of catalyst 1 (53% and 61% yields, entries 2 and 3, Table
1). Higher yields (70% and 76%) of amine 4b12 along with
traces of regioisomers13 were obtained from coupling to the
electron-deficient p-methoxycarbonylphenyl boronic acid,
reflecting minimal boronic acid dimerization14 (entries 8 and
9, Table 1). Ethyl N-aryliminoacetates bearing electron-
withdrawing substituents Y (CF3, COOMe) performed poorly
(<15%) using catalysts 1 and 3. Unexpectedly, Pd(OAc)2
catalyst 3 proved to be notably more effective in coupling
to the synthetically important N-PMP-protected15 imines,
providing amines 4c and 4d in better yields (54% and 74%,
entries 12 and 13, Table 1) than the yields achieved with
catalyst 1 (36% and 62%, entries 10 and 11, Table 1).12
Traces of regioisomers were only detected in the crude
products from entries 10 and 13 (Table 1).13 The diastereo-
control12 of coupling to N-PMP-protected imines (dr >
10:1) is notable. The observed difference in selectivities of
catalysts 1 and 3 might reflect the involvement of two distinct
catalytic intermediates, complex A formed from catalyst 1
(Figure 1)16 and complex C formed from catalyst 3 (Figure
Table 1. Three-Component Coupling to Iminoacetates
entry
catalyst
ligand
product
yield (%)b
dr
1
2
3
4
5
6
7
8
9
10
11
12
13
1
1
1
2
2
3
3
1
1
1
1
3
3
-
4a
4a
4a
4a
4a
4a
4a
4b
4b
4c
4d
4c
4d
35
53
61
39
51
41
56
70
76
36
62
54
74
8:1
5:1
7:1
4:1
8:1
c
P(t-Bu)3
P(o-Tol)3
-
P(o-Tol)3
-
S-PHOSd
P(t-Bu)3
P(o-Tol)3
P(t-Bu)3
P(t-Bu)3
6:1
6:1
c
18:1
13:1
11:1
13:1
10:1
12:1
c
c
c
P(t-Bu)3
P(t-Bu)3
c
a Method: boronic acid/allene/imine ) 2:5:1 (mol equiv), 10 mol % of
Pd catalyst 1, 2, or 3, 10 mol % of ligand L, CsF (4.0 equiv), THF, rt, 24
h. b Isolated yields. c The ligand was used as its tetrafluoroborate salt HP(t-
Bu)3BF4. d 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl.
Figure 1. Catalytic intermediate arising from catalyst 1.
mechanistically distinct, Ni-catalyzed elaborations of dienes
and allenes fail to control the regiochemistry, providing
mixtures of branched and linear homoallylic alcohols.9
To extend our coupling protocol,6b a reaction between
p-methoxyphenylboronic acid, 1,2-nonadiene, and activated
ethyl iminoacetates10 with various N-protecting groups11
catalyzed by complexes 1-3 was investigated (Table 1). In
contrast to our prior work,6b commercial allylpalladium
complex 2 and Pd(OAc)2 catalyst 3 in the presence of
optimum phosphine ligands (P(o-Tol)3 and S-PHOS, Table
1) afforded amine 4a in surprisingly high yields of 51-56%
(entries 4-7, Table 1),12 competitive with the performance
2),17 or a change in the rate-determining step. Amine 4a
prepared by a reaction catalyzed by complex 1 was essen-
tially racemic, and optimization of the asymmetric induction
has not yet been pursued.18
A plausible catalytic cycle for the reactions catalyzed by
Pd(OAc)2 catalyst 3 is shown in Figure 2. Transmetalation19
and migratory insertion20 would provide intermediate B
from catalyst 3. Transmetalation to complex B would afford
(aryl)(allyl)Pd(II)L complex C.21 With the appropriate lig-
and L, complex C21 would feature the allyl fragment in the
η1-bonding mode and undergo a nucleophilic allyl transfer
(8) (a) Cooper, I. R.; Grigg, R.; MacLachlan, W. S.; Thornton-Pett, M.;
Sridharan, B. Chem. Commun. 2002, 1372. (b) Cleghorn, L. A. T.; Grigg,
R.; Kilner, C.; MacLachlan, W. S.; Sridharan, V. Chem. Commun. 2005,
3071.
(9) (a) Montgomery, J.; Song, M. Tetrahedron 2005, 61, 11440. (b)
Montgomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890. (c) Molinaro, C.;
Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 8076.
(10) (a) Beenen, M. A.; Weix, D. J.; Ellman, J. A. J. Am. Chem. Soc.
2006, 128, 6304. (b) Taggi, A. E.; Hafez, A. M.; Lectka, T. Acc. Chem.
Res. 2003, 36, 10.
(11) See additional results in the Supporting Information, including the
details of the optimization studies and the importance of the auxiliary ligand
choice, which affected the initial reaction rates without improvement in
the yields of amines. A reaction catalyzed by Pd2dba3/HP(t-Bu)3BF4 under
the same conditions afforded a 22% yield of amine 4a (see the Supporting
Information).
(13) In entry 2, Table 1, traces (<3% of mass balance) of a mixture of
several coupling products were present. The spectral pattern of this fraction
was analogous to the byproduct fraction isolated from certain experiments
described in Table 2, for which the structure assignment was realized. See
ref 29.
(14) 4,4-Bis(methoxy)biphenyl was detected in the crude reaction
mixtures (entries 2, 3, and 10, Table 1) by GC/MS. The observed decrease
in the dimerization of the electron-deficient p-methoxycarbonylphenyl
boronic acid agrees with known electronic effects. See: Moreno-Man˜as,
M.; Pe´rez, M.; Pleixats, R. J. Org. Chem. 1996, 61, 2346.
(15) PMP ) p-methoxyphenyl protecting group.
(16) For a catalytic cycle proposed by us for an analogous reaction
mediated by catalyst 1, see ref 6b.
(17) A symmetrical bis-π-allylpalladium complex featuring two “pre-
assembled” allyl ligands (see ref 6b) appears to be an unlikely intermediate
in the high-yielding reactions catalyzed by catalyst 3, due to a complex
pathway that would lead to its formation.
(18) The greater complexity of the allyl fragment in comparison to known
cases (see ref 7) may cause the lack of facial selectivity in the allyl transfer
from intermediate A (Figure 1).
(12) Because amines 4a-d are oils and the J(H2,H3) coupling constants
in 1H NMR spectra of the two diastereomers of amines 4a-d have similar
values, the relative stereochemistry could not be unequivocally assigned.
See the Supporting Information.
5972
Org. Lett., Vol. 8, No. 26, 2006