COMMUNICATION "This is the peer reviewed version of the following article: Angew. Chem., Intl. Ed. 2017, 56, 3187-3190 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/anie.201611720/full purposes in accordance with Wiley Terms and Conditions for Self-Archiving." Ni-Catalyzed Stannylation of Aryl Esters via C–O Bond Cleavage Yiting Gu, and Ruben Martin* Abstract: A Ni-catalyzed stannylation of aryl esters with air- and 2 moisture-insensitive silylstannyl reagents via C(sp )–O cleavage is described. This protocol is characterized by its wide scope, including challenging combinations, thus enabling access to versatile building blocks and orthogonal C–heteroatom bond-formations. Owing to the low-cost, benign character and availability of phenol, C–O electrophiles have emerged as powerful alternatives to aryl halides in the cross-coupling arena.[1] Although predisposed to site-selectivity issues with multiple C–O reaction sites, aryl esters have become attractive counterparts due to their accessibility, thermal/moisture stability and exquisite orthogonality with aryl halides, representing an added value when compared to highly reactive organic sulfonates.[1] In contrast to commonly practiced C–C bond-formations using organometallic species (Scheme 1, path a),[2, 3] the paucity of C– heteroatom bond-formations of aryl esters is certainly striking (Scheme 1, path b), [4] a testament to the attenuated reactivity of heteroatom-based nucleophiles. Undoubtedly, such void terrain constitutes a unique opportunity for discovering new fundamental reactivity while expanding our synthetic repertoire for accessing essential molecular architectures. Catalytic C–O cleavage reactions of aryl esters C-X bond formation X X path b X=heteroatom C-C bond formation C [M] path a R2 O O C [M]=Mg,Zn,B no R-[M] required limited precedents well-defined R-[M] ample precedents This work: catalytic stannylation of aryl esters via C–O cleavage δ– δ+ O δ+ δ– SnBu3 R2 "SnBu3" Ni R1 R1 O formal catalytic electrophile nucleophile umpolung [a] [b] non-π-extended arenes wide substrate scope orthogonal scenarios chemoselective Y. Gu, Prof. R. Martin Institute of Chemical Research of Catalonia (ICIQ) The Barcelona Institute of Science and Technology Av. Països Catalans 16, 43007 Tarragona (Spain) E-mail: rmartinromo@iciq.es Prof. R. Martin ICREA, Passeig Lluïs Companys, 23, 08010 Barcelona Spain Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate)) Scheme 1. Catalytic C–O Bond-Cleavage of Aryl Esters. At present, the existing precedents for C–heteroatom bondformation of aryl esters via C–O cleavage remain essentially confined to C–P and C–N bond-formations.[4a,4d] Aimed at providing better flexibility in synthetic design via further derivatization techniques, aryl esters have recently been converted to aryl trialkylsilanes or aryl boronates via C–O cleavage;[4b,4c] unfortunately, a limited number of transformations are amenable via C–Si bond-cleavage of aryl trialkyl silanes, whereas high temperatures and noble catalysts are needed to forge C–B bonds from aryl esters, thus reinforcing a change in strategy. Prompted by our interest in C–O functionalization,[4c,5] we questioned whether an umpolung strategy could be designed to convert electrophilic aryl esters into nucleophilic organotin reagents, superb reaction intermediates via C–Sn cleavage (Scheme 1, bottom).[6] Indeed, the Migita-Kosugi-Stille (MKS) reaction of organotin reagents remains one of the most robust, versatile, mild and widely applicable cross-couplings.[7] Not surprisingly, the MKS reaction is frequently used in total synthesis of natural products[8] or in densely functionalized polyheterocyclic cores,[9] privileged motifs in a wide variety of pharmaceuticals that are not particularly trivial to assemble via classical cross-coupling reactions.[10] Herein, we describe a new Ni-catalyzed stannylation of aryl esters via C(sp2)–O cleavage. The transformation is distinguished by its wide scope, including the coupling of non-p-extended arenes or even heterocyclic cores, setting the basis for designing iterative cross-coupling scenarios as well as further derivatization techniques via C–Sn cleavage. Initial mechanistic studies suggest that a catalytic cycle initiated by oxidative addition comes into play. COMMUNICATION OPiv + Bu3SnSiMe3 (1.3 equiv) 2a 1a Ni(COD)2 (10 mol %) L1 (10 mol %) SnBu3 CsF (1.0 equiv) PhMe, 90 °C, 8 h Entry Deviation from standard conditions none 2 PCy3 instead of L1 0 3 L2 instead of L1 46 4 L3 instead of L1 or 5 Ni(acac)2 instead of Ni(COD)2 23 7 Cs2CO3 instead of CsF 61 8 THF instead of PhMe 0 9 LiF instead of CsF 22 10 Using (Bu3Sn)2 instead of 2a 0 11 No Ni(COD)2, no CsF or no dcype 0 1a-r 28 6 or 2a (1.30 equiv) CsF (1.0 equiv) PhMe, 90 ºC OPiv R 0[e] NiCl2(L1) instead of Ni(COD)2 SnBu3 R Ni(COD)2 (10 mol%) L1 (10 mol%) 3a 3a (%)[a],[b] 1 OPiv R SnBu3 R 3a-r 91[c] (69)[d] R Cy2P SnBu3 PCy2 L1 Cy2P PCy2 L2 R = H, 92%, 91%[a] (3a) R = OMe, 84% (3b) R = OTBS, 72% (3c) R = SnBu3, 81% (3d)[b] iPr iPr N iPr iPr Cl L3 SnBu3 N SnBu3 CO2Me 68% Me N 61% (3h) Piv Scheme 2. Optimization of the Reaction Conditions. [a] 1a (0.20 mmol), 2a SnBu3 SnBu3 SnBu3 R R = SiMe3, 88% (3i) R = CN, 82% (3j)[c] R = CO2Me, 79% (3k) R (0.26 mmol), Ni(COD)2 (10 mol%), L1 (10 mol%), CsF (0.20 mmol) in PhMe (0.20 M) at 90 ºC. [b] GC yields using decane as internal standard. [c] Isolated yield. [d] Ni(COD)2 (5 mol%). [e] with NaOtBu (20 mol%). 73% (3f) N (3g)[c, d] N 85% (3e) SnBu3 N SnBu3 O SnBu3 R = H, 84% (3m)[c] R = Me, 69% (3n)[e] 80% (3l) 89% (3o)[f] SnBu3 We started our investigations by reacting 1a with 2a, a benchstable stannyl reagent that can be prepared quantitatively in one-step and in bulk quantities (Scheme 2). [11-13] After systematic experimentation,[14] a combination of Ni(COD)2, L1 and CsF in toluene at 90 ºC provided the best results, affording 3a in 91% isolated yield (entry 1). In line with our expectations, the nature of the ligand proved to be critical. While traces of 3a, if any, were observed with PCy3 and L3 that have shown to be particularly useful in a myriad of C–O bond-functionalization techniques (entries 2 and 4),[1] the use of structurally related L2 resulted in considerably lower yields of 3a (entry 3). Although 2a could serve as a sacrificial reducing agent, lower results were found when using Ni(II) precatalysts, suggesting that COD might be stabilizing the transient metal species within the catalytic cycle. [15] Similarly, a significant erosion in yield was observed when using solvents, bases and stannyl reagents other than toluene, CsF or 2a (entries 7-10). As expected, rigorous control experiments demonstrated that all of the reaction parameters were crucial for the stannylation to occur (entry 11). [16] N Me 65% (3p)[b] SnBu3 SnBu3 O N 87% (3q) 90% (3r) Scheme 3. Scope of p-extended aromatic pivalates. Reaction conditions: as scheme 2, entry 1; Yields of Isolated products, average of at least two independent runs. equiv). [e] [a] T = 110 ºC. 1a (5.0 mmol). [f] [b] 2a (2.3 equiv). [c] t = 6 h. [d] 2a (2.0 1-(naphthalen-2-yl)allyl pivalate (1o) as substrate. As shown in Scheme 3, our stannylation event turned out to be widely applicable regardless of the electronic and steric environments on the aryl ring.[17] Interestingly, amides (3f), silyl ethers (3c), aryl silanes (3i), nitriles (3j), esters (3h and 3k), carbazoles (3p), carbamates (3l) or benzofurans (3q) could all perfectly be accommodated. Notably, the stannylation of 1a could be executed at gram scale (5 mmol) without noticeable erosion in yield. As shown for 3d, a two-fold stannylation event could be easily within reach by carefully adjusting the stoichiometry of the reaction. Although heterocycles containing nitrogen donors could potentially hinder the reaction, this was not the case (3g, 3r). Notably, the reaction could be extended to primary or secondary benzylic pivalates possessing b-hydrogens delivering 3m and 3n in good yields. In addition, the use of 1(naphthalen-2-yl)allyl pivalate gave rise to 3o in 89% yield. To put these results into perspective, 3m-3o could not be obtained in the absence of Ni catalyst. COMMUNICATION OPiv Ni(COD)2 (10 mol%) L1 (10 mol%) or OPiv R orthogonal cross-coupling scenarios SnBu3 R 4a-k SnBu3 2a (1.30 equiv) CsF (1.0 equiv) PhMe, 90 ºC R R or SnBu3 R 5a-k SnBu3 SnBu3 Br O SnBu3 MeO SnBu3 N 9 Cu catalyst (ref. 18) 63% yield OPiv H2N Pd XPhos Cl O SnBu3 MeO2C N SnBu3 SnBu3 N 59% (5k) 82% (5l) R N 65% (5m)[a] Scheme 4. Scope of non p-extended aryl pivalates. Reaction conditions: as X X = F; 73% (10) X = I; 85% (11) R Het 5o [a] N PhMe 85% (12) N Pd(PPh3)4 (5 mol%) CF3 2a (2.0equiv). Br N N N Cl Despite the formidable advances realized in C–O functionalization, the utilization of non-p-extended coupling counterparts is not as commonly practiced as one might anticipate.[18] As shown in Scheme 4, we found that our stannylation protocol could equally be applied for regular aryl pivalates. In line with our expectations, the stannylation could be performed independently of whether electron-rich or electronpoor substituents were located at either meta, para or ortho position. Likewise, aryl pivalates containing esters (5e, 5h), nitriles (5j) or aryl fluorides (5d) could be coupled with similar ease. Notably, extensions to benzyl or allyl pivalates posed no problems (5l and 5m).[19] Particularly interesting was the ability to tolerate the presence of heterocycle cores containing basic nitrogen donors, as these motifs could compete with L1 for metal binding (5k and 5m). Next, we questioned whether we could implement orthogonal scenarios in the presence of aryl halides with conventional Cu or Pd catalysts (Scheme 5, top). Specifically, we found that a Cucatalyzed amidation took place exclusively at the aryl bromide terminus (7).[20] A subsequent Pd-catalyzed Suzuki-Miyaura protocol based on XPhos resulted in 8,[21] that was ultimately exposed under our stannylation protocol to cleanly afford 9. These results represent a testament to the robustness of aryl esters, an added value when compared to their organic sulfonate congeners. The synthetic applicability of our stannylation protocol is further illustrated in Scheme 5 (bottom). As shown, 10 or 11 could be easily prepared from 3a upon treatment with either NFSI or iodine, thus representing a formal ipso-halogenation of aryl esters. Although polyheterocyclic motifs are traditionally difficult to assemble via classical Pdcatalyzed cross-coupling reactions,[10] we found that 12 or 13 could be obtained in high yields under neutral conditions with Pd(PPh3)4 as catalyst, thus demonstrating the generality and flexibility of the Migita-Kosugi-Stille coupling when compared to other cross-coupling reactions for assembling rather sophisticated backbones. Taken together, the results of Schemes 3-5 show the prospective impact of this methodology. CF3 5n Pd(PPh3)4 (5 mol%) SnBu3 NFSI or I2 scheme 2, entry 1; Yields of Isolated products, average of at least two independent runs. 8 Het as Table 1 (entry 1) SnBu3 N OPiv 62% (5j)[a] 73% (5i) O PhB(OH)2, K3PO4, THF-H2O, rt 83% yield Cl 7 synthetic applicability 62% (5h) as Table 1 (entry 1) 74% yield 2a OPiv 57% (5g) NC O Ni Cl 6 NH R = F, 61% (5d) R = CO2Me, 71% (5e) R = CF3, 80% (5f) Pd Cu Ph R R = H, 77% (5a)[a] R = Me, 66% (5b)[a] R = Ph, 66% (5c) SnBu3 OPiv 92% (13) 5n N N 5o N Scheme 5. Orthogonal Scenarios and Synthetic Applicability. stoichiometric & catalytic studies with Ni-1 Cy2P Ni PCy2 OPiv Cy2P Ni PCy2 OPiv Ni-1 (10 mol%) 2a, CsF (1 equiv) PhMe, 90 ºC 71% yield Ni-1 CsF (1 equiv) 3a PhMe, 90 ºC 64% yield 1a + 2a mechanistic proposal Ni(0)L1 SnBu3 OPiv R R Cy2P R Ni PCy2 SnBu3 Cy2P R Ni PCy2 OPiv 2a + CsF CsOPiv + Me3SiF Scheme 6. Mechanistic Considerations. Although unraveling all mechanistic intricacies of this transformation should await further investigations, we decided to study the reactivity of the putative oxidation species, as Ni-1 could be readily prepared upon exposure of 1a to Ni(COD)2 and L1.[22],[23] Interestingly, Ni-1 was found to be competent as reaction intermediate, as 3a was invariably formed in good yields regardless of whether Ni-1 was used in a stoichiometric or in a catalytic manner (Scheme 6). Although we cannot rigorously rule out other conceivable scenarios,[24] at present we propose a mechanistic rationale based on the initial formation of Ni-1 COMMUNICATION followed by transmetallation of 2a mediated by fluoride source.[25] A final C–Sn bond reductive elimination event would deliver the aryltin derivative while recovering back the active propagating Ni(0)L1 species.[26],[27] In summary, we have documented an unconventional Nicatalyzed stannylation of aryl esters, representing a step-forward towards implementing heteroatom-based nucleophiles in C–O bond-cleavage, thus contributing to expand the rather limited portfolio of C–heteroatom bond-forming reactions via C–O functionalization. The salient features of this protocol are the broad scope and excellent chemoselectivity profile, allowing for the use of non-p-extended arenes or heteroaryl motifs, even in iterative-type scenarios. Further extensions to other C–O electrophiles are currently underway in our laboratories. [6] [7] [8] Acknowledgements We thank ICIQ, the European Research Council (ERC-277883), MINECO (CTQ2015-65496-R & Severo Ochoa Excellence Accreditation 2014-2018, SEV-2013-0319) and Cellex Foundation for support. Johnson Matthey, Umicore and Nippon Chemical Industrial are acknowledged for a gift of metal & ligand sources. Y. G. thanks Severo Occhoa for a scholarship. Keywords: cross-coupling • nickel • aryl ester • C–O cleavage [1] [2] [3] [4] [5] a) C. Zarate, M. Van Gemmeren, R. J. Somerville, R. Martin, Adv. Organomet. Chem. 2016, 66, 143-222. b) M. Tobisu, N. Chatani, Acc. Chem. Res. 2015, 48, 1717-1726. c) E. J. Tollefson, L. E. Hanna, E. R. Jarvo, Acc. Chem. Res. 2015, 48, 2344-2353. d) B. Su, Z.–C. Cao, Z.– J. Shi, Acc. Chem. Res. 2015, 48, 886-896. e) J. Cornella, C. Zarate, R. Martin, Chem. Soc. Rev. 2014, 43, 8081-8097. f) J. Yamaguchi, K. Muto, K. Itami, Eur. J. Org. Chem. 2013, 19-30. g) B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A.-M. Resmerita, N. K. Garg, V. Percec, Chem. Rev. 2011, 111, 1346-1416. Selected C–C bond-formations using aryl esters and well-defined organometallic reagents: a) L. Guo, C.-C. Hsiao, H. Yue, X. Liu, M. Rueping, ACS Catal. 2016, 6, 4438-4442. b) G. A. Molander, F. Beaumard, Org. Lett. 2010, 12, 4022-4025. c) K. W. Quasdorf, X. Tian, N. K. Garg, J. Am. Chem. Soc. 2008, 130, 14422-14423. d) B.-J. Li, Y.Z. Li, X,-Y. Lu, J. Liu, B.-T. Guan, Z.-J. Shi, Angew. Chem. Int. Ed. 2008, 47, 10124-10127; Angew. Chem. 2008, 120, 10278-10281. e) B.T. Guan, Y. Wang, B.-J. Li, D.-G, Yu, Z.-J. Shi, J. Am. Chem. Soc. 2008, 130, 14468-14470. Selected references using other carbon-based nucleophiles: a) J. Cornella, E. P. Jackson, R. Martin, Angew. Chem. Int. Ed. 2015, 54, 4075-4078; Angew. Chem. 2015, 127, 4147-4150. b) R. Taksie, K. Muto, J. Yamaguchi, K. Itami, Angew. Chem. Int. Ed. 2014, 53, 67916794; Angew. Chem. 2014, 126, 6909-6912. c) K. Muto, J. Yamaguchi, K. Itami, J. Am. Chem. Soc. 2012, 134, 169-172. d) A. R. Ehle, Q. Zhou, M. P. Watson, Org. Lett. 2012, 14, 1202-1205. a) J. Yang, T. Chen, L.-B. Han, J. Am. Chem. Soc. 2015, 137, 17821785. b) H. Kinuta, J. Hasegawa, M. Tobisu, N. Chatani, Chem. Lett. 2015, 44, 366-368. c) C. Zarate, R. Martin, J. Am. Chem. Soc. 2014, 136, 2236-2239. d) T. Shimasaki, M. Tobisu, N. Chatani, Angew. Chem. Int. Ed. 2010, 49, 2929-2932; Angew. Chem. 2010, 122, 2991-2994. Selected references: a) C. Zarate, M. Nakajima, R. Martin, J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.6b10998. b) C. Zarate, R. Manzano, R. Martin, J. Am. Chem. Soc. 2015, 137, 6754-6757. c) A. Correa, T. León, R. Martin, J. Am. Chem. Soc. 2014, 136, 1062-1069. d) A. Correa, R. Martin, J. Am. Chem. Soc. 2014, 136, 7253-7256. e) J. Cornella, E. Gómez-Bengoa, R. Martin, J. Am. Chem. Soc. 2013, 135, [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] 1997-2009. f) P. Alvarez-Bercedo, R. Martin, J. Am. Chem. Soc. 2010, 132, 17352-17353. See for example: a) A. G. Davies, M. Gielen, K. H. Pannell, E. R. st Tiekink, Tin Chemistry: Fundamentals Frontiers and Applications, 1 ed.; Wiley: Chichester, U.K., 2008. b) H. Yoshida, Synthesis 2016, 48, 2540-2552. c) K. J. Makaravage, A. F. Brooks, A. V. Mossine, M. S. Sanford, P. J. H. Scott, Org. Lett. 2016, 18, 5440-5443. d) C. Huang, T. Liang, S. Harada, E. Lee, T. Ritter, J. Am. Chem. Soc. 2011, 133, 13308-13310. e) P. Tang, T. Furuya, T. Ritter, J. Am. Chem. Soc. 2010, 132, 12150-12154. f) T. Furuya, A. E. Strom, T. Ritter, J. Am. Chem. Soc. 2009, 131, 1662-1663. g) A. Donovan, J. Forbes, P. Dorff, P. Schaffer, J. Babich, J. F. Valliant, J. Am. Chem. Soc. 2006, 128, 35363537, and citations therein. For selected review, see: a) C. Cordovilla, C. Bartolomé, J. M. Martínez-Ilarduya, P. Espinet, ACS Catal. 2015, 5, 3040-3053. b) P. Espinet, A. M. Echavarren, Angew. Chem. Int. Ed. 2004, 43, 4704-4734; Angew. Chem. 2004, 116, 4804-4839. c) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002, 102, 1359-1470. For selected examples: a) M. M. Logan, T. Toma, R. Thomas-Tran, J. Du Bois, Science 2016, 354, 865-869. b) J. Li, P. Yang, M. Yao, J. Deng, A. Li, J. Am. Chem. Soc. 2014, 136, 16477-16480. c) D. Mailhol, J. Willwacher, N. Kausch-Busies, E. E. Rubitski, Z. Sobol, M. Schuler, M.-H. Lam, S. Musto, F. Loganzo, A. Maderna, A. Fürstner, J. Am. Chem. Soc. 2014, 136, 15719-15729. d) G. Valot, C. S. Regens, D. P. O’Malley, E. Godineau, H. Takikawa, A. Fürstner, Angew. Chem. Int. Ed. 2013, 52, 9534-9538; Angew. Chem. 2013, 125, 9713-9717. e) E. Alonso, H. Fuwa, C. Vale, Y. Suga, T. Goto, Y. Konno, M. Sasaki, F. M. LaFerla, M. R. Vieytes, L. Giménez-Llort, L. M. Botana, J. Am. Chem. Soc. 2012, 134, 7467-7479. a) J. Kim, H. Kim, S. B. Park, J. Am. Chem. Soc. 2014, 136, 1462914638. b) T. Eicher, S. Hauptmann, The Chemistry of Heterocycles – Structure, Reactions, Synthesis and Application, VCH, Weinheim, 2003. For an illustrative large-scale application (>50 g scale) of Pfizer in which a densely functionalized polyheterocyclic core could only be accessed by Migita-Kosugi-Stille reaction: J. A. Ragan, J. W. Raggon, P. D. Hill, B. P. Jones, R. E. McDermott, M. J. Muchhof, M. A. Marx, J. M. Casavant, B. A. Cooper, J. L. Doty, Y. Lu, Org. Process Res. Dev. 2003, 7, 676-683. For an additional example by Merck producing 1.5 Kg via Migita-Kosugi-Stille coupling: N. Yasuda, C. Yang, K. M. Wells, M. S. Jensen, D. L. Hughes, Tetrahedron Lett. 1999, 40, 427-430. For the synthesis of 2a, see: D.-Y. Wang, C. Wang, M. Uchiyama, J. Am. Chem. Soc. 2015, 137, 10488-10491. For selected references using 2a in organic synthesis: a) R. R. Singidi, A. M. Kutney, J. C. Gallucci, T. V. RajanBabu, J. Am. Chem. Soc. 2010, 132, 13078-13087. b) S. Gréau, B. Radetich, T. V. RajanBabu, J. Am. Chem. Soc. 2000, 122, 8579-8580. c) M. Mori, N. Kaneta, M. Shibasaki, J. Org. Chem. 1991, 56, 3486-3493. For elegant silylstannylation techniques of alkenes, but not employing 2a as reagent, see: H. Yoshida, Y. Hayashi, Y. Ito, K, Takaki, Chem. Commun. 2015, 51, 9440-9442. For details, see Supporting Information See for example: a) A. Fürstner, K. Majima, R. Martin, H. Krause, E. Kattnig, R. Goddard, W. Lehmann, J. Am. Chem. Soc. 2008, 130, 1992-2004. b) ref. 4e. Notably, no homocoupling was observed by Migita-Kosugi-Stille coupling of in situ generated 3a with 1a. For a recent Migita-KosugiStille coupling of unconventional cross-coupling partners: D.–Y. Wang, M. Kawahata, Z.–K. Yang, K. Miyamoto, S. Komagawa, K. Yamaguchi, C. Wang, M. Uchiyama, Nat. Commun. 2016, 7, No. 12937. The mass balance of the reactions accounts for unreactive starting material and reduced product Selected catalytic C–O bond-cleavage limited to the use of p-extended systems: a) H. M. Wisniewska, E. C. Swift, E. R. Jarvo, J. Am. Chem. Soc. 2013, 135, 9083-9090. b) Q. Zhou, H. D. Srinivas, S. Dasgupta, M. P. Watson, J. Am. Chem. Soc. 2013, 135, 3307-3310. c) B. L. Taylor, M. R. Harris, E. R. Jarvo, Angew. Chem., Int. Ed. 2012, 51, 7790-7793; Angew. Chem. 2012, 124, 1-5. d) B. L. H. Taylor, E. C. Swift, J. D. Waetzig, E. R. Jarvo, J. Am. Chem. Soc. 2011, 133, 389-391. e) D.-G. Yu, Z.-J. Shi, Angew. Chem., Int. Ed. 2011, 50, 7097-7100; Angew. Chem. 2011, 123, 7235-7238. f) D.-G. Yu, B.-J. Li, S.-F. Zheng, B.-T. COMMUNICATION [19] [20] [21] [22] [23] [24] [25] [26] [27] Guan, B.-Q. Wang, Z.-J. Shi, Angew. Chem., Int. Ed. 2010, 49, 45664570; Angew. Chem. 2010, 122, 4670-4674. No reaction occurred in the absence of Ni(COD)2/L1. A. Klapars, X. Huang, S. L. Buchwald, J. Am. Chem. Soc. 2002, 124, 7421-7428. T. Kinzel, Y. Zhang, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132, 14073-14075. K. Muto, J. Yamaguchi, A. Lei, K. Itami, J. Am. Chem. Soc. 2013, 135, 16384-16387 A slightly modified procedure to that used in ref. 21 was followed to prepare Ni-1 in large amounts. See ref. 14. The available experimental data does not allow us to rule out the intermediacy of Ni(I) intermediates generated by comproportionation events. See for example, ref. 5d. This notion gains credence by in situ monitoring the reaction of 1a with 2a and Ni(COD)2/L1, observing the clean formation of Ni-1 in the crude reaction mixture. See ref. 14. 19 29 Me3SiF was formed quantitatively, as judged by F-NMR and Si NMR 113 1 spectroscopy. Likewise, Cs-NMR and H-NMR corroborated the formation of CsOPiv as byproduct. Stoichiometric experiments with 2a and Ni(COD)2/L1 revealed that Ni(COD)L1 was formed quantitatively, thus ruling out an alternative scenario consisting of an oxidative addition of Ni(0) into the Sn–Si bond. 10 For an oxidative addition of silylstannanes to other d metals, see: T. Sagawa, Y. Sakamoto, R. Tanaka, H. Katayama, F. Ozawa, Organometallics 2003, 22, 4433-4445. COMMUNICATION COMMUNICATION Yiting Gu, Ruben Martin* Page No. – Page No. Title Ni-Catalyzed stannylation of aryl A versatile and widely applicable Ni-catalyzed stannylation of aryl esters has been developed, contributing to expand the rather limited portfolio of C–heteroatom bond-formations via C–O functionalization. The reaction is characterized by its excellent chemoselectivity profile and broad substrate scope, including challenging substrate combinations and iterative techniques that shows the prospective impact of this methodology in complex settings. f we have documented an unconventional Ni-catalyzed stannylation of aryl esters, representing a step-forward towards implementing heteroatom-based nucleophiles in C–O bond-cleavage. The salient features of this protocol are the broad substrate scope and excellent chemoselectivity profile, allowing for the use of non-p -extended arenes or heteroaryl motifs, even in iterative-type scenarios. Fff esters via C-O bond cleavage