Three-component synthesis of homoallylamines by scandium(III) triflate-mediated allylation with allylgermane: A highly imine selective allylation reaction

Article abstract of DOI:10.1055/s-1998-1650

Investigated is a three-component synthesis of homoallylamines by scandium(III) triflate catalyzed allylation of imines, generated in situ from aldehyde and amine, with allyltriethylgermane. Imines were allylated exclusively in the presence of aldehydes.

Full text of DOI:10.1055/s-1998-1650

March 1998
SYNLETT
273
Three-Component Synthesis of Homoallylamines by Scandium(III) Triflate-Mediated
Allylation with Allylgermane: A Highly Imine Selective Allylation Reaction
*
Takahiko Akiyama and Junko Iwai
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima, Tokyo 171-8588, Japan
E-mail: takahiko.akiyama@gakushuin.ac.jp
Received 18 December 1997
Abstract: Investigated is
a
three-component synthesis of
On treatment of N-benzylideneaniline with allyltriethylgermane (1.5
12
homoallylamines by scandium(III) triflate catalyzed allylation of
imines, generated in situ from aldehyde and amine, with
allyltriethylgermane. Imines were allylated exclusively in the presence
of aldehydes.
equiv) in the presence of scandium(III) triflate (10 mol%) and MS 4A
13
in nitromethane, the allylation reaction was complete in 20 min at
room temperature to afford a homoallylamine in 85% yield (Table 1,
Entry 1). Although use of MS 4A is not mandatory for the present
reaction, addition of MS 4A slightly improved the yield of the adduct
(Entry 2). Other aromatic imines were also allylated smoothly to furnish
homoallylamines in excellent yields (Entries 3-5). When
tetraallylgermane was employed as a nucleophile under the identical
reaction conditions, the yields of the homoallylamines were much
lower. Although other lanthanide triflates such as ytterbium triflate and
samarium triflates also promoted the allylation reactions of imines
similarly, they generally afforded the homoallylamines in slightly lower
yields.
The allylation of imines with allyl organometallics is an important
reaction in the preparation of homoallylamines and has been extensively
studied. Allylic metals bearing group 14 elements such as allylsilane
and allylstannane have been established as useful allyl anion
equivalents. Although allylsilanes reacted sluggishly with imines,
allyltrialkylstannanes reacted smoothly with imine under the influence
of conventional Lewis acids, affording homoallylamines in good yields.
Although more than 1 equivalent of Lewis acid used to be required,
1
2
3
catalytic allylation of imines promoted by lanthanide triflate has been
With regard to the reactions of imines, their instability is an inherent
drawback. It is desirable, from a synthetic point of view, to generate
imine in situ and to react with a nucleophile immediately. A three
4
reported. Quite recently, Kobayashi et al. disclosed lanthanide triflate
5
catalyzed aldimine selective allylation with allylstannanes and group 4
6
metal triflate catalyzed one pot allylation of imines. Sc(OTf) -
component reaction of aldehyde, amine, and allylgermane was thus
3
6,7,14
catalyzed three-component reactions of aldehyde, amine, and
allyltributylstannane in micellar system leading to homoallylamines has
tested.
Gratifyingly, the one-pot synthesis of homoallylamines was
successfully achieved. Treatment of benzaldehyde (1.0 eq.), aniline (1.0
eq.), and allyltriethylgermane (1.5 eq.) under the influence of
7
emerged from the same author. Yamamoto et al. also reported
transition metal-catalyzed allylation of aldehydes and imines with
allyltrialkylstannanes.
scandium(III) triflate in CH NO at room temperature afforded the
3
2
8
15
desired homoallylamine in 81% yield (Table 2, Entry 1). An imine,
generated in situ from benzaldehyde and o-methoxyaniline also
furnished a homoallylamine in a good yield (Entry 2). Imines derived
from aliphatic aldehydes also produced the corresponding
homoallylamines in good yields (Entry 6 and 7). Formation of the
homoallyl alcohols was not observed. It should be noted that present
three-component reaction proceeded smoothly by mixing an aldehyde,
In sharp contrast to organotin and organosilicon compounds,
organogermanium compounds have attracted less attention of synthetic
9,10
organic chemists.
In terms of it having lower toxicity than organotin
compounds, elaboration of synthetic utility of organogermanium
compounds is of importance. Recently, we have reported that
tetraallylgermane reacted readily with aldehydes by means of
scandium(III) triflate in aqueous nitromethane to afford homoallyl
an amine, and an allylgermane in the suspension of Sc(OTf) in
3
11
nitromethane; generation of imines before the addition of allylgermane
is not necessary.
alcohols in high yields. It is noted that the allylation reaction showed
high chemical selectivity toward aldehyde in preference to ketone. It
was found that allyltriethylgermane turned out to work effectively as an
allyl anion equivalent in the reaction with imines. We wish to disclose
In order to investigate the reason why the present allylation reaction
gave rise to imine adducts exclusively, chemoselectivity of the present
herein
a
three-component synthesis of homoallylamines by
scandium(III) triflate-promoted allylation
allyltriethylgermane.
of imines with

274
LETTERS
SYNLETT
allylation was studied. In the coexistence of aldehyde and imine derived
from the same aldehyde (1:1 / mol : mol), allyltriethylgermane (1.5
equiv) was treated with scandium(III) triflate and the results are shown
in Table 3. Homoallylamines were obtained exclusively in high yields
and the corresponding homoallyl alcohols were not observed at all.
Allyltriethylgermane turned out to show no reactivity toward aldehyde.
Indeed, treatment of benzaldehyde and allyltriethylgermane in the
for this research by a grant from Iketani Science and Technology
Foundation.
References and Notes
(1) Kleinman, E. F.; Volkmann, R. A. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I. Eds.; Pergamon: Oxford,
1991; Vol. 2; p 975. Yamamoto, Y.; Asao, N. Chem. Rev. 1993,
93, 2207.
presence of Sc(OTf) (10 mol%) in nitromethane at room temperature
3
for 7 days, the desired homoallyl alcohol was obtained in less than 5%
yield.
(2) Fleming, I. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 2; p 563.
(3) Keck, G. E.; Enholm, E. J. Org. Chem. 1985, 50, 146. Ciufolini,
M. A.; Spencer, G. O. J. Org. Chem. 1989, 54, 4739.
(4) Bellucci, C.; Cozzi, P. G.; Umani-Ronchi, A. Tetrahedron Lett.
1995, 36, 7289.
(5) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119,
10049.
(6) Kobayashi, S.; Iwamoto, S.; Nagayama, S. Synlett 1997, 1099.
(7) Kobayashi, S.; Busujima, T.; Nagayama, S. J. Chem. Soc., Chem.
Commun. in press.
(8) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc.
1996, 118, 6641.
(9) For organogermanium compounds in organic synthesis:
Yokoyama, Y.; Mochida, K. Tetrahedron Lett. 1997, 38, 3443.
Curran, D. P.; Diederichsen, U.; Palovich, M. J. Am. Chem. Soc.
1997, 119, 4797. Akiyama, T.; Suzuki, M. J. Chem. Soc., Chem.
Commun. 1997, 2357. See also references cited therein.
(10) For the use of allylgermane as an allylmetal: Sano, H.; Miyazaki,
Y.; Okawara, M.; Ueno, Y.; Synthesis 1986, 776. Yamamoto, Y.;
Hatsuya, S.; Yamada, J. J. Org. Chem. 1990, 55, 3118. Sato, T.;
Otera, J.; Nozaki, H. J. Org. Chem. 1990, 55, 6116. Yamamoto,
Y.; Okano, H.; Yamada, J. Tetrahedron Lett. 1991,32, 4749.
Denmark, S. E.; Almstead, N. G. J. Org. Chem. 1991, 56, 6485.
Hashimoto, Y.; Kagoshima, H.; Saigo, K. Tetrahedron Lett. 1994,
35, 4805.
It turned out that the present reaction system exhibited excellent
chemoselectivity toward imines in preference to aldehydes. In general,
the reactivity of allylmetal to aldehydes is higher than that to imines
8
under the conventional Lewis acid-promoted conditions. Recently,
Kobayashi elucidated that ytterbium(III) triflate coordinated more
13
8,16
strongly toward imines than to aldehydes by C NMR analysis.
The
unique reactivity of the present allylation reaction would also be
ascribed to the stronger activation of imines by scandium(III) triflate in
comparison to that of aldehydes. Furthermore, the overall difference in
the reactivity towards aldehydes between tetraallylgermane and
allyltriethylgermane is of great interest; tetraallylgermane showed high
(11) Akiyama, T.; Iwai, J. Tetrahedron Lett. 1997, 38, 853.
(12) Kobayashi, S. Synlett 1994, 689. Hachiya, I.; Kobayashi, S. J.
Org. Chem. 1993, 58, 6958. Kobayashi, S.; Hachiya, I.; Ishitani,
H.; Araki, M. Synlett 1993, 472.
11
reactivity toward aldehydes whereas allyltriethylgermane showed no
17
reactivity. In general, the reactivity order of allylmetals bearing a 14
(13) The allylation reaction in CH CN completed in 4 hr to afford the
3
18
group metal is Sn > Ge > Si. The present chemoselectivity is ascribed
allylation product in 83% yield.
to the moderate reactivity of germanium compounds in comparison to
organotin compounds.
(14) Veenstra, S. J.; Schmid, P. Tetrahedron Lett. 1997, 38, 997.
(15) A typical experimental procedure for Entry 1 of Table 2. To a
suspension of scandium trifluoromethanesulfonate (11.7 mg,
0.0238 mmol) in nitromethane (1.6 mL) was added successively
allyltriethylgermane (72 µL, 0.36 mmol), benzaldehyde (24 µL,
0.24 mmol), and aniline (22 µL, 0.24 mmol) at room temperature.
After being stirred at that temperature for 45 min, the reaction was
quenched by addition of water. The aqueous layer was extracted
with ethyl acetate and the combined organic layers were washed
Although one-pot synthesis of homoallylamines from aldehyde and
14
6,7
amine utilizing allysilane as well as allystannanes
have been
already reported, present protocol will provide us with a novel and
simple method for the preparation of homoallylamines.
In summary, we have developed a novel allylation reaction of imines
utilizing allylgermane. Salient features of the present allylation reaction
are: 1) allylation of imine proceeded smoothly by use of catalytic
amount of Lewis acid under mild conditions, 2) allylation of imine
proceeded efficiently by three component synthesis from aldehyde,
amine, and allylgermane by one-pot procedure, 3) allylation exhibited
excellent selectivity toward imine in the presence of aldehyde, 4) the
less toxic organogermanium compound has been employed as an
allylmetal.
with brine, dried over anhydrous Na SO , and concentrated to
2
4
dryness. Purification of the crude mixture by preparative TLC
(SiO , hexane: ethyl acetate = 6 : 1, v/v) gave a homoallylamine
2
(42.7 mg) in 81% yield.
(16) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1997, 62, 232.
(17) Yb(OTf)
catalyzed
allylation
of
aldehyde
with
3
allyltributylstannane; Aspinall, H. C.; Browning, A. F.; Greeves,
Acknowledgments. We thank Professor S. Kobayashi of Science
N.; Ravenscroft, P. Tetrahedron Lett. 1994, 35, 4639.
University of Tokyo (Japan) for providing us with a preprint on the
allylation reaction in surfactant. We appreciate partial financial support
(18) Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938.
7