Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

  1. Yingdong Luo,
  2. Guozhu Zhang,
  3. Erik S. Hwang,
  4. Thomas A. Wilcoxon and
  5. Liming Zhang

Department of Chemistry and Biochemistry, University of California, Santa Barbara, California, 93106, USA

  1. Corresponding author email

This article is part of the Thematic Series "Allene chemistry".

Guest Editor: K. M. Brummond
Beilstein J. Org. Chem. 2011, 7, 596–600. doi:10.3762/bjoc.7.69
Received 16 Mar 2011, Accepted 15 Apr 2011, Published 11 May 2011


Synthetically useful α-methanesulfonyloxy methyl ketones are readily prepared in one-step from terminal allenes in fair to good yields. The chemistry relies on a gold-catalyzed intermolecular oxidation of the 1,2-diene unit using 3,5-dichloropyridine N-oxide as the oxidant. The reaction tolerates a range of functional groups and shows excellent regioselectivity.

Keywords: allene; catalysis; gold; oxidation; regioselectivity


While alkynes are the most studied substrates in homogeneous gold catalysis [1-9], allenes [10] occupy a not-so-distant second place, and many versatile transformations have been developed either using allenes as substrates [11-17] or via allenes generated in situ [18-21]. We have recently shown that highly reactive gold carbenes can be generated from alkynes via gold-promoted intermolecular oxidation by pyridine/quinoline N-oxides [22-25], making benign alkynes effective surrogates of toxic and potentially explosive α-diazo ketones (Scheme 1A). Synthetically useful structures such as oxetan-3-ones [22], dihydrofuran-3-ones [23], azetidin-3-ones [24] and α,β-unsaturated ketones [25] are readily accessed via these gold carbene intermediates. This led us to consider whether or not allenes could also be oxidized by these N-oxides in the presence of gold catalysts. As shown in Scheme 1B, intermediate C, likely formed via an initial nucleophilic attack of a gold-activated allene, cannot undergo elimination in the same way as intermediate A, hence gold carbene intermediate B would not be formed. While C may revert back to the allene substrate, we suspect that a SN2'-type reaction by an external nucleophile could facilitate the fragmentation of the O–Y bond, ultimately leading to useful products via intermediate D. Herein we report our preliminary studies, which led to a facile synthesis of α-methanesulfonyloxy methyl ketones.


Scheme 1: Gold-catalyzed intermolecular oxidation of alkynes and allenes.

Results and Discussion

Initially, trideca-1,2-diene (1a) was treated with commercially available pyridine N-oxide in the presence of MsOH (5 equiv) and Ph3PAuNTf2 (5 mol %) in DCE at room temperature. Consumption of 1a was initially observed and was complete in two days. A relatively polar compound was detected and subsequently isolated (Table 1, entry 1). NMR and MS analysis showed it to be the α-methanesulfonyloxy ketone 2a. Interestingly, its regioisomer (i.e., 3) was not observed, suggesting excellent regioselectivity in terms of the MsO delivery. The reaction time was shortened to 8 h by increasing the reaction temperature (entry 2). Attempts to increase the reaction efficiency by varying the N-oxide (entries 3–5) revealed that 3,5-dichloropyridine N-oxide was a superior oxidant, and 2a was formed in 75% NMR yield. While less reactive but bulky gold catalysts, such as IPrAuNTf2 (entry 6) and Cy-JohnPhosAuNTf2 (entry 7), did not fare as well as Ph3PAuNTf2, the more Lewis acidic (4-CF3Ph)3PAuNTf2 was better, and 2a was formed in 77% isolated yield (entry 8). A decrease in the amount of MsOH was counterproductive (entry 9), whilst no desired product was observed in the absence of a gold catalyst (entry 10).

Table 1: Initial studies and condition optimizationa.

[Graphic 1]
Entry Catalyst (5 mol %) N-Oxide (2 equiv) Reaction conditions Yieldb (%)
1 Ph3PAuNTf2 pyridine N-oxide rt, 2 d 46
2 Ph3PAuNTf2 pyridine N-oxide 40 °C, 8 h 52
3 Ph3PAuNTf2 quinoline N-oxide 40 °C, 8 h 51/6c
4 Ph3PAuNTf2 2-bromopyridine N-oxide 40 °C, 8 h 44/10c
5 Ph3PAuNTf2 3,5-dichloropyridine N-oxide 40 °C, 8 h 75
6 IPrAuNTf2 3,5-dichloropyridine N-oxide 40 °C, 8 h 10/53c
7 Cy-JohnPhosAuNTf2 3,5-dichloropyridine N-oxide 40 °C, 8 h 47/7c
8 (4-CF3Ph)3PAuNTf2 3,5-dichloropyridine N-oxide 40 °C, 8 h 80(77d)
9e (4-CF3Ph)3PAuNTf2 3,5-dichloropyridine N-oxide 40 °C, 8 h 55/13c
10 3,5-dichloropyridine N-oxide 40 °C, 8 h

a[1a] = 0.05 M; bdetermined by 1H NMR using diethyl phthalate as the external standard; cunreacted starting material; disolated yield; e2.5 equiv of MsOH.

With the optimized reaction conditions established (Table 1, entry 8), the scope of this chemistry was studied. As shown in Table 2, remote functional groups were readily tolerated. For example, good yields were obtained in the presence of a distal acetoxy (entry 1) or benzoyloxy (entry 2) group; moreover, reactive tosyloxy and mesyloxy groups were also tolerated (entries 3 and 4). A chloro (entry 5), a benzyloxy (entry 6), a protected amino (entry 7) and a phenyl group (entry 8) were also allowed, and the corresponding α-functionalized ketones were isolated in useful yields. Besides linear allenes, exocyclic allenes such as 1j and 1k were also suitable substrates and gave mesylates 2j and 2k in 72% and 59% yield, respectively (entries 9 and 10).

Table 2: Reaction scopea.

[Graphic 2]
Entry Allene Products Yieldb
1 [Graphic 3] 1b [Graphic 4] 2b 79%
2 [Graphic 5] 1c [Graphic 6] 2c 75%
3 [Graphic 7] 1d [Graphic 8] 2d 80%
4 [Graphic 9] 1e [Graphic 10] 2e 73%
5 [Graphic 11] 1f [Graphic 12] 2f 63%
6 [Graphic 13] 1g [Graphic 14] 2g 61%
7 [Graphic 15] 1h [Graphic 16] 2h 76%
8 [Graphic 17] 1i [Graphic 18] 2i 60%
9 [Graphic 19] 1j [Graphic 20] 2j 72%
10 [Graphic 21] 1k [Graphic 22] 2k 59%

a[1] = 0.05 M; bisolated yield.

Some substrates, however, did not participate in this reaction effectively. For example, allenes derived by replacing the acetoxy group of 1b with a free OH or an OTBS group did not lead to the desired products. Presumably, the nucleophilic OH group in the substrate, or one generated via acidic desilylation, interfered with the reaction. This reasoning was supported by the isolation of piperidine 4 upon subjecting 1l to the optimized reaction conditions (Scheme 2). In addition, allenylbenzene was not a good substrate, and <10% of the desired ketone was detected by NMR. Somewhat surprisingly, pentadeca-7,8-diene [26], an internal allene, did not participate in the reaction.


Scheme 2: A side reaction from 1l.

It is of note that α-methanesulfonyloxy ketones are versatile synthetic intermediates that can undergo various reactions [27], including substitution [28], elimination [29], the formation of zinc homoenolates [30], the formation of cyclopropane rings under photo-irradiation [31-33], the formation of aminoimidazoles [34], the generation of cyclopropanone–oxyallyl intermediates [35], and ring contraction [36]. Their direct synthesis from corresponding ketones can be realized via oxidation by using either CuO/MsOH [37,38] or PhI(OH)OMs [39]. However, the former method uses stoichiometric amounts of copper, whilst the latter suffers from low regioselectivities. This gold-catalyzed approach offers an attractive alternative that is highly regioselective, catalytic on gold and takes place under relatively mild reaction conditions.

The mechanism of this highly regioselective gold-catalyzed oxidation of allenes is proposed in Scheme 3. The first step, as in the case of alkyne oxidation [22,23,25], is probably an attack by the pyridine N-oxide on the gold-activated allene. Selective reaction at the terminal C–C double bond should occur due to steric preference. The allyl gold intermediate E can then undergo protonation to form intermediate F with MsO as the counter anion. An SN2'-type substitution by the anion would afford the observed product. This substitution is facilitated by the fragmentation of the weak N–O bond and the annihilation of the charges.


Scheme 3: A proposed reaction mechanism.


We have successfully realized the first gold-catalyzed intermolecular oxidation of allenes. With 3,5-dichloropyridine N-oxide as the oxidant and in the presence of MsOH, α-methanesulfonyloxy methyl ketones are formed in one step in fair to good yield with excellent regioselectivities under relatively mild reaction conditions. The reaction tolerates a wide range of functional groups. Studies to explore the synthetic potential of this allene oxidation strategy are currently underway.

Supporting Information

Supporting Information File 1: Experimental procedures and characterization data.
Format: PDF Size: 304.0 KB Download
Supporting Information File 2: NMR spectra of compounds.
Format: PDF Size: 2.6 MB Download


The authors thank NSF (CAREER CHE-0969157) and UCSB for general financial support. LZ is an Alfred P. Sloan fellow.


  1. Abu Sohel, S. Md.; Liu, R.-S. Chem. Soc. Rev. 2009, 38, 2269–2281. doi:10.1039/b807499m
    Return to citation in text: [1]
  2. Arcadi, A. Chem. Rev. 2008, 108, 3266–3325. doi:10.1021/cr068435d
    Return to citation in text: [1]
  3. Fürstner, A.; Davis, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410–3449. doi:10.1002/anie.200604335
    Return to citation in text: [1]
  4. Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351–3378. doi:10.1021/cr068430g
    Return to citation in text: [1]
  5. Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180–3211. doi:10.1021/cr000436x
    Return to citation in text: [1]
  6. Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239–3265. doi:10.1021/cr068434l
    Return to citation in text: [1]
  7. Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395–3442. doi:10.1021/cr050041j
    Return to citation in text: [1]
  8. Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271–2296. doi:10.1002/adsc.200600368
    Return to citation in text: [1]
  9. Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200–203. doi:10.1002/anie.200502999
    Return to citation in text: [1]
  10. Krause, N.; Hashmi, A. S. K., Eds. Modern Allene Chemistry; Wiley-VCH: Weinheim, Germany, 2004.
    Return to citation in text: [1]
  11. Hoffmann-Röder, A.; Krause, N. Org. Lett. 2001, 3, 2537–2538. doi:10.1021/ol016205+
    Return to citation in text: [1]
  12. Morita, N.; Krause, N. Org. Lett. 2004, 6, 4121–4123. doi:10.1021/ol0481838
    Return to citation in text: [1]
  13. Morita, N.; Krause, N. Angew. Chem., Int. Ed. 2006, 45, 1897–1899. doi:10.1002/anie.200503846
    Return to citation in text: [1]
  14. Buzas, A. K.; Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 985–988. doi:10.1021/ol063031t
    Return to citation in text: [1]
  15. LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452–2453. doi:10.1021/ja068819l
    Return to citation in text: [1]
  16. Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, 9066–9073. doi:10.1021/ja062045r
    Return to citation in text: [1]
  17. Kong, W.; Fu, C.; Ma, S. Eur. J. Org. Chem. 2010, 2010, 6545–6555. doi:10.1002/ejoc.201001112
    Return to citation in text: [1]
  18. Wang, S.; Zhang, G.; Zhang, L. Synlett 2010, 2010, 692–706. doi:10.1055/s-0029-1219527
    Return to citation in text: [1]
  19. Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804–16805. doi:10.1021/ja056419c
    Return to citation in text: [1]
  20. Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414–8415. doi:10.1021/ja062777j
    Return to citation in text: [1]
  21. Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442–1443. doi:10.1021/ja057327q
    Return to citation in text: [1]
  22. Ye, L.; He, W.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 8550–8551. doi:10.1021/ja1033952
    Return to citation in text: [1] [2] [3]
  23. Ye, L.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258–3259. doi:10.1021/ja100041e
    Return to citation in text: [1] [2] [3]
  24. Ye, L.; He, W.; Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 3236–3239. doi:10.1002/anie.201007624
    Return to citation in text: [1] [2]
  25. Lu, B.; Li, C.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 14070–14072. doi:10.1021/ja1072614
    Return to citation in text: [1] [2] [3]
  26. Bolte, B.; Odabachian, Y.; Gagosz, F. J. Am. Chem. Soc. 2010, 132, 7294–7296. doi:10.1021/ja1020469
    Return to citation in text: [1]
  27. Creary, X. Acc. Chem. Res. 1985, 18, 3–8. doi:10.1021/ar00109a002
    Return to citation in text: [1]
  28. Hisanaga, Y.; Asumi, Y.; Takahashi, M.; Shimizu, Y.; Mase, N.; Yoda, H.; Takabe, K. Tetrahedron Lett. 2008, 49, 548–551. doi:10.1016/j.tetlet.2007.11.065
    Return to citation in text: [1]
  29. Hui, B. W.-Q.; Chiba, S. Org. Lett. 2009, 11, 729–732. doi:10.1021/ol802816k
    Return to citation in text: [1]
  30. Nomura, K.; Matsubara, S. Chem. Lett. 2007, 36, 164–165. doi:10.1246/cl.2007.164
    Return to citation in text: [1]
  31. Mühling, O.; Wessig, P. Photochem. Photobiol. Sci. 2006, 5, 1000–1005. doi:10.1039/b610181j
    Return to citation in text: [1]
  32. Wessig, P.; Mühling, O. Angew. Chem., Int. Ed. 2001, 40, 1064–1065. doi:10.1002/1521-3773(20010316)40:6<1064::AID-ANIE10640>3.0.CO;2-5
    Return to citation in text: [1]
  33. Wessig, P.; Mühling, O. Helv. Chim. Acta 2003, 86, 865–893. doi:10.1002/hlca.200390086
    Return to citation in text: [1]
  34. Yang, C.-G.; Wang, J.; Jiang, B. Tetrahedron Lett. 2002, 43, 1063–1066. doi:10.1016/S0040-4039(01)02331-0
    Return to citation in text: [1]
  35. Föhlisch, B.; Herrscher, I. Chem. Ber. 1986, 119, 524–534. doi:10.1002/cber.19861190216
    Return to citation in text: [1]
  36. Barrett, D. G.; Liang, G.-B.; McQuade, D. T.; Desper, J. M.; Schladetzky, K. D.; Gellman, S. H. J. Am. Chem. Soc. 1994, 116, 10525–10532. doi:10.1021/ja00102a020
    Return to citation in text: [1]
  37. Dowd, P.; Choi, S.-C. Tetrahedron Lett. 1989, 30, 6129–6132. doi:10.1016/S0040-4039(01)93322-2
    Return to citation in text: [1]
  38. Lee, J. C.; Choi, Y. Tetrahedron Lett. 1998, 39, 3171–3172. doi:10.1016/S0040-4039(98)00451-1
    Return to citation in text: [1]
  39. Lodaya, J. S.; Koser, G. F. J. Org. Chem. 1988, 53, 210–212. doi:10.1021/jo00236a048
    Return to citation in text: [1]

© 2011 Luo et al; licensee Beilstein-Institut.
This is an Open Access article under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (

Back to Article List