Gold-catalyzed cyclization of tert-butyl allenoate: General synthesis of 2,4-functionalized butenolides

Article abstract of DOI:10.1016/j.tetlet.2005.08.084

AuCl₃ efficiently catalyzes cyclization of tert-butyl allenoates into γ-butenolides. Advantage of directly using allenic ester precursor instead of corresponding acid is demonstrated in the synthesis of a variety of 2,4-disubstituted butenolides. A low catalyst loading and mild reaction condition makes this process an attractive alternative over conventional methods using strong Lewis acids.

Full text of DOI:10.1016/j.tetlet.2005.08.084

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7431–7433
Gold-catalyzed cyclization of tert-butyl allenoate:
general synthesis of 2,4-functionalized butenolides
Ji-Eun Kang, Eun-Sun Lee, Sang-Il Park and Seunghoon Shin*
Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea
Received 9 July 2005; revised 16 August 2005; accepted 18 August 2005
Available online 9 September 2005
Abstract—AuCl3 efficiently catalyzes cyclization of tert-butyl allenoates into c-butenolides. Advantage of directly using allenic ester
precursor instead of corresponding acid is demonstrated in the synthesis of a variety of 2,4-disubstituted butenolides. A low catalyst
loading and mild reaction condition makes this process an attractive alternative over conventional methods using strong Lewis acids.
Ó 2005 Elsevier Ltd. All rights reserved.
c-Butenolide is one of the most widely occurring struc-
tural motif in a variety of biologically active natural
products and also serves as a valuable platform for var-
ious diastereoselective transformations.1,2 Not surpris-
ingly, a great degree of synthetic efforts have been
devoted for developing versatile and efficient route to
butenolides.3
In the course of ongoing projects in our laboratory on
the reactivity of electron-deficient allenyl compounds,
we were interested in Au(III)-catalyzed cyclization of
allenic ester (Scheme 1). Prototypical examples of this
process require stoichiometric amount of electro-
philic reagents, such as Br2, PhSeCl,3b,6 or CuX2.3c–f
In light of exceptional ÔcarbophilicÕ Lewis acidity of
Au(III) complexes in cycloisomerization of a-hydroxy-
allene and a-amino-allene,5,6 we envisioned that a
similar reaction with tert-butyl allenoate would afford
c-butenolides.
Of particular interest is cyclization of allenic acid pre-
cursors catalyzed by transition metal, such as Pd(II),
Ag(I), and Au(III).3 Most of the reported procedure
starts from allenic acid, which, in turn, is obtained from
hydrolysis of the corresponding ester. Direct use of alle-
nic ester has several advantages over allenic acid: it obvi-
ates not only the need for extra deprotection step, but
also problems in the deprotection step, such as isomeri-
zation into alkynyl acetic acid and/or racemization of
axial chirality of allene axis in hydrolytic conditions
(LiOH, BCl3, or TBAF) can be prevented.3b Therefore,
direct use of allenoate ester, whose asymmetric prepara-
tion is amply precedented, seems to be a more attractive
strategy,4 although examples using allenoate precursor
is quite limited.3b,g Herein, we report gold(III)-catalyzed
cyclization of tert-butyl allenoate, providing a general
entry into 2,4-disubstituted c-butenolide under excep-
tionally mild conditions.
R1
PPh3
R1
O
Et3N
(or iPr2NEt)
R2
CO2But
R2
+
ButO2C
Cl
2a-c
3aa-3cc
1a (R=H)
1b (R=Me)
1c (R=Bn)
a
b
a. 1. MeI, 2. aq. NaOH, 99 %
b. 1. BnBr, TBAI(10%), THF, 2. NaOH, 95 %
ð1Þ
Preparation of tert-butyl allenoate is shown in Eq. 1.
Procedures based on Wittig olefination of ketene were
widely applicable to the preparation of various 2,4-
disubstituted allenic esters in 42–89% yield.7 We tested
R1
R1
catalyst
O
CO2But
R2
Keywords: Gold catalysis; Butenolide; Allenoate; Silver catalysis;
Phosphine ligand.
O
R2
R3
Scheme 1. Cyclization of tert-butyl allenoate.
R3
*
Corresponding author. Tel.: +82 2 2220 0948; fax: +82 2 2200
0762; e-mail: sshin@hanyang.ac.kr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.084

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J.-E. Kang et al. / Tetrahedron Letters 46 (2005) 7431–7433
Table 1. Cyclization of allenoate 3aa under various conditions
with varying efficiency (entries 1–4). The conversion effi-
ciency dramatically increased by employing AuCl3 (5%),
where and the conversion was essentially complete after
2 h at 80 °C to give 88% yield of 4aa (entry 4). Even at
rt, a significant catalytic activity remained, although a
longer reaction time was required (entry 5). We also
tried various other conditions, such as phosphine cataly-
sis or AuCl3 in combination with inorganic and organic
bases, of no avail (entries 6–9). Use of ligand in combi-
nation with AuCl3 is an area of increasing attention be-
cause of the possibility of tuning the reactivity as well as
the potential applicability to asymmetric catalysis (en-
tries 10–12).8 When we used AuCl3 along with PPh3,
no reaction was observed after 24 h at 80 °C. In con-
trast, use of electron-deficient P(C6F5)3 with AuCl3 led
to 78% yield (99% brsm) of butenolide in 2 h at 80 °C.
Finally, among the various solvents, CH2Cl2 turned
out to be the most beneficial (entries 13 and 14).
O
AuCl3
CO2But
O
CH2Cl2
Ph
Ph
3aa
4aa
Entry
Catalyst (mol %)
Conditiona
Yield (%)b
1
2
3
4
5
6
7
CuOTf (10)
AgOTf (10)
PtCl2 (10)
AuCl3 (5)
AuCl3 (5)
PPh3 (10)
PPh3 (10)
HOAc (10)
AuCl3 (10)
Et3N (10)
AuCl3 (10)
K2CO3 (10)
AuCl3 (5)
PPh3 (5)
AuCl3 (5)
P(C6F5)3 (5)
AuCl3 (5)
P(OEt)3 (5)
AuCl3 (5)
AuCl3 (5)
80 °C/ 1.5 h
80 °C/ 1.5 h
80 °C/ 24 h
80 °C/ 2 h
rt/ 8 h
80 °C/ 24 h
80 °C/ 24 h
37
65
NRc
88
70
NR
NR
8
80 °C/ 24 h
80 °C/ 24 h
80 °C/ 24 h
80 °C/ 2 h
80 °C/ 1 h
NR
9
NR
With our optimized conditions, we tested the scope of
current method. Various allenoates 3aa–eb underwent
a smooth reaction to afford corresponding butenolides
(Table 2). Alkyl substituent at 2-position generally led
to higher yield of obtained butenolide. Alkyl, aryl, and
allyl substituents at 4-position were well accommodated
in the current reaction without event. For example, for
the formation of 4ca–cc, no ring-opened by-product
was observed. However, the reaction of 4-phenyl alleno-
ates 3bc was very sluggish and extensive decomposition
was observed. In some cases, a higher temperature was
not beneficial, presumably because of the undesired
decomposition (entries 3 and 4).
10
11
12
NR
85 (99d)
55 (73d)
13
14
80 °C/ 36 h THF
80 °C/ 24 h CH3CN
70
20
a Dry CH2Cl2 in a sealed tube.
b Isolated yield.
c No reaction.
d Based on recovered starting material.
the feasibility of cyclization of allenic ester 3aa under a
variety of conditions (Table 1). Group 11 metals, such as
CuOTf, AgOTf, and AuCl3 showed promising activity
Mechanistically two scenarios are possible: (1) Au(III)-
coordinated allene is first attacked by adjacent carbonyl
Table 2. AuCl3-catalyzed cyclization of allenoates
O
R2
5 mol %
AuCl3
R2
CO2But
R1
O
CH2Cl2
3
R1
4
Entry
Allenoate
R1
R2
Temp (°C)a/time (h)
Yield (%)b
1
2
3
4
5
6
3aa
3ab
3ac
3ac
3bc
3ca
PhCH2
PhCH2
PhCH2
PhCH2
Ph
H
CH3
PhCH2
PhCH2
PhCH2
H
80/2
80/5
80/10 min
rt/1.5
80/20
80/2
88
77
72
96
32
57
7
3cb
3cc
CH3
PhCH2
H
80/3
71
8
80/0.5
80/1.5
80/0.6
81
9
3da
3eac
CH3(CH2)8
65
10
H
64d
11
3ebc
CH3
80/1
72d
a Dry CH2Cl2 in sealed tube.
b Isolated yield.
c Diastereomeric mixture (1:1) of 3eb was used.
d 4eb was obtained as 1:1 mixture of diastereomers.

J.-E. Kang et al. / Tetrahedron Letters 46 (2005) 7431–7433
7433
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followed by removal of butene or (2) Au(III) promotes
cleavage of tert-butyl group to generate allenic acid,
which immediately cyclize into butenolide. We observed
no allenic acid by TLC in the course of cyclizations of 3.
However, a control experiment using tert-butyl 5-phen-
yl-penta-2,4-dienoate (5) showed that the corresponding
acid indeed slowly formed under AuCl3 catalysis at
80 °C (Eq. 2). Even at rt, a significant amount of dienoic
acid was still observed. Therefore, we believe that
Au(III)-catalyst, at least in part, plays a dual role of
facilitation of hydrolysis of tert-butyl ester as well as
cyclization of allenoic acid into 4.
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O
O
AuCl3 (5 %)
CH2Cl2, 80 o
O
OH
C
~30 % conv.
after 36 h
5
4. For a review, see: (a) Modern Allene Chemistry; Krause, N.,
Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004;
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Pessoa, J. C.; Paixao, J. A.; Beja, A. M.; Silva, M. R.
Tetrahedron Lett. 2003, 44, 6409.
ð2Þ
In conclusion, we have demonstrated that AuCl3 effi-
ciently catalyzes the cyclization of tert-butyl allenoates,
providing a variety of c-butenolides. Possibility of chi-
rality transfer of enantiopure substrate is currently being
explored in our laboratory.
Acknowledgments
5. For an excellent review on homogeneous gold catalysis, see:
(a) Hashmi, A. S. K. Gold Bull. 2004, 37, 51; (b) Hoffmann-
Roeder, A.; Krause, N. Org. Biomol. Chem. 2005, 3, 387;
For recent reports on the novel reactivity of Au(I) and
Au(III) catalyst, see: Rearrangement: (c) Sherry, B. D.;
Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978; (d) Shi,
X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc. 2005,
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J. Am. Chem. Soc. 2005, 127, 9708; Cyclization: (f) Nieto-
Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.;
Cardenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed.
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Soc. 2004, 126, 11806; (h) Shi, Z.; He, C. J. Am. Chem. Soc.
2004, 126, 5964; (i) Asao, N.; Sato, K.; Menggenbateer;
Yamamoto, Y. J. Org. Chem. 2005, 70, 3682; Heterocycles:
(j) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc.
2004, 126, 11164; (k) Hashmi, A. S. K.; Schwarz, L.; Chio,
J.-H.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 39,
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3349.
This was supported by the research fund from Korea
Sanhak Foundation in 2005. This work was also sup-
ported by a research fund from Research Institute for
Natural Sciences at Hanyang University in 2004.
J.E.K. thanks the BK21 program for the financial
support.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2005.
08.084.
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