Palladium(II)-catalyzed highly stereoselective sandwich-type triple cyclization reaction of 1,5-bisallenes and 2,3-allenoic acids

Article abstract of DOI:10.1002/chem.201000992

(Figure Presented) Triple-decker sandwich: A sandwich-type triple cyclization of two molecules of 2,3-allenoic acid and one molecule of 1,5-bisallene in the presence of a palladium catalyst with excellent stereoselectivity has been developed. The diallyl-substituted cis products may easily be transformed to fused tetracyclic compounds with a 12-membered ring (see scheme). Based on the result of optically active 2,3-allenoic acids, a possible catalytic cycle has been proposed.

Full text of DOI:10.1002/chem.201000992

DOI: 10.1002/chem.201000992
Palladium(II)-Catalyzed Highly Stereoselective Sandwich-Type Triple
Cyclization Reaction of 1,5-Bisallenes and 2,3-Allenoic Acids
Xiongdong Lian[a] and Shengming Ma*[a, b]
Transition-metal-catalyzed cyclization of functionalized al-
lenes has become one of the most efficient and powerful
tools for the synthesis of carbo- and heterocyclic systems.[1,2]
In this area, the metal-catalyzed homodimerization reaction
of 1,2-allenyl ketones was first reported by Hashmi et al.,
which led to the formation of furan derivatives.[3] In 2006,
Alcaide and co-workers also reported the cross-coupling
cyclization reaction of allenols in the presence of 2,3-allenyl
carboxylates.[4] Since 2002,[5] we have demonstrated the cyc-
lization of 2,3-allenoic acids in the presence of 1,2-allenyl
ketones[5] or 2,3-allenols,[6] affording differently substituted
2ACHTUNGTRENNUNG(5H)-furanones. We also studied the cyclization reaction of
2,3-allenoic acids in the presence of simple monoallenes,
Scheme 1. Palladium-catalyzed cyclizations of 2,3-allenoic acids in the
presence of monoallenes or 1,5-bisallenes (BQ=benzoquinone).
which yielded the stereodefined 4-(bromo-2(E)-alken-2-yl)-
2ACHTUNGTRENNUNG
(5H)furanones (Scheme 1).[7] Based on this, we reasoned
that the cyclization of 2,3-allenoic acids in the presence of
1,5-bisallenes may involve further cyclization to form 3-type
of products based on the regioselectivity of carbopalladation
of allenes.[8] Herein, we wish to disclose our recent unex-
pected observation of PdII-catalyzed sandwich-type triple
cyclization of 2,3-allenoic acids in the presence of 1,5-bisal-
lenes affording 4-type tricyclic products (Scheme 2). By ap-
plying the optically active 2,3-allenoic acids, an efficient
chirality transfer has also been achieved.
The expected product 3a was not formed, instead, unknown
products were formed as an inseparable mixture. Interest-
ingly, when the reaction was conducted in the absence of
LiBr by using [PdCl2ACHTUNTGRENUNG(PhCN)2] as the catalyst in DMSO at
608C for 2 h, two tricyclic products cis-4a (32%) and 5a
(10%) were afforded, which were confirmed by spectro-
scopic analysis: two molecules of allenoic acids formed the
two butenolide moieties connected to a central five- or nine-
membered ring formed from the cyclization of the bisallene
1a (Scheme 2).
At first, we conducted the reaction of 2,4-dimethyl-2,3-
pentadienoic acid (2a) in the presence of bis(2,3-butadienyl)
tosylamide (1a) under the conditions described in Ref. [7].
Optimization of reaction conditions with the purpose of
improving the selectivity of cis-4a/5a was then conducted
with some of the representative results being listed in
Table 1. First, the solvent effect was examined and the reac-
tion in MeCN afforded cis-4a and 5a in 45% (41% isolat-
ed) and 15% (10% isolated) yield, respectively (Table 1,
entry 5). Fortunately, cis-4a was afforded exclusively and
the yield was improved significantly when the reaction was
carried out in MeCN by adding 1,4-bis(diphenylphosphino)-
butane (dppb; 5 mol%) as the ligand (Table 1, entry 9).
Then some bidentate phosphine ligands were screened and
1,2-bis(diphenylphosphino)ethane (dppe) was found to be
[a] X. Lian, Prof. Dr. S. Ma
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Linglin Lu, Shanghai 200032 (P.R. China)
[b] Prof. Dr. S. Ma
Shanghai Key Laboratory of Green Chemistry and Chemical Process
Department of Chemistry, East China Normal University
3663 North Zhongshan Lu, Shanghai 200062 (P.R. China)
Fax : (+86)21-64167510
E-mail: masm@mail.sioc.ac.cn
1
the best, affording cis-4a in 79% H NMR yield (Table 1,
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000992.
entry 10).
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COMMUNICATION
bonds[10] through a ring-closing
metathesis (RCM) reaction[11]
(Scheme 3). The structure of
the product was further deter-
mined by the X-ray diffraction
study of cis-6a (Figure 1b).[12]
However, the reaction of rac-
emic allenoic acid 2e with axial
chirality gave diastereomeric
mixtures.[13] Interestingly, when
the corresponding optically
active (R)-2,3-allenoic acid
2e[14] was treated with 1a under
the standard reaction condi-
tions, the optically active prod-
uct (R,S,R,R)-4i was isolated
(Scheme 4a). To determine the
absolute configurations in the
product, bisallene 1d with a
bromine atom was prepared.
(S)-2,3-Allenoic acids 2 f and
2g were able to couple with 1d
under the similar conditions
yielding the products (S,R,S,S)-
4j and (S,R,S,S)-4k, respective-
ly, in acceptable yields (Sche-
me 4b). The absolute configura-
tions of the products were then
unambiguously assigned by the
X-ray diffraction study of
(S,R,S,S)-4k, indicating the ex-
cellent chirality transfer from
the axial chirality of the optical-
ly active allenoic acid to the
product (Figure 1c).[15]
Scheme 2. Pd-catalyzed cyclization reaction of 1,5-bisallene 1a and 2,3-allenoic acid 2a.
Table 1. Pd-catalyzed cyclization reaction of 2,3-allenoic acid 2a in the presence of 1,5-bisallene 1a: Optimiza-
tion of reaction conditions.[a]
Entry
Palladium complex/solvent
[PdCl2A(PhCN)2]/DMSO
[PdCl2A(PhCN)2]/DMF
[PdCl2A(PhCN)2]/DCE
[PdCl2A(PhCN)2]/toluene
[PdCl2A(PhCN)2]/MeCN
[PdCl2A(PhCN)2]/THF
[PdCl2A(PhCN)2]/MeCN
[PdCl2A(Sphos)2]/MeCN
[PdCl2A(PhCN)2], dppb/MeCN
[PdCl2A(PhCN)2], dppe/MeCN
[PdCl2A(PhCN)2], binap/MeCN
Yield of cis-4a [%][b]
Yield of 5a [%][b]
1
2
3
4
5
6
7
8
G
G
32
35
6
10
10
n.d.
n.d.
15
E
E
R
8
R
45
24
25
44
69
79
41
E
7
G
n.d.
n.d.
n.d.
n.d.
21
With the explicit absolute
stereochemical information for
the starting materials and the
products, a possible mechanism
for this transformation is shown
in Scheme 5 by using the Pd-
catalyzed triple cyclization of
(S)-2g with 1,5-bisallene 1d af-
R
9
10
11
E
T
A
[a] The reaction was carried out under argon in a Schlenk tube by using 1a (0.2 mmol), 2a (0.6 mmol), BQ
(0.25 mmol), and the palladium complex (5 mol%) in a solvent (3 mL) at 708C. [b] Determined by 1H NMR
analysis with 1,3,5-trimethyl benzene as the internal standard (n.d.=not determined).
The optimized reaction conditions were then applied to a
range of different 1,5-bisallenes and 2,3-allenoic acids
(Table 2). For the 2,3-allenoic acids, the fully alkyl-, 2-allyl-,
disubstituted, and monosubstituted acids may all react with
differently tethered 1,5-bisallenes (Z=CH2, NTs, O) to
afford the tricyclic products cis-4 in moderate to good yields
with excellent stereoselectivity. In all these cases, only the
cis product was formed. The structure of the product cis-4c
was further determined by its X-ray diffraction study (Fig-
ure 1a).[9]
Note that the diallyl-substituted cis products 4c and 4g
may be easily converted to fused tetracyclic products 6a and
Scheme 3. The RCM reaction to construct the fused twelve-membered
À
6b with a twelve-membered ring that has three Z C=C
rings (Grubbs 2nd=Grubbs second-generation Ru catalyst).
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7961

S. Ma and X. Lian
Table 2. PdII-catalyzed cyclization reaction of bimolecular 2,3-allenoic
acids 2 in the presence of 1,5-bisallene 1: The substrate scope.[a]
Entry
R1
R2
Z
Yield of cis-4 [%][b]
1
2
3
4
5
6
7
8
Me
H
allyl
H
Me
H
allyl
H
Me (2a)
Me (2b)
Me (2c)
TsN (1a)
TsN (1a)
TsN (1a)
TsN (1a)
CH2 (1b)
CH2 (1b)
CH2 (1b)
O (1c)
73 (cis-4a)
81 (cis-4b)
59 (cis-4c)
59 (cis-4d)
68 (cis-4e)
79 (cis-4 f)
52 (cis-4g)
54 (cis-4h)
À
À
ACHTUNGTRENNUNG(CH2)5 (2d)
Me (2a)
Me (2b)
Me (2c)
Me (2a)
[a] The reaction was conducted under an Ar atmosphere with
(0.2 mmol), 2 (0.6 mmol), [PdCl2A(PhCN)2] (5 mol%), dppe (5 mol%),
and BQ (0.25 mmol) in MeCN (3 mL) at 708C. [b] Isolated yield.
1
CTHUNGTRENNUNG
Scheme 4. PdII-catalyzed cyclization reaction of optically active 2,3-alle-
noic acids 2e–g in the presence of 1,5-bisallenes a) 1a and b) 1d.
fording (S,R,S,S)-4k as the typical example. Firstly, the
highly stereoselective cyclic anti-oxypalladation[2g] of (S)-2g
would form intermediate M1 with a center of chirality. Sub-
sequent carbopalladation of one allene moiety in bisallene
1d with M1 would form the p-allylic intermediate M2-a or
M2-b.[8] Owing to the steric interaction between the pseu-
Figure 1. ORTEP representations of a) cis-4c, b) cis-6a, and c) (S,R,S,S)-
4k shown with ellipsoids at the 30% probability level.
doaxial proton and the 2ACTHUNGTRENNG(U 5H)-furanonyl vinyl group in M2-
b, the reaction proceeds via the intermediate M2-a to gener-
ate cis-M3.[8,16] A second molecule of 2,3-allenoic acid (S)-
2g would undergo sequential coordination and anti-oxypal-
ladation[2g] with the vinyl palladium cis-M3 to generate cis-
M4, which upon reductive elimination would release the
final tricyclic product (S,R,S,S)-4k and Pd0. The PdII catalyst
would finally be regenerated by the reaction of Pd0 with BQ
and H+.[17]
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PdII-Catalyzed Sandwich-Type Triple Cyclizations
COMMUNICATION
Acknowledgements
Financial support from the State Key Basic Research & Development
Program (2006CB806105) and National Natural Science Foundation of
China (20732005) are greatly appreciated. We thank Jie Chen in this
group for reproducing the preparation of cis-4c and cis-4g in Table 2,
and (R,S,R,R)-4i and (S,R,S,S)-4k in Scheme 4.
Keywords: allenes · chirality · cyclization · palladium · ring-
closing metathesis reaction
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Chem. 2006, 1387.
Scheme 5. Plausible catalytic cycle for the formation of (S,R,S,S)-4k from
(S)-2g and 1d.
In summary, we have observed an unexpected sandwich-
type triple cyclization of two molecules of 2,3-allenoic acid
in the presence of one molecule of 1,5-bisallene with excel-
lent stereoselectivity. The axial chiralities of the optically
active 2,3-allenoic acids can be transferred to the products
efficiently. Based on the careful X-ray diffraction studies of
some of the products, a possible mechanism involving se-
quential highly stereoselective anti-oxypalladation, intermo-
lecular carbopalladation, cyclic cis-carbopalladation, anti-
oxypalladation, and reductive elimination to afford the tricy-
clic products have been proposed. Further study in this area
is being carried out in our laboratory.
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Li, S. Ma, Chem. Eur. J. 2008, 14, 4263.
Experimental Section
[7] Z. Gu, X. Wang, W. Shu, S. Ma, J. Am. Chem. Soc. 2007, 129, 10948.
[8] For a comprehensive review on the regioselectivity of carbopallada-
tion of allenes, see: T. Bai, S. Ma, G. Jia, Coord. Chem. Rev. 2009,
253, 423.
[9] Crystal data for cis-4c: Recrystallization from acetone/diethyl ether
(1:10); C33H39NO6S; MW =577.71; monoclinic; P21/c; a=14.215(6),
b=8.829(4), c=25.699(10) ꢂ; a=90, b=100.439(10), g=908; V=
3168(2) ꢂ3; Z=4; T=293(2) K; MoKa; l=0.71073 ꢂ; final R indices
Typical procedure: 1,5-Bisallene 1a (55 mg, 0.20 mmol), 2,3-allenoic acid
2a (74 mg, 0.59 mmol), [PdCl2ACTHNUTRGNE(UGN PhCN)2] (4 mg, 0.010 mmol), dppe (5 mg,
0.013 mmol), BQ (29 mg, 0.27 mmol), and MeCN (3 mL) were sequen-
tially added to a dried Schlenk tube under an Ar atmosphere. The result-
ing mixture was stirred at 708C under an Ar atmosphere and after com-
pletion of the reaction (monitored by TLC), the resulting mixture was di-
luted with CH2Cl2 (50 mL) and was washed sequentially with aqueous
K2CO3 (10%, 30 mL) and water (30 mL). Drying over Na2SO4, filtration,
evaporation, and purification by column chromatography on silica gel
(eluent: CH2Cl2/diethyl ether=10:1) afforded the product cis-4a as a
white solid (76 mg, 73% yield). M.p. 197–1998C (acetone/ethyl ether=
1:10); 1H NMR (300 MHz, CDCl3): d=7.73 (d, J=7.8 Hz, 2H), 7.36 (d,
J=7.8 Hz, 2H), 5.45 (s, 2H), 5.22 (s, 2H), 3.64–3.54 (m, 2H), 3.50–3.40
(m, 2H), 3.05–2.94 (m, 2H), 2.45 (s, 3H), 1.76 (s, 6H), 1.40 (s, 6H),
1.38 ppm (s, 6H); 13C NMR (CDCl3, 75.4 MHz): d=172.1, 165.1, 144.0,
137.5, 133.5, 129.8, 127.1, 124.9, 120.7, 85.4, 51.2, 43.7, 25.9, 25.8, 21.3,
10.0 ppm; IR (neat): n˜ =1749, 1667, 1621, 1596, 1487, 1465, 1367, 1331,
1279, 1220, 1198, 1163, 1132, 1091, 1046, 1015, 972, 955, 926, 903, 810,
763, 723, 705, 661, 623 cmÀ1; EIMS: m/z (%): 525 [M+] (4.38), 480 [M+
À3CH3] (6.24), 370 [M+ÀTs] (68.99), 91 [CH3C6H4+] (100); elemental
analysis calcd (%) for C29H35NO6S: C 66.26, H 6.71, N 2.66; found: C
66.29, H 6.68, N 2.58.
[I>2s(I)], R1=0.0744, wR2=0.1781;
R indices (all data) R1=
0.1374, wR2=0.2053; reflections collected/unique=16275/5899
(Rint =0.1565); number of observations [I>2s(I)]=2836; parame-
ters=375. CCDC-763152 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[10] For a review on the synthesis of medium-sized rings by using the
RCM strategy, see: M. E. Maier, Angew. Chem. 2000, 112, 2153;
Angew. Chem. Int. Ed. 2000, 39, 2073.
[11] a) Handbook of Metathesis (Ed.: R. H. Grubbs), Wiley-VCH, Wein-
heim, 2003; b) R. H. Grubbs, Tetrahedron 2004, 60, 7117; c) R. H.
Grubbs, Angew. Chem. 2006, 118, 3845; Angew. Chem. Int. Ed. 2006,
45, 3760.
Chem. Eur. J. 2010, 16, 7960 – 7964
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S. Ma and X. Lian
[12] Crystal data for 6a·1= Et2O: Recrystallization from acetone/diethyl
V=1312.5(9) ꢂ3; Z=2; T=293(2) K; MoKa; l=0.71073 ꢂ; final R
indices [I>2s(I)], R1=0.0631, wR2=0.1425; R indices (all data):
R1=0.1083, wR2=0.1582; reflections collected/unique=6708/4596
(Rint =0.1090); number of observation [I>2s(I)]=2439; parameters
320. CCDC-763153 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
2
ether (1:10); C33H40NO6.5S; MW =586.72; monoclinic; P21/c; ; a=
10.4161(13), b=12.9402(17), c=13.4539(18) ꢂ; a=111.791(2), b=
92.116(3), g=109.239(3)8; V=1563.3(4) ꢂ3; Z=2; T=293(2) K;
MoKa; l=0.71073 ꢂ; final R indices [I>2s(I)], R1=0.0775, wR2=
0.2097; R indices (all data): R1=0.1126, wR2=0.2334 reflections
collected/unique=8581/6010 (Rint =0.1109); number of observations
[I>2s(I)]=3494; parameters 367. CCDC-763154 contains the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[16] For the reports on the formation of vinylic palladium intermediates
from the carbopalladation of allenes, see: a) W. Oppolzer, A. Pimm,
B. Stammen, W. E. Hume, Helv. Chim. Acta 1997, 80, 623; b) J.
Bçhmer, R. Grigg, J. D. Marchbank, Chem. Commun. 2002, 768;
c) G. Zhu, Z. Zhang, Org. Lett. 2004, 6, 4041.
1
[13] See the Supporting Information for the crude H NMR spectra.
[14] K. Kobayashi, H. Naka, A. E. H. Wheatley, Y. Kondo, Org. Lett.
2008, 10, 3375.
[15] Crystal data for (S,R,S,S)-4k: Recrystallization from acetone/diethyl
ether (1:10); C26H28BrNO6S; MW =562.46; monoclinic; P21/c; a=
9.893(4), b=7.771(3), c=17.251(7) ꢂ; a=90, b=98.223(7), g=908;
[17] For a seminal paper, see: H. Grennberg, A. Gogoll, J.-E. Bꢃckvall,
Organometallics 1993, 12, 1790.
Received: April 14, 2010
Published online: June 14, 2010
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Chem. Eur. J. 2010, 16, 7960 – 7964