Chemoselective allylation of aldimine with allyltriethylgermane by the combined use of BF3·OEt2 and AcOH

Article abstract of DOI:10.1039/a907538k

Allyltriethylgermane reacts with aldimines in preference to aldehydes by means of BF₃·OEt₂ and AcOH to afford homoallylic amines in high yields; three component syntheses of homoallytic amines starting from aldehyde, aniline and ally

Full text of DOI:10.1039/a907538k

Chemoselective allylation of aldimine with allyltriethylgermane by the
combined use of BF3•OEt2 and AcOH
Takahiko Akiyama,* Junko Iwai, Yuji Onuma and Hirotaka Kagoshima
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima-ku, Tokyo 171,
Japan. E-mail: takahiko.akiyama@gakushuin.ac.jp
Received (in Cambridge, UK) 17th September 1999, Accepted 28th September 1999
Allyltriethylgermane reacts with aldimines in preference to
aldehydes by means of BF3•OEt2 and AcOH to afford
homoallylic amines in high yields; three component synthe-
ses of homoallytic amines starting from aldehyde, aniline
and allylgermane were successfully achieved.
Allylation of the aldimines proceeded smoothly and showed
high chemoselectively in preference to the aldehyde.
Since aldimines are not always stable, it would be synthet-
ically quite useful if the allylation of imines could be achieved
via reaction with aldimines generated in situ from aldehydes
and amines. The three component synthesis of homoallylic
amines starting from aldehyde, amine and allylgermane took
place smoothly in the presence of BF3•OEt2 (0.5 equiv.), AcOH
(1.0 equiv.) and MS 3A in MeCN to afford homoallylic amines
in high yields; the results are shown in Table 3. Not only
aldimines derived from aromatic aldehydes but also those
derived from aliphatic and a-keto aldehydes worked reasonably
well to afford the corresponding homoallylic amines in high
yields.
Finally, the chemoselectivity of Si, Ge and Sn reagents was
studied. In the presence of equimolar amounts of aldimine and
aldehyde, allylic metals were treated with BF3•OEt2 (0.5 equiv.)
and AcOH (1.0 equiv.) and the results are shown in Table 4. The
reaction with allylsilane was sluggish and the corresponding
adduct was obtained in a low yield. Although the reactivity of
Lewis acid promoted nucleophilic addition of allylic organo-
metallics to imines constitutes an important reaction for the
preparation of homoallylic amines.1 Although numerous kinds
of activator of aldimines have been reported, the addition
toward aldimines has been less extensively explored due to its
inherent lower reactivity in comparison with that toward
aldehydes.2 Recently, several groups have developed imine
selective activators.3 For instance, Yamamoto and co-workers
reported PdII catalyzed chemoselective allylation of aldimines
with allylstannanes.4 Kobayashi and co-workers found that
lanthanide or scandium triflate5 mediated allylation reactions
proceeded smoothly toward aldimines in preference to alde-
hydes.6 BF3•OEt2 catalyzed chemoselective allylation of aldi-
mines, generated from aldehydes and carbamates7 or sulfona-
mides,8 with allylsilane has been realized. We have also
reported that Sc(OTf)3 catalyzed allylation with allylgermane
took place highly chemoselectively toward aldimines in
preference to aldehydes.9
Table 1 Effect of the additive
We have recently shown that Brønsted acids activate imines
chemoselectively in the presence of aldehydes in aqueous
media.10 Thus, upon reaction of aldimines and silyl enolates in
the presence of a catalytic amount of HBF4, Mannich-type
reactions proceeded smoothly in aqueous media to afford b-
amino carbonyl compounds in high yields. Three component
syntheses of b-amino carbonyl compounds starting from
aldehydes and anilines have been also successfully achieved.
Furthermore, the Brønsted acid catalyzed Mannich-type reac-
tion proceeded smoothly in water without organic solvent in the
presence of surfactants such as SDS.11
We report herein that aldimines underwent allylation with
allylgermane highly chemoselectively in preference to alde-
hydes by the combined use of BF3•OEt2 and AcOH and that
three-component syntheses utilizing aldehydes, amines and
allylgermanes furnished homoallylic amines in high yields.
In the first place, the chemoselectivity of the allylation with
allylgermane was studied and the results are shown in Table 1.
On reaction of an equimolar amount of benzaldehyde and N-
benzylideneaniline in the presence of allyltriethylgermane (1.5
equiv.) and BF3•OEt2 (1.0 equiv.) in MeCN at room tem-
perature, allylation proceeded towards aldehyde to afford a
homoallylic alcohol 1a in a good yield accompanied by a
homoallylic amine 2a. Interestingly, addition of a proton source
changed the reaction course dramatically and the aldimine
underwent allylation exclusively. As an additive, AcOH gave
the best result. It is noted that the present allylation did not
proceed at all with the aldimine derived from benzaldehyde and
benzylamine. The presence of the N-aryl group is mandatory.
After screening the reaction conditions, use of 1.0 equiv. of
BF3•OEt2 and 0.5 equiv. of AcOH gave the best results.12,13 It
is noted that allylation did not proceed at all with AcOH alone
without BF3•OEt2. Results for the chemoselective allylation
with several aromatic aldimines are shown in Table 2.
Entry
Additive
Yield of 1a (%) Yield of 2a (%)
1
2
3
4
5
None
H2O
MeOH
AcOH
BzOH
42
72
79
86
75
88
< 1
< 1
7
< 1
Table 2 Results of the allylation
Entry
R
Yield of 1 (%)
Yield of 2 (%)
1
2
3
4
5
Ph
90
87
86
75
72
< 1
6
< 1
7
p-NO2C6H4
p-ClC6H4
p-CH3C6H4
p-MeOC6H4
< 1
Chem. Commun., 1999, 2191–2192
This journal is © The Royal Society of Chemistry 1999
2191

Table 3 Results of the three-component allylation
benign organogermanium reagents are employed, (ii) the
combination of a conventional Lewis acid and a Brønsted acid
is found to be an effective activator of aldimines, and (iii)
addition of a small amount of protic acid to BF3•OEt2 alters the
reactivity dramatically.
Partial financial support from the Ministry of Education,
Science and Culture of Japan (Grant-in-Aid for Scientific
Research) and the Takeda Award in Synthetic Organic
Chemistry, Japan, is gratefully acknowledged.
Entry
R
Yield of 1 (%)
Notes and references
1
2
3
4
5
6
Ph
81
87
83
80
80
88
p-NO2C6H4
p-ClC6H4
c-C6H11
But
1 E. F. Kleinman and R. A. Volkmann, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol.
2, p. 975; Y. Yamamoto and N. Asao, Chem. Rev., 1993, 93, 2207.
2 R. A. Volkmann, in Comprehensive Organic Synthesis, ed. B. M. Trost
and I. Fleming, Pergamon, Oxford, 1991, vol. 1, p. 355; R. Bloch, Chem.
Rev., 1998, 98, 1407.
PhCOa
a PhCOCHO•H2O was employed.
3 Although Grieco and co-workers reported three allylations of aldimines
generated in situ from aldehyde, only formaldehyde was employed. See:
S. D. Larsen, P. A. Grieco and W. F. Fobare, J. Am. Chem. Soc., 1986,
108, 3512; P. A. Grieco and A. Bahsas, J. Org. Chem., 1987, 52,
1378.
Table 4 Reactivity of 14-group allylic organometallics
4 H. Nakamura, N. Asao and Y. Yamamoto, J. Chem. Soc., Chem.
Commun., 1995, 1273; H. Nakamura, H. Iwama and Y. Yamamoto,
J. Am. Chem. Soc., 1996, 118, 6641.
5 S. Kobayashi, Synlett, 1994, 689; S. Kobayashi, Eur. J. Org. Chem.,
1999, 15.
6 S. Kobayashi and S. Nagayama, J. Org. Chem., 1997, 62, 232; S.
Kobayashi and S. Nagayama, J. Am. Chem. Soc., 1997, 119, 10049.
7 S. J. Veenstra and P. Schmid, Tetrahedron Lett., 1997, 38, 997.
8 Y. Masuyama, J. Tosa and Y. Kurusu, Chem. Commun., 1999, 1075.
9 T. Akiyama and J. Iwai, Synlett, 1998, 273.
Entry
MR3
Yield of 1a (%) Yield of 2a (%)
10 T. Akiyama, J. Takaya and H. Kagoshima, Synlett, 1999, 1045; T.
Akiyama, J. Takaya and H. Kagoshima, Chem. Lett., 1999, 947.
11 T. Akiyama, J. Takaya and H. Kagoshima, Synlett, 1999, 1426.
12 Use of commercially available BF3•2AcOH gave comparable results.
13 Brønsted acid, generated from BF3•OEt2 and 0.5 equiv. of AcOH, may
be the active species. For examples of the intramolecular allylation of
imines with allylstannanes wherein protic acids have been employed,
see: I. Kadota, J.-Y. Park and Y. Yamamoto, Chem. Commun., 1996,
841; J.-Y. Park, I. Kadota and Y. Yamamoto, J. Org. Chem., 1999, 64,
4901.
1
2
3
SiMe3
GeEt3
SnBu3
19
79
82
< 1
< 1
9
allylstannane turned out to be higher than that of allylgermane,
allylgermane showed the highest chemoselectivity toward
aldimines.
In summary, we have found a simple method for the selective
allylation of aldimines. Salient features are (i) environmentally
Communication 9/07538K
2192
Chem. Commun., 1999, 2191–2192