A common catalyst system for the Stille reaction is
Pd2dba3·dba (dba = dibenzylideneacetone) with added PPh3
(14). The reaction catalysed by 14 provided Z-9 in 41% yield
after 24 h, as a mixture of isomers (E : Z, 1 : 2.15) (entry 6).
Changing the catalyst to Pd2dba3·dba–PPh3 with added NBS
provided Z-9 exclusively in 76% yield (entry 7).
Pd(Bn)(PPh3)2Br 16 was screened, providing Z-9 in 54% yield,
as an isomeric mixture (entry 8). The isolated catalyst 6 gave Z-
9 in 98% yield after only 3 h (entry 9). The synthesis of
Pd(NCOC2H4CO)(dppe)Br 17 (dppe = diphenylphosphino-
ethane) was carried out in a similar manner to 6.10 Complex 17
was also shown to catalyse the reaction of 7 + Z-8 ? Z-9 in 90%
yield after 24 h (E : Z, 1 : 29).
entry 5, catalyst 5 gave only a 11% yield of the coupled product
as an isomeric mixture (Z-C5 : E-C5, 1.2 : 1). An increase in
yield occurred using 16, and no isomerisation was observed.
Here 6 is noticeably superior to 5 and 16, providing the Z-
isomer exclusively in 62% yield.
It should be noted that on completion of each reaction using
6, the colour of the solution remains yellow, which presumably
indicates a Pd(II) catalytic resting state. Collodial palladium
black was produced with all the other catalyst systems 5, 10, 14
and 16. The Pd(II) resting state was confirmed by following the
reaction of 7 + Z-8 ? Z-9 using 6 in d8-toluene at 70 °C by 31
P
NMR (202 MHz) which shows one signal at d 25.34 (singlet),
which remains at the end of reaction. This species is not 6, nor
is it Pd(Bn)(PPh3)2Br. Furthermore 6 was not detected at the
start, during or at the end of the reaction. Therefore 6 is a
precatalyst. Mechanistic studies to identify the active catalyst
are underway.
Table 1 Effect of Pd-catalyst and succinimide additivesa
In summary, we have discovered that 6 can be used to effect
the Stille reaction. Complex 6 can be synthesised in one step
from Pd2dba3·CHCl3, PPh3 and NBS, which should facilitate its
mainstream use. The catalytic activity of other monomeric and
dimeric succinimido-based Pd(II) complexes will be reported in
due course.
We thank the EPSRC for a PhD studentship for C.M.C (GR/
N06977). Dr J. L. Serrano is thanked for providing spectral data
for the original synthesis of 6. I.J.S.F acknowledges the
University of York for financial support.
Entry
Catalystb
Time/h
Yield (%)e
1
2
3
4
5
6
7
8
9
Pd(PPh3)4 (5)
24
24
24
18
24
24
18
24
3
17
46f
61
83
33
41f
76
54g
98
Pd(OAc)2 + PPh3 (10)
Pd(PPh3)4 + NCS (11)
Pd(PPh3)4 + NBS (12)
Pd(PPh3)4 + NIS (13)
Pd2dba3·dba + PPh3 (14)c
Pd2dba3·dba + PPh3 + NBSd (15)
Pd(Bn)(PPh3)2Br (16)
Pd(NCOC2H4CO)(PPh3)2Br (6)
Notes and references
a Reaction conditions: 7 (0.5 mmol), Z-8 (0.6 mmol), C6H5CH3 (5 mL) at 60
°C, under an inert atmosphere of N2. b 5 mol% [Pd] unless stated otherwise.
c Pd2dba3·dba (2.5 mol%) and PPh3 (10 mol%). d As for entry 5 with added
NBS (5 mol%). e Isolated yield after KF workup and chromatography.
f Isomeric mixture: see text. g Diene (E:Z, 1.6:1) : skip-diene, 1.0 : 0.9 (by
1H NMR).
† Modified synthetic procedure for 6: to a Schlenk tube containing vacuum
dried Pd2dba3·CHCl3 (100 mg, 0.097 mmol) in dry CH2Cl2 (2 mL), under
N2, was added a solution of PPh3 (101.4 mg, 0.387 mmol) in dry CH2Cl2 (2
mL). The mixture was stirred for 0.2 h, after which time an orange colour
persisted. A solution of recrystallised N-bromosuccinimide (34.5 mg, 0.194
mmol) in dry CH2Cl2 (2 mL) was added in one portion and the mixture
stirred for a further 0.2 h. The resulting yellow solution was concentrated in
vacuo to a third of its original volume and petroleum ether added to
precipitate complex 6. The creamy yellow solid was filtered and washed
with small quantities of hexane (104 mg, 74% yield). A small quantity of 6
was recrystallised. Single crystals were obtained from CH2Cl2 by slow
vapour diffusion with Et2O (1 : 5, v/v) at 0 °C for 2 d. nmax (KBr)/cm21 1631
(CNO); dH (CD2Cl2, 400 MHz) 1.61 (2H, m, 2 3 CHA), 2.27 (2H, m, 2 3
CHB), 7.1–7.6 (30H, m, Ph–H); dP (CD2Cl2, 202 MHz) 23.96 (1P, 2JPP 8.49
Hz) and 32.91 (1P, 2JPP 8.49 Hz). Crystal data. C40H34BrNO2P2Pd, M =
808.93, monoclinic, a = 12.3222(11), b = 19.880(2), c = 13.6371(13) Å,
U = 3340.6(6) Å3, T = 115(2) K, space group P21/n, Z = 4, m(Mo–Ka) =
1.885 mm21, 18654 reflections measured, 5990 unique (Rint = 0.0733)
which were used in all calculations. Final R1 = 0.0849 and wR(F2) =
b304960d/ for crystallographic data in .cif or other electronic format.
The substrate scope of 6 and related catalysts with several
allylic and benzylic substrates and organostannanes were
studied (Table 2). One of the well-known drawbacks of the
Stille reaction is the removal of tin halide by-products.3 We
generally use a KF workup,2a although for certain substrates a
DBU–I2–Et2O workup11 proved beneficial. It is important to
note that in reactions of Z-8 or E-8 the latter workup resulted in
a rapid regio- and stereo-isomerisation ( < 2 min).
The yields of the cross-coupled products from reactions
employing 6, compare well to 5 and 16 in entries 1, 5 and 6. For
Table 2 Allylic and benzylic substrate screening with organostannanesa
Entry RBr
1
RASnBu3
Cat. Yield (%)b
1 M. Kosugi, Y. Shimizu and T. Migita, Chem. Lett., 1977, 1423.
2 (a) D. Milstein and J. K. Stille, J. Am. Chem. Soc., 1978, 100, 3636; (b)
J. K. Stille, Angew. Chem., Int. Ed., 1986, 25, 508.
5
6
73
95 (4.5 h)
16
5
6
5
71
3 For a comprehensive review of the Stille reaction, see: V. Farina, V.
Krishnamurthy and W. J. Scott, Org. React., 1997, 50, 1.
4 For use of Stille coupling in our research, see: (a) G. Macdonald, L.
Alcaraz, X. Wei and R. J. K. Taylor, Tetrahedron, 1998, 54, 9823; (b)
L. Alcaraz, G. Macdonald, J. Ragot, N. J. Lewis and R. J. K. Taylor,
Tetrahedron, 1999, 55, 3707; (c) L. R. Marrison, J. M. Dickinson, R.
Ahmed and I. J. S. Fairlamb, Tetrahedron Lett., 2002, 43, 8853; (d) L.
R. Marrison, J. M. Dickinson and I. J. S. Fairlamb, Bioorg. Med. Chem.
Lett., 2002, 12, 3509.
5 A. F. Littke and G. Fu, Angew. Chem., Int. Ed., 2002, 41, 4176.
6 R. B. Bedford, Chem. Commun., 2003, 1787.
7 (a) A. F. Littke, L. Schwarz and G. C. Fu, J. Am. Chem. Soc., 2002, 124,
6343; (b) A. F. Littke and G. C. Fu, Angew. Chem., Int. Ed., 1999, 38,
2411.
2
3
9c
67c
90
93
6
4
5
5
6
51
56
5
6
11d
62
16
5
32
56e
6
6
16
81 (13 h)
58
8 G. A. Grasa and S. P. Nolan, Org. Lett., 2001, 3, 119.
9 T. Henkel and A. Zeeck, Liebigs Ann. Chem., 1991, 367.
10 J. L. Serrano, Y. Zheng, J. R. Dilworth and G. Sánchez, Inorg. Chem.
Commun., 1999, 2, 407.
a Reaction conditions as for Table 1: 24 h unless other stated in brackets.
b Isolated yields after KF workup and chromatography. Numbers in
brackets are reaction times. c A DBU–I2–Et2O workup was used. d Isomeric
mixture: see text. e Diene (E only) : skip-diene, 1.2 : 1 (by 1H NMR).
11 D. P. Curran and C.-T. Chang, J. Org. Chem., 1989, 54, 3140.
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