Allylic-type diindium reagents. Reactivity toward electrophiles and cascade coupling reactions with imines

Article abstract of DOI:10.1021/jo026609v

The allylic-type diindium reagents A and B were prepared from 3-bromo-1-iodopropene (1a) and 4-bromo-2-iodobut-2-ene (1b), respectively, and their reactions with electrophiles were investigated. The diindium reagents A and B were initially reacted with im

Full text of DOI:10.1021/jo026609v

Allylic-Typ e Diin d iu m Rea gen ts. Rea ctivity tow a r d Electr op h iles
a n d Ca sca d e Cou p lin g Rea ction s w ith Im in es†
Tsunehisa Hirashita,* Yousuke Hayashi, Kazuma Mitsui, and Shuki Araki
Department of Applied Chemistry, Nagoya Institute of Technology,
Gokiso-cho, Showa-ku, Nagoya 466-8555, J apan
hirasita@ach.nitech.ac.jp
Received October 25, 2002
The allylic-type diindium reagents A and B were prepared from 3-bromo-1-iodopropene (1a ) and
4-bromo-2-iodobut-2-ene (1b), respectively, and their reactions with electrophiles were investigated.
The diindium reagents A and B were initially reacted with imines and the resulting vinylindium
compounds were then treated with organic halides in the presence of Pd(PPh3)4 to give linear N-aryl
and N-tosyl homoallylic amines. Diindium A is stable in a small amount of water in solvent, whereas
B is easily protonated to give a crotylindium reagent. The reaction of B with benzaldehyde gives
mainly the 1,3- and 1,5-diols via a spontaneous coupling with two molecules of the aldehyde, in
contrast to A, which reacts with one molecule of carbonyl compounds to give the vinylindium
compounds.
SCHEME 1
In tr od u ction
Organodimetallic compounds, which contain two metal-
carbon bonds in one molecule, are attractive reagents
from a viewpoint of organic synthesis.1 A differentiation
of the two carbon-metal bonds under cross-coupling
reactions with electrophiles provides a versatile method
for the formation of two types of carbon-carbon bond in
a single operation. Although a number of organodime-
tallic compounds have been prepared, allylic-type dime-
tallic compounds such as A remain unexplored and only
a few examples such as M ) Li,2,3 Zn,4-7 and Sn8,9 have
been reported. During the investigation on a series of
organoindium reagents, we reported the preparation of
diindiopropene A by oxidative addition of indium to
3-bromo-1-iodopropene (1a ).10 This diindium reagent first
couples with a carbonyl compound and the resulting
vinylindium compound further reacts with aryl, alkenyl,
or allyl halide in the presence of Pd(PPh3)4 leading to
linear homoallylic alcohols (Scheme 1). In light of the
success of constructing two carbon-carbon bonds using
carbonyl compounds as the first electrophile, we have
presently examined the reaction of allylic diindium A
with imines at the initial coupling in the cascade.
Furthermore, to recognize electronic and steric substitu-
tion effects on diindium A, a new diindium reagent B
bearing a methyl group was prepared from 4-bromo-2-
iodobut-2-ene (1b) and its reactions with various elec-
trophiles were investigated. It has been found that the
allylic-type diindium reagents A and B show distinctive
reaction behavior toward water and carbonyl compounds.
Resu lts a n d Discu ssion
Th e Rea ction s of Allylic-Typ e Diin d iu m Rea gen ts
w ith Im in es. The indium-mediated reaction of 1a with
imine 2a was first examined (Table 1). In DMA (N,N-
dimethylacetamide), homoallylic amine 3a was obtained
together with homoallylic alcohol 5a (entry 1). Alcohol
5a is considered to come from the allylation of benzal-
dehyde resulting from the hydrolysis of 2a with a small
amount of water in the solvent. When dry THF was used,
3a was solely obtained (entries 2 and 3). It is known that
sulfonimine 2b is much less reactive for hydrolysis than
2a .11 Indeed, the reaction with 2b in DMA as well as in
1,3-dimethyl-2-imidazolidinone (DMI) gave the corre-
† Dedicated to Emeritus Professor Yasuo Butsugan on the occasion
of his 70th birthday.
(1) Marek, I.; Normant, L.-F. Chem. Rev. 1996, 96, 3241.
(2) Vollhardt, J .; Gais, H, J .; Lukas, K. L. Angew. Chem., Int. Ed.
Engl. 1985, 24, 610.
(3) Gais, H. J .; Vollhardt, J . Tetrahedron Lett. 1988, 29, 1529.
(4) Normant, J . F.; Quirion, J . C.; Alexakis, A.; Masuda, Y. Tetra-
hedron Lett. 1989, 30, 3955.
(5) Labaudiniere, L.; Hanaizi, J .; Normant, J . F. J . Org. Chem. 1992,
57, 6903.
(6) Normant, J . F. New J . Chem. 1990, 14, 461.
(7) Labaudiniere, L.; Normant, J . F. Tetrahedron Lett. 1992, 33,
6139.
(8) Madec, D.; Fe´re´zou, J .-P. Tetrahedron Lett. 1997, 38, 6657.
(9) Madec, D.; Fe´re´zou, J .-P. Tetrahedron Lett. 1997, 38, 6661.
(10) Hirashita, T.; Yamamura, H.; Kawai, M.; Araki, S. Chem.
Commun. 2001, 387.
(11) Lu, W.; Chan, T. H. J . Org. Chem. 2001, 66, 3467.
10.1021/jo026609v CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/21/2003
J . Org. Chem. 2003, 68, 1309-1313
1309

Hirashita et al.
TABLE 1. In d iu m -m ed ia ted Rea ction s of 1 w ith Im in es
2a
TABLE 2. Th e Ca sca d e Rea ction s of 1 w ith Im in es a n d
Or ga n ic Ha lid esa
products and yields (%)
entry
1
2
conditions
1
2
3
4
5
6
1a 2a DMA, rt, 2 h
1a 2a THF, rt, 36 h
1a 2a THF, 50 °C, 5 h
1a 2b DMA, rt, 2 h
1a 2b DMI, rt, 2 h
1a 2b DMI-H2O (1:1),
rt, 6 h
3a
3a
3a
3b
3b
3b
55
74
75
86
93
0
5a 31
5a trace
5a trace
5a
5a
0
0
5a 76
5b 17c
5b 16
7
8
9
1b 2b DMA, rt, 4 h
3c + 4 43
(32:68b)
1b 2b THF, D2O (1 drop), 3c + 4 82
rt, 6 h
(8:92d,e
3c + 4 48
(96:4)
)
1b 2b THF, rt, 6 h
5b
0
a
All reactions were carried out with 1 (0.50 mmol), 2 (0.50
a
mmol), and indium (1.0 mmol). Syn:anti ) 79:21. c Syn:anti )
b
Unless otherwise noted, reactions were carried out in DMI
87:13. Syn:anti ) 77:23. e Deuterium (79%) was incorporated in
d
with 1 (0.50 mmol), imine (0.50 mmol), and indium (1.0 mmol) at
room temperature for 2 h, then halide (1.0 mmol), Pd(PPh3)4 (5
mol %), and LiCl (1.0 mmol) were added and heated at 110 °C for
4.
b
d
17 h. In DMA. c In THF at reflux. In THF-DMI (1:2).
sponding homoallylic amide 3b in high yield without the
formation of 5a (entries 4 and 5); nevertheless, 2b was
completely hydrolyzed in aqueous DMI, giving 5b exclu-
sively (entry 6). Next, the reaction of 4-bromo-2-iodobut-
2-ene (1b) with 2b was examined. This coupling was
found to be affected greatly by water in the solvents; in
DMA a mixture of regioisomers 3c and 4 was obtained,
together with homoallylic alcohol 5b (entry 7). The
reaction in THF containing a small amount of D2O gave
4-d, where deuterium was introduced to the allylic carbon
(entry 8). This fact indicates that the organodiindium
compound B was protonated with H2O (D2O) at the
substituted carbon prior to the coupling with 2b, then
reacted with 2b as a crotylindium reagent. Crotylindium
is known to couple with sulfonimine 2b to give the
branched amide 4.11,12 The high reactivity of this reagent
B toward water is in contrast to diindium A, which is
not protonated by water in polar solvents such as DMA
and NMP (N-methyl-2-pyrrolidone).10 In carefully dried
THF, the diindium reagent B coupled with sulfonimine
to afford 3c selectively (entry 9). When this reaction was
quenched with diluted DCl, (Z)-3c-d (93% D) was ob-
tained, indicating the existence of an (E)-vinylindium
intermediate.
cascade coupling of the vinylindium intermediates with
the second electrophiles was examined (Table 2). The
vinylindium compound, prepared from 1a and imine 2a ,
was subjected to the coupling with iodobenzene in the
presence of Pd(PPh3)4 to afford the expected linear
homoallylic amine 6a in 57% yield (entry 1). It is noted
that the geometry of the CdC bond of 6a was perfectly
regulated to be E, whereas in the case of aldehydes the
products were a mixture of the E and Z isomers.10
Similarly, the reaction of sulfonimine 2b gave homoallylic
amide 6b in good yield (entry 2). Again, the E-selectivity
was confirmed. Allyl chloride and â-bromostyrene were
also coupled with the vinylindium intermediate to give
the corresponding homoallylic amides 6c and 6d (entries
3 and 4). Sulfonimines derived from aliphatic aldehydes
could equally be used in this reaction (entries 5 and 6).
The vinylindium compound derived from 1b was also
examined for the Pd-catalyzed C-C bond formation. As
mentioned above, dry THF was the solvent of choice for
the selective formation of this vinylindium compound.
However, the Pd-catalyzed coupling with iodobenzene in
refluxing THF gave poor yield of 6g (entry 7). To perform
the reaction at higher temperature, DMI was added as
a cosolvent and the reaction mixture was heated at 110
Th e P a lla d iu m -Ca ta lyzed Ca sca d e Rea ction s of
Allylic-Typ e Diin d iu m Rea gen ts w ith Im in es a n d
Or ga n ic Ha lid es. Recently, the Pd-catalyzed cross-
coupling reactions of vinylindium compounds with ha-
lides have been reported.10,13-17 Next the Pd-catalyzed
(14) Pe´rez, I.; Sestelo, J . P.; Sarandeses, L. A. J . Am. Chem. Soc.
2001, 123, 4155.
(15) Takami, K.; Yorimitsu, H.; Shinokubo, H.; Matsubara, S.;
Oshima, K. Org. Lett. 2001, 3, 1997.
(16) Legros, J .-Y.; Primault, G.; Fiaud, J .-C. Tetrahedron 2001, 57,
2507.
(17) Fujiwara, J .; Watanabe, M.; Sato, T. J . Chem. Soc., Chem.
Commun. 1994, 349.
(12) Chan, T. H.; Lu, W. Tetrahedron Lett. 1998, 39, 8605.
(13) Pe´rez, I.; Sestelo, J . P.; Sarandeses, L. A. Org. Lett. 1999, 1,
1267.
1310 J . Org. Chem., Vol. 68, No. 4, 2003

Allylic-Type Diindium Reagents
SCHEME 2
°C for 17 h. This reaction gave the three-component
coupling product 6g in 52% yield (entry 8). â-Bromo-
styrene was also used to furnish the corresponding linear
homoallylic amide 6h in moderate yield (entry 9).
TABLE 3. In d iu m -Med ia ted Rea ction of 1b w ith
Ben za ld eh yd ea
Th e In d iu m -Med ia ted Rea ction of 1b w ith Ben z-
a ld eh yd e. Although the coupling reactions of 1a with
aldehydes have been investigated by us,10 the marked
differences between 1a and 1b in the reaction with
imines (Table 1, entries 1-6 vs 7-8) prompted us to
investigate the indium-mediated reaction of 1b with
aldehydes. As the diindium reagent B was found to be
highly reactive to water, the reaction was first performed
in the strict absence of moisture. In contrast to the
reaction of 1a with aldehydes or imines, the indium-
mediated reaction of 1b with benzaldehyde in dry THF
gave a set of mixtures composed of homoallylic alcohols
5b and 7, diols 8a and 8b, and a trace amount of
aldehyde 9 (Table 3, entry 1). The expected linear
homoallylic alcohol 7 was obtained in low yield. After 1b
was mixed with indium for 3 h, benzaldehyde was added
to the resultant mixture. This Grignard-type reaction
gave a mixture of the same products in lower combined
yield (entry 2). When the same Gringard-type reaction
was carried out in DMI containing a small amount of
D2O, homoallylic alcohol 5b was obtained in 91% yield
with 73% D (entry 3). This fact indicates that the
diindium reagent B was easily transformed to a crotyl-
indium reagent, as was observed in the reaction with
imine (Table 1, entry 7), and then coupled with benzal-
dehyde to afford 5b. However, Barbier-type reactions, by
mixing 1b, indium, and benzaldehyde at once in aqueous
THF or pure water afforded not only 5b but also homo-
allylic alcohol 7 and diols 8a and 8b (entries 4 and 5). It
is noted that diols 8a and 8b were obtained as a single
diastereomer on the basis of 13C NMR analysis.
yield (%)
entry
1d
solvent
THF
5bb (syn/anti) 7b (E/Z) 8a c 8bc
9
trace
3 (39:61)
15 (9:91) 64 11 trace
3 (20:80) 40 12
0
8 (13:87) 10 40
8 (14:86) 12 28
2d,e THF
0
0
0
0
3e
4
DMI-D2O (30:1) 91 (71:29)f
THF-H2O (1:1)
H2O
0
0
22 (61:39)
17 (64:36)
5g
a
Unless otherwise noted, reactions were carried out by mixing
1b (0.50 mmol), benzaldehyde (1.0 mmol), and indium (1.0 mmol)
at rt for 3 h. The yields were estimated by 1H NMR analysis of
b
a mixture of 7 and 5b. c Isolated yield. PhCHO (0.50 mmol) was
d
used. e The reaction was performed in a Grignard-type manner.
f 73% D. Reaction time 24 h.
g
ing diindium B to give 9 via an intramolecular rear-
rangement of the phenyl group. A similar formation of
aldehyde 9 is documented in the coupling between
benzaldehyde and allylstannane possessing a good leav-
ing group such as OTf or Cl at the γ-position.17 We
previously found that the In-mediated reaction of 1,3-
dibromopropene with benzaldehyde gives a mixture of
vinylepoxide and homoallylic alcohol.18 The latter came
from the diindium reagent A depicted in Scheme 1,
whereas the former is considered to be derived from
Rea ction Mech a n ism . Plausible reaction courses for
the reaction of 1b are depicted in Scheme 2. The oxidative
addition of indium to 1b produces the allylic monoindium
reagent C, which further reacts with indium to give the
allylic-type diindium reagent B. γ-Iodoallylindium C
reacts with benzaldehyde to some extent before generat-
(18) (a) Araki, S.; Hirashita, T.; Shimizu, H.; Yamamura, H.; Kawai,
M.; Butsugan, Y. Tetrahedron Lett. 1996, 37, 8417. (b) Hirashita, T.;
Kamei, T.; Horie, T.; Yamamura, H.; Kawai, M.; Araki, S. J . Org. Chem.
1999, 64, 172.
J . Org. Chem, Vol. 68, No. 4, 2003 1311

Hirashita et al.
methylpropylidene-4-methylbenzenesulfonamide23 were pre-
pared according to the literature.
γ-bromoallylindium species (monoindium). In the present
case, we did not find the corresponding epoxide but a
trace amount of aldehyde 9. Therefore, the monoindium
reagent C is converted to diindium B before reacting with
benzaldehyde. The reaction of B with imine proceeds
regioselectively at the methylene carbon to give the
corresponding vinylindium D in dry THF (path A) and
the resulted vinylindium D gives rise to homoallylic
amine 3c during acidic workup. In the presence of the
Pd(0) catalyst, D couples with iodobenzene to afford 6g.
On the other hand, diindium B reacts with water in the
solvents at the methyl-substituted carbon to give crotyl-
indium E (path B), followed by the reaction with benz-
aldehyde or imine leading to homoallylic alcohol 5b or
homoallylic amine 4. The higher reactivity of B toward
water compared with A is considered to be owing to the
electron-donating nature of the methyl group on diindium
B. The coupling of B with benzaldehyde proceeds mainly
at the substituted carbon to give a new allylic indium
compound F (path C), which is further reacted with
another benzaldehyde to afford diols 8a and 8b. Although
the reason is not clear at the present stage why the
different regioselectivity was observed in the coupling of
B with aldehyde and imine, only a minor amount of
benzaldehyde couples at the methylene carbon of B to
furnish 7. It is noted that the In-mediated reaction of
1,3-dibromopropene with aldehyde in aqueous media
suggests a possibility of a stepwise mechanism that does
not involve the diindium species A.19 Therefore, the
reaction courses and intermediates may not be the same
in organic and aqueous media.
In d iu m -Med ia ted Rea ction of 3-Br om o-1-iod op r op en e
(1a ) a n d Im in es. The following reaction with imine 2b (Table
1, entry 5) represents the general procedure. A mixture of
indium powder (57 mg, 0.50 mmol), 3-bromo-1-iodopropene
(1a ) (E:Z ) 43:57, 50 µL, 0.50 mmol), and sulfonimine 2b (107
mg, 0.50 mmol) was stirred in DMI (2 mL) at room tempera-
ture for 2 h. The reaction mixture was quenched with 1 N
hydrochloric acid and the product was extracted with diethyl
ether. The extracts were washed with brine and dried over
Na2SO4. After the solvent was removed under reduced pres-
sure, the residue was purified by column chromatography on
silica gel (elution with EtOAc:hexane ) 1:10 and gradually
changed to 1:5 then EtOAc) to give N-(1-phenylbut-3-enyl)-
benzenesulfonamide (3b) (124 mg, 93%).
In d iu m -Med ia ted Rea ction of 4-Br om o-2-iod obu t-2-
en e (1b) a n d Im in es. The following reaction with imine 2b
(Table 1, entry 9) represents the general procedure. A mixture
of indium powder (57 mg, 0.50 mmol), 1b (E only, 50 µL, 0.50
mmol), and sulfonimine 2b (107 mg, 0.50 mmol) was stirred
in THF (2 mL) at room temperature for 2 h. The reaction
mixture was quenched with 1 N hydrochloric acid and the
product was extracted with diethyl ether. The extracts were
washed with brine and dried over Na2SO4. After the solvent
was removed under reduced pressure, the residue was purified
by column chromatography on silica gel (elution with EtOAc:
hexane 1:10 to 1:5 then EtOAc) to give a mixture of (Z)-N-(1-
phenylpent-3-enyl)benzenesulfonamide (3c) and N-(1-phenyl-
2-methylbut-3-enyl)benzenesulfonamide (4) (72 mg, 48%, 3c:4
1
96:4). The ratio of 3c/4 was determined by H NMR.
Ca sca d e Rea ction of 3-Br om o-1-iod op r op en e (1a ) w ith
Im in es a n d Ha lid es. The following reaction with sulfonimine
2b (Table 2, entry 2) represents the general procedure. A
mixture of indium powder (57 mg, 0.50 mmol), 1a (50 µL, 0.50
mmol), and sulfonimine 2b (123 mg, 0.50 mmol) was stirred
in DMI (2 mL) at room temperature for 2 h. To this mixture
was added a solution of Pd(PPh3)4 (15 mg, 0.01 mmol), LiCl
(65 mg, 1.5 mmol), and PhI (58 µL, 0.50 mmol) in DMI (4 mL)
premixed at room temperature for 1.5 h. The reaction was
continued at 110 °C for another 17 h and quenched with 1 N
hydrochloric acid. The product was extracted with diethyl
ether. The extracts were washed with brine and dried over
Na2SO4. After the solvent was removed under reduced pres-
sure, the residue was purified by column chromatography on
silica gel (elution with EtOAc:hexane 1:10 gradually 1:5 then
EtOAc) to give N-(1,4-diphenylbut-3-enyl)benzenesulfonamide
(5b) (140 mg, 77%).
Ca sca d e Rea ction of 4-Br om o-2-iod obu t-2-en e (1b)
w ith Im in es a n d Ha lid es. The following reaction with
sulfonimine 2b (Table 2, entry 8) represents the general
procedure. A mixture of indium powder (57 mg, 0.50 mmol),
1b (50 µL, 0.50 mmol), and sulfonimine 2b (107 mg, 0.50
mmol) was stirred in THF (2 mL) at room temperature for 2
h. To this mixture was added a solution of Pd(PPh3)4 (15 mg,
0.01 mmol), LiCl (65 mg, 1.5 mmol), and PhI (58 µL, 0.50
mmol) in DMI (4 mL) premixed at room temperature for 1.5
h. The reaction was continued at 110 °C for another 17 h and
quenched with 1 N hydrochloric acid. The product was
extracted with diethyl ether. The extracts were washed with
brine and dried over Na2SO4. After the solvent was removed
under reduced pressure, the residue was purified by column
chromatography on silica gel (elution with EtOAc:hexane 1:10
to 1:5 then EtOAc) to give N-(1,4-diphenylbut-3-enyl)ben-
zenesulfonamide (6g) (98 mg, 52%).
Con clu sion s
The reactions of the allylic-type diindium reagents A
and B with electrophiles were investigated and their
reaction behavior toward water and aldehyde was found
to be of marked difference. Diindium A is capable of
reacting with both aldehyde and imine at the methylene
carbon to give the corresponding vinylindium compounds
even in the existence of a small amount of water. On the
contrary, diindium B is easily protonated by water in
solvent and reacts as a crotylindium reagent. In dry THF,
diindium B couples with aldehyde at the quaternary
carbon and the resulting allylic indium reacts further
with another aldehyde to give the diols, whereas with
imines it reacts at the methylene carbon affording the
vinylindium compounds as diindium A does. The cascade
reactions of the allylic-type diindium reagents A and B
with imines provide a versatile synthetic route for linear
homoallylic amines.
Exp er im en ta l Section
All reactions were performed under an argon atmosphere.
THF was distilled from LiAlH4 prior to use. The bromides 1a 20
and 1b21 were prepared according to the reported procedures.
Imine 2a is commercially available and used as received. Imine
2b,22 4-methyl-N-pentylidenebenzenesulfonamide,23 and N-2-
In d iu m -Med ia ted Rea ction of 4-Br om o-2-iod obu t-2-
en e (1b) w ith Ben za ld eh yd e (Ta ble 3, En tr y 4). A mixture
(19) Chen, D.-L.; Li, C.-J . Tetrahedron Lett. 1996, 37, 295.
(20) Beruben, D.; Marek, I.; Normant, J .-F. Tetrahedron 1996, 52.
7235.
(21) Paquette, L. A.; Hormuth, S.; Lovely, C. J . J . Org. Chem. 1995,
60, 4813.
(22) Davis, F. A.; Lamendola, J ., J r.; Nadir, U.; Kluger, E. W.;
Sedergran T. C.; Panunto, T. W.; Billmers, R.; J enkins, R., J r.; Turchi,
I. J .; Watson, W. H.; Chen, J . S.; Mimura, M. J . Am. Chem. Soc. 1980,
102, 2000.
(23) Chemla, F.; Hebbe, V.; Normant, J .-F. Synthesis 2000, 75.
1312 J . Org. Chem., Vol. 68, No. 4, 2003

Allylic-Type Diindium Reagents
of indium powder (57 mg, 0.50 mmol), 1b (50 µL, 0.50 mmol),
and benzaldehyde (103 µL, 1.0 mmol) was stirred in distillated
water (2 mL) at room temperature for 1 day. The product was
extracted with diethyl ether and the extracts were washed
with brine and dried over Na2SO4. After the solvent was
removed under reduced pressure, the residue was purified by
column chromatography on silica gel (elution with EtOAc:
hexane 1:10 to 1:5 then EtOAc) to give a mixture of 5b and 7
(20 mg, 25%, 5b:7 68:32), 8a (8 mg, 12%), and 8b (18 mg, 28%).
from the Ministry of Education, Science, Sports and
Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Spectral and ana-
lytical data for all new compounds and 1H NMR spectra for
3c, 6a -h , 8a , and 8b and 13C NMR spectra for 8a and 8b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
1
The ratio of 7 and 5b was estimated by H NMR analysis.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research (No. 12640515)
J O026609V
J . Org. Chem, Vol. 68, No. 4, 2003 1313