UPDATES
thank the EPSRC NMSSC in Swansea for mass spectromet-
ric analyses. Professor Andrew D. Smith of the University of
St. Andrews is gratefully thanked for his support.
previously released cationic gold fragment, so to form
gem-diaurated species, such as III,[27e,28] which could
be rather a resting state of the catalytic cycle as previ-
ously observed for Au-catalysed transformations.[29]
Therefore, in order to gain insight into the mecha-
nism,[30] we followed the conversion of 2a into 3a cata-
lysed at different concentrations of 1a, ranging from References
200 to 1000 ppm, in CDCl3.[31] The reaction exhibited
first-order dependence to 2a.[32] A first-order depend-
ence with respect to 1a is determined, with slight de-
viation from linearity at lower catalyst concentrations
that might suggest a more complex mechanistic pic-
ture. These initial results suggest that cooperative cat-
alysis might not be solely operative for this intramo-
lecular transformation.[33]
[1] a) K.-H. Lee, G. K. Rice, I. H. Hall, V. Amarnath, J.
Med. Chem. 1987, 30, 586–588; b) X.-p. Fang, J. E. An-
derson, C.-j. Chang, J. L. McLaughlin, Tetrahedron
1991, 47, 9751–9758; c) X. Yang, Y. Shimizu, J. R. Stein-
er, J. Clardy, Tetrahedron Lett. 1993, 34, 761–764;
d) W. F. a. S. Schulz, Comprehensive Natural Products
Chemistry, Vol. 8, Elsevier, Amsterdam, 1999; e) D. J.
Faulkner, Nat. Prod. Rep. 2001, 18, 1R–49R; f) S.
Schulz, S. Hotling, Nat. Prod. Rep. 2015, 32, 1042–1066.
[2] M. A. Churchill, H. Sibhatu, C. Uhlson, in: Quorum
Sensing, Vol. 692, (Ed.: K. P. Rumbaugh), Humana
Press, 2011, pp 159–171.
Finally, the dinuclear gold(I) complex 1a proved es-
sential for the synthesis of e-lactones, which suggests
that a different mechanism may indeed be at play in
the intramolecular cyclization of heptynoic acids.
In conclusion, an efficient and improved synthesis
of g-, d- and e-lactones has been presented. The pro-
cess provides access to a wide range of molecules in
a highly regio- and stereoselective manner. The meth-
odology satisfies some basic principles of green
chemistry: where no need of additives is required, sol-
vent-free conditions are used and extremely low cata-
lyst loadings (down to 25 ppm) are employed. The
rather mild reaction conditions compared to previous
methodologies open the way to explore even more
complex structures. Further investigations are being
carried out in order to shed light on the activation
mode and reaction mechanism of the transformation.
Efforts aimed at widening the scope to other applica-
tions are ongoing in our laboratories.
[3] I. K. Monika, J. P. Balbina, Mini-Rev. Med. Chem. 2005,
5, 73–95.
[4] a) M. Teplitski, J. B. Robinson, W. D. Bauer, Mol.
Plant-Microbe Interact. 2000, 13, 637–648; b) H. Lade,
D. Paul, J. H. Kweon, BioMed Res. Int. 2014, 2014, 25.
[5] a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004,
104, 3079–3160; b) N. T. Patil, R. D. Kavthe, V. S.
Shinde, Tetrahedron 2012, 68, 8079–8146; c) M. ꢄlvar-
ez-Corral, M. MuÇoz-Dorado, I. Rodrꢅguez-Garcꢅa,
Chem. Rev. 2008, 108, 3174–3198.
[6] a) C. Lambert, K. Utimoto, H. Nozaki, Tetrahedron
Lett. 1984, 25, 5323–5326; b) D. Bouyssi, J. Gore, G.
Balme, Tetrahedron Lett. 1992, 33, 2811–2814; c) A.
Arcadi, A. Burini, S. Cacchi, M. Delmastro, F. Marine-
lli, B. R. Pietroni, J. Org. Chem. 1992, 57, 976–982; d) J.
Garcia-Alvarez, J. Diez, C. Vidal, Green Chem. 2012,
14, 3190–3196; e) R. Rossi, F. Bellina, M. Biagetti, A.
Catanese, L. Mannina, Tetrahedron Lett. 2000, 41,
5281–5286; f) N. Nebra, J. Monot, R. Shaw, B. Martin-
Vaca, D. Bourissou, ACS Catal. 2013, 3, 2930–2934;
g) N. Conde, R. SanMartin, M. T. Herrero, E. Domꢅ-
nguez, Adv. Synth. Catal. 2016, 358, 3283–3292.
[7] a) T. B. Marder, D. M. T. Chan, W. C. Fultz, J. C. Cal-
abrese, D. Milstein, J. Chem. Soc. Chem. Commun.
1987, 1885–1887; b) D. M. T. Chan, T. B. Marder, D.
Milstein, N. J. Taylor, J. Am. Chem. Soc. 1987, 109,
6385–6388.
[8] a) M. Yamamoto, J. Chem. Soc. Chem. Commun. 1978,
649–650; b) G. A. Krafft, J. A. Katzenellenbogen, J.
Am. Chem. Soc. 1981, 103, 5459–5466; c) A. Jellal, J.
Grimaldi, M. Santelli, Tetrahedron Lett. 1984, 25, 3179–
3182.
[9] C. Sun, Y. Fang, S. Li, Y. Zhang, Q. Zhao, S. Zhu, C.
Li, Org. Lett. 2009, 11, 4084–4087.
[10] a) P. Pale, J. Chuche, Tetrahedron Lett. 1987, 28, 6447–
6448; b) J. A. Marshall, M. A. Wolf, E. M. Wallace, J.
Org. Chem. 1997, 62, 367–371; c) R. Rossi, F. Bellina,
C. Bechini, L. Mannina, P. Vergamini, Tetrahedron
1998, 54, 135–156; d) V. Dalla, P. Pale, N. J. Chem.
1999, 23, 803–805.
Experimental Section
General Procedure for the Gold-Catalysed
Cyclisation of Alkynoic Acids
In a scintillation vial, the alkynoic acid (0.25–1 mmol) and
[{Au(IPr)}2(m-OH)][BF4] 1a (25 ppm–1 mol%) or [Au(I-
Pr)(OH)] 1b (0.2 mol%), were stirred in absence of solvent
or in CH2Cl2 at room temperature or 658C (400 rpm). The
reaction was monitored by 1H NMR spectroscopy or GC
until complete cyclisation of the alkynoic acid (5 min–48 h).
After the reaction was completed the mixture was diluted
with Et2O or pentane (ca. 1 mL), filtered through a short
plug of MgSO4 and concentrated under vacuum. The residue
was then purified by pentane washing (3ꢃ5 mL) to afford
the corresponding product.
Acknowledgements
Support from the ERC (FUNCAT) (to SPN), Umicore AG
and King Saud University is gratefully acknowledged. We
[11] A. Fꢆrstner, P. W. Davies, Angew. Chem. 2007, 119,
3478–3519; Angew. Chem. Int. Ed. 2007, 46, 3410–3449.
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!