Zwei machen die Show: Mechanistische Studien über die Cyclisierung von allenischen Arenen zeigen, dass die Ruheform des Katalysators ein zweikerniges verbrücktes Vinylsystem ist. Dieses wurde..

Gagné, Michel R.

Tarselli, Michael A.

Weber, Dieter

PubMed

Carolina Digital Repository

Mechanistic Surprises in the Gold(I)-Catalyzed IntramolecularHydroarylation of Allenes**Dieter Weber, Michael A. Tarselli, and Michel R. Gagné*Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290(USA)Keywordsgold catalysis; vinyl-gold(I) complex; mechanistic studies; allenes; hydroarylationGold CatalysisGold(I)-catalyzed carbon-carbon bond forming reactions continue to fascinate the syntheticcommunity but are less well investigated than many conventional metal catalysts.[1] Inmany cases a cationic gold(I)-species activates an unsaturated C-C bond and isomerizes orfunctionalizes it to build molecular complexity through reactive intermediates that includegold-π-complexes, gold-vinyls, and gold-carbenes. Support for these intermediates is mainlybased on gold(I) organometallic chemistry, though computational studies and the isolationof proposed catalytic intermediates have been reported.[2–5]We report mechanistic studies on a seemingly simple gold(I)-catalyzed reaction anddemonstrate the importance of dinuclear organometallic intermediates. While similardinuclear species have been postulated in DFT studies,[5b] di-gold intermediates have yet tobe detected in situ and their reactivity characterized.We previously showed that the transformation of 1 to 2 could be catalyzed by R3PAu+.[6]The proposed cycle is shown in Scheme 1, with R3PAu+ initiating the process by π-coordination to 1,[7] which activated it for nucleophilic attack by the aromatic ring.[1b]Subsequent rearomatization generated vinyl-gold(I) complex 3, which protodeaurated withthe generated acid to give 2 and R3PAu+.[8] The seemingly well-behaved nature of thisreaction led us to initiate studies to refute or validate this mechanism, and this has led tosurprising results concerning the nature of the catalyst resting state.Preliminary studies identified the Gagosz catalyst Ph3PAuNTf2 (4) as a convenient source ofPh3PAu+ that did not require in situ activation with silver salts.[9] Monitoring by 31P-NMRthe reaction of 1 with 10 mol% 4 indicated that the catalyst rests as a single species 5a, withtwo distinct peaks in a 1:1 ratio (~36 ppm).[10] Upon completion of the reaction, thesepeaks diminished, and the Gagosz catalyst reappeared at 30 ppm. The stoichiometricreaction of 1 with 4 in the presence of 2,6-di-tert-butyl-pyridine (to inhibit protodeauration)**We thank Prof. Dr. A. Stephen K. Hashmi for fruitful discussions and Dr. Peter White for assistance with crystallography(pwhite@unc.edu for correspondence). The Fulbright Foreign Student Program (for Dieter Weber) is gratefully acknowledged as isthe National Institute of General Medicine (GM-60578).*mgagne@unc.edu.Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author.NIH Public AccessAuthor ManuscriptAngew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.Published in final edited form as:Angew Chem Int Ed Engl. 2009 ; 48(31): 5733–5736. doi:10.1002/anie.200902049.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptresulted in incomplete consumption of 1, but gave the same peaks at 36 ppm. Addition of asecond equivalent of 4 converted all starting material to 5a.The 1H-NMR of isolated 5a showed a single carbocycle consistent with a vinyl-gold(I)connectivity, but with other features inconsistent with 3. These included the two peaks at~36 ppm (31P-NMR) rather than the expected singlet at ~44 ppm,[3b–h] and the 2:1 ratio ofthe PPh3 to carbocycle resonance in the 1H-NMR. A closer examination of the multiplicityof the vinyl peaks in the 1H-NMR additionally revealed a heteronuclear coupling betweenthe vinyl proton that was anti to Au and two phosphorous atoms, rather than the singlephosphine expected for a simple vinyl-gold(I) complex like 3. These data thereforesuggested that the resting state 5a was a doubly metalated variant of 3.Compound 5a was air stable and amenable to aqueous workup without protodeauration;however attempts to purify it through Florisil® or silica led to immediate decomposition andelution of 2. On the other hand, neutral alumina cleanly converted 5a to 3, whosemonometalated nature was confirmed by NMR[11] and X-Ray crystallography (Figure 1).[12,13] In contrast to 5a, the 1H-NMR showed large upfield shifts of the syn (6.43 ppm (5a)to 4.97 ppm (3)) and anti (5.91 ppm (5a) to 5.62 ppm (3)) vinyl hydrogens, suggestingsignificantly different chemical environments in the two compounds.The reactivity of 3 and 5a also differed greatly.[3b–d,4] Treatment with excess acetic acid(pKa=4.76) immediately protodeaurated 3 (to 2),[14] while 5a was untouched andunreactive with even α-bromo-acetic acid (pKa=2.86) (12 h). Excess TFA (pKa=−0.25),however, resulted in a rapid decomposition to only traces of 2. The second equivalent ofPh3PAu+ in 5a therefore hinders protodeauration.These spectroscopic and reactivity observations coupled with the work of Grandberg,[4]Nesmeyanov,[15b,c] and Schmidbaur[3g] on arylgold(I) organometallic complexessuggested that 5a was a diaurated structure that engaged the vinyl anion in a bridging 3-center-2-electron mode and was stabilized by a Au-Au interaction (Scheme 2). X-ray crystalstructures of numerous bridging aryl compounds are known,[15] and a recent computationalstudy implicated the intermediacy of a bridging vinyl in the cycloisomerization of ene-ynes.[5b] The phosphines in such a chiral structure would be diastereotopic and account for theinequivalent resonances in the 31P-NMR.Grandberg has reported the geminally diaurated parent species[(Ph3PAu)2CH=CH2]+[BF4]− to be unstable and characterizable only by its IR andreactivity;[16] the more crowded nature of 5a presumably contributes to its thermal stability.The enhanced acid stability of a bridging vinyl can be rationalized by noting that the three-center two-electron bond should be more electron deficient and crowded than the traditionalvinyl-gold(I) complex 3. The stabilizing Au-Au bond interactions are well established andmeasured to be worth 5–10 kcal mol−1.[17]The isolation of 3 and 5a provided a rare opportunity to study the comparative reactivity ofbone fide reaction intermediates. Compound 3 was found to readily react with stoichiometricquantities of HX (X = Cl, NTf2) to yield 2 and the expected gold(I) species (Scheme 3).[18]When only 0.5 equivalent of HNTf2 was added, clean conversion to 5a and 2 occurred.Similarly clean and rapid was the conversion of 3 and 4 to 5a, a process that presumablycompetes favourably with protodeauration under catalysis conditions.In reactivity paralleling that of Nesmeyanov and Grandberg in diaurated aryl compounds, 5aextrudes Ph3PAuL and 3 upon reaction with a suitable ligand [Eq. 1]. Although 5a and 3were expectedly unreactive with 1, they could each be activated with HNTf2 to reveal 4. TheWeber et al. Page 2Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptsubsequent conversion of 1 to 2 showed the viability of both 3 and 5a as catalyticintermediates [Eq. 2].(1)(2)To elucidate whether the resting of the catalyst at 5a was dependent on NTf2−, differentsilver salts were investigated in an in situ activation protocol (Table 1). In each case, 5a–ewas observed by 31P-NMR suggesting a purely outer sphere role for the anions with thepossible exception of OTf− which generated a broadened singlet at 36 ppm.The above results indicate that 3 and 5a are each viable intermediates in the intramolecularhydroarylation of allenes and that an additional structure needs to be added to themechanism in Scheme 1. The bridging structure in 5a was found to be considerably morestable than 3, and served to sequester the key Lewis acidic species Ph3PAu+ more quicklythan the latter promoted allene activation. Although 5a was less reactive to Brønsted acidsthan 3, both could be activated by HNTf2 to generate catalytically active 4. It is not yet clearwhether 5a operates on or off the cycle under true catalytic conditions, but it is clear that themechanism is more complex than previously envisioned.In conclusion, this report describes the synthesis, characterization, and reactivity of twointermediates in the Ph3PAu+-catalyzed cycloisomerization of arene-allenes. It reports, forthe first time, the experimental viability of the computationally predicted diaurated reactionintermediates, and therefore provides important insights into the burgeoning field of goldcatalysis.Experimental SectionFor experimental procedures and data see the supporting information.Supplementary MaterialRefer to Web version on PubMed Central for supplementary material.References1. a) Li Z, Brouwer C, He C. Chem.Rev. 2008; 108:3239–3265. [PubMed: 18613729] b) WidenhoeferRA. Chem. Eur. J. 2008; 14:5382–5391. c) Gorin DJ, Sherry BD, Toste FD. Chem. Rev. 2008;108:3351–3378. [PubMed: 18652511] d) Arcadi A. Chem. Rev. 2008; 108:3266–3325. [PubMed:Weber et al. Page 3Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript18651778] e) Jiménez-Núñez E, Echavarren AM. Chem. Rev. 2008; 108:3326–3350. [PubMed:18636778] f) Bongers N, Krause N. Angew. Chem. Int. Ed. 2008; 47:2178–2181. g) Gorin DJ,Toste FD. Nature. 2007; 446:395–403. [PubMed: 17377576] h) Hashmi ASK. Chem. Rev. 2007;107:3180–3211. [PubMed: 17580975] i) Fürstner A, Davies PW. Angew. Chem. Int. Ed. 2007;46:3410–3449. j) Hashmi ASK, Hutchings GJ. Angew. Chem. Int. Ed. 2006; 45:7896–7936.2. Recent examples of mechanistic studies on gold(I)-catalyzed reactions: a) Seidel G, Mynott R,Fürstner A. Angew. Chem. Int. Ed. 2009; 48:2510–2513. b) Pérez AG, López CS, Marco-ContellesJ, Faza ON, Soriano E, de Lera AR. J. Org. Chem. 2009; 74:2982–2991. [PubMed: 19323481] c)Mauleón P, Krinsky JL, Toste FD. J. Am. Chem. Soc. 2009; 131:4513–4520. [PubMed: 19275228]3. Selected examples of X-ray crystal structures of proposed gold(I)-intermediates: Gold(I)-carbodicarbene-complex: a) Fürstner A, Alcarazo M, Goddard R, Lehmann CW. Angew. Chem. Int.Ed. 2008; 47:3210–3214. Vinyl-gold(I)-complexes: b) Hashmi ASK, Ramamurthi TD, Rominger F.J. Organomet. Chem. 2009; 694:592–597. c) Shi Y, Ramgren SD, Blum SA. Organometallics.2009; 28:1275–1277. d) Mohr F, Falvello LR, Laguna M. Eur. J. Inorg. Chem. 2006:833–838. andreferences therein; e) Fañanás-Mastral M, Aznar F. Organometallics. 2009; 28:666–668. Aryl-gold(I)-complexes: f) Partyka DV, Updegraff JB III, Zeller M, Hunter AD, Gray TG.Organometallics. 2007; 26:183–186. g) Porter KA, Schier A, Schmidbaur H. Organometallics.2003; 22:4922–4927. h) Raubenheimer HG, Desmet M, Kruger GJ. J. Chem. Soc. Dalton Trans.1995:2067–2071. π-arene-gold(I) complex: i) Herrero-Gómez E, Nieto-Oberhuber C, López S,Benet-Buchholz J, Echavarren AM. Angew. Chem. Int. Ed. 2006; 45:5455–5459. Chelated η2-alkene-gold(I) complex: j) Shapiro ND, Toste FD. Proc. Natl. Acad. Sci. USA. 2008; 105:2779–2782. Cationic gold(I) π-alkene complex: k) Brown TJ, Dickens MG, Widenhoefer RA. J. Am.Chem Soc. 20094. a) Grandberg KI, Dyadchenko VP. J. Organomet. Chem. 1994; 474:1–21. b) Grandberg KI. Russ.Chem. Rev. 1982; 51:249–262.5. a) Liu L, Xu B, Mashuta MS, Hammond GB. J. Am. Chem. Soc. 2008; 130:17642–17643.[PubMed: 19055329] For DFT studies see: b) Cheong PH, Morganelli P, Luzung MR, Houk KN,Toste FD. J. Am. Chem. Soc. 2008; 130:4517–4526. [PubMed: 18327944]6. a) Tarselli MA, Gagné MR. J. Org. Chem. 2008; 73:2439–2441. [PubMed: 18278940] b) TarselliMA, Liu A, Gagné MR. Tetrahedron. 2009; 65:1785–1789. [PubMed: 21512612] . Other examples:c) Zhang Z, Liu C, Kinder RE, Han X, Qian H, Widenhoefer RA. J. Am. Chem. Soc. 2006;128:9066–9073. [PubMed: 16834380] d) Liu Z, Wasmuth AS, Nelson SG. J. Am. Chem. Soc. 2006;128:10352–10353. [PubMed: 16895385] e) Park C, Lee PH. Org. Lett. 2008; 10:3359–3362.[PubMed: 18613690] f) Hashmi ASK, Schwarz L, Choi J, Frost TM. Angew. Chem. Int. Ed. 2000;39:2285–2288.7. Gandon V, Lemière G, Hours A, Fensterbank L, Malacria M. Angew. Chem. Int. Ed. 2008;47:7534–7538.8. For this specific substrate regioselective elimination is observed, however some ene-alleneseliminate to a regioisomer mixture; see Tarselli MA, Chianese AR, Lee SJ, Gagné MR. Angew.Chem. Int. Ed. 2007; 46:6670–6673.9. Mézailles N, Ricard L, Gagosz F. Org. Lett. 2005; 7:4133–4136. [PubMed: 16146370]10. Similar reactivity studies by 31P-NMR: a) Grisé CM, Barriault L. Org. Lett. 2006; 8:5905–5908.[PubMed: 17134302] b) Grisé CM, Rodrigue EM, Barriault L. Tetrahedron. 2008; 64:797–808.11. The 31P-NMR showed the expected singlet at 43.0 ppm for a classical Ph3PAu-vinyl; see reference[3d].12. Compound 3 is one of only a few vinyl-gold(I) species not stabilized by an electron withdrawinggroup; see reference [3d].13. The observed distances are similar to those published by Laguna; see reference [3d]. X-ray crystalstructure data for 3 at 100K: C36H36AuO6P, Mr =792.61 g mol−1, triclinic, space group P-1, a =8.7814(5)Å, b = 13.7359(7)Å, c = 14.3110(7)Å, α = 105.099(2)°, β = 96.500(2)°, γ = 97.267(2)°,V = 1633.85(15)Å3, Z = 2, ρcalcd = 1.611 g cm−3, R1 = 0.0186 (0.0188), wR2 = 0.0448 (0.0449),for 5692 reflections with I>2σ(I) (for 5759 reflections (Rint = 0.0294) with a total of 27480measured reflections), goodness of fit on F2 = 1.121, largest diff. peak (hole) = 0.0930 (−0.725eÅ−3); see supporting information.Weber et al. Page 4Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript14. Compound 3 also protodeaurated on flash silica and only partially survives short plugs of alumina;see references [3c] and [5a] for comparison.15. See reference [3g]; a) Usón R, Laguna A, Fernandez EJ, Media A, Jones PG. J. Organomet. Chem.1988; 350:129–138. b) Nesmeyanov AN, Perevalova EG, Grandberg KI, Lemenovskii DA,Baukova TV, Afanassova OB. J. Organomet. Chem. 1974; 65:131–144. c) Nesmeyanov AN,Perevalova EG, Grandberg KI, Lemenovskii DA. Izv. Akad. Nauk SSSR, Ser. Khim. 1974;5:1124–1137. and references therein.16. Grandberg KI, Smyslova EI, Kosina AN. Izv. Akad. Nauk SSSR, Ser. Khim. 1973; 12:2787–2789.17. Schmidbaur H. Chem. Soc. Rev. (London). 1995:391–400.18. Products were not isolated but characterized by 1H- and 31P-NMR and compared to literaturevalues (see supporting information).Weber et al. Page 5Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptFigure 1.ORTEP diagram of intermediate 3 with 50% probability ellipsoids; most hydrogen atomsomitted for clarity. Key bond lengths [Å] include: Au1-P1 [2.2913(5)], Au1-C2 [2.050(2)],and C1-C2 [1.324(4)].[13]Weber et al. Page 6Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptScheme 1.Proposed cycle for the gold(I)-catalyzed hydroarylation of allenes.Weber et al. Page 7Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptScheme 2.Proposed structure of resting state 5a (X=NTf2).Weber et al. Page 8Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptScheme 3.Reactivity of intermediate 3.Weber et al. Page 9Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptWeber et al. Page 10Table 1Activation protocol with different silver salts.Entry Catalyst/Activator Resting State[a]1 Ph3PAuNTf2 5a2 Ph3PAuCl / AgNTf2 5a3 Ph3PAuCl / AgPF6 5b[b]4 Ph3PAuCl / AgSbF6 5c[c]5 Ph3PAuCl / AgOTf 5d[d]6 Ph3PAuCl / AgBF4 5e[e][a]Monitored by 31P-NMR.[b]X = PF6 (5b) Signals at 35.4 ppm and 35.1 ppm were observed.[c]X = SbF6 (5c) Signals at 35.7 ppm and 35.4 ppm were observed.[d]X = OTf (5d) A broad peak 35.8 ppm was observed instead of two sharp singlets.[e]X = BF4 (5e) Signals at 35.9 ppm and 35.6 ppm were observed.Angew Chem Int Ed Engl. Author manuscript; available in PMC 2010 November 11.

Mechanistic Surprises in the Gold(I)-Catalyzed Intramolecular Hydroarylation of Allenes

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