Angewandte
Chemie
Table 1: Comparative reactivity of silylmethylureas, amide, and ester in
Table 2: The synthetic scope of the methyl-transfer method.[a]
alkyl-transfer reactions.[a]
Entry
t [h]
T [8C]
Product[b]
Conv. [%][c]
E/Z/Di[d]
1
20
70
20
95(85)
93
92:4:4
93:1:6
1
Entry
Reagent
t [h]
T[8C]
Yield [%]
2
10
20
99(86)
87:1:13
1
2
3
4
5
6
7
8
6
7
8
9a
10b
11b
12b
13b
6
72
8
0.66
0.75
2
70
80
70
70
70
60
20
75
90[b]
30[b,c]
70[b,d]
>90[b]
>90[b]
90[b]
3
4
16
3
20
50
97(80)
94(80)
98:1:1
84:8:8
0.5
30
70
20
90
95(90)
92:8:0
99:1:0
5
12
10
78[e]
10[f]
6[e]
8,16
3
40,70
70
85(73)
40
1:99:0
58:42:0
1:99:0
[a] 1 equiv of monosilyl reagents, 0.5 equiv of disilyl reagents (see
Scheme 2). [b] R=Me. [c] Competing alkene acetoxylation. [d] Compet-
ing alkene acetoxylation and dimethylation. [e] 4:1 preference for R=Ph
over R=Me. [f] R=Et; acetoxylation is the dominant reaction with minor
ethylation.
7
8
9
1
2
70
70
33
62[f]
demonstrates that all three silicon-bound methyl groups are
available for transfer, although the second and particularly
the third steps are slower than the first. In reaction of 12b,
methyl transfer competes to some extent with phenyl transfer.
At present, utility is limited to methylations, since the
triethylsilyl reagent 13b is ineffective.
[a] Reactions were carried out in AcOH solution with 5 mol% Pd(OAc)2,
1 equiv benzoquinone, and 0.5 equiv 10b based on alkene. [b] Precur-
sors to compounds 13–21 have H atoms at the site of the highlighted
methyl groups. [c] Yields of isolated product in parentheses. [d] Di: a,a’-
disubstituted product. [e] Carried out with 10 mol% catalyst and 2 equiv
benzoquinone, 8 h at 408C then 16 h at 708C. [f] 3-Methylcyclohexanone
is the minor product.
The scope of reaction was further explored using the
readily prepared disilylurea 10b. Styrenes reacted with this
methyl-transfer agent to form 13 and 14 with high stereose-
lectivity at ambient temperature; at higher temperatures,
greater amounts of Z isomer and dimethylated product were
observed (Table 2, entries 1 and 2). In separate experiments,
p-methylstyrene displays similar initial reactivity to p-tri-
fluoromethylstyrene but tailed in the latter part of the
reaction. When the two reactants are run together, tailing
disappeared and they exhibited similar reactivity throughout.
This indicates that stronger coordination of the more electro-
philic alkene stabilizes the catalyst. The electron-deficient
vinylsulfone and vinylphosphonate gave products 15 and 16
smoothly (Table 2, entries 3 and 4), and dimethyl itaconate
reacted with high selectivity to give the E isomer 17 (Table 2,
entry 5). The slower formation of (Z)-18 from the Baylis–
Hillman derived precursor reflects competing participation
from the OH function, and weaker stereocontrol by CN
compared to CO2R (Table 2, entry 6). Formation of 19 by
methylation of Baylis–Hillman precursor was slow at 708C
and gave 40% of a 58:42 (E/Z) mixture after 3 h (Table 2,
entry 7). Formation of 20 was also sluggish (33%, 1 h, 708C)
but favors the Z isomer (Table 2, entry 8). In such slower
reactions, benzoquinone is consumed in excess of the
methylated product formed, indicating oxidative side reac-
tions. The procedure also worked with cyclohex-2-enone
(Table 2, entry 9), although some saturated product was
formed concurrently.[13]
Such formation of acetates finds analogy in the original work
of Fujiwara and Moritani on Pd C H activation/coupling.
It may be understood in the context of a catalytic cycle
(Scheme 3, step f), based on previous postulates for Heck
reactions under oxidative conditions.[15]
II
[14]
À
Further examples show limitations to the present method-
ology but help elucidate the mechanism. With p-methoxy-
styrene, 22a and 22b were isolated (ratio ca. 4:1), indicating
À
Scheme 3. Proposed pathway for Si Me activation and transfer to
alkenes: a) methyl transfer to Pd, b) alkene addition, c) alkene inser-
À
tion, d) Pd H elimination in competition with f) SN1 solvolysis (Ar=4-
solvolytic C Pd cleavage to form the stabilized benzyl cation.
MeOC6H4), e) reoxidation to PdII.
À
Angew. Chem. Int. Ed. 2008, 47, 4228 –4230
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim