Gold(I)-catalyzed one-pot tandem coupling/cyclization: An efficient synthesis of pyrrolo-/pyrido[2,1-b]benzo[d][1,3]oxazin-1-ones

Article abstract of DOI:10.1002/adsc.200900724

A highly efficient method has been developed for the one-pot synthesis of multi-ring heterocyclic compounds such as pyrrolo-/pyrido[2,1-b]benzo[d][1,3] oxazin-1-ones from o-aminobenzyl alcohols via a gold(I)-catalyzed tandem coupling/cyclization reaction. Significantly, the strategy presents a straightforward and efficient approach to construct novel tricyclic or polycyclic molecular architectures in which two new C-N bonds and one C-O bond are formed in a one-pot reaction operation from two simple starting materials. Moreover, a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields.

Full text of DOI:10.1002/adsc.200900724

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DOI: 10.1002/adsc.200900724
Gold(I)-Catalyzed One-Pot Tandem Coupling/Cyclization: An
Efficient Synthesis of Pyrrolo-/Pyrido
N
N
1-ones
Yu Zhou,a Yun Zhai,a Xun Ji,a,b Guannan Liu,a Enguang Feng,a Deju Ye,a
Linxiang Zhao,b Hualiang Jiang,a and Hong Liua,*
a
Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, Peopleꢀs Republic of China
Fax : (+86)-21-5080-7042; e-mail: hliu@mail.shcnc.ac.cn
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, Peopleꢀs
b
Republic of China
Received: October 18, 2009; Revised: November 18, 2009; Published online: February 9, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900724.
Abstract: A highly efficient method has been devel-
oped for the one-pot synthesis of multi-ring hetero-
to activate alkyne, alkene, and allene functionalities
under mild conditions and at low catalyst loadings.[3]
In spite of impressive progress, several significant lim-
itations remain to be addressed, e.g., the vast majority
of the reported cascade sequences employed an intra-
molecular reaction with a single starting material con-
taining multiple functional groups strategically posi-
tioned along a chain, terminating with an alkyne func-
tionality.[2a,4] Construction of complex fused heterocy-
clic multi-ring architectures via an intermolecular
union of simple starting materials through a one-pot
operation still represents significant synthetic chal-
lenges. To the best of our knowledge, there is no
cyclic compounds such as pyrrolo-/pyrido
ACHTUNGTNER[NUNG 2,1-
b]benzo[d][1,3]oxazin-1-ones from o-aminobenzyl
ACHTUNGTRENNUNG
alcohols via a gold(I)-catalyzed tandem coupling/
cyclization reaction. Significantly, the strategy pres-
ents a straightforward and efficient approach to
construct novel tricyclic or polycyclic molecular ar-
À
chitectures in which two new C N bonds and one
C O bond are formed in a one-pot reaction opera-
À
tion from two simple starting materials. Moreover,
a broad spectrum of substrates can participate in
the process effectively to produce the desired prod-
ucts in good yields.
report on the cascade synthesis of pyrrolo-/pyrido
ACHTUNGTRENNUNG[2,1-
b]benzo[d][1,3] oxazin-1-ones from o-aminobenzyl al-
AHCTUNGTRENNUNG
Keywords: alkynes; gold; pyrrolo-/pyrido
b]benzo[d][1,3]oxazin-1-ones; tandem reactions
[2,1-
cohols and 4-pentynoic acid/5-hexynoic acid via a
gold-catalyzed, one-pot domino process. In our ongo-
ing efforts to develop new convenient and efficient
approaches to the synthesis of potentially useful het-
erocyclic compounds with transition metal catalysts,[5]
we herein report an efficient gold-catalyzed, one-pot
ACHTUNGTRENNUNG
Owing to the prevalence of polycyclic heterocyclic tandem reaction protocol for the synthesis of highly
compounds in medicinal chemistry and the fact that substituted pyrrolo-/pyrido[2,1-b]benzo[d][1,3]oxazin-
they are considered to be “privileged structures” in 1-ones (Scheme 1).
the pharmaceutical and agrochemical industries, the Initially, we investigated the effectiveness of various
A
ACHTUNGTRENNUNG
development of new and effective transition metal- gold catalysts and the optimum reaction conditions
catalyzed reactions for the synthesis of fused hetero- using o-aminophenylmethanol (1A) and 4-pentynoic
cycles is being actively researched for the purpose of acid (2a) as model substrates in a sealed tube. The re-
obtaining novel bioactive lead compounds.[1] One of sults of these experiments are shown in Table 1, dif-
the most effective ways for forming such fused ring ferent gold catalysts such as AuBr3, AuI, AuCl
systems is to develop remarkably powerful domino re- [Au{P
(t-Bu)2(o-biphenyl)}]Cl (Au1 catalyst), [Au{P
actions that enable multiple bond-forming and bond- Bu)2(o-biphenyl)}{CH3CN}]SbF6 catalyst)
(Au2
cleavage events to occur in one synthetic operation.[2] and [Au
{1,3-bis(2,6-diisopropylphenyl)imidazol-2-yli-
Recently, gold-catalyzed tandem reactions have at-
dene}]Cl (Au3 catalyst) were probed at 1208C in THF.
tracted considerable attention because of their ability Among the catalysts tested, the Au2 catalyst was
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Adv. Synth. Catal. 2010, 352, 373 – 378
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Yu Zhou et al.
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Scheme 1. Synthesis of pyrrolo-/pyridoACTHNUTRGENN[UG 2,1-b]benzo[d]ACHTUNGTERN[NUGN 1,3]oxazin-1-ones.
Table 1. Optimization of the reaction conditions of tandem found to be the most effective (Table 1, entries 1–6).
synthesis of 3Aa.[a]
Meanwhile, the amount of Au2 catalyst was also opti-
mized. When the amount of catalyst was reduced to
2 mol%, it was found that a better yield was obtained.
However, treatment with 1 mol% of the catalyst re-
sulted in a slightly decreased yield relative to the
treatment with 2 mol% of the catalyst (Table 1,
entry 7). In addition, no desirable product was formed
in the absence of the Au catalyst (Table 1, entry 8).
Some Brønsted acids and protonic acids are usually
used as a co-catalyst for gold catalysts. AgSbF6,
AgBF4, TFA and TsOH were thus investigated as a
co-catalyst, respectively, but no good results were ob-
tained (Table 1, entries 9–12). The reaction time is an
important factor for this reaction, the yield decreased
considerably when the reaction time was prolonged to
48 h. A shorter reaction time (12 h) also led to a de-
crease in the yield of target compound 3Aa (Table 1,
entry 13). Besides, the reaction temperature was also
found to be an important factor for this tandem trans-
formation; for example, compound 3Aa was obtained
in 62% yield when the reaction temperature was re-
duced to below 1008C. When the reaction tempera-
ture was increased to 1408C the yield decreased
(Table 1, entry 14). Subsequently, we screened differ-
ent solvents, and the results showed that THF was the
most effective solvent for this transformation
(Table 1, entries 7 and 15–20). However, toluene also
appears to be an effective reaction solvent (Table 1,
entry16). Without Ar protection, the yield of 3Aa was
not affected drastically (Table 1, entry 21). Although
this transformation was also performed under micro-
wave irradiation, no improved yield was observed
(Table 1, entry 22). Briefly, the optimum results were
obtained when o-aminophenylmethanol (0.1 mmol,
1A) and 4-pentynoic acid (0.25 mmol, 2a) in THF
were treated with 2 mol% of Au2 catalyst in a sealed
tube under Ar protection at 1208C for 24 h.
Entry
Catalyst system[b]
Solvent
Yield [%]
1
2
3
4
5
6
7
8
AuBr3
AuI
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
CH2Cl2
Toluene
Dioxane
CH3CN
CH3OH
H2O
25[c]
18[c]
AuCl
N
62[c]
64[c]
85[c]
70[c]
91 (89[d])
0
45
50
61
9
Au2 catalyst/AgSbF6
Au2 catalyst/AgBF4
Au2 catalyst/TFA
Au2 catalyst/TsOH
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
Au2 catalyst
10
11
12
13
14
15
16
17
18
19
20
21
22
20
72[e] (85[f])
62[g] (88[h])
84
88
34
37
40
50
THF
THF
90[i]
58[j]
[a]
1A (0.1 mmol), 2a (0.25 mmol), Au catalyst (2 mol%),
Ar protection.
[b]
Au1 catalyst=[Au{P
ACHTUNGTRENNUNG
lyst=[Au{P
lyst [Au
ACHTUNGTRENNUNGdene}]Cl.
ACHTUNGTRENNUNG(t-Bu)2(o-biphenyl)}ACTHUNGTRENNUNG
ACHTUNGTRENNUNG
=
[c]
[d]
Reaction performed in the presence of 5 mol% Au2 cata-
lyst.
Reaction performed in the presence of 1 mol% Au2 cata-
lyst.
To evaluate the scope of the proposed gold-cata-
lyzed reaction, we attempted to investigate the cas-
cade cyclization reaction by probing changes in both
the substituted o-aminobenzyl alcohols and the alky-
noic acids under the above-mentioned optimum reac-
tion conditions (Table 2, entries 1–18). We found that
a variety of substituted o-aminobenzyl alcohols par-
ticipated in the process to afford products 3Aa–3Kb
with moderate to excellent yields (53–98%). The posi-
[e]
[f]
[g]
[h]
[i]
The reaction time was prolonged to 48 h.
The reaction time was shortened to 12 h.
The reaction temperature was below 1008C.
The reaction temperature was 1408C.
Reaction performed without Ar protection.
Reaction performed under M.W. irradiation.
[j]
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Gold(I)-Catalyzed One-Pot Tandem Coupling/Cyclization
Table 2. One-pot tandem synthesis of 3 from 2-aminobenzyl alcohols in THF.[a]
Entry
1
Product
Yield [%]
91
Entry
10
Product
Yield [%]
69
3Aa
3Ba
3Ja
2
3
98
86
11
12
3Ka
96[c]
3Ca
3La
65 (5:1 dr)
4
5
3Da
3Ea
53
74
13
14
3Ab
3Bb
82 (1:1.1 dr)
97 (1:1.3 dr)
6
7
8
3Fa
3Ga
3Ha
3Ia
61
15
16
17
18
3Cb
3Gb
3Ib
93 (1:1.2 dr)
95 (1:1.4 dr)
88 (1:1 dr)
95
57 (82[b])
9
86
3Kb
94 (1.3:1 dr)
[a]
1A (0.1 mmol), 2a (0.25 mmol), Au2 catalyst (2 mol%), THF (2–3 mL), Ar protection.
Reaction performed in 2 mL of toluene.
The reaction time was prolonged to 36 h.
[b]
[c]
tion and type of substituent on the o-aminobenzyl al- duction of Cl and CH3 at the 8- and 9-positions of o-
cohols were found to be important impact factors for aminobenzyl alcohol resulted in a drastic decrease in
the yields of the target compounds (Table 2, en- the yield of the product, respectively (Table 2, en-
tries 1–10). High yields were obtained when the 7-po- tries 4 and 8). However, treatment of 9-methyl-substi-
sition of the o-aminobenzyl alcohol was substituted tuted o-aminobenzyl alcohol with 4-pentynoic acid in
by F, Cl, Br, CH3, or the phenyl group (Table 2, en- toluene afforded a good yield (Table 2, entry 8). (3-
tries 2, 3, 5, 7 and 9) or when there was no substituent Aminonaphthalen-2-yl)methanol formed by the anne-
at the 7-position (Table 2, entry 1), respectively. Intro- lation of o-aminobenzyl alcohol was tolerated in the
Adv. Synth. Catal. 2010, 352, 373 – 378
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Yu Zhou et al.
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Table 3. Gold-catalyzed one-pot synthesis of a broad spectrum of fused heterocycles 3.[a]
Entry
1
Product
Yield [%]
73
Entry
6
Product
Yield [%]
58
3Ac
3Bc
3Cc
3Dc
3Ec
3Fc
3Gc
3Ic
2
3
4
77
66
60
65
7
8
9
76
63
78
3Kc
5
[a]
1A (0.1 mmol), 2a (0.25 mmol), Au2 catalyst (2 mol%), toluene (2–3 mL), Ar protection.
reaction, but the reaction required a longer time novel polycyclic molecular architectures that could be
(36 h) for full conversion (Table 2, entry 11). When potential ꢂprivileged structuresꢀ in the pharmaceutical
sterically hindered groups were introduced adjacent and agrochemical industries. The product 3Ea was re-
to the hydroxy group of the o-aminobenzyl alcohol, crystallized from a solvent mixture of petroleum ether
the cyclization cascade was also successful and good and ethyl acetate and was characterized with crystal-
yields were obtained (Table 2, entry 12). Furthermore, lography (Figure 1, see the Supporting Information
substitution of an alkyl group (n-hexyl group) into the for details).[6]
alkynoic acid chain was also tolerated and excellent
yields were observed (Table 2, entries 13–18).
On the basis of our previous knowledge and the re-
sults of our present study, we propose a plausible
Further experiments under the optimized reaction mechanism for the construction of polycyclic hetero-
conditions demonstrated that the proposed reaction
could be extended to generate pyrido
ACHTUNGTREN[NUGN 2,1-b]benzo[d]-
ACHTUNGTRENNUNG[1,3]-oxazin-1-ones by the treatment of o-aminobenzyl
alcohols with 5-hexynoic acid. Although good yields
were observed in the above-mentioned experimental
examples under the optimum conditions, we did not
obtain the same good results when o-aminobenzyl al-
cohols were treated with 5-hexynoic acid in THF
under the same catalyst conditions (data not shown).
However, when this cascade cyclization reaction was
performed in toluene with the same gold catalyst,
good results were obtained. As shown in Table 3, o-
aminobenzyl alcohols with substituents exhibiting
steric and electronic properties are tolerated in the
cascade reactions, and good yields were obtained
(Table 3, entries 1–9). Therefore, this synthetic strat-
egy is an alternative approach to the synthesis of Figure 1. X-ray crystallographic structure of 3Ea.
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Adv. Synth. Catal. 2010, 352, 373 – 378

Gold(I)-Catalyzed One-Pot Tandem Coupling/Cyclization
Scheme 2. A plausible mechanism.
cyclic frameworks. As shown in Scheme 2, alkynoic Experimental Section
acids were first activated by gold(I) catalyst to gener-
ate cyclic activated enol lactone intermediates A,[7] General Procedure for Synthesis of 3Aa (Table 2,
which were then attacked by an amino group of the entry 1)
o-aminobenzyl alcohols 1 to form ammonolysis prod-
To a solution of 4-pentynoic acid (1.25 mmol) in dry THF
ucts. The resulting keto amide B underwent gold-cata-
lyzed N-acyliminium ion formation/cyclization and
was converted into the transition state C. Finally, nu-
cleophilic attack by the hydroxy group yielded the
final product 3.[8]
(3 mL) was added the Au2 catalyst (2 mol%). After stirring
for 10 min at room temperature under Ar protection, o-ami-
nobenzyl alcohol (0.5 mmol) was added. Subsequently, the
reaction vial was sealed under Ar protection and the mix-
ture was heated to 1208C for 24 h. Then, the cold mixture
was concentrated under vacuum, the resulting residue was
purified by flash column chromatography (petroleum ether/
ethyl acetate=4/1) to afford the expected tricyclic heterocy-
clic product 3Aa.
In summary, we have developed an efficient
method for one-pot synthesis of multi-ring heterocy-
clic compounds such as pyrrolo-/pyrido
ACHTUNGTREN[NUNG 2,1-b]benzo-
A
ACHTUNGTRENNUNG
The characterization data obtained for 3Aa are as follows:
1H NMR (CDCl3, 300 MHz): d=8.29 (d, J=8.1 Hz, 1H),
7.29 (d, J=7.5 Hz, 1H), 7.11 (m, 1H), 7.05 (d, J=6.9 Hz,
1H), 5.03 (d, J=15.2 Hz, 1H), 4.86 (d, J=15.3 Hz, 1H),
2.60 (m, 2H), 2.23 (m, 2H), 1.43 (s, 3H). 13C NMR (CDCl3,
100 MHz): d=171.3, 132.8, 127.5, 124.1, 124.0, 123.0, 120.4,
90.0, 62.8, 33.0, 30.2, 21.2; LR-MS (EI): m/z=203 (M+);
HR-MS (EI): m/z=203.0946, calcd. for C12H13NO2 (M+):
203.0946.
a gold(I)-catalyzed tandem coupling/cyclization reac-
tion. This reaction is atom economic and has high
functional group tolerance. Significantly, the strategy
presents a straightforward and efficient approach to
construct novel tricyclic molecular architectures in
which several carbon-nitrogen and carbon-oxygen
bonds are formed in a one-pot reaction operation
from two simple starting materials. We expect that
these potential “privileged structures” will find wide
applications in related medicinal chemistry. Further,
one-pot reaction cascade sequences catalyzed by
single and/or multiple catalytic entities are under in-
vestigation and the results will be reported in due
course.
Acknowledgements
We gratefully acknowledge financial support from the Na-
tional Natural Science Foundation of China (Grants
20721003 and 20872153) National S&T Major Project
(Grants 2009ZX09301-001 and 2009ZX09501-001), the 863
Hi-Tech Program of China (Grants 2006AA020602 and
2006AA10A201) and the Shanghai Postdoctoral Science
Foundation (Grant 09R21418000).
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Yu Zhou et al.
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References
2007, 129, 3798; f) J. H. Lee, F. D. Toste, Angew. Chem.
2007, 119, 930; Angew. Chem. Int. Ed. 2007, 46, 912;
g) S. Wang, L. Zhang, J. Am. Chem. Soc. 2006, 128,
14274; h) S. Couty, C. Meyer, J. Cossy, Angew. Chem.
2006, 118, 6878; Angew. Chem. Int. Ed. 2006, 45, 6726;
i) E. Jimenez-Nunez, C. K. Claverie, C. Nieto-Oberhub-
er, A. M. Echavarren, Angew. Chem. 2006, 118, 5578;
Angew. Chem. Int. Ed. 2006, 45, 5452; j) J. Zhao, C. O.
Hughes, F. D. Toste, J. Am. Chem. Soc. 2006, 128, 7436;
k) D. Hildebrandt, G. Dyker, J. Org. Chem. 2006, 71,
6728; l) M. Shi, L.-P. Liu, J. Tang, Org. Lett. 2006, 8,
4043.
[1] For selected examples, see: a) Y. Murata, D. Yamashita,
K. Kitahara, Y. Minasako, A. Nakazaki, S. Kobayashi,
Angew. Chem. 2009, 121, 1428; Angew. Chem. Int. Ed.
2009, 48, 1400; b) A. Dieguez-Vazquez, C. C. Tzschucke,
W. Y. Lam, S. V. Ley, Angew. Chem. 2008, 120, 216;
Angew. Chem. Int. Ed. 2008, 47, 209; c) H. Li, T. P. Loh,
J. Am. Chem. Soc. 2008, 130, 7194; d) R. Felstead, S. E.
Gibson, A. Rooney, E. S. Y. Tse, Eur. J. Org. Chem.
2008, 4963; e) M. R. Axet, J. B. Buchholz, C. Claver, S.
Castillon, Adv. Synth. Catal. 2007, 349, 1983; f) D.
Enders, M. R. M. Huttl, C. Grondal, G. Raabe, Nature
2006, 441, 861.
[2] a) T. Yang, L. Campbell, D. J. Dixon, J. Am. Chem. Soc.
2007, 129, 12070; b) K. C. Nicolaou, D. J. Edmonds, P. G.
Bulger, Angew. Chem. 2006, 118, 7292; Angew. Chem.
Int. Ed. 2006, 45, 7134; c) S. Park, D. Lee, J. Am. Chem.
Soc. 2006, 128, 10664; d) K. C. Nicolaou, D. J. Edmonds,
P. G. Bulger, Angew. Chem. 2006, 118, 7292; Angew.
Chem. Int. Ed. 2006, 45, 7134.
[3] For selected reviews on gold catalysis, see: a) N. Bong-
ers, N. Krause, Angew. Chem. 2008, 120, 2208; Angew.
Chem. Int. Ed. 2008, 47, 2178; b) D. J. Gorin, B. D.
Sherry, F. D. Toste, Chem. Rev. 2008, 108, 3351; c) E. Ji-
menez-Nunez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326; d) Z. Li, C. Brouwer, C. He, Chem. Rev. 2008, 108,
3239; e) R. Skouta, C. J. Li, Tetrahedron 2008, 64, 4917;
f) J. Muzart, Tetrahedron 2008, 64, 5815; g) H. C. Shen,
Tetrahedron 2008, 64, 3885; h) D. J. Gorin, D. Toste,
Nature 2007, 446, 395; i) A. Fꢃrstner, P. W. Davies,
Angew. Chem. 2007, 119, 3478; Angew. Chem. Int. Ed.
2007, 46, 3410; j) E. Jimꢄnez-NfflÇez, A. M. Echavarren,
Chem. Commun. 2007, 333; k) A. S. K. Hashmi, Chem.
Rev. 2007, 107, 3180.
[4] For selected examples see: a) P. Y. Toullec, T. Blarre, V.
Michelet, Org. Lett. 2009, 11, 2888; b) B. Baskar, H. J.
Bae, S. E. An, J. Y. Cheong, Y. H. Rhee, A. Duschek,
S. F. Kirsch, Org. Lett. 2008, 10, 2605; c) C. A. Witham,
P. Mauleón, N. D. Shapiro, B. D. Sherry, F. D. Toste, J.
Am. Chem. Soc. 2007, 129, 5838; d) N. D. Shapiro, F. D.
Toste, J. Am. Chem. Soc. 2007, 129, 4160; e) C.-C. Lin,
T.-M. Teng, A. Odedra, R.-S. Liu, J. Am. Chem. Soc.
[5] a) Y. Zhou, E. Feng, G. Liu, D. Ye, J. Li, H. Jiang, H.
Liu, J. Org. Chem. 2009, 74, 7344; b) D. Ye, J. Wang, X.
Zhang, Y. Zhou, X. Ding, E. Feng, H. Sun, G. Liu, H.
Jiang, H. Liu, Green Chem. 2009, 11, 1201; c) H. Huang,
H. Jiang, K. Chen, H. Liu, J. Org. Chem. 2009, 74, 5476;
d) E. Feng, H. Huang, Y. Zhou, D. Ye, H. Jiang, H. Liu,
J. Org. Chem. 2009, 74, 2846; e) Z. Li, H. Sun, H. Jiang,
H. Liu, Org. Lett. 2008, 10, 3263; f) Z. Li, H. Huang, H.
Sun, H. Jiang, H. Liu, J. Comb. Chem. 2008, 10, 484.
[6] CCDC 755261 contains the supplementary crystallo-
graphic data for 3Ea. These data can be obtained free of
charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[7] a) E. Genin, P. Y. Toullec, S. Antoniotti, C. Brancour, J.-
P. GenÞt, V. Michelet, J. Am. Chem. Soc. 2006, 128,
3112; b) H. Harkat, J. M. Weibel, P. Pale, Tetrahedron
Lett. 2006, 47, 6273.
[8] To further explore the proposed mechanism, we have
treated one of commercially available intermediates A
(alpha-angelica lactone) from Scheme 2 with o-amino-
benzyl alcohol under the above optimal reaction condi-
tions, and the desired product 3Aa was obtained in 90%
yield. Synthetic procedure: To a solution of alpha-angeli-
ca lactone (1.25 mmol) in dry THF (3 mL) were added
Au2 catalyst (2 mol%), and o-aminobenzyl alcohol
(0.5 mmol) was added. Subsequently, the reaction vial
was sealed under Ar protection and the mixture was
heated to 1208C for 24 h. The cold mixture was concen-
trated under vacuum, and the resulting residue was puri-
fied by flash column chromatography (petroleum ether/
ethyl acetate=4/1) to afford the expected product 3Aa.
378
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Adv. Synth. Catal. 2010, 352, 373 – 378