pathways were explored.
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Figure 5. Selected transition states and intermediates involved in Figure 1 and Figure 6. Key bond lengths are given in æ.
plex I-9 is energetically costly. The energy required for loss of LiI (I-9 to I-12) is calculated to be 52.9 kcal mol¢1, rendering this path toward b-hydride elimination too high in energy. Thus, from the calculations above, and those from prior reports, we conclude: 1) for the C¢N bond cleavage step, PPh3 dissociates from the Pd center before the C¢N bond is broken; 2) in non-polar solvents, LiOtBu coordination promotes the reductive elimination and the high barrier to LiI elimination prevents the b-hydride elimination; 3) two steps in the catalytic cycle are turnover limiting, that is, the reductive elimination of the alkylpalladium iodide and cleavage of the C¢N bond. Both of these steps are inhibited by phosphine.
Mechanistic considerations Figure 6. The free energy profile for the C¢N bond cleavage with one PPh3 coordinating to Pd.
Reductive elimination versus b-hydride elimination As shown in Figure 7, reductive elimination from the intermediate I-9 via a three-membered-ring transition state (TS-5) requires 35.9 kcal mol¢1 and leads to the complex I-10. In I-10, the iodide of R¢I and the Li atom are weakly coordinated to the palladium. Ligand exchange steps then lead to regeneration of [Pd(PPh3)2] and closing of the catalytic cycle. We also calculated the reductive elimination step without participation of LiOtBu (Figure 8). Starting from intermediate I9, release of LiOtBu to generate I-8 followed by reductive elimination to form the C(sp3)¢I bond via a three-membered ring TS-5’ was examined. The optimized transition state of this reductive elimination was very similar to the work reported by Houk and Lautens et al.[11] This process, however, was calculated to require 44.9 kcal mol¢1 (Figure 8). Comparing these two calculated pathways, we consider that the LiOtBu-mediated reductive elimination is preferred. The mechanism of the competing b-hydride elimination pathway starting from I-9 was then investigated and is shown in Figure 7. For the intermediate I-9, LiI would be formed before b-hydride elimination. In the gas phase and in nonpolar solvent systems, the release of LiI from the neutral comChem. Eur. J. 2016, 22, 3422 – 3429
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To determine if the DFT calculations outlined above are in line with solution chemistry, a series of stoichiometric reactions were conducted. Treatment of ortho-iodoaniline derivative 1 a with in situ generated [Pd(PPh3)2] in cyclohexane at room temperature[25] results in oxidative addition to give I-2-PPh3 in 90 % yield (Scheme 4). This observation indicates that oxidative addition, and the proceeding steps, occurs with low barriers relative to the subsequent steps. The crystal structure of I-2PPh3 shows trans-PPh3 ligands coordinated to the Pd (Figure 3), as is typically observed in related structures. To explore the alkyne insertion and C¢N bond cleavage steps, 3-hexyne was combined with intermediate I-2-PPh3 and heated to 100 8C in cyclohexane, resulting in only 50 % conversion to the alkylpalladium iodide product in 12 h. Heating at
Scheme 4. The formation of intermediate I-2-PPh3 through oxidative addition.
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Figure 7. The free energy profile for reductive elimination versus b-hydride elimination.
insertion and C¢N bond cleavage steps. The observation that the oxidative addition, alkyne insertion, and C¢N bond cleavage proceed in the absence of LiOtBu indicates that LiOtBu is not necessary in these steps. Furthermore, reductive elimination does not take place in the absence of LiOtBu, even at 130 8C. The DFT calculations are in agreement with these experimental results.
Conclusion
Figure 8. The free energy profile for reductive elimination without LiOtBu.
130 8C for 12 h, however, resulted in consumption of the starting I-2-PPh3 and formation of the alkylpalladium iodide intermediate I’, which was isolated in 68 % yield (Scheme 5). These experiments illustrate that high temperature is required for the Chem. Eur. J. 2016, 22, 3422 – 3429
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b-Hydride elimination is, perhaps, the most common decomposition pathway for transition-metal alkyl complexes. In fact, chemists have invested significant effort to circumvent b-hydride elimination, most recently in cross-coupling reactions to form bonds between sp3-hybridized carbon atoms.[7, 8] We recently discovered an unusual reaction of palladium alkyl iodide complexes that preferentially undergo reductive elimination over the expected b-hydride elimination pathway. Inspired by this observation, a DFT study was conducted herein on the reductive elimination pathway. The C(sp3)¢I reductive elimination was compared to the b-hydride elimination pathway to understand the energetics that govern product formation. Our study suggests that b-hydride elimination was not observed because of the high barrier to eliminate LiI from the LiOtBu adduct, [(Ph3P)Pd(alkyl)(I)(LiOtBu)], in non-polar solvents under experimental (cyclohexane) and computational
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Scheme 5. The formation of alkylpalladium iodide I’ by alkyne insertion and C¢N bond cleavage.
(gas-phase) conditions. Thus, reductive elimination of [(Ph3P)Pd(alkyl)(I)(LiOtBu)] is more favorable. As such, LiOtBu plays a key role in the overall catalytic cycle and, specifically, in the reductive elimination step. It will be interesting to determine if the results of this study are generalizable to other palladium catalyzed processes. This is a topic of current research in our laboratories.
Acknowledgements This work was supported by the 973 Program (2012CB821600) and the Natural Science Foundation of China. PJW acknowledges the US NSF (CHE-1464744). We thank Prof. Guosheng Liu (Shanghai Institute of Organic Chemistry), Prof. Zhangjie Shi (Peking University), Prof. Zhixiang Yu (Peking University), and Prof. Zhenyang Lin (The Hong Kong University of Science and Technology) for helpful discussions. Keywords: alkylpalladium iodide complexes · computational chemistry · reaction mechanisms · reductive elimination · synthetic methods [1] a) R. H. Crabtree, The Organometallic Chemistry of the Transition Metals, 4th ed., John Wiley & Sons, New York, 2005; b) J. F. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, University of Science Books, Sausalito, 2010. [2] a) M. Larhed, A. Hallberg, in Handbook of Organopalladium Chemistry for Organic Synthesis (Ed.: E.-I. Negishi), Wiley-Interscience, New York, 2002; b) S. Brse, A. de Meijere, in Metal-Catalyzed Cross-Coupling Reactions (Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004; c) M. Beller, A. Zapf, T. H. Riermeier, in Transition Metals in Organic Synthesis; Building Blocks and Fine Chemicals, Vol. 1 (Eds.: M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004; d) A. C. Frisch, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 674 – 688; Angew. Chem. 2005, 117, 680 – 695. [3] a) R. Ettorre, Inorg. Nucl. Chem. Lett. 1969, 5, 45 – 49; b) A. M. Echavarren, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 5478 – 5486. [4] a) A. H. Roy, J. F. Hartwig, J. Am. Chem. Soc. 2001, 123, 1232 – 1233; b) A. H. Roy, J. F. Hartwig, J. Am. Chem. Soc. 2003, 125, 13944 – 13945; c) A. H. Roy, J. F. Hartwig, Organometallics 2004, 23, 1533 – 1541. [5] For other reductive elimination of aryl halides from aryl palladium(II) halides, see: a) D. V. Yandulov, N. T. Tran, J. Am. Chem. Soc. 2007, 129, 1342 – 1358; b) V. V. Grushin, W. J. Marshall, Organometallics 2007, 26, 4997 – 5002; c) S. G. Newman, M. Lautens, J. Am. Chem. Soc. 2010, 132, 11416 – 11417; d) T. J. Maimone, P. J. Milner, T. Kinzel, Y. Zhang, M. K. Takase, S. L. Buchwald, J. Am. Chem. Soc. 2011, 133, 18106 – 18109; e) H. G. Lee, P. J. Milner, S. L. Buchwald, Org. Lett. 2013, 15, 5602 – 5605; f) C. M. Le, P. J. C. Menzies, D. A. Petrone, M. Lautens, Angew. Chem. Int. Ed. 2015, 54, 254 – 257; Angew. Chem. 2015, 127, 256 – 259. [6] a) D. A. Watson, M. Su, G. Teverovskiy, Y. Zhang, J. Garca-Fortanet, T. Kinzel, S. L. Buchwald, Science 2009, 325, 1661 – 1664; b) X. Shen, A. Hyde, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132, 14076 – 14078; c) J. Pan, X. Wang, Y. Zhang, S. L. Buchwald, Org. Lett. 2011, 13, 4974 – 4976. Chem. Eur. J. 2016, 22, 3422 – 3429
www.chemeurj.org
[7] a) C. M. Frech, D. Milstein, J. Am. Chem. Soc. 2006, 128, 12434 – 12435; b) M. Feller, M. A. Iron, L. J. W. Shimon, Y. Diskin-Posner, G. Leitus, D. Milstein, J. Am. Chem. Soc. 2008, 130, 14374 – 14375; c) M. Feller, Y. DiskinPosner, G. Leitus, L. J. W. Shimon, D. Milstein, J. Am. Chem. Soc. 2013, 135, 11040 – 11047. [8] For reductive elimination of alkyl halides from alkylpalladium(II) halides, see: a) S. G. Newman, M. Lautens, J. Am. Chem. Soc. 2011, 133, 1778 – 1780; b) H. Liu, C. Chen, L. Wang, X. Tong, Org. Lett. 2011, 13, 5072 – 5075; c) H. Liu, C. Li, D. Qiu, X. Tong, J. Am. Chem. Soc. 2011, 133, 6187 – 6193; d) S. G. Newman, J. K. Howell, N. Nicolaus, M. Lautens, J. Am. Chem. Soc. 2011, 133, 14916 – 14919; e) D. A. Petrone, H. A. Malik, A. Clemenceau, M. Lautens, Org. Lett. 2012, 14, 4806 – 4809; f) X. Jia, D. A. Petrone, M. Lautens, Angew. Chem. Int. Ed. 2012, 51, 9870 – 9872; Angew. Chem. 2012, 124, 10008 – 10010; g) D. A. Petrone, M. Lischka, M. Lautens, Angew. Chem. Int. Ed. 2013, 52, 10635 – 10638; Angew. Chem. 2013, 125, 10829 – 10832; h) D. A. Petrone, H. Yoon, H. Weinstabl, M. Lautens, Angew. Chem. Int. Ed. 2014, 53, 7908 – 7913; Angew. Chem. 2014, 126, 8042 – 8046; i) C. Chen, L. Hou, M. Cheng, J. Su, X. Tong, Angew. Chem. Int. Ed. 2015, 54, 3092 – 3096; Angew. Chem. 2015, 127, 3135 – 3139. [9] For reductive elimination from PdIV and PdIII complexes, see: a) S. Ma, X. Lu, J. Org. Chem. 1993, 58, 1245 – 1250; b) R. van Belzen, H. Hoffmann, C. J. Elsevier, Angew. Chem. Int. Ed. Engl. 1997, 36, 1743 – 1745; Angew. Chem. 1997, 109, 1833 – 1835; c) R. van Belzen, C. J. Elsevier, A. Dedieu, N. Veldman, A. L. Spek, Organometallics 2003, 22, 722 – 736; d) G. Yin, G. Liu, Angew. Chem. Int. Ed. 2008, 47, 5442 – 5445; Angew. Chem. 2008, 120, 5522 – 5525; e) T. Furuya, T. Ritter, J. Am. Chem. Soc. 2008, 130, 10060 – 10061; f) D. C. Powers, T. Ritter, Nat. Chem. 2009, 1, 302 – 309; g) N. D. Ball, M. S. Sanford, J. Am. Chem. Soc. 2009, 131, 3796 – 3797; h) T. Wu, G. Yin, G. Liu, J. Am. Chem. Soc. 2009, 131, 16354 – 16355; i) Y. Li, X. Liu, H. Jiang, Z. Feng, Angew. Chem. Int. Ed. 2010, 49, 3338 – 3341; Angew. Chem. 2010, 122, 3410 – 3413; j) T. Furuya, D. Benitez, E. Tkatchouk, A. E. Strom, P. Tang, W. A. Goddard III, T. Ritter, J. Am. Chem. Soc. 2010, 132, 3793 – 3807; k) J. Vicente, A. Arcas, F. Juli-Hernndez, D. Bautista, Chem. Commun. 2010, 46, 7253 – 7255; l) D. C. Powers, D. Benitez, E. Tkatchouk, W. A. Goddard III, T. Ritter, J. Am. Chem. Soc. 2010, 132, 14092 – 14103; m) W. Oloo, P. Y. Zavalij, J. Zhang, E. Khaskin, A. N. Vedernikov, J. Am. Chem. Soc. 2010, 132, 14400 – 14402; n) D. C. Powers, D. Y. Xiao, M. A. L. Geibel, T. Ritter, J. Am. Chem. Soc. 2010, 132, 14530 – 14536; o) Y. Li, X. Liu, H. Jiang, B. Liu, Z. Chen, P. Zhou, Angew. Chem. Int. Ed. 2011, 50, 6341 – 6345; Angew. Chem. 2011, 123, 6465 – 6469; p) K. S. L. Chan, M. Wasa, X. Wang, J.-Q. Yu, Angew. Chem. Int. Ed. 2011, 50, 9081 – 9084; Angew. Chem. 2011, 123, 9247 – 9250; q) J. M. Racowski, J. B. Gary, M. S. Sanford, Angew. Chem. Int. Ed. 2012, 51, 3414 – 3417; Angew. Chem. 2012, 124, 3470 – 3473; r) M. H. P¦rez-Temprano, J. M. Racowski, J. W. Kampf, M. S. Sanford, J. Am. Chem. Soc. 2014, 136, 4097 – 4100; s) E. P. A. Talbot, T. de A. Fernandes, J. M. McKenna, F. D. Toste, J. Am. Chem. Soc. 2014, 136, 4101 – 4104. [10] For reviews on reductive elimination, see: a) A. Vigalok, Chem. Eur. J. 2008, 14, 5102 – 5108; b) V. V. Grushin, Acc. Chem. Res. 2010, 43, 160 – 171; c) T. Furuya, J. E. M. N. Klein, T. Ritter, Synthesis 2010, 1804 – 1821; d) K. M. Engle, T.-S. Mei, X. Wang, J.-Q. Yu, Angew. Chem. Int. Ed. 2011, 50, 1478 – 1491; Angew. Chem. 2011, 123, 1514 – 1528; e) T. Furuya, A. S. Kamlet, T. Ritter, Nature 2011, 473, 470 – 477; f) X. Jiang, H. Liu, Z. Gu, Asian J. Org. Chem. 2012, 1, 16 – 24; g) C. Chen, X. Tong, Org. Chem. Front. 2014, 1, 439 – 446. [11] Y. Lan, P. Liu, S. G. Newman, M. Lautens, K. N. Houk, Chem. Sci. 2012, 3, 1987 – 1995. [12] a) X. Lu, Top. Catal. 2005, 35, 73 – 86; b) A. C. Bissember, A. Levina, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 14232 – 14237. [13] a) W. Hao, J. Wei, W.-X. Zhang, Z. Xi, Angew. Chem. Int. Ed. 2014, 53, 14533 – 14537; Angew. Chem. 2014, 126, 14761 – 14765; b) W. Hao, H. Wang, P. J. Walsh, Z. Xi, Org. Chem. Front. 2015, 2, 1080 – 1084. [14] a) W. Geng, W.-X. Zhang, W. Hao, Z. Xi, J. Am. Chem. Soc. 2012, 134, 20230 – 20233; b) W. Hao, W. Geng, W.-X. Zhang, Z. Xi, Chem. Eur. J. 2014, 20, 2605 – 2612; c) K. Ouyang, W. Hao, W.-X. Zhang, Z. Xi, Chem. Rev. 2015, 115, 12045 – 12090. [15] a) F. Ozawa, A. Kubo, T. Hayashi, Chem. Lett. 1992, 2177 – 2180; b) C. Amatore, A. Jutand, Acc. Chem. Res. 2000, 33, 314 – 321; c) I. D. Hills, G. C. Fu, J. Am. Chem. Soc. 2004, 126, 13178 – 13179; d) K. Ouyang, Z. Xi, Acta Chim. Sinica 2013, 71, 13 – 25.
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Full Paper [16] a) C. Vila, M. Giannerini, V. Hornillos, M. FaÇans-Mastral, B. L. Feringa, Chem. Sci. 2014, 5, 1361 – 1365; b) C. Li, T. Chen, B. Li, G. Xiao, W. Tang, Angew. Chem. Int. Ed. 2015, 54, 3792 – 3796; Angew. Chem. 2015, 127, 3863 – 3867. [17] Gaussian 09, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, ©. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian, Inc. Wallingford CT, 2010. [18] a) P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299 – 310; b) Y. Zhao, D. G. Truhlar, Acc. Chem. Res. 2008, 41, 157 – 167. [19] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999 – 3093. [20] a) S. H. Vosko, L. Wilk, M. Nusair, Can. J. Phys. 1980, 58, 1200 – 1211; b) A. D. Becke, J. Chem. Phys. 1993, 98, 5648 – 5652; c) C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785 – 791. [21] C. A. Tolman, J. Am. Chem. Soc. 1970, 92, 2956 – 2965. [22] a) J. Granell, D. Sainz, J. Sales, X. Solans, M. Font-Altaba, J. Chem. Soc. Dalton Trans. 1986, 1785 – 1790; b) T. Aoki, Y. Ishii, Y. Mizobe, M. Hidai, Chem. Lett. 1991, 615 – 618; c) T. I. Wallow, F. E. Goodson, B. M. Novak, Organometallics 1996, 15, 3708 – 3716; d) V. V. Grushin, Organometallics 2000, 19, 1888 – 1900; e) M. Retbøll, A. J. Edwards, A. D. Rae, A. C. Willis, M. A. Bennett, E. Wenger, J. Am. Chem. Soc. 2002, 124, 8348 – 8360; f) D.
Chem. Eur. J. 2016, 22, 3422 – 3429
www.chemeurj.org
[23]
[24] [25]
[26]
Sol¦, L. Vallverdu, X. Solans, M. Font-Bardia, J. Bonjoch, Organometallics 2004, 23, 1438 – 1447; g) J. Vicente, J.-A. Abad, R.-M. Lûpez-Nicols, P. G. Jones, Organometallics 2004, 23, 4325 – 4327; h) V. V. Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006, 128, 12644 – 12645; i) R. S. Chauhan, C. P. Prabhu, P. P. Phadnis, G. Kedarnath, J. A. Golen, A. L. Rheingold, V. K. Jain, J. Organomet. Chem. 2013, 723, 163 – 170; j) J. Zhang, A. Bellomo, N. Trongsiriwat, T. Jia, P. J. Carroll, S. D. Dreher, M. T. Tudge, H. Yin, J. R. Tobinson, E. J. Schelter, P. J. Walsh, J. Am. Chem. Soc. 2014, 136, 6276 – 6287. a) M. Ahlquist, P. Fristrup, D. Tanner, P.-O. Norrby, Organometallics 2006, 25, 2066 – 2073; b) Z. Li, Y. Fu, Q.-X. Guo, L. Liu, Organometallics 2008, 27, 4043 – 4049; c) A. Ariafard, B. F. Yates, J. Am. Chem. Soc. 2009, 131, 13981 – 13991; d) Z. Li, Y. Fu, S.-L. Zhang, Q.-X. Guo, L. Liu, Chem. Asian J. 2010, 5, 1475 – 1486. F. Schoenebeck, K. N. Houk, J. Am. Chem. Soc. 2010, 132, 2496 – 2497. a) E. A. Mitchell, M. C. Baird, Organometallics 2007, 26, 5230 – 5238; b) D. M. Norton, E. A. Mitchell, N. R. Botros, P. G. Jessop, M. C. Baird, J. Org. Chem. 2009, 74, 6674 – 6680; c) L. Xue, Z. Lin, Chem. Soc. Rev. 2010, 39, 1692 – 1705; d) B. E. Jaksic, J. Jiang, A. W. Fraser, M. C. Baird, Organometallics 2013, 32, 4192 – 4198. a) F. Soki, J.-M. Neudçrfl, B. Goldfuss, J. Organomet. Chem. 2008, 693, 2139 – 2146; b) L. R. Collins, J. P. Lowe, M. F. Mahon, R. C. Poulten, M. K. Whittlesey, Inorg. Chem. 2014, 53, 2699 – 2707; c) J. A. Bellow, M. Yousif, D. Fang, E. G. Kratz, G. A. Cisneros, S. Groysman, Inorg. Chem. 2015, 54, 5624 – 5633. For the aggregate state of salts, see: d) A. B. Charette, C. Molinaro, C. Brochu, J. Am. Chem. Soc. 2001, 123, 12160 – 12167; e) T. Wang, Y. Liang, Z.-X. Yu, J. Am. Chem. Soc. 2011, 133, 9343 – 9353.
Received: September 29, 2015 Published online on January 25, 2016
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