From allene to allene: A palladium-catalyzed approach to β-allenyl butenolides and their application to the synthesis of polysubstituted benzene derivatives

Article abstract of DOI:10.1039/b513371h

An allene to allene protocol for the synthesis of β-allenyl butenolides in moderate to high yields from 2,3-allenoic acids and propargylic carbonates catalyzed by Pd(OAc)₂-TFP has been developed; the products were applied successfully to the Di

Full text of DOI:10.1039/b513371h

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From allene to allene: a palladium-catalyzed approach to b-allenyl
butenolides and their application to the synthesis of polysubstituted
benzene derivatives{
Shengming Ma,*ab Zhenhua Gua and Youqian Dengb
Received (in Cambridge, UK) 21st September 2005, Accepted 26th October 2005
First published as an Advance Article on the web 14th November 2005
DOI: 10.1039/b513371h
high reactivity of the allene-ene functionality,7 the products have
An allene to allene protocol for the synthesis of b-allenyl
been successfully applied to the Diels–Alder reaction to afford
polysubstituted benzene derivatives.
butenolides in moderate to high yields from 2,3-allenoic acids
and propargylic carbonates catalyzed by Pd(OAc)2–TFP has
been developed; the products were applied successfully to
the Diels–Alder reaction with electron-deficient alkynes to
afford polysubstituted benzene derivatives with an excellent
regioselectivity.
On the basis of the previous work, we reasoned that the
b-allenyl butenolides 1 may be generally constructed from the
reaction of propargylic carbonates 38 with intermediate 2, which
may be generated easily via cyclic oxypalladation of the 2,3-
allenoic acid 4 with Pd(II) species (Scheme 1).2f The challenge here
is the formation of the allene moiety via b-heteroatom elimination9
and avoiding further reactions of the in situ formed allene moiety.
Our first approach was based on the reaction of 2,3-allenoic acid
4a and 3a. A survey of some of bidentate phosphine ligands
indicates that (R)-BINAP can only afford a trace amount of
product 1aa (Entry 1, Table 1). However, it is quite fortunate to
see that dppb [1,4-bis(diphenylphosphino)butane] and dppp [1,3-
bis(diphenylphosphino)propane] indeed afforded 1aa in 10% and
14% yields, respectively (Entries 2, and 3, Table 1). Furthermore,
using dppe [1,2-bis(diphenylphosphino)ethane] as the ligand the
reaction can afford a moderate yield of 1aa (Entry 4, Table 1).
Further screening indicates that using tri-(2-furyl)phosphine (TFP)
as the ligand can afford 1aa in 59% yield (Entry 7, Table 1).10 In
terms of solvent effect, DMSO is better than other solvents, such
as NMP, DMF, DME etc. (see supporting information for the
results in different solvents{). The reduction of K2CO3 to 5 mol%
led to a lower yield of 1aa (Entry 8, Table 1). Thus, we
have established the proposed protocol for the cross-coupling
Allenes are a class of compounds of current interest with
unique reactivity.1–3 Recently, our group and others have
established two- or three-component monoallene cyclization
approaches to carbo- or heterocycles.2f,4 Hashmi et al. reported
the Au(III)- and Pd(II)-catalyzed homodimerization reaction of 1,2-
allenyl ketones forming corresponding 2- or 3-alkenyl furans.5 We
also noticed the bisallene approaches of two 2,3-allenoic acids and
the heterodimerization reaction of 2,3-allenoic acids with 1,2-
allenyl ketones to afford bisbutenolides and 4-(furan-39-yl)-
butenolides, respectively.6 Although these functionalized allenes
afforded cyclic products efficiently, no allene structure was present
in the products. In this communication we wish to report a Pd-
catalyzed two-component reaction of 2,3-allenoic acid with
propargylic carbonates, in which 2,3-allenoic acids cyclized to
form the butenolide’s skeleton while a new allenyl moiety was
formed from the propargylic carbonates (Scheme 1). Due to the
Table 1 The ligand effect on the Pd(OAc)2-catalyzed cross-coupling
reaction of 4a with 3aa
Entry
Ligand
Time/h
Yield of 1aa (%)b
1
2
3
4
5
6
7
8d
a
(R)-BINAPc
Dppbc
Dpppc
Dppec
19.5
17.5
21
17
19.5
21
Trace
10
14
51
14
17
59
50
Scheme 1 The proposed synthetic route.
aState Key Laboratory of Organometallic Chemistry Shanghai Institute
of Organic Chemistry Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, P. R. China. E-mail: masm@mail.sioc.ac.cn;
Fax: +86 21-6416-7510
PCy3
P(o-tolyl)3
TFP
TFP
14
23
bLaboratory of Molecular Synthesis and Recognition, Department of
Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027,
P. R. China
Under an argon atmosphere, the mixture of 0.25 mmol of 4a,
0.50 mmol of 3a, 5 mol% Pd(OAc)2, and 10 mol% ligand in
b
c
{ Electronic supplementary information (ESI) available: Experimental
procedures and characterization data of all new compounds. See DOI:
10.1039/b513371h
3 mL DMSO was stirred at 25 uC. Isolated yield. 5 mol% ligand
was used. 5 mol% of K2CO3 was used.
d
94 | Chem. Commun., 2006, 94–96
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Fig. 1 ORTEP structures of 1aa and 6fda.
cyclization of 2,3-allenoic acids 4 with 3 affording b-allenyl
butenolides 1 (Entry 7, Table 1). The X-ray diffraction study of
1aa clearly proved the presence of the allenyl group in the
b-position of the butenolide skeletons, which has not been further
transformed under the current reaction conditions (Fig. 1).{
The optimized reaction conditions proved to be generally
applicable, allowing for an efficient coupling of 2,3-allenoic acids 4
with 3. Some typical results are listed in Table 2. Various
differently substituted 2,3-allenoic acids with R1 being alkyl
(Entries 1–9, Table 2) or hydrogen (Entries 10–12, Table 2), R2 =
aryl (Entries 1–8, and 10–12, Table 2) or alkyl (Entry 9, Table 2),
and R3 being hydrogen (Entries 1–9, Table 2) or alkyl
(Entries 10–12, Table 2) can smoothly afford the products 1 in
moderate to high yields.
Scheme 2 The Diels–Alder reaction of 1 with alkynes 5.
benzo-c-lactones was further established by the X-ray studies
of 6fda (Fig. 1).§
In conclusion, we have established a protocol for palladium-
catalyzed coupling reaction of 2,3-allenoic acids with propargylic
carbonates forming b-allenyl butenolides, in which the newly
formed allene moiety does not undergo further transformation.
These compounds may be applied to the highly selective synthesis
of polysubstituted benzene derivatives.
Synthesis of differently polysubstituted benzenes is a synthetic
challenge.11 The Diels–Alder reaction of 1 with the electron-
deficient alkynes 5a or 5b afforded polysubstituted benzo-
c-lactones 6 highly regioselectively in the presence of 7–14 mol%
of hydroquninone in xylene (Scheme 2).12 The structure of these
Notes and references
Table 2 The Pd-catalyzed cross-coupling reaction of 4 with 3a
{ Crystal data for 1aa: C16H16O2, MW = 240.29, Orthorhombic, space
group Pbca, Final R indices [I > 2s(I)], R1 = 0.0409, wR2 = 0.0625, R
˚
indices (all data) R1 = 0.1877, wR2 = 0.0882, a = 11.592(2) A, b =
3
˚
˚
˚
14.568(3) A, c = 16.342(3) A, a = 90u, b = 90u, c = 90u, V = 2759.7(8) A ,
T = 293(2) K, Z = 8, reflections collected/unique: 15724/3266 (Rint
=
0.1496), number of observations [>2s(I)] 917, parameters: 227. CCDC
270605. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b513371h
Substrate 4
Entry R1 R2
Substrate 3
§ Crystal data for 6fda: C26H30O6, MW = 438.50, Monoclinic, space group
P2(1)/n, Final R indices [I > 2s(I)], R1 = 0.0511, wR2 = 0.0965, R indices
Yield of 1
Time/h (%)b
R3
R4 R5 R6
˚
(all data) R1 = 0.0992, wR2 = 0.1120, a = 10.0344(17) A, b = 13.210(2) A,
˚
3
˚
˚
c = 18.172(3) A, a = 90u, b = 99.356(4)u, c = 90u, V = 2376.7(7) A , T =
293(2) K, Z = 4, reflections collected/unique: 14147/5404 (Rint = 0.0670),
number of observations [>2s(I)] 2955, parameters: 328. CCDC 273892. For
crystallographic data in CIF or other electronic format see DOI: 10.1039/
b513371h
1
2
Me Ph
Me Ph
Pr Ph
Pr Ph
H (4a) –(CH2)5– H (3b)
H (4a) Et Et H (3c) 10
H (4b) Me Me H (3a) 11
5
68 (1ab)
60 (1ac)
54 (1ba)
64 (1bc)
63 (1ca)
52 (1cb)
68 (1cc)
71 (1dc)
54 (1ea)
82 (1fc)
93 (1fd)
91 (1ge)
3
4c
5
H (4b) Et Et H (3c)
9
Me 19-Nap H (4c) Me Me H (3a) 10
Me 19-Nap H (4c) –(CH2)5– H (3b) 10
Me 19-Nap H (4c) Et Et H (3c) 10
Pr 19-Nap H (4d) Et Et H (3c) 10
6c
7c
8
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Me Me
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a
H
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H
Ph
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Me (4f) Et Et H (3c) 12
Me (4f) Me Me Bu (3d) 16
Et (4g) Me Me Ph (3e) 17
Under an argon atmosphere, the mixture of 0.25 mmol of 4,
0.50 mmol of 3, 5 mol% Pd(OAc)2, and 10 mol% TFP in 1 mL of
DMSO was stirred at 35 uC for the time indicated in the table.
b
c
Isolated yield. The reaction was carried out at 40 uC.
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96 | Chem. Commun., 2006, 94–96
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