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COMMUNICATION
Journal Name
The developed acid-assisted activation mechanism was then number 180234. C.A.-F. and J.B. expresses gratituVdieew fAortricleEOPnSlRinCe
utilised in enyne cycloisomerization and nucleophilic alcohol funding (EP/S005315/1). M.Sc. Karina MoDslOoIv:a10a.1c0k3n9o/Dw0leCdCg0e5d99f9oDr
(ROH) addition cascade reaction, following previous L-Au(I) measuring elemental analysis.
catalysis reports (Scheme 4, Table S3).18,22 Full conversion was
achieved for each case, and MeOH delivered the best yield of
98% for 12a while allyl and benzyl alcohols gave lower yields.
Conflicts of interest
Similarly, good yields were obtained for OMe-substituted vinyl
enyne substrates (9d-9f), but benzyl alcohol nucleophile
substituted the methoxy group in the product 12e.
There are no conflicts to declare.
Notes and references
Table 2 Screening of additives for enyne cycloisomerization
1
2
D. J. Gorin, B. D. Sherry and F. D. Toste, Chem. Rev., 2008, 108, 3351.
W. Wang, G. B. Hammond and B. Xu, J. Am. Chem. Soc., 2012, 134,
5697.
M. Jia and M. Bandini, ACS Catal., 2015, 5, 1638.
A. Zhdanko and M. E. Maie, ACS Catal., 2015, 5, 5994.
a) Minqiang Jia and Marco Bandini, ACS Catal., 2015, 5, 1638; b) B.
Ranieri, I. Escofeta and A. M. Echavarren, Org. Biomol. Chem., 2015,
13, 7103; c) D. Zuccaccia, A. Del Zotto and W. Baratta, Coord. Chem.
Rev., 2019, 396, 103.
T. Zhou, L. Xu and Y. Xia, Org. Lett., 2013, 15, 6074.
M. Wegener, F. Huber, C. Bolli, C. Jenne and S. F. Kirsch, Chem.
Eur. J. 2015, 21, 1328.
C. Nevado and A. M. Echavarren, Chem. Eur. J. 2005, 11, 3155.
E. Peris, Chem. Rev. 2018, 118, 9988.
O
O
O
O
O
O
O
2a
O
2 mol%
O
O
O
O
5 mol% acid
+
3
4
5
CH2Cl2, RT
R
9
10
11
R
R'
R'
R, R' = Me
R
R'
a
Entry
1
2
3
4
5
6
7
8
Additive
-
pKa
-
∆G(Au-X)b
-
t
Yieldc 10:11 (%)
trace:0
trace:0
trace:0
50:0
1 h
1 h
1 h
1 h
1 h
40 min
15 min
15 min
10 min
1h
TFE
AcOH
73.2
59.3
54.5
50.7
48.4
46.2
41.4
41.3
41.3
-
6
7
-0.5
4.2
7.2
9.3
9.4
ClCH2COOH
Cl2CHCOOH
åCl3CCOOH
TFA
99:0
99:0
99:0
45:54
66:33
trace:0
8
9
10 a) M. Muuronen, J. E. Perea-Buceta, M. Nieger, M. Patzschke and J.
Helaja, Organometallics, 2012, 31, 4320; b) M. Muuronen, PhD
thesis, University of Helsinki, 2015.
MsOH
12.0
14.1
14.1
9
p-TsOH
p-TsOH + 5a
10
11 a) E. Mendivil-Tomás, P. Y. Toullec, J. Díez, S. Conejero, V. Michelet
and V. Cadierno, Org. Lett., 2012, 14, 2520; b) E. Tomás-Mendivil, P.
Y. Toullec, J. Borge, S. Conejero, V. Michelet and V. Cadierno, ACS
Catal., 2013, 3, 3086.
a
b
Computed pKa values in DCM, see SI for details. Au-X bond strength with the
conjugate base relative to Au-Cl in kcal/mol, see SI for details. c Determined by 1H
NMR using trimethoxybenzene as an internal standard.
O
O
O
O
12 S. Sen and F. P. Gabbai, Chem. Commun., 2017, 53, 13356.
13 Key references: a) A. S. K. Hashmi, J. P. Weyrauch, W. Frey and J. W.
Bats, Org. Lett., 2004, 6, 4391; b) G. Verniest and A. Padwa, Org.
Lett., 2008, 10, 4379; c) D. Aguilar, M. Contel, R. Navarro, T. Soler
and P. E. Urriolabeitia, J. Organomet. Chem., 2009, 694, 486; d) J. P.
Weyrauch, A. S. K. Hashmi, A. Schuster, T. Hengst, S. Schetter, A.
Littmann, M. Rudolph, M. Hamzic, J. Visus, F. Rominger, W. Frey and
J. W. Bats, Chem. Eur. J., 2010, 16, 956; e) O. A. Egorova, H. Seo, Y.
Kim, D. Moon, Y. M. Rhee and K. H. Ahn, Angew. Chem. Int. Ed. 2011,
50, 11446.
O
2a
2 mol%
O
O
5 mol% TsOH
O
10 11
+ (
/
)
3:1
DCM:ROH
10min
R
R
R'
9a-b
R' OR
ROH = MeOH, BnOH
or allylOH
12a-g
O
O
O
O
O
O
O
O
O
R, R' = Me
O
O
O
OAllyl
OBn
OMe
98%
14 A. S. K. Hashmi, A. M. Schuster, M. Schmuck and F. Rominger, Eur.
J. Org. Chem. 2011, 4595.
15 R. BabaAhmadi, P. Ghanbari, N. A. Rajabi, A. S. K. Hashmi, B. F. Yates
and A. Ariafard, Organometallics, 2015, 34, 3186.
12a
12b
12c
74% + (20%)
30% + (55%)
R = H
R' = OMe
O
O
O
O
O
O
O
O
O
O
O
O
16 M. Chiarucci and M. Bandini Beilstein J. Org. Chem., 2013, 9, 2586.
17 C. M. Krauter, A. S. K. Hashmi and M. Pernpointner, ChemCatChem,
2010, 2, 1226.
18 C. Nieto-Oberhuber, M. P. Muñoz, E. Buñuel, C. Nevado, D. J.
Cárdenas and A. M. Echavarren, Angew. Chem. Int. Ed., 2004, 43,
2402.
O
O
BnO
OMe
OAllyl
OBn
51%
12d
12e
12f
68%
85%
Scheme 4 Substrate scope in enyne cycloisomerization, with isolated yields.
Yield in parenthesis is the combined yield of products 10 and 11.
19 Previously, an acid additive (HSbF6) has been reported to cause
similar mixture of isomers in the NHC-Au(I) catalysis: S. Ferrer, A. M.
Echavarren, Organometallics, 2018, 37, 781.
20 Z. Lu, J. Han, O. E. Okoromoba, N. Shimizu, H. Amii, C. F. Tormena, G.
B. Hammond and B. Xu, Org. Lett., 2017, 19, 5848.
21 E. Paenurk, K. Kaupmees, D. Himmel, A. Kütt, I. Kaljurand, I. A.
Koppel, I. Krossing and I. Leito, Chem. Sci. 2017, 8, 6964.
Y. Tang, I. Benaissa, M. Huynh, L. Vendier, N. Lugan, S. Bastin, P.
Belmont, V. César and V. Michelet, Angew. Chem. Int. Ed., 2019, 58,
7977.
In conclusion, we have developed H-bond donor tethered
NHC-ligands for in situ activated L-Au(I)Cl catalysis. Ethyl tosyl
amide functionalised Au(I) complex 2a catalysed the oxazole
synthesis selectively from terminal alkynes, and successful
enyne cycloisomerization was accomplished with an acid
additive. Computational analysis supports the mechanistic
scenario that the H-bond donor ligand assists in the Au-Cl bond
activation.
Financial support from Academy of Finland [project no. 129062
(J.H.)] is acknowledged. The Finnish National Centre for Scientific
Computing (CSC) is recognized for computational resources. O.S.
acknowledges the Emil Aaltonen foundation for funding, grant
22 Y. Tang, I. Benaissa, M. Huynh, L. Vendier, N. Lugan, S. Bastin, P.
Belmont, V. César, V. Michelet Angew. Chem. Int. Ed. 2019, 58, 7977.
4 | J. Name., 2012, 00, 1-3
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