Palladium-catalyzed cross-couplings of 1,3-butadien-2-yl species with organoindiums generated from allenylmethyl bromide and indium

Article abstract of DOI:10.1039/b823037d

An organoindium generated from the reaction of indium with allenylmethyl bromide is an efficient nucleophile in Pd-catalyzed cross-couplings, producing 1,3-butadienes; cross-couplings followed by [4 + 2] cycloadditions gave six-membered carbocycles in a o

Full text of DOI:10.1039/b823037d

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Palladium-catalyzed cross-couplings of 1,3-butadien-2-yl species with
organoindiums generated from allenylmethyl bromide and indiumwz
Sundae Kim, Dong Seomoon and Phil Ho Lee*
Received (in College Park, MD, USA) 22nd December 2008, Accepted 23rd January 2009
First published as an Advance Article on the web 23rd February 2009
DOI: 10.1039/b823037d
An organoindium generated from the reaction of indium with
allenylmethyl bromide is an efficient nucleophile in Pd-catalyzed
cross-couplings, producing 1,3-butadienes; cross-couplings
followed by [4
+ 2] cycloadditions gave six-membered
carbocycles in a one-pot process.
Scheme
1 Pd-catalyzed 1,3-butadien-2-yl cross-coupling and its
Transition metal-catalyzed cross-couplings represent an extremely
versatile tool in organic synthesis.1 Reactions leading to C–C
bond formation are often key steps in a wide range of organic
processes.2 During the past decades, a variety of organometallic
reagents, such as alkyl-, allyl-, allenyl-, benzyl-, vinyl-, and
arylmetals, have been used as nucleophiles in cross-couplings.1
application to Diels–Alder reaction in a one-pot process (R = vinyl,
aryl; X = I, Br, OTf; E = electron-withdrawing group; R1 = H, Me,
Ph; R2 = H, Me; –R1–R2– = –(CH2)5–).
in situ from 1-bromo-2,3-butadiene (1a)10 and indium
(Table 1). The use of 2 mol% Pd2dba3CHCl3 (dba =
dibenzylidene acetone) and 16 mol% PPh3 selectively
produced 3a in 46% yield in the presence of LiI (3 equiv.) in
DMF at 100 1C for 1 h (entry 1). A variety of ligands
were subsequently examined to increase the product yield
(entries 2–6). The use of Xantphos and P(p-CF3–C6H4)3 gave
3a in 53% and 52% yields, respectively (entries 2 and 3).
However, dppf (1,10-bis(diphenylphosphino)ferrocene), DPEphos
(bis(2-diphenylphosphinophenyl)ether), and 2-(PCy2)biPh
afforded 3a in only 18–27% yields (entries 4–6). Because an
increase of the catalyst amount from 2 to 4 mol% was not
effective, an organoindium generated in situ from 2 equiv. of
indium and 3 equiv. of 1a was applied, resulting in the
formation of 3a in 86% yield (entry 7). Of the catalytic systems
However,
a
transition metal-catalyzed 1,3-butadien-2-yl
cross-coupling is still rare in organic reactions. Although the
synthesis of 2-aryl-1,3-butadienes by the reaction of arylmetals
with 2-halo-1,3-butadiene has been reported,3 there is
still a strong need for an efficient cross-coupling using a
1,3-butadien-2-yl metal generated in situ. The previously
reported 1,3-butadien-2-yl metals have been used mainly for
addition to aldehydes and ketones, ring opening of epoxides,
and Diels–Alder reactions.4 Of these, 2-(1,3-butadien-2-yl)-
magnesium chloride, prepared from the reaction of 2-chloro-
1,3-butadiene with Mg in the presence of a catalytic amount of
ZnCl2 in THF or the reaction of 1-chloro-2,3-butadiene with
Mg in Et2O, suffers from poor chemoselectivity as well as
solvent incompatibility in cross-couplings.5 Homoallenyl
silanes,6 stannanes,7 and boronates8 acting as 1,3-butadien-2-yl
anions are not convenient to prepare. Recently, 2-BF3-substituted
1,3-butadienes were used in Diels–Alder reactions.9 Because so
much is now known about the Diels–Alder reaction, we were
convinced that upon development of a synthetic route to
an efficient transition metal-catalyzed 1,3-butadien-2-yl
cross-coupling, this would prove useful for the synthesis of a
variety of 2-substituted 1,3-dienes and six-membered
carbocycles. Herein, we report a Pd-catalyzed 1,3-butadien-2-yl
cross-coupling of 1,3-butadien-2-yl indium, generated in situ
from allenylmethyl bromide and indium, with electrophiles and
their application to Diels–Alder reactions in a one-pot process
for the synthesis of six-membered carbocycles (Scheme 1).
Our initial study focused on Pd-catalyzed cross-couplings of
1-iodonaphthalene (2a) with an organoindium generated
Table 1 Optimization of Pd-catalyzed cross-coupling of 1-iodo-
naphthalene with 1a and indium
Equiv.
Entry (In/1a) Liganda
Additive
(equiv.)
Yield
T/1C t/h (%)b
1
2
3
4
5
6
7
8
9
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
1/1.5
2/3
2/3
2/3
2/3
2/3
16 PPh3
8 Xantphos
LiI (3)
LiI (3)
16 P(p-CF3C6H4)3 LiI (3)
100
100
90
100
100
100
100
1
2
1
2
2
2
1
1
3
2
1
1
46 (47)
53 (34)
52 (35)
18 (77)
27 (68)
21 (71)
86
8 dppf
LiI (3)
LiI (3)
LiI (3)
LiI (3)
LiBr (3) 100
LiCl (3) 100
8 DPEphos
16 2-(PCy2)biPh
16 PPh3
16 PPh3
16 PPh3
16 PPh3 —
16 PPh3 LiI (1)
16 P(p-CF3C6H4)3 LiI (1)
85
Department of Chemistry and Institute for Molecular Science and
Fusion Technology, Kangwon National University, Chunchon 200-701,
Republic of Korea. E-mail: phlee@kangwon.ac.kr;
Fax: +83 33 253 7582; Tel: +82 33 250 8493
w Dedicated to Professor Sung Ho Kang on the occasion of his 60th
birthday.
77 (15)c
46 (37)c
87
10
11
12
100
100
90
2/3
86
a
b
Numbers indicate mol%. Numbers in parentheses indicate the
c
recovery yields of 2a. Yield of naphthalene.
z Electronic supplementary information (ESI) available: Experimental
details and spectra. See DOI: 10.1039/b823037d
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examined, the best results were obtained with 2 mol%
Pd2dba3CHCl3 and 16 mol% Ph3P in the presence of 1 equiv.
of LiI in DMF at 100 1C for 1 h under a nitrogen atmosphere,
affording selectively 3a in 87% yield (entry 11). Surprisingly, no
allenylmethyl cross-coupling product is formed in any
reactions. This regioselectivity can be rationalized by the
extended conjugation from the aromatic group to the C–C
Table 2 Pd-catalyzed 1,3-butadien-2-yl cross-couplingsa
Yield
R1 R2 Product (%)
double bond. DMF gave
a better result than THF
Entry Reactant Ar
X
I
(87% vs. 17%). The reaction did not proceed without indium.
Compound 2a pre-treated with indium did not react with 1a in
the presence of Pd2dba3CHCl3, Ph3P and LiI, indicating that
Pd-catalyzed SN20 addition of iodide to the allenic bromides
was not involved in this reaction.11 The use of LiI as an
additive is essential for satisfactory results (entries 7–10).
Screening of the amount of LiI showed that 1 equiv. of LiI
is enough to give the optimum reaction conditions (entry 11).
Although the role of LiI is not completely established at
present, it can be reasoned that the addition of LiI accelerates
formation of the organoindium through substitution.
1-Iodo-2,3-butadiene was detected in part in the 1H NMR
spectrum, upon treatment of 1a with LiI in DMF-d7,
indicating that iodide anion substituted bromide in 1a, and
then the corresponding iodide smoothly reacted with indium
to produce an organoindium.
1
2
3
4
5
2a
2b
2c
2d
2d
2e
2f
1-Naphthyl
1-Naphthyl
CH3 CH3 3b
78
OTf H
H
H
H
3a
3c
3d
61b (22)
82
86
2-MeOC6H4
3-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-n-BuC6H4
2-EtO2CC6H4
3-EtO2CC6H4
4-EtO2CC6H4
4-EtO2CC6H4
4-EtO2CC6H4
I
I
I
I
I
I
I
I
I
I
H
H
CH3 CH3 3e
85
80
85
79
83
87
91
93
6
7
H
H
H
H
H
H
H
H
H
H
3f
3g
3h
3i
8
9
10
11
12
2g
2h
2i
2i
2i
3j
CH3 CH3 3k
Ph 3l
H
(1 : 3.4)c
94
13
14
15
16
17
18
19
20
21
22
23
24
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
2r
2s
4-EtO2CC6H4
4-EtO2CC6H4
3-O2NC6H4
4-O2NC6H4
4-BnHNOCC6H4
4-OHCC6H4
2-AcC6H4
3-HOC6H4
4-HOC6H4
3-Pyridyl
I
Br
I
I
I
I
I
I
I
–(CH2)5– 3m
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3j
41b (43)
86
3n
3o
3p
3q
3r
3s
3t
73b,d
81b
82
83
To demonstrate the efficiency and scope of the present
method, we applied this catalytic system to the reaction of a
variety of electrophiles with an organoindium generated in situ
from indium and 1 (Table 2). Electronic variation of the
aromatic substituents, such as methoxy, n-butyl, ethoxycarbonyl,
nitro, benzylaminocarbonyl, formyl, acetyl, and hydroxyl
groups, did not diminish the efficiency and selectivity of
Pd-catalyzed 1,3-butadien-2-yl cross-couplings (entries 3–21).
Reaction of 2d and 2h with 1a and indium produced
2-aryl-1,3-butadienes 3d and 3i in 86% and 83% yields,
respectively (entries 4 and 9). Results of entries 3–6 and
8–10 indicate that the present reactions are not significantly
influenced by steric and electronic variation. It is noted that 2n
and 2o, possessing labile formyl and acetyl groups, toward
organoindium provided 3q and 3r in 82% and 83% yields,
respectively (entries 18 and 19). The reaction also worked
74
86b
80
I
I
I
3u
3-Pyridyl
4-IC6H4
CH3 CH3 3v
3w
82
70e
H
H
a
2 equiv. of In, 3 equiv. of 1, and 1 equiv. of LiI were used. Numbers
b
in parentheses indicate the recovery yields of 2. 16 mol%
c
d
P(p-CF3–C6H4)3 was used. Diastereomeric ratio. Reaction
e
performed at 90 1C. 4 mol% Pd2dba3CHCl3, 32 mol% PPh3,
4 equiv. of In, 6 equiv. of 1, and 2 equiv. of LiI were used at 90 1C
for 30 min. n = 2.
obtaining the result that use of P(p-CF3–C6H4)3 increased the
yield (61%) of 3a (entry 2). In the case of 2l, 2m, and 2q, the
use of P(p-CF3–C6H4)3 gave better results than PPh3
(entries 16, 17, and 21). Subjecting 2j to 1a and indium
provided 3j in 41% yield even though this ligand was used
(entry 14). We were pleased to obtain acyclic cross-conjugated
polyenes 4a, 4b, and 4c ([3]dendralene)13 from the reaction of
vinyl bromides and triflates with 1a and 1b in the presence of
indium, respectively (Table 3).
equally well with
a variety of allenylmethyl bromides
(1b, 1c, and 1d),12 producing 3 in good to excellent yields
(entries 1, 5, 11–13, and 23). The present reaction using
organoindium was compared to an organozinc reagent.
Although reaction of 2a with an organozinc reagent generated
in situ from 1.5 equiv. of zinc and 2.5 equiv. of 1a produced 3a
in 85% yield, the use of 2n gave 3q in only 17% yield
together with a mixture of alcohols obtained from addition
of 1,3-butadien-2-yl or 1,2-butadien-4-yl anion to the aldehyde
group. The reaction of 2n with 1a and magnesium did not
produce 3q. It is noteworthy that protection of a hydroxyl
group on substrates is not necessary (entries 20 and 21).
3-Iodopyridine (2r) turned out to be compatible with the
employed reaction conditions, producing 3u and 3v in 80%
and 82% yields, respectively (entries 22 and 23). Reaction of 2s
with 4 equiv. of indium and 6 equiv. of 1a afforded 3w in 70%
yield (entry 24). Although treatment of 2a with 1a gave 3a in
87% yield, the use of the corresponding triflate (2b) produced
3a in only 32% yield. Therefore, we screened again ligands,
Next, we envisioned that Pd-catalyzed 1,3-butadien-2-yl
cross-couplings followed by treatment of dienophiles would
prove useful for the synthesis of six-membered carbocycles in a
one-pot process. First, we tried cross-couplings of 2f with
3 equiv. of 1a and 2 equiv. of indium in the presence of 2 mol%
of Pd2dba3CHCl3, 16 mol% of PPh3, and LiI (1 equiv.) at
100 1C for 1 h. After being cooled to 25 1C, the reaction
mixture was treated with 2 equiv. of tetra(cyano)ethylene
at 25 1C for 30 min to afford 5a in 83% yield (entry 1,
Table 4). This transformation showed that a cross-coupling
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Table 3 Pd-catalyzed 1,3-butadien-2-yl cross-couplings using vinyl
bromide and triflatesa
bromide, producing a variety of 2-aryl or vinyl substituted
1,3-butadiene derivatives. Moreover, the cross-couplings and
subsequent [4 + 2] cycloaddition provided the rapid synthesis
of six-membered carbocycles in a one-pot process.
Entry Electrophile
1
1
Product
t/h Yield (%)
This work was supported by the KOSEF through the
NRL Program funded by the MOST (No. M10600000203-
06J0000-20310), the Korea Research Foundation Grant
funded by the Korean Government (MOEHRD, Basic
Research Promotion Fund, KRF-2008-359-C00021) and
Korea Sanhak Foundation. Dr Sung Hong Kim at the KBSI
(Daegu) is thanked for obtaining the MS data.
1a
4a
4b
1
1
70
2
1a
1b
93 (5)b
3
4c 1.5 80
Notes and references
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Weinheim, 1998.
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A. Crastairs, Org. Process Res. Dev., 1999, 3, 248; (f) O. Baudoin,
M. Cesario, D. Guenard and F. Gueritte, J. Org. Chem., 2002,
67, 1199.
a
2 equiv. of In, 3 equiv. of 1, and 1 equiv. of LiI were used. Numbers
b
in parentheses indicate the recovery yields of 2. 1-Ethoxycarbonyl-1-
cyclohexene.
Table 4 Pd-catalyzed cross-coupling followed by [4 + 2] cyclo-
addition in a one-pot processa
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T/1C t/h (%)b
Entry Reactant Product
1
2
2f
2f
5a 25
0.5 83
5b 60
5c 60
1
1
70
81
6 (a) T. Nishiyama, T. Esumi, Y. Iwabuchi, H. Irie and
43;
3
2f
2t
S.
Hatakeyama,
Tetrahedron
Lett.,
1998,
39,
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4
5d 60
4
70
a
Reactions performed in the presence of 2 mol% Pd2dba3CHCl3,
16 mol% PPh3, In (2 equiv.), 1a (3 equiv.), and LiI (1 equiv.) in DMF
b
at 100 1C for 1 h. Dienophiles (2 equiv.) were used. 4-Iodoacetophenone.
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three components in a one-pot. The cross-coupling of 2f
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acetylenedicarboxylate) and N-methylmaleimide gave 5b and
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also worked equally well with 4-iodoacetophenone (2t) and
dimethyl fumarate, producing 5d in 70% yield (entry 4).
In summary, we have developed efficient Pd-catalyzed
1,3-butadien-2-yl cross-couplings using an organoindium
generated in situ from the reaction of indium with allenylmethyl
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Chem. Commun., 2009, 1873–1875 | 1875