N-alkoxyimidoyl bromides as a new and efficient coupling partner in Pd-catalyzed Stille reaction

Article abstract of DOI:10.1055/s-2001-17480

N-Alkoxyimidoyl bromides have been successfully employed as an efficient organic partner in the Pd-catalyzed Stille coupling reaction with various organotin compounds, and the corresponding O-alkyloximes were obtained in good to excellent yields.

Full text of DOI:10.1055/s-2001-17480

LETTER
1557
N-Alkoxyimidoyl Bromides as a New and Efficient Coupling Partner in Pd-
Catalyzed Stille Reaction
N
-Alkoxyimid
u
oyl Bromide
k
s
a
s
a
N
ew C
b
oupling Part
o
ner in Pd-Ca
k
talyzed
S
tille Rea
cC
tion hang,*a Myunghee Lee,a Sunggak Kim*b
a
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
b
Center for Molecular Design and Synthesis and Department of Chemistry, Korea Advanced Institute of Science and Technology,
Taejon 305-701, Korea
Fax +82(2)32772384; E-mail: sbchang@mm.ewha.ac.kr
Received 7 August 2001
In our initial studies, N-benzyloxybenzimidoyl chloride8
was examined as a test substrate in the Pd-catalyzed cou-
pling reaction with tributyl(vinyl)tin (2 equiv to imidoyl
chloride) under various conditions. While the coupling
was sluggish in the absence of additives in toluene under
reflux, improved conversion and better yields for the de-
sired product were observed by the addition of certain in-
organic bases with the use of Pd(PPh3)4 as a catalyst.
Among several bases examined, potassium fluoride (2
equiv to the halide) turned out to be the most efficient ad-
ditive on the coupling reaction although the desired prod-
uct, phenyl vinyl (O-benzyl)oxime, was still isolated in a
rather unsatisfactory yield (1 h, 58%). Change of halide in
substrate from chloride to bromide resulted in much
cleaner reaction, and the coupled product was isolated in
90% yield from the reaction of N-benzyloxybenzimidoyl
bromide in the presence of 2.0 equiv of KF (30 min). Oth-
er Pd catalysts such as Pd(OAc)2/PR3 (R=Ph, 2-Me-Ph,
cyclohexyl) or Pd2(dba)3 effected the coupling reaction
with much lower efficiency compared to Pd(PPh3)4. The
coupling reaction proceeded slowly at temperatures lower
than 110 °C (for example, 59% yield after 12 h at 80 °C)
under otherwise identical conditions.
Abstract: N-Alkoxyimidoyl bromides have been successfully em-
ployed as an efficient organic partner in the Pd-catalyzed Stille cou-
pling reaction with various organotin compounds, and the
corresponding O-alkyloximes were obtained in good to excellent
yields.
Key Words: catalysis, cross-coupling, palladium, Stille reaction,
tin
Stille cross-coupling reaction of organotin compounds
with aryl halides and triflates is a powerful and widely
used method for carbon-carbon bond formation.1 Due to
its prominent aspects such as excellent tolerance to vari-
ous functional groups, ready availability of organotin
compounds, retention of geometry during the reaction
pathway, and high product yields, extensive studies have
been carried out in order to find more efficient types of or-
ganic donors.2 During the course of studies on the synthet-
ic utility of certain oximyl ether derivatives,3 we surmised
that N-alkoxyimidoyl halides could be utilized as an effi-
cient organic donor in transition metal-catalyzed coupling
reactions. Since the produced O-alkyloximes can be fur-
ther utilized either as a valuable intermediate in organic
synthesis4 or as a carbonyl equivalent in chemical trans-
foramtions, easy and preparative methods for O-alky-
loximes would be highly desirable.5 Although there have
been some related examples of Pd-catalyzed coupling re-
actions with trifluoroacetimidoyl iodides6a and imidoyl
chlorides,6b some limitations such as long reaction times
(up to 63 h) or low to moderate product yields are appar-
ently found. We have discovered that N-alkoxyimines can
be produced with extremely high efficiency by the Pd-cat-
alyzed coupling reaction of N-alkoxyimidoyl bromides
with organotin compounds (Scheme), which will be de-
scribed in this letter.7
The Pd-catalyzed coupling reaction turned out to be gen-
eral with respect to both organotin compounds and N-
alkoxyimidoyl bromides (Table). N-Alkoxyimidoyl bro-
mides used in this study were prepared in good yields (60–
85%) from the reaction of the corresponding N-alkoxya-
mides with CBr4/PPh3 in acetonitrile (85 °C, 3–5 h).9 Not
only olefinic groups could be readily transferred from
tributyl(alkenyl)stannanes but also alkynyl (entry 3), al-
lylic (entry 4), and aryl group (entry 5) were all smoothly
coupled with the imidoyl bromides affording the corre-
sponding O-alkyloximes in good to excellent yields.10
Electronic variation on the imidoyl bromide gave little ef-
fect on the efficiency of the coupling (entries 6–9). Cin-
namylimidoyl bromide was also successfully employed as
an efficient coupling partner in the Pd-catalyzed Stille re-
action (entries 10–12). Methyl- (entry 13) and formyl im-
idoyl bromide (entry 14) also reacted with organotin
compounds under the same conditions to provide coupled
products in high yields.11 Substrates having a different N-
alkoxy group were similarly prepared9 and coupling reac-
tion using those were examined to see the feasibility of the
present coupling reaction. We were pleased to observe
that N-methoxyimidoyl bromides were also efficiently
coupled with various organotin compounds, and that the
OR2
OR2
N
N
Pd (cat)
R3 SnBu3
+
R1
R3
R1
Br
Scheme
Synlett 2001, No. 10, 28 09 2001. Article Identifier:
1437-2096,E;2001,0,10,1557,1558,ftx,en;Y14401ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1558
S. Chang et al.
LETTER
desired O-methyloxime compounds were obtained in
good yields (entries 15–17). It is known that both O-
benzyloximes3 and O-methyloximes12 can be readily hy-
drolyzed to generate corresponding carbonyl compounds
in high yields by aqueous HCl solution and a titanium re-
agent, respectively.
References and Notes
(1) (a) Stille, J. K.Angew. Chem. Int. Ed. Engl. 1986, 25, 508.
(b) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React.
1997, 50, 1. (c) Mitchell, T. N. Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998, Chap. 4.
(2) For some recent progresses on the Stille reaction, see:
(a) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99,
1549. (b) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed.
1999, 38, 2411. (c) Maleczka, R. E. Jr.; Gallagher, W. P.;
Terstiege, I. J. Am. Chem. Soc. 2000, 122, 384.
(3) (a) Kim, S.; Lee, I. Y.; Yoon, J.-Y.; Oh, D. H. J. Am. Chem.
Soc. 1996, 118, 5138. (b) Kim, S.; Kim, Y.; Yoon, K. S.
Tetrahedron Lett. 1997, 38, 2487. (c) Ryu, I.;Kuriyama, H.;
Minakata, S.; Komatsu, M.; Yoon, J.-Y.; Kim, S. J. Am.
Chem. Soc. 1999, 121, 12190. (d) Kim, S.; Kim, N.; Yoon,
J.-Y.; Oh, D. H. Synlett 2000, 1148.
(4) For example, see: (a) Feuer, H.; Braunstein, D. M. J. Org.
Chem. 1969, 34, 1817. (b) Hunt, J. C. A.; Laurent, P.;
Moody, C. J. Chem. Commun. 2000, 1771.
Table Pd-Catalyzed Cross-Coupling Reaction of N-Alkoxyimidoyl
Bromide with Organotin Compoundsa
Pd(PPh3)4 (5 mol%)
KF (2.0 equiv)
OR2
Br
OR2
R3
N
N
+
R3 SnBu3
toluene
110 oC
(2.0 equiv)
R1
R1
Entry R1
R2
R3
Time
Yield (%)b
1
2
C6H5
C6H5
Bn
Bn
30 min 90
30 min 71
H2C CH
Me
(5) Although initial reports were published from Stille group
and others on the Pd-catalyzed coupling of acyl halides with
organotins, several limitations are apparently found (for
example, limited scope of substrates or stannous donors,
requirement of HMPA as a solvent, etc.): (a) Milstein, D.;
Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636. (b) Kosugi,
M.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 1423.
(6) (a) Kobayashi, T.-A.; Sakakura, T.; Tanaka, M. Tetrahedron
Lett 1985, 26, 3463. (b) Uneyama, K.; Watanabe, H.
Tetrahedron Lett. 1991, 32, 1459.
(7) For recent progresses in the synthesis of oxime derivatives
from hydroxyimidoyl chlorides, see: (a) Kanemasa, S.;
Nishiuchi, M.; Kamimura, A.; Hori, K. J. Am. Chem. Soc.
1994, 116, 2324. (b) Bode, J. W.; Fraefel, N.; Muri, D.;
Carreira, E. M.Angew. Chem. Int. Ed. 2001, 40, 2082.
(8) The compound was prepared in 86% yield from a reaction of
the corresponding O-benzylbenzaldoxime with NCS in
DMF (40 °C, 20 h) with a slight modification of a known
procedure: (a) Liu, K.-C.; Shelton, B. R.; Howe, R. K. J.
Org. Chem. 1980, 45, 3916. (b) Larsen, K. E.; Torssell, K.
B. G. Tetrahedron 1984, 40, 2985.
3
4
C6H5
C6H5
Bn
Bn
20 min 95
HC
C
2 h
92
5
6
7
8
C6H5
Bn C6H5
Bn
1 h
1 h
82
97
(p-MeO)C6H4
(p-MeO)C6H4
(p-MeO)C6H4
H2C CH
Bn
Bn
20 min 86
MeC
C
2 h
98
Me
9
(p-Cl)C6H4
Bn
Bn
1 h
1 h
98
97
H2C CH
H2C CH
10
C6H5
C6H5
11
12
Bn
Bn
20 min 77
20 min 95
Me
HC
C
C6H5
13
14
15
16
17
Me
Bn
Bn
Me
Me
Me
1 h
3 h
2 h
1 h
3 h
82
62
74
99
92
H2C CH
H2C CH
H2C CH
H2C CH
(9) Sakamoto, T.; Mori, H.; Takizawa, M.; Kikugawa, Y.
Synthesis 1991, 750.
H
(10) All new compounds were fully characterized by
spectroscopic means including 1H, 13C NMR, IR and HRMS.
(11) Representative experimental procedure: To a stirred
solution of N-benzyloxybenzimidoyl bromide (116 mg, 0.4
mmol) in toluene (4 mL) were added tributyl(vinyl)tin (254
mg, 0.8 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), and KF (47
mg, 0.8 mmol) and the reaction mixture was stirred under
reflux for 30 min. After removal of the solvent under
reduced pressure, the residue was column chromatographed
on silica gel (EtOAc/hexane = 1:30) to afford the desired
product (85 mg, 90%): 1H NMR (CDCl3, 250 MHz) 7.53–
7.38 (10 H, m), 7.23 (1 H, dd, J = 17.9, 11.2 Hz), 5.69 (1 H,
dd, J = 11.3, 1.4 Hz), 5.54 (1 H, dd, J = 17.9, 1.4 Hz), 5.30
(2 H, s); 13C NMR (CDCl3, 62.5 MHz) 157.5, 138.1, 134.8,
129.5, 128.8, 128.7, 128.6, 128.3, 127.2, 126.3, 125.5, 77.5;
HRMS (EI) calcd for C16H15NO 237.1155, found 237.1154.
(12) (a) Donaldson, R. E.; Saddler, J. C.; Byrn, S.; McKenzie, A.
T.; Fuchs, P. L. J. Org. Chem. 1983, 48, 2167. (b)Corey, E.
J.; Niimura, K.; Konishi, Y.; Hashimoto, S.; Hamada, Y.
Tetrahedron Lett. 1986, 27, 2199.
(p-Cl)C6H4
(p-MeO)C6H4
(p-MeO)C6H4
Me
a All reactions were carried out in 0.1 M concentration.
b Isolated yields after purification by silica gel column chromatogra-
phy.
In conclusion, it has been demonstrated that a series of N-
alkoxyimidoyl bromides can be added as a new type of ef-
ficient coupling partner in the Pd-catalyzed Stille reaction,
and various O-alkyloximes with unsaturated functional
groups could be readily obtained in good to excellent
yields from the coupling reactions.
Acknowledgement
This work was supported by Center for Molecular Design and Syn-
thesis (CMDS) at KAIST.
Synlett 2001, No. 10, 1557–1558 ISSN 0936-5214 © Thieme Stuttgart · New York