Palladium-Indium Iodide-Mediated Allylation and Propargylation of Glyoxylic Oxime Ether and Hydrazone: The Role of Water in Directing the Diastereoselective Allylation

Article abstract of DOI:10.1021/jo035442i

Allylation and propargylation of glyoxylic oxime ether in the presence of a catalytic amount of palladium(O) complex and indium(I) iodide were studied. Excellent diastereoselectivities in allylation were achieved in the presence of water, although low dia

Full text of DOI:10.1021/jo035442i

SCHEME 1
P a lla d iu m -In d iu m Iod id e-Med ia ted
Allyla tion a n d P r op a r gyla tion of Glyoxylic
Oxim e Eth er a n d Hyd r a zon e: Th e Role of
Wa ter in Dir ectin g th e Dia ster eoselective
Allyla tion
Hideto Miyabe,† Yousuke Yamaoka,†
Takeaki Naito,‡ and Yoshiji Takemoto*,†
Graduate School of Pharmaceutical Sciences,
Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501,
J apan, Kobe Pharmaceutical University, Motoyamakita,
Higashinada, Kobe 658-8558, J apan
TABLE 1. Rea ction of 1A-D w ith 2a a
takemoto@pharm.kyoto-u.ac.jp
Received October 2, 2003
entry imine
conditions
time (h) yield (%)b
1
2
3
4
5
1A
1B
1A
1C
1D
2a , Pd(PPh3)4
2a , Pd(PPh3)4
2a , BF3‚OEt2, Pd(PPh3)4
2a , Pd(PPh3)4
1
10
3
92
nr (97)
nr (93)
82
Abstr a ct: Allylation and propargylation of glyoxylic oxime
ether in the presence of a catalytic amount of palladium(0)
complex and indium(I) iodide were studied. Excellent dia-
stereoselectivities in allylation were achieved in the presence
of water, although low diastereoselectivities were observed
in the absence of water. Propargylation of glyoxylic oxime
ether proceeded with good diastereoselectivities in the
presence of LiBr or LiCl.
1
2a , Pd(PPh3)4
10
nr (89)
a
Reactions were carried out with 1A-D and 2a in the presence
b
of InI at 20 °C. Isolated yields; yields in parentheses are for the
recovered starting material.
fore, the allylation and propargylation of imine deriva-
tives and its stereocontrol have been a subject of current
interest. As a part of our program directed toward the
development of indium-mediated reaction of imine de-
rivatives,6 we recently reported the palladium-indium
iodide-mediated regioselective allylation of glyoxylic oxime
ether.7 In this study, the selective formation of R-adducts
was observed in anhydrous THF, although the γ-adducts
were formed in the presence of water. Herein, we now
report the reactivity of glyoxylic imines, the effect of
water in simple allylation, and diastereoselective pro-
pargylation.
We first investigated the reactivity of imines 1A-D
toward an allylindium reagent (Scheme 1). The reaction
of glyoxylic oxime ether 1A with allyl acetate 2a was
carried out in the presence of Pd(PPh3)4 (0.05 equiv) and
indium(I) iodide (2 equiv) in THF (Table 1, entry 1). As
expected, glyoxylic oxime ether 1A exhibits a good
reactivity to give the allylated product 3A in 92% yield
after being stirred at 20 °C for 1 h, without formation of
significant byproducts such as a reduced product. In
contrast, allylation reaction of aldoxime ether 1B did not
take place under similar reaction conditions, and 97% of
starting compound 1B was recovered (entry 2). These
results suggest that the reactivity of 1A is enhanced by
the neighboring electron-withdrawing substituent. How-
Indium-mediated allylation reactions have been of
great importance from both economic and environmental
points of view.1 Recently, a new method for preparation
of allylindium reagents via transient organopalladium
intermediates has been studied by Araki et al.,2 and then
several successful examples of palladium-indium iodide-
mediated allylation of aldehydes under new reaction
conditions were reported by Grigg’s group, Kang’s group,
and our group.3 Recently, the palladium-indium iodide-
mediated propargylation of aldehydes was also studied
by Marshall et al.4 However, the corresponding reaction
of imine derivatives has not been widely studied;5 there-
† Kyoto University.
‡ Kobe Pharmaceutical University.
(1) For a recent review, see: Li, C. J .; Chan, T. H. Tetrahedron 1999,
55, 11149. For some examples of indium-mediated reaction, see: (a)
Yang, Y.; Chan, T. H. J . Am. Chem. Soc. 2000, 122, 402. (b) Chan, T.
H.; Yang, Y. J . Am. Chem. Soc. 1999, 121, 3228. (c) Paquette, L. A.;
Rothhaar, R. R. J . Org. Chem. 1999, 64, 217. (d) Woo, S.; Sqires, N.;
Fallis, A. G. Org. Lett. 1999, 1, 573. (e) Engstrom, G.; Morelli, M.;
Palomo, C.; Mitzel, T. Tetrahedron Lett. 1999, 40, 5967. (f) Loh, T.-P.;
Zhou, J . R. Tetrahedron Lett. 1999, 40, 9115. For examples of metallic
indium-mediated allylation of imines, see: (g) Lu, W.; Chan, T. H. J .
Org. Chem. 2001, 66, 3467. (h) Yanada, R.; Kaieda, A.; Takemoto, Y.
J . Org. Chem. 2001, 66, 7516. (i) Lu, W.; Chan, T. H. J . Org. Chem.
2000, 65, 8589. (j) Chan, T. H.; Lu, W. Tetrahedron Lett. 1998, 39,
8605. (k) Basile, T.; Bocoum, A.; Savoia, D.; Umani-Ronichi, A. J . Org.
Chem. 1994, 59, 7766. (l) Beuchet, P.; Marrec, N. L.; Mosset, P.
Tetrahedron Lett. 1992, 33, 5959. (m) Lee, J . G.; Choi, K. I.; Pae, A.
N.; Koh, H. Y.; Kang, Y.; Cho, Y. S. J . Chem. Soc., Perkin Trans. 1
2002, 1314.
(4) (a) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 696.
(b) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 8214. (c)
Marshall, J . A.; Chobanian, H. R.; Yanik, M. M. Org. Lett. 2001, 3,
3369.
(5) Cooper, I. R.; Grigg, R.; MacLachlan, W. S.; Thornton-Pett, M.;
Sridharan, V. Chem. Commun. 2002, 1372.
(6) For indium-mediated radical reaction of imine derivatives, see:
(a) Miyabe, H.; Ueda, M.; Nishimura, A.; Naito, T. Org. Lett. 2002, 4,
131. (b) Miyabe, H.; Nishimura, A.; Ueda, M.; Naito, T. Chem.
Commun. 2002, 1454. (c) Yanada, R.; Nishimori, N.; Matsumura, A.;
Fujii, N.; Takemoto, Y. Tetrahedron Lett. 2002, 43, 4585.
(7) Miyabe, H.; Yamaoka, Y.; Naito, T.; Takemoto, Y. J . Org. Chem.
2003, 68, 6745.
(2) Araki, S.; Kamei, T.; Hirashita, T.; Yamamura, H.; Kawai, M.
Org. Lett. 2000, 2, 847.
(3) (a) Anwar, U.; Grigg, R.; Rasparini, M.; Savic, V.; Sridharan, V.
Chem. Commun. 2000, 645. (b) Anwar, U.; Grigg, R.; Sridharan, V.
Chem. Commun. 2000, 933. (c) Kang, S.-K.; Lee, S.-W.; J ung, J .; Lim,
Y. J . Org. Chem. 2002, 67, 4376. We reported InI-Pd(0)-promoted
metalation and addition of chiral 2-vinylaziridines. See: (d) Takemoto,
Y.; Anzai, M.; Yanada, R.; Fujii, N.; Ohno, H.; Ibuka, T. Tetrahedron
Lett. 2001, 42, 1725. (e) Anzai, M.; Yanada, R.; Fujii, N.; Ohno, H.;
Ibuka, T.; Takemoto, Y. Tetrahedron 2002, 58, 5231.
10.1021/jo035442i CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/21/2004
J . Org. Chem. 2004, 69, 1415-1418
1415

TABLE 2. Rea ction of 4 w ith 2a -fa
SCHEME 2
time
(h)
yield
de
entry
reagent
solvent
(%)b (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
2a (2 equiv)
2a (2 equiv)
2a (2 equiv)
2b (2 equiv)
2c (1.2 equiv) THF
2d (2 equiv) THF
2e (1.2 equiv) THF
2f (1.2 equiv)
2a (2 equiv)
2a (2 equiv)
2a (2 equiv)
2b (1.2 equiv) THF-H2O (10:1)
2c (2 equiv)
2d (2 equiv)
2e (1.2 equiv) THF-H2O (10:1)
2f (1.2 equiv)
THF
THF
THF
THF
0.25
1
3
1
1
1
1
1
89
89
91
89
93
91
83
78
88
91
95
96
95
96
90
90
62
31
20
37
35
42
45
36
92
91
91
92
94
91
93
92
THF
THF-H2O (10:1)
0.25
1
THF-H2O (10:1)
THF-H2O (10:1) 20
1
1
1
1
1
THF-H2O (10:1)
THF-H2O (10:1)
THF-H2O (10:1)
a
Reactions were carried out with 4 and 2a -f in the presence
of Pd(PPh3)4 and InI at 20 °C. Isolated yields. c Diastereoselec-
b
tivities of the product were determined by 1H NMR analysis of
the diastereomeric mixture obtained after rough purification of
chromatography.
ever, the reaction of 1A did not proceed in the presence
of BF3‚OEt2 and starting compound 1A was recovered
(entry 3), because the reaction would proceed via the six-
membered ring transition state between the allylic in-
dium reagent and the CdN bond of 1A. The reaction of
glyoxylic hydrazone 1C having a benzoylamino group also
proceeded smoothly to afford the desired allylated prod-
uct 3C in 82% yield (entry 4). In contrast, the reaction
of glyoxylic hydrazone 1D having a diphenylamino group
did not proceed, probably because the basic diphenyl-
amino group on 1D would suppress the formation of the
six-membered ring transition state (entry 5). These
results suggest that the formation of six-membered ring
transition state is also an important point for successful
allylation of imine derivatives.
We next examined the reaction of Oppolzer’s camphor-
sultam derivative of glyoxylic oxime ether 4, which has
shown excellent reactivity in our previous work on radical
reactions (Scheme 2).8 Recently, we have observed that
the palladium-indium iodide-mediated reaction of gly-
oxylic oxime ether 4 with monosubstituted allyl acetates
or carbonates afforded either the γ-adducts or the R-ad-
ducts by change of the reaction conditions.7 Thus, we
expected that the study on allylation using unsubstituted
allyl reagents would lead to informative suggestions
regarding the reaction pathway.
At first, we studied the allylation in anhydrous THF
by using several allylic reagents 2a -f (Table 2). The
reaction of 4 with allyl acetate 2a (2 equiv) in the
presence of Pd(PPh3)4 (0.05 equiv) and indium(I) iodide
(2 equiv) proceeded smoothly at 20 °C to give 89% yield
of the desired product 5 with 62% de (entry 1). Addition-
ally, the diastereoselectivity of 5 was shown to be
dependent on the reaction time; thus, the prolonged
reaction led to lower selectivity (entries 1-3). To our
surprise, the low diastereoselectivities were also observed
in the reaction using allylic reagents 2b-f in anhydrous
THF (entries 4-8). In our previous studies on metallic
indium(0)-mediated reaction of 4 in aqueous media, the
desired product 5 was obtained with 90% de.6b In contrast
to indium(0)-mediated allylation,6b the indium iodide-
mediated allylation of oxime ether 4 with allyl halides
2c, 2e, and 2f did not proceed in the absence of the
palladium catalyst. Additionally, we observed the effect
of water on regioselectivity in reaction of 4 using mono-
substituted allylic reagents.7 Therefore, we next inves-
tigated the effect of water on the allyaltion reaction
(entries 9-16). As expected, in the presence of water, the
desired product 5 was obtained from allyl acetate 2a
(2 equiv) in 88% yield with 92%, after being stirred at
20 °C for 0.25 h (entry 9). Prolonged reaction in THF-
H2O (10:1, v/v) did not lead to lower selectivity, and good
diastereoselectivity was observed after being stirred at
20 °C even for 20 h (entries 9-11). These diastereose-
lectivities are comparable to that obtained by metallic
indium-mediated reaction reported in our previous work.6b
The absolute configuration of major product was assigned
to be S by comparison with authentic spectral data.6b,9
The replacement of allyl acetate 2a with other allylic
reagents 2b-f led to similar chemical yields and selec-
tivities (entries 12-16).
Although the precise reason for the effect of water was
unclear, these observations would be explained by the
reversibility of allylation reaction (Scheme 3). Under the
anhydrous reaction conditions, the prolonged reaction
would allow reversibility between oxime ether 4 and the
adduct B, giving isomers (S)-5 and (R)-5 having thermo-
dynamically similar stability with low diastereoselectivi-
ties. In contrast, water suppresses the reversibility as a
result of the quick trapping reaction of the branched
adduct B with H2O; therefore, the product (S)-5 was
kinetically formed via a stable six-membered ring transi-
tion state A having lower energy. The reversibility in
(9) Zinc-mediated allylation reaction of glyoxylic oxime ether was
reported by Hanessian’s group. They also reported a potential route
to amino acids. The allylglycine derivative can be prepared from
product 5 through selective cleavage of the N-O bond using Mo(CO)6
and the hydrolysis of sultam auxiliary by treatment with aqueous
LiOH. See: (a) Hanessian, S.; Yang, R.-Y. Tetrahedron Lett. 1996, 37,
5273. (b) Hanessian, S.; Bernstein, N.; Yang, R.-Y.; Maguire, R. Bioorg.
Med. Chem. Lett. 1999, 9, 1437. (c) Hanessian, S.; Lu, P.-P.; Sanceau,
J .-Y.; Chemla, P.; Gohda, K.; Fonne-Pfister, R.; Prade, L.; Cowan-J acob,
S. W. Angew. Chem., Int. Ed. 1999, 38, 3160.
(8) We reported radical addition to glyoxylic oxime ether. See:
Miyabe, H.; Ushiro, C.; Ueda, M.; Yamakawa, K.; Naito, T. J . Org.
Chem. 2000, 65, 176.
1416 J . Org. Chem., Vol. 69, No. 4, 2004

TABLE 3. Rea ction of 4 w ith 6a a
SCHEME 3
entry
catalyst
additive
time (h)
yield (%)b
1
2
3
4
5
6
7
8
9
none
none
none
HMPA
LiBr
LiBr
LiBr
LiCl
LiI
20
50
20
25
15
15
15
15
20
nr (78)
67 (14)
20
75
73
78
72
58
trace
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(dppf)Cl2
Pd(OAc)2‚PPh3
Pd(dppf)Cl2
Pd(dppf)Cl2
none
LiBr
a
Reactions were carried out with 4 and 6a in the presence of
b
InI in THF at 20 °C. Isolated yields of major product; yields in
parentheses are for the recovered starting material.
SCHEME 5
SCHEME 4
allylation reaction of imines using other allylmetals has
been observed.10-12 Recently, a new mechanism involving
[3,3]-sigmatropic rearrangement was also proposed by
T.-P. Loh et al.13
We next investigated propargylation of glyoxylic oxime
ether 4 in anhydrous THF (Scheme 4). Among several
propargylic alcohol derivatives evaluated (6a -c), mesy-
late 6a was the most effective for propargylation of oxime
ether 4. The palladium-indium iodide-mediated reaction
of 4 with mesylate 6a proceeded slowly to give the
propargylated product 7 in 67% yield as a major product,
accompanied with 14% of starting compound 4 (Table 3,
entry 2), although no reaction took place in the absence
of palladium catalyst (entry 1). Several palladium cata-
lysts and additives were investigated (entries 3-9).
Although the use of HMPA led to a low yield (entry 3),4
the reaction was found to proceed smoothly in the
presence of LiBr or LiCl as an additive (entries 4-7).14
The reaction of 4 in the presence of Pd(dppf)Cl2 and LiBr
proceeded smoothly to give the major product 7 in 73%
yield, after being stirred at 20 °C for 15 h (entry 5).
Pd(OAc)2‚PPh3 also served as an effective catalyst (entry
6).15 Although the exact diastereoselectivities of the
product could not determined by 1H NMR analysis of the
diastereomeric mixture, the combined yields of other
diastereoisomers were less than 7%. The absolute con-
figuration at the newly formed stereocenter of 7 was
determined by X-ray analysis.16
We finally investigated the palladium-indium iodide-
mediated reaction of 4 with mesylate 8 (Scheme 5). The
reaction of 4 with 8 (2 equiv) in the presence of Pd(dppf)-
Cl2, LiCl, and indium(I) iodide proceeded smoothly to give
44% yield of the propargylic product 9 with 90% de and
17% yield of the allenic product 10 with 90% de. These
results indicated that the interconversion of allenic
isomer B and propargylic isomer C would lead to the
propargylic product 9 and the allenic product 10, respec-
tively.
(10) Crossover experiment was performed. See: Supporting Infor-
mation.
(11) (a) Yanagisawa, A.; Ogasawara, K.; Yasue, K.; Yamamoto, H.
J . Chem. Soc., Chem. Commun. 1996, 367. (b) Miginiac, L.; Mauze´, B.
Bull. Soc. Chim. Fr. 1968, 4674. (c) Mauze´, B.; Miginiac, L. Bull. Soc.
Chim. Fr. 1973, 1832. (d) Mauze´, B.; Miginiac, L. Bull. Soc. Chim. Fr.
1973, 1838. (e) Mauze´, B.; Miginiac, L. Bull. Soc. Chim. Fr. 1973, 1082.
(12) Isomerization of indium reagents via the allylic rearrangement
of indium atom was reported. See: Hirashita, T.; Hayahi, Y. Mitsui,
K.; Araki, S. J . Org. Chem. 2003, 68, 1309.
(13) (a) Tan, K.-T.; Chng, S.-S.; Cheng, H.-S.; Loh, T.-P. J . Am.
Chem. Soc. 2003, 125, 2958. (b) Loh, T.-P.; Tan, K.-T.; Hu, Q.-Y.
Tetrahedron Lett. 2001, 42, 8705.
(14) Lee, K.; Seomoon, D.; Lee, P. H. Angew. Chem., Int. Ed. 2002,
41, 3901.
In conclusion, we have demonstrated that the pal-
ladium-indium iodide-mediated allylation and propar-
gylation of glyoxylic oxime ether afforded allylated and
propargylated products. As the important effect of water
on diastereoselectivity, the allylated products were ki-
netically formed with excellent diastereoselectivities in
(15) Oppolzer, W.; Flachsmann, F. Tetrahedron Lett. 1998, 39, 5019.
(16) X-ray analysis of 7 and a rationalized stereochemical feature
for propargylation are provided in Supporting Information.
J . Org. Chem, Vol. 69, No. 4, 2004 1417

the presence of water. In contrast, propargylation pro-
ceeded with good diastereoselectivities in anhydrous
THF.
J apan Private School Promotion Foundation for Reseach
Grants, 21st Century COE Program “Knowledge Infor-
mation Infrastructure for Genome Science”, and Mit-
subishi Chemical Corporation Fund (H.M.).
Ack n ow led gm en t . We thank Dr. H. Nagata and
Dr. K. Aoe, Tanabe Seiyaku, Co. Ltd, for X-ray analysis.
This work was supported in part by The J apan Health
Sciences Foundation and Grants-in-Aid for Scientific
Research (C) (Y.T.), for Scientific Research (B) (T.N.),
and for Young Scientists (B) (H.M.) from the Ministry
of Education, Culture, Sports, Science and Technology
of J apan, the Science Research Promotion Fund of the
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure and characterization data for all obtained compounds,
1H and 13C NMR spectrum of all obtained compounds, cross-
over experiment, X-ray crystal data of 7, and rationalized
stereochemical feature for propargylation. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O035442I
1418 J . Org. Chem., Vol. 69, No. 4, 2004