Chiral π-allylpalladium-catalyzed asymmetric allylation of imines: Replacement of allylstannanes by allylsilanes

Full text of DOI:10.1021/jo9901081

2614
J . Org. Chem. 1999, 64, 2614-2615
summarized in Table 1. The reaction of 1a , derived from
Ch ir a l π-Allylp a lla d iu m -Ca ta lyzed
Asym m etr ic Allyla tion of Im in es:
Rep la cem en t of Allylsta n n a n es by
Allylsila n es
benzaldehyde and benzylamine, with 2a (2 equiv) proceeded
very smoothly at room temperature in the presence of a
catalytic amount of π-allylpalladium chloride dimer 3a (5
mol %) and TBAF (0.5 equiv) in n-hexane-THF (4:1)
cosolvent, giving the corresponding homoallylamine 4a in
69% yield (entry 1).6 The use of THF as a solvent gave 4a in
lower yield (∼30%). Other palladium catalysts such as PdCl2-
(PPh3)2, PdCl2(dppe), or PtCl2(PPh3)2, other fluoride ion
sources such as CsF, KF-crown ether, 3HF-NEt3, TBAH2F3,
or TBAHF2,7 and other allylsilanes such as allyltriethoxysi-
lane or allyltrichlorosilane were not effective. The imines
1b and 1c gave the corresponding homoallylamines 4b and
4c, respectively, in high yields (entries 2 and 3). The imine
1d reacted slowly even in the presence of 3 equiv of 2a to
afford 4d in 50% yield (entry 4). The allylation reaction of
1e and 1f resulted in modest yields (57% and 62%, respec-
tively; entries 5 and 6). Needless to say, the allylation
products were not obtained in the absence of palladium
catalysts and/or TBAF. The use of palladium-TBAF cocata-
lyst is essential for obtaining good to high yields of the
allylation products.
The reaction of imine 1a with 2a is representative. To a
solution of 1a (0.5 mmol) and 3a (0.025 mmol) in n-hexane
(2 mL) was added 2a (1.0 mmol). The resulting mixture was
stirred for about half an hour, and then TBAF (0.25 mmol,
1.0 M solution in THF) and THF (0.25 mL) were added. The
reaction mixture became two phases: the upper phase was
a homogeneous n-hexane-THF solution and the bottom
phase contained a TBAF solution. The mixture was stirred
for 31 h at room temperature. The reaction progress was
monitored by TLC and 1H NMR. After 1a was consumed
completely, the reaction was quenched with water. The
reaction mixture was extracted with ether. The organic layer
was washed with a saturated aqueous NaCl solution, dried
over anhydrous MgSO4, and then concentrated. Purification
by silica gel column chromatography (n-hexane/ethyl acetate
) 10:1) gave 4a in 69% yield.
Kaori Nakamura, Hiroyuki Nakamura, and
Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-8578, J apan
Received J anuary 20, 1999
The stereoselective addition of allylmetal reagents to
aldehydes and imines is one of the most powerful and
important reactions for carbon-carbon bond formation.1
Among various allylmetal reagents, allylsilanes and allyl-
stannanes are utilized very frequently in organic synthesis;
the former reagents are in general more stable, less reactive,
and less toxic, whereas the latter reagents are less stable,
more reactive, and significantly toxic. We recently reported
that imines undergo catalytic asymmetric allylation reaction
with allyltributylstannanes in the presence of chiral π-al-
lylpalladium catalysts.2,3 However, the use of allyltributyl-
stannanes is not necessarily desirable from the point of green
chemistry. The use of allylsilanes is more desirable, but in
general the reaction of imines with allylsilanes is quite
sluggish.4 We have solved this dilemma and herein report a
novel allylation reaction of imines, as well as aldehydes, with
allyltrimethylsilanes using a palladium-TBAF cocatalyst
5
system (eqs 1 and 2) and its extension to asymmetric
allylation of imines using a chiral π-allylpalladium catalyst
(eq 1).
We next examined the allylation of various aldehydes
using the palladium-TBAF cocatalyst system. The allylation
reaction of aromatic and alkenyl aldehydes 5a -d gave the
corresponding homoallyl alcohols 6a -d in modest to good
yields (entries 7-10). However, the allylation reaction of
aliphatic aldehydes 5e and 5f resulted in poor yields (entries
11 and 12). The cyclic ketone 5g also underwent the
allylation to give 6g in 21% yield (entry 13). It is known that
the allylation of aldehydes with 2a proceeds in the presence
of a catalytic amount of fluoride ions at higher temperatures
(under reflux of THF).8 The present allylation proceeds at
room temperature; obviously palladium catalysts facilitate
the allylation.
First we examined the palladium-catalyzed allylation of
imines 1 with allyltrimethylsilane 2a . The results are
Inspired by the above results, we applied the palladium-
TBAF cocatalyst system to the asymmetric allylation of
2
imines 1 using chiral π-allylpalladium catalyst 3b (5 mol
(1) For recent reviews of allylmetal additions, see: (a) Yamamoto, Y.;
Asao, N. Chem. Rev. 1993, 93, 2207. (b) Marshall, J . A. CHEMTRACTS
1992, 5, 75. (c) Roush, W. R. In Comprehensive Organic Synthesis;
Heatchcock, C. H., Ed.; Pergamon Press: Oxford, 1991; Vol. 2, pp 1-53.
(2) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J . Am. Chem. Soc. 1998,
120, 4242.
(3) For the allylation of aldehydes and imines catalyzed by bis-π-
allylpalladium complexes, see: Nakamura, H.; Iwama, H.; Yamamoto, Y.
J . Am. Chem. Soc. 1996, 118, 6641.
(4) Allylation and crotylation reaction of aldimines by allyltrifluorosilane
with cesium fluoride: (a) Kira, M.; Hino, T.; Sakurai, H. Chem. Lett. 1991,
277. Allylation reaction of aromatic N-galactosyl imines by allyltrimethyl-
silane in the presence of SnCl4: (b) Laschat, S.; Kunz, H. Synlett 1990, 51.
(c) Laschat, S.; Kunz, H. J . Org. Chem. 1991, 56, 5883.
(5) For the palladium-catalyzed coupling reactions of organosilicone
compounds, see: (a) Hatanaka, Y.; Goda, K.; Hiyama, T. Tetrahedron Lett.
1994, 35, 6511. See also: (b) Horn, K. A. Chem. Rev. 1995, 95, 1317.
%) at 0 °C. The results are summarized in Table 2. The
allylation reaction of 1a gave 4a in 79% yield with an
enantiomeric excess of 80% (entry 1).9 The reaction of 1g
(6) The allylation reaction proceeded even in the presence of 0.1 equiv
of TBAF in 70% yield. On the other hand, the use of 2.0 equiv of TBAF in
n-hexane solvent was not effective; 4a was obtained in 45% yield.
(7) TBAH2F3 ) tetra n-butylammonium dihydrogentrifluoride, TBAHF2
) tetra n-butylammonium hydrogendifluoride: Kuroboshi, M.; Hiyama, T.
Tetrahedron Lett. 1991, 32, 1215.
(8) (a) Hosomi, A.; Shirahata, A.; Sakurai, H. Tetrahedron Lett. 1978,
3043. For reviews, see: (b) Sakurai, H. Pure Appl. Chem. 1982, 54, 1. (c)
Sakurai, H. Pure Appl. Chem. 1985, 57, 1759.
(9) The absolute configuration of the homoallylamine 4a was determined
to be R by converting it to 1-phenylbutylamine. Details are shown in ref 2.
10.1021/jo9901081 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/26/1999

Communications
J . Org. Chem., Vol. 64, No. 8, 1999 2615
Ta ble 1. π-Allylp a lla d iu m -TBAF -Ca ta lyzed Allyla tion of
The addition of benzaldehyde 5a to the mixture caused the
disappearance of the signals due to 7, and new signals
assigned to the corresponding homoallyl alcohol appeared.
On the basis of these observations, it is clear that the
allylation reaction would proceed via 7. Perhaps fluoride ions
would coordinate 2a to produce the corresponding pentaco-
ordinate allylsilicate, which would undergo quite easily
transmetalation to Pd(II), giving the key intermediate 7. As
mentioned above, the allylation did not proceed in the
absence of palladium catalysts. Therefore, the role of fluoride
ions in the present allylation reaction is not to produce free
allyl anions, which may react with aldehydes and imines.8,11
It is reported that certain pentacoordinate allylsilicates react
with aldehydes12 and imines4a to give the corresponding
allylated products, but we confirmed that [(allyl)SiMe3F]-
formed in situ from 2a and TBAF did not react with them
under the reaction conditions.13
Im in es a n d Ald eh yd es w ith Allyltr im eth ylsila n ea
entry imine 1 or aldehyde 5 reactn time (h) product yield (%)b
1
2
1a
1b
1c
1d
1e
1f
31
19
4a
4b
4c
4d
4e
4f
69
96
89
50c
57
62
84
82
67
75
28
36
21
3
15
4
139
155
17
5
6
7
5a
5b
5c
5d
5e
5f
20
6a
6b
6c
6d
6e
6f
8
17
9
32
10
11
12
13
28
97
28
5g
97
6g
a
Unless otherwise specified, the reaction was carried out using
π-allylpalladium chloride dimer 3a (5 mol %), allyltrimethylsilane
2a (2 equiv), TBAF (0.5 equiv), and imines 1 or aldehydes 5 (1
equiv) in n-hexane-HF at room temperature for indicated times.
The allylation reaction with 2b and 2c 14 was investigated
(eqs 3 and 4). The reaction of benzaldehyde 5a with 2b
b
Isolated yield. c Three equivalents of 2a were used.
(trans/cis ) 87/13) was very sluggish at room temperature,
15
and after 8 days only the γ-addition product 8
was
Ta ble 2. Ch ir a l π-Allylp a lla d iu m -TBAF -Ca ta lyzed
Asym m etr ic Allyla tion of Im in es w ith
Allyltr im eth ylsila n ea
obtained in 27% yield. Interestingly, the reaction of 2c was
entry imine 1 reactn time (h) product yield (%)b ee (%)c
1
2
3
4
5
6
7
8
1a
1g
1b
1c
1d
1e
1f
46
53
4a
4g
4b
4c
4d
4e
4f
79
79
95
96
34
60
77
88
80d
79
3
36
48
5
155
136
41
76
84
64
68
1h
47
4h
a
The reaction was carried out using π-allylpalladium chloride
dimer 3b (5 mol %), allyltrimethylsilane 2a (2 equiv), TBAF (0.5
equiv), and imines 1 (1 equiv) in n-hexane-THF at 0 °C for
b
indicated times. Isolated yield. c Determined by HPLC analysis
faster than that of 2b and was completed in 12 h, giving
only the R-addition product 8 in 91% yield. Furthermore, in
both cases, the syn/anti diastereomer ratios of the products
were almost same; 75/25 and 74/26 (see eqs 3 and 4).15 These
results suggest that the rate-determining step of the ally-
lation reaction is the transmetalation step; the transmeta-
lation from 2b is very slow whereas that from 2c is faster,
and the same bis-π-allylpalladium is produced from 2b and
2c.16
We have found that smooth allylation of imines and
aldehydes with allylsilanes and catalytic asymmetric ally-
lation of imines proceed in the presence of a palladium-
TBAF cocatalyst system. We are now in a position to switch
allylstannanes to nontoxic allyltrimethylsilane and approach
green chemistry.
d
(see ref 2). The absolute configuration was determined to be R
(see ref 2).
gave 4g in 79% yield with 79% ee (entry 2). Although the
allylation of 1b and 1c proceeded very smoothly, an almost
racemic mixture of the products was obtained (entries 3 and
4). Perhaps the sterically bulky phenyl group prevented
efficient coordination of the nitrogen atom of the imine to
the palladium atom, diminishing the influence of the chiral
ligand on the asymmetric induction. The reaction of 1d was
very sluggish as mentioned above and gave the correspond-
ing homoallylamine 4d in low yield, but with modest
enantiomeric excess (76% ee; entry 5). The reaction of 1e
proceeded slowly to give 4e in 60% yield with the highest
enantiomeric excess among the imines examined (84% ee;
entry 6). These results suggest that a sterically less bulky
group attached to the nitrogen atom produces a higher ee
than sterically bulky groups. The imines 1f and 1h under-
went the asymmetric allylation to give 4f and 4h in good
yields with modest enantiomeric excesses (64% ee and 68%
ee, respectively; entries 7 and 8).
J O9901081
(11) For proposed mechnisms, see: Chuit, C.; Corriu, R. J . P.; Reye, C.;
Young, J . C. Chem. Rev. 1993, 93, 1371.
(12) (a) Hosomi, A.; Kohra, S.; Tominaga, Y. J . Chem. Soc., Chem.
Commun. 1987, 1517. (b) Kira, M.; Kobayashi, M.; Sakurai, H. Tetrahedron
Lett. 1987, 28, 4081. (c) Cerveau, G.; Chuit, C.; Corriu, R. J . P.; Reye, C. J .
Organomet. Chem. 1987, 328, C 17 (d) Kira, M.; Zhang, L. C.; Kabuto, C.;
Sakurai, H. Organometallics 1996, 15, 5335.
(13) A referee pointed out that the fluoride anion is only present in a
catalytic amount; therefore turnover would require breaking the notoriously
stable silicon-fluoride bond. There are few examples for the reactions using
a catalytic amount of fluoride ions: see ref 9a and Noyori, R.; Yokoyama,
K.; Sakata, J .; Kuwajima, I.; Nakamura, E.; Shimizu, M. J . Am. Chem. Soc.
1977, 99, 1265.
(14) For preparation of allylsilanes reagents 2b and 2c, see: (a) Slutsky,
J .; Kwart, H. J . Am. Chem. Soc. 1973, 95, 8678. (b) Hosomi, A.; Iguchi, H.;
Sakurai, H. Chem. Lett. 1982, 223.
To clarify the mechanism of the allylation reaction cata-
lyzed by the palladium-TBAF cocatalyst system, the struc-
ture of an intermediate produced from a stoichiometric
reaction of 2a and 3a and TBAF in CDCl3 was investigated.10
The 1H NMR spectra of this mixture at 25 °C indicated
clearly the formation of bis-π-allylpalladium complex 7.10
(15) The structure and the diastereomer ratios of the resulting homoallyl
alcohols were determined by comparison with the reported data: Yamamoto,
Y.; Yatagai, H.; Maruyama, K. J . Am. Chem. Soc. 1981, 103, 1969.
(16) Normally, in the allylation reactions of aldehydes and imines with
allylmetal reagents, which would proceed via the six-membered cyclic
transition state, the geometries of starting allylmetal reagents should have
an effect on the corresponding products. For example, see refs 1 and 4a.
See also: Yamamoto, Y.; Nishii, S.; Maruyama, K.; Komatsu, T.; Ito, W. J .
Am. Chem. Soc. 1986, 108, 7778.
(10) The experimental procedure similar to that described in ref 3 was
used again.