An efficient silver tetrafluoroborate-catalyzed cycloisomerization of ynamides

Article abstract of DOI:10.3987/COM-18-S(F)21

A silver catalyzed-cycloisomerization of N-Boc protected ynamides has been developed under mild reaction conditions to provide a wide range of oxazol-2(3H)-ones in good to excellent yields. Moreover, the acid-promoted Pictet-Spengler cyclization of oxazol

Full text of DOI:10.3987/COM-18-S(F)21

HETEROCYCLES, Vol. 99, No. , 2019, pp. -. © 2019 The Japan Institute of Heterocyclic Chemistry
Received, 18th July, 2018, Accepted, 15th August, 2018, Published online, 29th August, 2018
DOI: 10.3987/COM-18-S(F)21
AN EFFICIENT SILVER TETRAFLUOROBORATE-CATALYZED
CYCLOISOMERIZATION OF YNAMIDES
Winai Ieawsuwana* and Somsak Ruchirawata,b,c
a
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54
Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand.
b Chemical Biology Program, Chulabhorn Graduate Institute, 54 Kamphaeng Phet
6 Road, Laksi, Bangkok, 10210, Thailand.
c Center of Excellence on Environmental Health and Toxicology (EHT), Ministry
of Education, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand
E-mail: winai@cri.or.th
This paper is dedicated to Professor Tohru Fukuyama on the occasion of his 70th
birthday.
Abstract – A silver catalyzed-cycloisomerization of N-Boc protected ynamides
has been developed under mild reaction conditions to provide a wide range of
oxazol-2(3H)-ones in good to excellent yields. Moreover, the acid-promoted
Pictet-Spengler cyclization of oxazol-2(3H)-ones was described to furnish the
corresponding trans-oxazolidones in moderate yields.
The heterocycle oxazol-2(3H)-ones have emerged as versatile building blocks for synthetic organic
chemists and pharmacologists.1 Some substituted oxazol-2(3H)-ones exhibiting herbicidal, antibacterial,
antitumor, and neuroleptic activities as well as inhibition against cyclooxygenase-2 have been studied for
several decades (Figure 1).2 Additionally, the commercially available Linezolid drug (Zyvox®),
containing 2-oxazolidone core structure, has been developed against Gram-positive bacteria.3 A number
of synthetic routes of various substituted oxazol-2(3H)-ones usually involved carbonyl condensation
processes to establish the cyclic carbamate moiety.4 Alternatively, photochemical promoted chlorination5
and electrochemical oxidation6 of 2-oxazolidones followed by thermal elimination process have also been
studied for the synthesis of various oxazol-2(3H)-ones. Further synthetic applications of
oxazol-2(3H)-one derivatives have been demonstrated for the introduction of additional functionalities,
such as, substitution at the nitrogen atom by alkylation or acylation, substitution at the carbonyl oxygen

by halogenation reaction, and electrophilic addition of the reactive olefin moiety.7 Therefore, the
modifications and transformations for the new types of oxazol-2(3H)-ones to prepare the valuable
N-containing heterocycles still remain a challenge.
Figure 1. Some biologically active compounds containing oxazol-2(3H)-one and 2-oxazolidone skeletons
Recently, we reported the synthesis of the corresponding tetrahydroisoquinoline-oxazol-2(3H)-ones 2
from ynamides 1 via [bis(trifluoroacetoxy)iodo]benzene (PIFA) and BF3·OEt2-mediated domino
cyclization reaction (Scheme 1).8 Interestingly, the obtained tetrahydroisoquinoline-oxazol-2(3H)-ones 2
have attracted our attention for their potent anticancer activities. Therefore, the structural modification of
tetrahydroisoquinoline-oxazol-2(3H)-ones 2 was also investigated by hydrogenation of the olefin moiety9
to provide the cis-oxazolidones 3 and the resulting anticancer activities of these compounds are still
promising. For comparing anticancer activities, the trans-oxazolidones 3 were contemplated and sought
after. Thus, we hypothesized that the trans-oxazolidone 3 would be synthesized from an acid-mediated
Pictet-Spengler cyclization of oxazol-2(3H)-ones 4 via an N-acyliminium ion 5.10 So far, the previous
procedures for the preparation of 3,5-disubstituted oxazol-2(3H)-ones from ynamides11 were reported by
using the expensive gold,12 palladium,13 and rhodium complexes14 or using copper catalysts.15
Nevertheless, most of those reaction conditions required relatively high temperatures to affect the
reactions. Additionally, Gagosz and coworkers also reported the use of expensive silver triflimide to
catalyzed the cycloisomerization of ynamide at ambient temperature only for a few substrates.12b,c During
the development of acid-mediated cyclization of a N-acyliminium ion, we required a practical and
efficient method to access various substituted oxazol-2(3H)-ones 4 from ynamide 1. Herein, we wish to
report our results on the development of such process, namely, the silver-catalyzed cycloisomerization16
of ynamide and the subsequent acid-mediated Pictet-Spengler cyclization reaction.

PIFA, BF3·OEt2
H2, Pd/C
EtOAc
RO
RO
RO
N
N
N
O
O
CH2Cl2
-96 °C, 3 h
Boc
ynamide 1
H
O
O
Ar
Ar
Ar
2
H
cis-oxazolidone 3
transition metal
catalyzed reaction
Pictet-Spengler
type cyclization
RO
RO

H+
RO
N
N
O
N
O
O
O
H
O
O
H
Ar
acyl-iminium ion 5
Ar
Ar
trans-oxazolidone 3
oxazol-2(3H)-one 4
Scheme 1. Synthetic routes for the preparation of cis- and trans-oxazolidone 3
Our initial experiment of the silver-catalyzed cycloisomerization of ynamide 1a concentrated on the
optimization of reaction parameters, such as silver salts, solvent, catalyst loading and reaction time. We
found that the use of 5 mol% of silver iodide, silver acetate, silver triflate, silver carbonate or silver oxide
in dichloromethane at room temperature (Table 1, entries 1-5) did not result in the formation of the
desired product. Treatment of the ynamide 1a with 5 mol% of silver fluoride, silver trifluoroacetate or
silver sulfate could furnish the product 4a; however, low conversions of about 10% were observed by 1H
NMR of the crude product (Table 1, entries 6-8). Performing the reaction with 5 mol% of silver triflimide,
silver nitrate, silver hexafluoroantimonate (V) or silver nitrite provided the corresponding product 4a after
18 h in the yields of 72-89% (Table 1, entries 9-12). Surprisingly, the reaction of ynamide 1a with 5
mol% of silver tetrafluoroborate provided the corresponding product 4a almost in quantitative yield after
18 h (Table 1, entry 13). Other solvents, such as chloroform, 1,2-dichloroethane, acetonitrile, toluene,
diethyl ether, ethyl acetate and acetone, were also investigated but all gave less satisfactory results
(0-62% yield). In order to ascertain whether silver tetrafluoroborate served as a true catalyst for this
cycloisomerization, a control experiment, whereby 5 mol% of triethylamine was added to capture any in
situ formed Brønsted acid, was performed.17 Under this reaction condition, the product 4a was still
generated in 82% yield (Table 1, entry 14); this result thus further supported the role of silver
tetrafluoroborate as a true catalyst for this reaction. Additionally, decreasing amount of silver
tetrafluoroborate to 1 and 0.5 mol% resulted in complete conversion of 1a after 36 and 48 h, respectively,
but yields of oxazol-2(3H)-one 4a were considerably lower (Table 1, entries 15 and 16). In addition,
complex mixtures were observed. This could be accounted for by the slow decomposition of the
corresponding oxazol-2(3H)-one product under Lewis acid conditions when the reaction time exceeded
18 h. Therefore, we decided to employ the reaction condition in entry 13 to investigate the scope of this
transformation.18

Table 1. Screening of silver salts
entrya Ag salt (mol%) Conversion (%)b Yield (%)c entrya Ag salt (mol%) Conversion (%)b Yieldꢀ(%)c
1
2
3
4
5
6
7
8
AgI (5)
nrd
nrd
nrd
nrd
nrd
10
–
9
AgNTf2 (5)
AgNO3 (5)
AgSbF6 (5)
AgNO2 (5)
AgBF4 (5)
AgBF4 (5)
AgBF4 (1)
100
100
100
100
100
100
100
100
72
79
81
89
98
82
90
AgOAc (5)
AgOTf (5)
Ag2CO3 (5)
Ag2O (5)
–
10
11
12
13
14e
15f
–
–
–
AgF (5)
trace
trace
trace
AgTFA (5)
Ag2SO4 (5)
10
10
16g AgBF4 (0.5)
81
a
b
Reaction conditions: 1a (0.05 mmol), Ag salt (0.05 equiv) in CH2Cl2 (1 mL) for 18 h. Percent
c
conversions were determined by 1H NMR analysis of the crude product. Isolated yields after column
d
e
chromatography. nr = no reaction. Reaction condition: 1a (0.10 mmol), AgBF4 (0.05 equiv), Et3N
f
(0.05 equiv) in CH2Cl2 (2 mL) for 18 h. Reaction condition: 1a (1.0 mmol), AgBF4 (0.01 equiv) in
g
CH2Cl2 (5 mL) for 36 h. Reaction condition: 1a (1.0 mmol), AgBF4 (0.005 equiv) in CH2Cl2 (5 mL)
for 48 h.
Next, various ynamides 1b-1r were investigated and we found that the use of 5 mol% of silver
tetrafluoroborate was quite general to transform the substituted ynamides bearing both aromatic groups on
Ar1 and R1 with the yields ranging from 70 to 99% (Table 2, entries 1-13 and 15-18). If Ar1 or R1 of the
ynamide substrates bear electron-donating or electron-withdrawing group, the resulting products were
formed without significant difference in terms of yields. However, the ynamide 1q with electronically
neutral phenyl groups as both Ar1 and R1 gave much lower yield of the corresponding product (Table 2,
entry 17). Surprisingly, this catalyst could also catalyze the cycloisomerization of the ynamide 1r bearing
an N-methylindole moiety as Ar1 to provide the corresponding product oxazol-2(3H)-one 4r as a sole
product in 87% yield (Table 2, entry 18). However, while treating the highly reactive alkene conjugated
ynamide 1n with 5 mol% of silver tetrafluoroborate resulted in full conversion, the corresponding
oxazol-2(3H)-one 4n was isolated only 32% yield (Table 2, entry 14). The lower yield of

oxazol-2(3H)-one 4n was probably due to the relatively high reactive conjugated alkene moiety in the
product 4n slowly decomposed under this reaction condition.
Table 2. AgBF4-catalyzed cycloisomerization of ynamide 1a-1r
entrya
Ynamide
Ar1
R1
Yield (%)b
1
3,4-(MeO)2-C6H3
Ph
4a, 98
4b, 75
4c, 78
4d, 97
4e, 97
4f, 98
4g, 95
4h, 96
4i, 90
4j, 97
4k, 88
4l, 89
4m, 78
4n, 32
4o, 95
4p, 99
4q, 70
1a
1b
1c
1d
1e
1f
2
3,4-(MeO)2-C6H3
3,4-OCH2O-C6H3
o-(MeO)-C6H4
m-(MeO)-C6H4
p-(MeO)-C6H4
p-F-C6H4
3
4
5
6
7
1g
1h
1i
8
3,4-OCH2O-C6H3
Ph
9
3,4-(MeO)2-C6H3
3,4-OCH2O-C6H3
o-(MeO)-C6H4
m-(MeO)-C6H4
p-(MeO)-C6H4
1-cyclohexene
Ph
10
11
12
13
14
15
16
17
1j
1k
1l
1m
1n
1o
1p
1q
1r
3,4,5-(MeO)3-C6H2
3,4-(MeO)2-C6H3
Ph
Ph
18
3-(N-methyl)indole
Ph
4r, 87
a
b
Reaction conditions: ynamide 1, AgBF4 (0.05 equiv) in CH2Cl2 (0.05 M) for 18 h. Isolated yields
after chromatography.
To study the generality of this AgBF4-catalyzed cycloisomerization of the substituted ynamides, we
decided to synthesize various substituted ynamides 6a-6k using CuSO4·5H2O catalyzed cross-coupling
method12b,19 and then employed these ynamides 6a-6k as substrates under the optimized reaction
condition. We found that ynamides 6a-c substituted with phenyl, 3,4-dimethoxybenzene or benzyl group

as R2 and substituted with phenyl as R3 yielded the corresponding oxazol-2(3H)-ones 7a-c in high yields
of 70-88% (Table 3, entries 1-3). While ynamides 6d-g substituted with electron-withdrawing groups,
such as p-chlorobenzene, o-bromobenzene, p-trifluoromethylbenzene or ethyl 2-acetate as R2 and
substituted with phenyl as R3 resulted in oxazol-2(3H)-ones 7d-g in moderate to excellent yields of
43-99% (Table 3, entries 4-7). The substituent effects on R3 were also investigated and we found that
ynamides 6h-i and 6k, substituted with silyl ether or ester groups as R3, afforded the corresponding
oxazol-2(3H)-ones 6h-i and 6k in good to excellent yields of 72-99% (Table 3, entries 8-9 and 11).
However, with ynamide 6j, substituted with 1-cyclohexene as R3, the desired oxazol-2(3H)-one 7j was
obtained only 39% yield (Table 3, entry 10).
Table 3. AgBF4-catalyzed cycloisomerization of ynamide 6a-6k
entrya
Ynamide
R2
R3
Yield (%)b
1
Ph
Ph
7a, 80
7b, 88
7c, 70
7d, 99
7e, 43
7f, 65
7g, 76
7h, 99
7i, 99
7j, 39
7k, 72
6a
6b
6c
6d
6e
6f
2
3,4-(MeO)2-C6H3
Ph
3
Bn
Ph
4
p-Cl-C6H4
o-Br-C6H4
p-CF3-C6H4
–CH2CO2Et
Ph
Ph
5
Ph
6
Ph
7
Ph
6g
6h
6i
8
–(CH2)8OTIPS
–CH2OAc
1-cyclohexene
–(CH2)8OTIPS
9
Ph
10
Ph
6j
11
Bn
6k
a
b
Reaction conditions: ynamide 6, AgBF4 (0.05 equiv) in CH2Cl2 (0.05 M) for 18 h. Isolated yields
after chromatography.
After having developed an efficient silver-catalyzed cycloisomerization of ynamides, we then considered
whether it would be possible to extend the obtained oxazol-2(3H)-one 4a to the more valuable
tetrahydroisoquinoline-oxazolidone 3a via an acid-mediated Pictet-Spengler cyclization process. Several
reaction conditions were screened and the best reaction condition was found to be the use of 2.5

equivalents of TsOH·H2O in acetonitrile under microwave irradiation at 200 W, 50 psi and 100 °C for 3 h
to provide oxazolidone 3a in 75% yield as a 10:1 mixture (trans:cis) (Table 4, entry 1).20 Unfortunately,
oxazol-2(3H)-ones 4b and 4c, substituted with 3,4-dimethoxybenzene and 3,4-methylenedioxybenzene as
the aryl ring C, resulted only in the decomposition of the starting material and oxazolidones 3b and 3c
were not detected under this optimized reaction condition (Table 4, entries 2-3). The decomposition of 4b
and 4c was probably due to the high electron density of the aryl ring C which rendered the
oxazol-2(3H)-one ring unstable under this strongly acidic condition. Finally, oxazol-2(3H)-ones 4h and
4o were also employed under this optimized reaction condition and trans-oxazolidones 3d and 3e were
obtained as sole geometrical products in 58 and 50% yields, respectively (Table 4, entries 4-5).
Table 4. An acid-mediated Pictet-Spengler cyclization under microwave irradiation
Entrya
R
Ar
Yield (%)b
trans:cisc
4
1
2
3
4
5
R4 = R5 = MeO, R6 = H
R4 = R5 = MeO, R6 = H
R4 = R5 = MeO, R6 = H
R4–R5 = OCH2O, R6 = H Ph
R4 = R5 = R6 = MeO
Ph
Ph
3a, 75
3b, ndd
3c, ndd
3d, 58
3e, 50
10:1
4a
4b
4c
4h
4o
3,4-(MeO)2-C6H3
3,4-OCH2O-C6H3
–
–
only trans
only trans
a Reaction conditions: 4 (0.05 mmol), TsOH·H2O (2.5 equiv) in MeCN (1 mL); microwave condition:
b
c
200W, 50 psi, 100 °C. Isolated yield after chromatography. Diastereomeric ratio was determined by
1H NMR analysis of the crude product. d nd = not detected
In summary, we have developed an efficient silver-catalyzed cycloisomerization of a wide range of
ynamides to provide the corresponding oxazol-2(3H)-one derivatives in good to excellent yields. The
operational simplicity and practicability and the mild reaction conditions, as well as the low catalyst
loading and low cost of silver tetrafluoroborate, as compared to gold, palladium and rhodium salts, render
this transformation an attractive approach to various oxazol-2(3H)-one heterocycles. Additionally, we
were able to demonstrate that the acid-mediated Pictet-Spengler cyclization of oxazol-2(3H)-ones could
furnish to the corresponding trans-oxazolidones as major products in moderate yields.

ACKNOWLEDGEMENTS
We are deeply appreciative of generous financial support from the Thailand Research Fund (TRF;
TRG5780054 for W.I.), the Development and Promotion of Science and Technology Talents Project
(DPST; 022/2558), the Institute for the Promotion of Teaching Science and Technology (IPST) and
Chulabhorn Research Institute.
REFERENCES AND NOTES
1. (a) D. W. Knight, 'Heterocycles in Natural Product Synthesis', ed. by K. C. Majumdar and S. K.
Chatopadhyay, Wiley-VCH, Weinheim, 2011, pp. 403-458; (b) S. P. Fearnley, Curr. Org. Chem.,
2004, 8, 1289.
2. (a) N. Kudo, M. Taniguchi, S. Furuta, K. Sato, T. Endo, and T. Honma, J. Agric. Food Chem., 1998,
46, 5305; (b) E. R. Pereira, M. Sancelme, A. Voldoire, and M. Prudhomme, Bioorg. Med. Chem.
Lett., 1997, 7, 2503; (c) M. Daneshtalab, Top. Heterocycl. Chem., 2006, 2, 153; (d) N.-H. Nam, Y.
Kim, Y.-J. You, D.-H. Hong, H.-M. Kim, and B.-Z. Ahn, Bioorg. Med. Chem. Lett., 2001, 11, 3073;
(e) G. Cascio, E. Manghisi, and G. Fregnan, J. Med. Chem., 1989, 32, 2241; (f) C. Puig, M. I.
Crespo, N. Godessart, J. Feixas, J. Ibarzo, J.-M. Jiménez, L. Soca, I. Cardelús, A. Heredia, M.
Miralpeix, J. Puig, J. Beleta, J. M. Huerta, M. López, V. Segarra, H. Ryder, and J. M. Palacios, J.
Med. Chem., 2000, 43, 214.
3. M. R. Barbachyn and C. W. Ford, Angew. Chem. Int. Ed., 2003, 42, 2010.
4. (a) H. Aichaoui, J. H. Poupaert, D. Lesieur, and J.-P. Hénichart, Tetrahedron, 1991, 47, 6649; (b) M.
O. Hamad, P. K. Kiptoo, A. L. Stinchcomb, and P. A. Crooks, Bioorg. Med. Chem., 2006, 14, 7051;
(c) S. A. Savarimuthu, S. A. Thomas, D. G. L. Prakash, and T. Gandhi, ChemistrySelect, 2016, 1,
2035.
5. (a) K.-H. Scholz, H.-G. Heine, and W. Hartmann, Liebigs Ann. Chem., 1976, 1976, 1319; b) T.
Kunieda, Y. Abe, Y. Iitaka, and M. Hirobe, J. Org. Chem., 1982, 47, 4291; (c) K.-H. Scholz, H.-G.
Heine, and W. Hartmann, Org. Synth., 1984, 62, 149; (d) F. C. Gaenzler and M. B. Smith, Synlett,
2007, 1299.
6. (a) P.-C. Wang, Heterocycles, 1985, 23, 2237; (b) D. Tavernier, S. van Damme, P. Ricquier, and M.
J. O. Anteunis, Bull. Soc. Chim. Belg., 1988, 97, 859.
7. For selected examples, see: (a) S. P. Fearnley and E. Market, Chem. Commun., 2002, 438; (b) G.
Butora, T. Hudlicky, S. P. Fearnley, A. G. Gum, M. R. Stabile, and K. Abboud, Tetrahedron Lett.,
1996, 37, 8155; (c) G. Butora, T. Hudlicky, S. P. Fearnley, M. R. Stabile, A. G. Gum, and D.
Gonzalez, Synthesis, 1998, 665; (d) T. Choshi, H. Fujimoto, E. Sugino, and S. Hibino, Heterocycles,
1996, 43, 1847; (e) H. Matsunaga, T. Ishizuka, and T. Kunieda, Tetrahedron, 1997, 53, 1275; (f) T.

Kunieda, T. Higuchi, Y. Abe, and M. Hirobe, Chem. Pharm. Bull., 1984, 32, 2174; (g) G. Kjellin,
and J. Sandström, Acta Chem. Scand., 1969, 23, 2879; (h) T. Morita, Y. Nagasawa, S. Yahiro, H.
Matsunaga, and T. Kunieda, Org. Lett., 2001, 3, 897; (i) T. Kunieda, T. Ishizuka, T. Higuchi, and M.
Hirobe, J. Org. Chem., 1988, 53, 3381.
8. W. Ieawsuwan and S. Ruchirawat, Bioorg. Med. Chem., 2017, 25, 2856.
9. Unpublished results.
10. For selected examples, see: (a) U. Martínez-Estibalez, A. Gómez-SanJuan, O. García-Calvo, E.
Aranzamendi, E. Lete, and N. Sotomayor, Eur. J. Org. Chem., 2011, 3610; (b) A. Pesquet, L. V.
Hijfte, and A. Daïch, ARKIVOC, 2010, viii, 27; (c) M. Chiurato, R. Boulahjar, S. Routier, Y. Troin,
and G. Guillaumet, Tetrahedron, 2010, 66, 4647; (d) M. Stojanović, R. Marković, E. Kleinpeter, and
M. Baranac-Stojanović, Tetrahedron, 2011, 67, 9541; (e) M. S. Ledovskaya, A. P. Molchanov, V. M.
Boitsov, R. R. Kostikov, and A. V. Stepakov, Tetrahedron, 2015, 71, 1952; (f) F. Berti, F. Malossi,
F. Marchetti, and M. Pineschi, Chem. Commun., 2015, 51, 13694; (g) S. Kano, Y. Yuasa, T.
Yokomatsu, and S. Shibuya, J. Org. Chem., 1983, 48, 3835; (h) Y. Zhang, R. P. Hsung, X. Zhang, J.
Huang, B. W. Slafer, and A. Davis, Org. Lett., 2005, 7, 1047.
11. For reviews, see: (a) K. A. DeKorver, H. Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang, and R. P.
Hsung, Chem. Rev., 2010, 110, 5064; (b) G. Evano, A. Coste, and K. Jouvin, Angew. Chem. Int. Ed.,
2010, 49, 2840; (c) G. Evano, K. Jouvin, and A. Coste, Synthesis, 2013, 45, 17; (d) X.-N. Wang,
H.-S. Yeom, L.-C. Fang, S. He, Z.-X. Ma, B. L. Kedrowski, and R. P. Hsung, Acc. Chem. Res., 2014,
47, 560; (e) J. A. Mulder, K. C. M. Kurtz, and R. P. Hsung, Synlett, 2003, 1379.
12. (a) A. S. K. Hashmi, R. Salathé, and W. Frey, Synlett, 2007, 1763; (b) F. M. Istrate, A. K. Buzas, I.
D. Jurberg, Y. Odabachian, and F. Gagosz, Org. Lett., 2008, 10, 925; (c) A. Buzas, F. Istrate, X. F.
Le Goff, Y. Odabachian, and F. Gagosz, J. Organomet. Chem., 2009, 694, 515.
13. (a) Z. Lu, X. Xu, Z. Yang, L. Kong, and G. Zhu, Tetrahedron Lett., 2012, 53, 3433; (b) H. Huang, G.
He, G. Zhu, X. Zhu, S. Qiu, and H. Zhu, J. Org. Chem., 2015, 80, 3480.
14. R. Rey-Rodriguez, G. Grelier, L. Habert, P. Retailleau, B. Darses, I. Gillaizeau, and P. Dauban, J.
Org. Chem., 2017, 82, 11897.
15. Z. Lu, Z. Yang, W. Cui, and G. Zhu, Chem. Lett., 2012, 41, 636.
16. For reviews, see: (a) P. Belmont, 'Silver in Organic Chemistry', ed. by M. Harmata, John Wiley &
Sons, Inc., New Jersey, 2010, pp. 143-166; (b) G. Fang and X. Bi, Chem. Soc. Rev., 2015, 44, 8124;
(c) Q.-Z. Zheng and N. Jiao, Chem. Soc. Rev., 2016, 45, 4590; (d) J.-M. Weibel, A. Blanc, and P.
Pale, Chem. Rev., 2008, 108, 3149; (e) M. Álvarez-Corral, M. Muñoz-Dorado, and I.
Rodríguez-García, Chem. Rev., 2008, 108, 3174; (f) Y. Yamamoto, Chem. Rev., 2008, 108, 3199; (g)
M. Naodovic and H. Yamamoto, Chem. Rev., 2008, 108, 3132; (h) N. T. Patil and Y. Yamamoto,

Chem. Rev., 2008, 108, 3395; (i) P. Belmont and E. Parker, Eur. J. Org. Chem., 2009, 2009, 6075.
17. T. T. Dang, F. Boeck, and L. Hintermann, J. Org. Chem., 2011, 76, 9353.
18. General procedure for the preparation of oxazol-2(3H)-one derivatives: To a 10 mL screw-cap
test-tube was charged with ynamides 1a (38.2 mg, 0.10 mmol) and AgBF4 (1.0 mg, 5.0 μmol) in dry
CH2Cl2 (2 mL). The reaction mixture was stirred at room temperature for 18 h and directly purified
by using column chromatography on silica gel (2:1, hexane:EtOAc as eluent) to afford the product
1
4a (32.0 mg, 98%) as a pale yellow solid (mp 136-138 °C). H NMR (300 MHz, CDCl3) δ:
7.44-7.30 (m, 4H), 7.27 (dd, J = 7.1, 7.0 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.78-6.69 (m, 2H), 6.50
13
(s, 1H), 3.86 (s, 3H), 3.85 (t, J = 7.1 Hz, 2H), 3.84 (s, 3H), 2.97 (t, J = 7.1 Hz, 2H) ppm; C NMR
(75 MHz, CDCl3) δ: 154.8, 149.0, 147.9, 138.7, 129.8, 128.8, 128.0, 127.3, 122.8, 120.8, 111.8,
111.4, 109.7, 55.9, 55.8, 45.7, 34.8 ppm; IR (neat): νmax = 2937, 2833, 1745, 1592, 1516, 1452, 1400,
1263, 1237, 1189, 1154, 1025, 806, 764, 741, 691 cm-1; EI-MS: m/z (relative intensity) = 325 (3,
M+), 178 (8), 164 (38), 149 (17), 129 (8), 111 (16), 97 (31), 83 (38), 71 (42), 69 (59), 57 (100);
TOF−HRMS calcd. for C19H20NO4 (M + H)+ 326.1387, found 326.1385.
19. (a) X. Zhang, Y. Zhang, J. Huang, R. P. Hsung, K. C. M. Kurtz, J. Oppenheimer, M. E. Petersen, I.
K. Sagamanova, L. Shen, and M. R. Tracey, J. Org. Chem., 2006, 71, 4170; (b) Y. Zhang, R. P.
Hsung, M. R. Tracey, K. C. M. Kurtz, and E. L. Vera, Org. Lett., 2004, 6, 1151.
20. General procedure for the preparation of oxazolidone derivatives: in a 10 mL microwave vessel, a
suspension of oxazol-2(3H)-one 4a (16.3 mg, 0.05 mmol) and TsOH·H2O (23.8 mg, 0.13 mmol) in
MeCN (1 mL) was irradiated using microwave. The microwave run time was set to 2 min, with
power at 200 Watt, temperature at 100 °C, and pressure at 50 psi, and the conditions held for 3 h.
The resulting solution was diluted with EtOAc (3 mL) and neutralized with sat.aq. NaHCO3. The
organic layer was separated and the aqueous layer was extracted with EtOAc (2 x 3 mL). The
combined organic layers were dried over anh. Na2SO4 and concentrated in vacuo. The crude product
was purified by preparative thin-layer chromatography on silica gel (2:1, hexane:EtOAc) to obtain
product 3a (12.2 mg, 75% with trans:cis ratio of 10:1). trans-3a as a white solid (mp 168-169 °C).
1H NMR (300 MHz, CDCl3) δ: 7.62-7.35 (m, 5H), 6.66 (s, 1H), 6.32 (s, 1H), 5.16 (d, J = 7.5 Hz,
1H), 4.87 (d, J = 7.5 Hz, 1H), 4.20 (dd, J = 12.7, 5.6 Hz, 1H), 3.87 (s, 3H), 3.71 (s, 3H), 3.25-3.11
13
(m, 1H), 3.11-2.96 (m, 1H), 2.68 (d, J = 15.5 Hz, 1H) ppm; C NMR (75 MHz, CDCl3) δ: 156.7,
148.5, 148.1, 137.8, 129.5, 129.1, 127.1, 125.8, 125.1, 112.0, 107.4, 84.0, 61.6, 55.9, 55.8, 38.6, 27.7
ppm; IR (neat): νmax = 2936, 2840, 1751, 1612, 1515, 1454, 1420, 1365, 1310, 1256, 1228, 1173,
1117, 1086, 1033, 997, 961, 872, 854, 767, 702 cm-1; EI-MS: m/z (relative intensity) = 325 (2, M+),
313 (10), 296 (67), 284 (22), 268 (33), 256 (19), 236 (12), 213 (18), 207 (14), 185 (28), 171 (21),
149 (18), 135 (24), 129 (53), 111 (35), 97 (78), 84 (61), 73 (77), 69 (100), 57 (89); TOF-HRMS

calcd. for C19H20NO4 (M + H)+ 326.1387, found 326.1385. cis-3a as a white solid (mp 163-165 °C).
1H NMR (400 MHz, CDCl3) δ: 7.23-7.17 (m, 3H), 7.12-7.06 (m, 2H), 6.47 (s, 1H), 5.88 (d, J = 8.5
Hz, 1H), 5.79 (s, 1H), 5.31 (d, J = 8.5 Hz, 1H), 4.19 (dd, J = 13.1, 5.1 Hz, 1H), 3.78 (s, 3H), 3.42 (s,
3H), 3.15 (ddd, J = 12.9, 12.6, 3.6 Hz, 1H), 2.98 (ddd, J = 15.9, 12.2, 5.5 Hz, 1H), 2.56 (dd, J = 15.8,
13
3.2 Hz, 1H) ppm; C NMR (100 MHz, CDCl3) δ: 157.8, 147.7, 146.8, 135.2, 128.8, 128.2, 127.4,
127.0, 122.3, 111.4, 110.2, 80.6, 59.5, 55.6, 55.5, 39.7, 27.4 ppm; IR (neat): νmax = 2925, 2853, 1747,
1611, 1516, 1456, 1420, 1360, 1331, 1256, 1231, 1209, 1173, 1120, 1088, 1030, 1009, 765, 736, 700
cm-1; EI-MS: m/z (relative intensity) = 325 (8, M+), 207 (8), 191 (100), 176 (32), 149 (11), 133 (7),
121 (9), 111 (15), 105 (34), 97 (25), 85 (17), 83 (27), 77 (24), 69 (24), 57 (30); TOF-HRMS calcd.
for C19H20NO4 (M + H)+ 326.1387, found 326.1398.