DABCO-catalyzed [2+2] cycloaddition reactions of allenoates and trifluoromethylketones: Synthesis of 2-alkyleneoxetanes

Article abstract of DOI:10.1016/j.tetlet.2011.08.057

DABCO was found to be an efficient catalyst for the formal [2+2] cycloaddition reaction of allenoates and trifluoromethylketones (Paterno-Buchi reaction) to give the corresponding 2-alkyleneoxetanes in good yields with good diastereoselectivities.

Full text of DOI:10.1016/j.tetlet.2011.08.057

Tetrahedron Letters 52 (2011) 5488–5490
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Tetrahedron Letters
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DABCO-catalyzed [2+2] cycloaddition reactions of allenoates and
trifluoromethylketones: synthesis of 2-alkyleneoxetanes
⇑
Tong Wang, Xiang-Yu Chen, Song Ye
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, China
a r t i c l e i n f o
a b s t r a c t
Article history:
DABCO was found to be an efficient catalyst for the formal [2+2] cycloaddition reaction of allenoates and
trifluoromethylketones (Paterno–Buchi reaction) to give the corresponding 2-alkyleneoxetanes in good
yields with good diastereoselectivities.
Received 22 June 2011
Revised 24 July 2011
Accepted 9 August 2011
Available online 18 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Lewis base catalysis
Paterno–Buchi reaction
Allenoates
Trifluoromethylketones
Introduction
Br OH
CuI, Ligand
O
R
Base, CH3CN
Substituted oxetanes present important motifs in a number of
natural products and biologically active compounds.1 In contrast
to their homologous heterocycles, such as oxiranes2, tetrahydrofu-
rans3 and tetrahydropyrans4, few methods have been developed
for the construction of the strained four-membered ring. Generally,
there are two approaches, intra- and intermolecular reactions, for
the construction of oxetanes.
The first intramolecular approach, reported by Hudrlik and
Mohtady employed the intramolecular O-alkylation of enolates in
1975.5 Recently, Li and co-worker reported an efficient 4-exo-ring
closure of the copper-catalyzed intramolecular coupling of vinyl
bromides with alcohols to give 2-methyleneoxetanes (Scheme 1).6
The photocycloaddition of allenes and carbonyl compounds is a
straightforward intermolecular approach to 2-alkyleneoxetanes
(Scheme 2).7 However, several disadvantages, such as usage of a
large excess of allenes, side reaction of further cycloadditions,
and poor selectivities, limit its usage in organic synthesis.
Since Lu’s pioneering report of the [3+2] cycloaddition of alleno-
ates with olefins,8 Lewis base-catalyzed [3+2] and [4+2] annulation
reactions of allenoates have emerged as powerful tools for the
synthesis of cyclic or heterocyclic compounds.9 In 2003, Shi and
co-workers reported an unexpected DABCO-catalyzed [2+2] cyclo-
addition of allenoates and imines to give azetidine derivatives.10,11
Recently, we reported the [3+2] and [4+2] annulation of allenoates
R
Scheme 1. Synthesis of methyloxetanes via copper-catalyzed intramolecular
coupling reaction of vinyl bromides with alcohols.
R
R
O
hv
+
O
R1
R2
R1 R2
Scheme 2. Synthesis of methyloxenanes via photocycloaddition of allenes and
carbonyl compounds.
with trifluoromethyl ketones to give dihydrofurans and dihydropy-
rans.12,13 In this Letter, we wish to report a DABCO-catalyzed [2+2]
cycloaddition of allenoates and trifluoromethyl ketones to give 2-
alkyleneoxetanes. To the best of our knowledge, this is the first
example of the Lewis-base-catalyzed [2+2] cycloaddition of alleno-
ates and carbonyl compounds.14
Results and discussion
Initially, the model reaction of ethyl allenoate 1a and trifluoro-
methyl ketones 2a was investigated (Table 1). We are happy to find
that the [2+2] cycloaddition product of oxetan-2-ylidene 3aa could
⇑
Corresponding author. Tel.: +86 10 6264 1156; fax: +86 10 6255 4449.
E-mail address: songye@iccas.ac.cn (S. Ye).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.057

T. Wang et al. / Tetrahedron Letters 52 (2011) 5488–5490
5489
Table 1
well but with low yield (entry 6). When the ethyl group was chan-
ged to cyclohexyl or t-butyl in substrate 1, the corresponding [2+2]
cycloaddition product could also be isolated in 79% or 60% yield,
respectively, (entries 7–8). Unfortunately, no reaction occurred
Condition screening for the reactions of allenoate 1a and trifluomethylketone 2a
catalyzed by amines
EtOOC
when
a-methyl or c-benzyl allenoate was used, and the reaction
O
COOEt
with ethyl 3,3,3-trifluoro-2-oxopropanoate gave no desired cyc-
loadduct but a complex.
The structure of the cycloadduct 3ba was unambiguously estab-
lished by the X-ray analysis of its crystal (Fig. 1).
cat. (20 mol%)
solvent, Temp.
O
+
Ph
CF3
( 2.0 equiv.)
Ph CF3
3aa -isomer (major)
E
1a
2a
The mechanism for this reaction is believed to go with a similar
catalytic cycle as the reaction with imines proposed by Shi and co-
workers (Fig. 2).10 The nucleophilic addition of DABCO to allenoate
1 produces the enolate intermediate A, which is in resonance with
Entry
Cat.
Solvent
Temp
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
DMAP
DABCO
Qunidine
Cinchonine
Et3N
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
CH3CN
EtOAc
THF
rt
rt
rt
rt
rt
rt
rt
rt
32
32
52
52
52
48
48
48
48
96
48
32
43
the allylic carbanion A0. The
c
-addition of A0 to trifluoromethyl ke-
,b-unsaturated ester B, which undergoes an intra-
NPb
NP
tone gives the
a
NP
molecular Michael addition to give the ring-closed zwitterion C.
The elimination of catalyst from C affords the product and regener-
ates DABCO.
Trace
Trace
29
rt
0 °C
Reflux
61
10
11
THF
THF
78
58 (6)c
a
b
c
Unless specified, isolated yield of E-3aa with E:Z > 20:1.
NP = no product.
Yield of Z-3aa in parenthesis.
Table 2
Formal [2+2] cycloaddition reaction catalyzed by DABCO
ROOC
COOR
O
DABCO (20 mol%)
THF, 0 oC
O
+
Ar
CF3
( 2.0 equiv.)
Ar CF3
-isomer ( : > 20:1)
1
3
2
E
E Z
Entry
1 (R)
2 (Ar)
Time (d)
4
3
Yielda (%)
1
2
3
4
5
6
7
8
1a (Et)
1a (Et)
1a (Et)
1a (Et)
1a (Et)
1a (Et)
1b (Cy)
1c (tBu)
2a (Ph)
3aa
3ab
3ac
3ad
3ae
3af
78
74
57
85
73
47
79
60
2b (4-MeC6H4)
2c (4-MeOC6H4)
2d (4-ClC6H4)
2e (3-MeC6H4)
2f (2-Thienyl)
2a (Ph)
3
3.5
2.5
2.5
3.5
3
3ba
3ca
2a (Ph)
3
a
Isolated yield of E-isomer with E:Z > 20:1.
Figure 1. X-ray structure of cycloadduct 3ba.
be isolated in reasonable yield with E:Z > 20:1, when DABCO or
DMAP was used as the catalyst for the reaction after 32 h (entries
1 and 2). It is noteworthy that there is no [3+2] cycloaddition or
Baylis–Hillmam adduct was observed. Lewis bases screening re-
vealed that qunidine, cinchonine and triethylamine could not cat-
alyze this reaction (entries 3–5). Solvent screening showed that the
reaction in THF gave the best yield, while only a trace or low yield
was resulted in toluene, acetonitrile or ethyl acetate (entries 6–9).
The yield was increased to 78% when the reaction was carried out
in 0 °C with prolonged reaction time (entry 10). The reaction in re-
flux THF gave the E-isomer of the cycloadduct in 58% yield along
with 6% yield of Z-isomer (entry 11).
ROOC
O
NR'3
•
COOR
R'3N
Ph CF3
(DABCO)
γ
α
NR'3
ROOC
R3N
COOR
COOR
O
A'
A
Ph CF3
C
γ-attack
O
With the optimized reaction conditions in hand, the reaction
scope was then briefly investigated (Table 2). Aryltrifluoromethyl
ketones with an electron-withdrawing substituent (Ar = 4-ClC6H4)
worked better than those with electron-donating substituents
(Ar = 4-Me, 4-MeOC6H4) (entries 2–4). Ketone 2e with a m-methyl-
phenyl group worked to give the corresponding cycloadduct 3ae in
73% yield (entry 5). Ketone 2f with a 2-thienyl group also worked
Ph
CF3
γ
Ph
F3C
β
COOR
O
R'3N
B
Figure 2. Proposed catalytic cycle.

5490
T. Wang et al. / Tetrahedron Letters 52 (2011) 5488–5490
In conclusion, the DABCO-catalyzed [2+2] cycloaddition of
References and notes
allenoates with trifluoromethylketones was reported, which pro-
vides a new catalytic approach to 2-alkyleneoxetanes in good
yields with high diastereoselectivities.
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m
2939, 1720, 1677, 1373, 1273, 1177, 1039, 821, 761, 697 cmꢀ1
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;
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Financial support from the National Science Foundation of Chi-
na (20932008), the Ministry of Science and Technology of China
(2011CB808600) and the Chinese Academy of Sciences are greatly
acknowledged.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.057.