Palladium Transmetalation in an

COMMUNICATION pubs.acs.org/Organometallics

Direct Observation of Gold/Palladium Transmetalation in an Organogold Heck Reaction Katrina E. Roth and Suzanne A. Blum* Department of Chemistry, University of California, Irvine, California 92697-2025, United States

bS Supporting Information ABSTRACT: A new Heck-type reaction accessed the migratory insertion chemistry of palladium from organogold complexes. Observation, isolation, and characterization of a palladium intermediate established the role of gold/palladium transmetalation in this reaction. Recent reports of combining the reactivity of organogold compounds with palladium in organic synthesis generally assume a gold-to-palladium transmetalation step, although this step had not been directly observed in these reactions. The results herein furnish experimental evidence for the mechanisms of reactions mediated or catalyzed by both gold and palladium and reveal a migratory insertion strategy for outcompeting homocoupling pathways. he combination of the unique catalytic reactivities of gold1 and palladium has recently emerged as a powerful method for functionalizing the intermediate carbon gold σ bond generated during gold-catalyzed substrate rearrangements.2 7 In this manner, the carbon gold bond can be transformed into a new carbon carbon or carbon tin bond that is not available through gold catalysis alone. The intermediacy of organopalladium complexes in these catalytic processes has yet to be determined experimentally.3,4 Herein, we not only report a new gold- and palladium-mediated Heck-type reaction but also provide the direct observation, isolation, characterization, and reactivity studies of an intermediate arylpalladium species in this reaction. This observation lends credence to the proposal that gold(I)-topalladium(II) transmetalation reactions operate within the multiple recently reported mono- and dual-catalytic reactions, even in the absence of single-electron-transfer redox pathways.4d,5 The reactivity of this isolable arylpalladium intermediate revealed strategies for the development of new reactions that outcompete homocoupling pathways. We envisioned that organogold chemistry could be linked to the olefin migratory-insertion chemistry of palladium (i.e., a Heck-type reaction) in analogy to the recent linkings2 of organogold chemistry with palladium-,3,4 nickel-,5 and rhodiumcatalyzed6 and iron-mediated7 cross-coupling with the eventual goal of dual catalysis (eq 1). Organogold complexes are inert toward migratory insertion reactions with olefins; however, migratory insertion reactions are well-established for palladium. Therefore, we expected that transmetalation of the organic moiety from gold to palladium would access a migratory insertion reaction unavailable to gold alone.

T

To explore the viability of this new organogold Heck-type reaction, organogold compound 1a, containing a tethered olefin, was treated with (PPh3)2PdCl2 and then AgOTf in d8-THF at room temperature (eq 2). Within 10 min the cyclized product 3 was generated in 53% 1H NMR spectroscopic yield. Employment of AgOTf as an additive was necessary, due to sluggish reactivity with neutral (PPh3)2PdCl2; the benefits of silver additives for cationic Heck reactions have been previously reported.8 Addition of excess triethylamine as a base inhibited the competing protodemetalation9 side reaction and provided 3 in 84% 1 H NMR spectroscopic yield. In the absence of palladium, no formation of product 3 occurred, strongly suggesting that this reaction proceeded via a gold/palladium transmetalation to form organopalladium intermediate 2a.10

Within our organogold Heck-type system we reasoned that by employing a shorter olefin tether we could trap the palladium species formed after transmetalation. It is known that intramolecular 5-endo-trig Heck cyclization reactions are not favored,11 15 and thus the palladium species formed in a short-tethered system was anticipated to pause after transmetalation and not undergo subsequent migratory insertion. Indeed, when (o-allylphenyl)(triphenylphosphine)gold (1b) was treated with (PPh3)2PdCl2 and AgOTf, the η2-olefin palladium complex 2b was observed by 1 H NMR spectroscopy and could be isolated from the crude reaction mixture for full characterization (eq 3). The structure of this palladium complex was confirmed by X-ray crystallography Received: July 26, 2011 Published: August 25, 2011

r 2011 American Chemical Society

4811

dx.doi.org/10.1021/om2006886 | Organometallics 2011, 30, 4811–4813

Organometallics

COMMUNICATION

Scheme 1. Proposed Mechanism for the Formation of 4

Figure 1. Palladium intermediate 2b formed via an observable discrete transmetalation from organogold compound 1b. Thermal ellipsoids are shown at the 50% probability level; hydrogen atoms and the outersphere solvent of crystallization are removed for clarity.

(Figure 1). Observation of this Au/Pd transmetalation provides the first illustration of this elementary step within the context of Au/Pd dual-mediated organic reactions and builds upon an earlier report of a Au/Pd transmetalation by van Koten.16

Due to the shorter tether length, complex 2b did not cyclize even at 60 °C; however, 2b was a viable intermediate in an organogold Heck-type reaction with two migratory insertion events that successively increased the chain length (eq 4). Treatment of organogold compound 1b with (PPh3)2PdCl2 and then AgOTf and 3-hexyne in one pot produced cyclized product 4 (49% 1H NMR yield; 6.5 h). This reaction established that 2b was a viable intermediate for Heck-type reactivity.

A plausible mechanism for the formation of 4 is shown in Scheme 1: (i) transmetalation of 1b with palladium to form 2b, (ii) intermolecular migratory insertion of the alkyne into the palladium carbon bond of 2b to form 5,3a,4a (iii) intramolecular migratory insertion of the unactivated tethered olefin to form 6,17 (iv) β-hydride elimination to form 7,17 and (v) olefin isomerization of 7 to yield 4.17,18 The order of addition of reagents provided control over product selectivity. Ditriflate (PPh3)2Pd(OTf)2 is not the complex responsible for the formation of 2b. When organogold compound 1b was treated with pregenerated (PPh3)2Pd(OTf)2 in a separate pot, homocoupled product 8 was formed predominantly rather than 2b (eq 5). This result is consistent with recent findings by Gagn
e, in which an attempted Au/Pd catalytic cross-coupling reaction was thwarted by undesired competing homocoupling processes.4d,19 Cationic palladium complexes are

Scheme 2. Fast Intramolecular Migratory Insertion Outcompetes Homocoupling

known to undergo more kinetically facile ligand transfer;20 thus, the preformed dicationic complex (PPh3)2Pd(OTf)2 may rapidly undergo transmetalation reactions with two organogold complexes. Subsequent reductive elimination from the diorganopalladium complex would then yield the homocoupled product 8 instead of 2b. In contrast, the active in situ generated palladium transmetalation partner may be the neutral (PPh3)2PdCl2 with chloride abstraction by AgOTf after transmetalation. However, the precise mechanism leading to this difference in reagent selectivity is still unclear.

A fundamental understanding of the intermediates involved led to a substrate-control strategy for avoiding homocoupling that was complementary to the reagent-control method (vide infra). When organogold compound 1a, with a longer olefin tether, was treated with preformed (PPh3)2Pd(OTf)2 under otherwise identical conditions, the migratory insertion pathway successfully proceeded to yield cyclized 3 as the major product (Scheme 2). No homocoupled product was generated with this substrate. Thus, homocoupling was outcompeted by employing a substrate with a tether length suitable for rapid downstream intramolecular migratory insertion reactivity. 4812

dx.doi.org/10.1021/om2006886 |Organometallics 2011, 30, 4811–4813

Organometallics In conclusion, we have demonstrated the first gold and palladium Heck-type reaction. Characterization of an organopalladium complex unambiguously established its intermediacy in the dual-metal reaction. Conditions to outcompete homocoupling reactivity between gold and palladium were developed by reagent and substrate control, demonstrating a successful migratory insertion strategy for the design of dual-metal reactions with gold and palladium. More broadly, these results provide key fundamental information for the future development of dual-catalytic reactions that combine the substrate rearrangement power of gold with the unique reactivity of a second transition metal.

’ ASSOCIATED CONTENT

bS

Supporting Information. Text and figures giving experimental details and compound characterization data and a CIF file giving crystallographic data for 2b. This material is available free of charge via the Internet at http://pubs.acs.org.

COMMUNICATION

(10) The organogold complex 1a (1.0 equiv) was treated with AgOTf (2.0 equiv) in d8-THF. No Heck-type product formation was observed by 1H NMR spectroscopy. No evidence for transmetalation with Ag was observed by 1H NMR spectroscopy, 31P NMR spectroscopy, or mass spectrometry. (11) Ichikawa, J.; Nadano, R.; Ito, N. Chem. Commun. 2006, 4425. (12) Barluenga, J.; Fern
andez, M. A.; Aznar, F.; Vald
es, C. Chem. Eur. J. 2005, 11, 2276. (13) Ackermann, L.; Althammer, A. Synlett 2006, 3125. (14) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734. (15) Baldwin, J. E.; Cutting, J.; Dupont, W.; Kruse, L. I.; Silberman, L.; Thomas, R. C. J. Chem. Soc., Chem. Commun. 1976, 736. (16) Contel, M.; Stol, M.; Casado, M. A.; van Klink, G. P. M.; Ellis, D. D.; Spek, A. L.; van Koten, G. Organometallics 2002, 21, 4556. (17) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. (18) Hartley, F. R. Chem. Rev. 1969, 69, 799. (19) For examples of gold-mediated homocouplings see ref 1a. For
. Chem. examples of palladium-mediated homocouplings see: Moln
ar, A Rev. 2011, 111, 2251. (20) Suzaki, Y.; Yagyu, T.; Osakada, K. J. Organomet. Chem. 2007, 692, 326.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

’ ACKNOWLEDGMENT We thank the National Science Foundation for funding through a CAREER Award for S.A.B. (CHE-0748312) and the University of California Irvine for funding. We thank Dr. Joseph W. Ziller and Mr. Ryan A. Zarkesh for assistance with X-ray crystallography. ’ REFERENCES (1) For reviews on gold-only catalyzed reactions see: (a) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (b) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351–3378. (c) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232. (2) Hirner, J. J.; Shi, Y.; Blum, S. Acc. Chem. Res. 2011, 44, 603. (3) For dual-catalytic gold and palladium reactions see: (a) Shi, Y.; Peterson, S. M.; Haberaecker, W. W., III.; Blum, S. A. J. Am. Chem. Soc. 2008, 130, 2168. (b) Shi, Y.; Roth, K. E.; Ramgren, S. D.; Blum, S. A. J. Am. Chem. Soc. 2009, 131, 18022. (c) Lauterbach, T.; Livendahl, M.;
n, A.; Espinet, P.; Echavarren, A. M. Org. Lett. 2010, 12, 3006. (d) Rosellο Jones, L. A.; Sanz, S.; Laguna, M. Catal. Today 2007, 122, 403. (e) Panda, B.; Sarkar, T. K. Chem. Commun. 2010, 46, 3131. (4) For palladium-catalyzed reactions to functionalize stoichiometric organogold reagents (i.e., monocatalytic reactions) see: (a) Shi, Y.; Ramgren, S. D.; Blum, S. A. Organometallics 2009, 28, 1275. (b) Hashmi, A. S. K.; Lothsch€utz, C.; D€opp, R.; Rudolph, M.; Ramamurthi, T. D.; Rominger, F. Angew. Chem., Int. Ed. 2009, 48, 8243. (c) Hashmi, A. S. K.; D€opp, R.; Lothsch€utz, C.; Rudolph, M.; Riedel, D.; Rominger, F. Adv. Synth. Catal. 2010, 352, 1307. (d) Weber, D.; Gagn
e, M. R. Chem. Commun. 2011, 47, 5172. (e) Pe~na-L
opez, M.; Ay
an-Varela, M.; Sarandeses, L. A.; Sestelo, J. P. Chem. Eur. J. 2010, 16, 9905. (5) For nickel-catalyzed cross coupling to functionalize organogold complexes see: Hirner, J. J.; Blum, S. A. Organometallics 2011, 30, 1299. (6) For rhodium-catalyzed functionalization of organogold complexes see: Shi, Y.; Blum, S. A. Organometallics 2011, 30, 1776. (7) For gold- and iron-mediated functionalization of phenylacetylene see: Molinari, L.; Hashmi, A. S. K. Organometallics 2011, 30, 3457. (8) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945. (9) Roth, K. E.; Blum, S. A. Organometallics 2010, 29, 1712. 4813

dx.doi.org/10.1021/om2006886 |Organometallics 2011, 30, 4811–4813