Lewis acid-catalyzed allylation reactions of acylhydrazones with tetraallyltin in aqueous media

Article abstract of DOI:10.1055/s-2001-15166

Allylation reactions of various benzoylhydrazones with tetraallyltin were found to proceed smoothly in the presence of scandium triflate as a Lewis acid catalyst at ambient temperature in aqueous media, to afford the corresponding homoallylic amine deriva

Full text of DOI:10.1055/s-2001-15166

1140
LETTER
Lewis Acid-Catalyzed Allylation Reactions of Acylhydrazones with
Tetraallyltin in Aqueous Media
Sh Kobayashi,* Tomoaki Hamada, Kei Manabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation (JST), Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan
Fax +81-3-5684-0634; E-mail: skobayas@mol.f.u-tokyo.ac.jp
Received 12 April 2001
First, the reaction of benzoylhydrazone 1, which is de-
Abstract: Allylation reactions of various benzoylhydrazones with
rived from an aliphatic aldehyde, with tetraallyltin in
aqueous solvents was carried out in the presence of vari-
ous Lewis acids. After several trials, we were pleased to
tetraallyltin were found to proceed smoothly in the presence of
scandium triflate as a Lewis acid catalyst at ambient temperature in
aqueous media, to afford the corresponding homoallylic amine de-
rivatives in high yields. Three-component reactions of aldehydes, find that the reaction proceeded smoothly in water/THF.
As shown in Table 1, Sc(OTf)39 was found to be the best
benzoylhydrazine, and tetraallyltin were also catalyzed by scandi-
catalyst among the Lewis acids tested.10
um triflate in the same media. Furthermore, a simple procedure to
prepare oxazolidinone derivatives utilizing these reactions was de-
veloped.
Table 1 Allylation of 1 in the Presence of Various Lewis Acids in
Aqueous Media
Key words: hydrazone, Lewis acid, allylation, aqueous media,
scandium triflate
Lewis acid
(10 mol %)
NHBz
BzHN
N
NH
Sn
4
+
H2O/THF
(1/9)
30 °C, 24 h
In recent years, organic reactions in aqueous media have
attracted a great deal of attention, not only because these
reactions eliminate the necessity of vigorous drying of
solvents and substrates, but also because unique reactivity
and selectivity are often observed in the aqueous reac-
tions.1 Along this line, we have developed several reac-
tions catalyzed by water-compatible Lewis acids such as
rare earth metal triflates in aqueous solvents.2
Ph(CH2)2
H
Ph(CH2)2
(30 mol %)
1
Lewis acid
Sc(OTf)3
Cu(OTf)2
Zn(OTf)2
AgOTf
Yield (%)
77
56
40
69
40
Lewis acid-mediated addition of allyltins or allylsilanes to
carbon nitrogen double bonds provides one of the most
important methods to obtain homoallylic amines, which
constitute versatile intermediates for the synthesis of ni-
trogen-containing compounds.3 We4 and others5 have re-
ported the allylation reactions of imines in the presence of
catalytic amounts of Lewis acids in organic solvents. Re-
cently, we have also reported the reactions of acylhydra-
zones with tetraallyltin using scandium triflate (Sc(OTf)3)
as a Lewis acid catalyst in acetonitrile.6 Acylhydrazones
are useful imine surrogates and are easily prepared from
acylhydrazines and carbonyl compounds. In addition,
most acylhydrazones, including the ones derived from al-
iphatic aldehydes, can be purified by recrystallization and
are easy to handle under air, while the corresponding imi-
ne derivatives are generally unstable. Furthermore, the
hydrazines produced by the reactions of hydrazones with
nucleophiles can be converted not only to amines by facile
cleavage of the nitrogen nitrogen single bonds7 but also
to various compounds retaining the nitrogen nitrogen
bonds.8 In spite of these attractive features for the use of
acylhydrazones as substrates, there has been no report on
Lewis acid-catalyzed allylation reaction of acylhydra-
zones in aqueous media. In this paper, we describe the
first example of such reaction.
Yb(OTf)3
This reaction system was applied to various benzoylhy-
drazones (Table 2). Not only aliphatic hydrazones (entries
1, 2) but also aromatic (entries 3 5) and , -unsaturated
hydrazones (entry 6) reacted under these conditions to
give the desired hydrazines in good yields. It is noted that
a hydrazone with -ester functionality also worked well
(entry 7). In addition, the hydrazone trimer derived from
formaldehyde afforded the 3-butenylhydrazine in good
yield (entry 8).
A typical experimental procedure is described for the re-
action of 1. A solution of tetraallyltin (0.24 mmol) in wa-
ter/THF (1/9, 0.77 mL) was added to a mixture of 1 (0.48
mmol) and Sc(OTf)3 (0.024 mmol) in water/THF (1/9,
1.18 mL) at 30 °C. After stirring for 20 h, the reaction was
quenched with saturated aqueous NaHCO3, and the aque-
ous layer was extracted with dichloromethane. The organ-
ic extract was dried over Na2SO4, concentrated, and
purified with silica gel chromatography (hexane/ethyl
acetate = 2/1) to give the desired product in 85% yield.
Multi-component reactions are one of the most efficient
methods to construct complex molecules from simple
Synlett 2001, No. 7, 1140–1142 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Lewis Acid-Catalyzed Allylation Reactions of Acylhydrazones
1141
Table 2 Sc(OTf)3-Catalyzed Allylation of Benzoylhydrazones in
Table 3 Three-Component Allylation Reactions in Aqueous
Aqueous Mediaa
Mediaa
Sc(OTf)3
(5 mol %)
NHBz
BzHN
R
O
NHBz
Sn
4
N
NH
+
+
Sn
4
+
NH2
R
H
H2O/THF
(1/9)
30 °C
R
H
(50 mol %)
Sc(OTf)3
(5 mol %)
BzHN
R
NH
Entry
R
Yield (%)
85
H2O/THF (1/9)
30 °C, 20 h
1
2
3
4
5
6
7
PhCH2CH2
Entry
R
PhCH2CH2
H b
Yield (%)
Me2CHCH2
Ph
84
1
2
3
85
72
68
58b
84
4-MeOC6H4
4-ClC6H4
b
ClCH2
77
a
The molar ratio of aldehyde:benzoylhydrazine:tetraallyltin is
PhCH=CH (trans)
86
1:1:0.5 for entry 1, and 1.2:1:0.5 for entries 2 and 3. b A commercial
aqueous solution of the aldehyde was directly used.
EtO2C
81
NHBz
N
(R = H)
8
79
N
N
O
BzHN
NHBz
NHBz
NHBz
HN
satd. aq. NaHCO3
N
a 20-68 h. b Sc(OTf)3 (10 mol%).
O
THF, 30 °C, 24 h
Cl
Equation 1
87%
starting materials in one pot.11 Therefore, we next studied
three-component reactions6a of aldehydes, benzoylhydra-
zine, and tetraallyltin in an aqueous solvent (Table 3). An
advantage of these reactions is that the reactions could be
carried out without a separate step for hydrazone prepara-
tion prior to the allylation. In the presence of 5 mol%
Sc(OTf)3, aldehydes reacted with benzoylhydrazine and
tetraallyltin successively at 30 °C in aqueous media to af-
ford the desired homoallylic amine derivatives in high
yields. The by-products produced by allylation of the al-
dehydes instead of the hydrazones were generated only in
very low yields. For example, in the case of entry 1, 1-
phenyl-5-hexen-3-ol was obtained only in 4% yield along
with the desired hydrazine. It should be also mentioned
that the aldehydes were successfully used as commercial
aqueous solutions (entries 2 and 3). These direct uses of
water-containing aldehydes clearly demonstrate an ad-
vantageous point in reactions catalyzed by water-compat-
ible Lewis acids in aqueous media.
Table 4 Synthesis of Oxazolidinone Derivativesa
R
O
O
+
Sn
4
+
NH
H
NH2
Cl
O
N
R
O
1) Sc(OTf)3 (5 mol %)
H2O/THF (1/9), 30 °C, 5 h
NH
O
2) Satd. aq. NaHCO3,
30 °C (time)
Entry
R
Time
23 h
43 h
8 d
Yield (%)
1
2
Ph
75
69
69
69
63
4-MeOC6H4
4-ClC6H4
4-ClC6H4
4-CF3C6H4
As an example for transformation of the allylation prod-
ucts to various compounds, we have developed a facile
method to produce oxazolidinones. By simply treating
with a saturated aqueous solution of NaHCO3, the product
derived from chloroacetaldehyde, benzoylhydrazine, and
tetraallyltin was easily transformed to the corresponding
oxazolidinone derivative as shown in Eq. 1.12 This reac-
3
4b
5
24 h
10 d
a The molar ratio of aldehyde:acylhydrazine:tetraallyltin is 1.2:1:0.5.
b
tion is useful to synthesize N-amido-4-allyl-oxazolidin-2- A commercial aqueous solution of the aldehyde was directly used.
The reaction temperature for the oxazolidinone formation is 60 °C.
one derivatives, and one-pot reactions could also be per-
formed for various benzoylhydrazines as shown in Table
4.
Synlett 2001, No. 7, 1140–1142 ISSN 0936-5214 © Thieme Stuttgart · New York

1142
S. Kobayashi et al.
LETTER
Drury III, W. J.; Lectka, T. J. Org. Chem. 1999, 64, 2168. Cf.
(c) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am.
Chem. Soc. 1998, 120, 4242. (d) Akiyama, T.; Iwai, J. Synlett
1998, 273.
In summary, the allylation reactions of various benzoyl-
hydrazones with tetraallyltin were smoothly catalyzed by
Sc(OTf)3 in aqueous media to afford the corresponding
homoallylic amine derivatives in high yields. In addition,
three-component reactions of aldehydes, benzoylhydra-
zine, and tetraallyltin also proceeded under the same con-
ditions. Furthermore, a simple procedure to synthesize
oxazolidinone derivatives was developed. It is noted that
the reactions proceeded smoothly at ambient temperature
in aqueous media, and that water-soluble materials were
successfully used in these systems. Since the nitrogen ni-
trogen bonds of acylhydrazines are known to be easily
cleaved, the present allylation will provide a useful meth-
od for the synthesis of homoallylic amines as well as ni-
trogen nitrogen bond-containing compounds.
(6) (a) Kobayashi, S.; Sugita, K.; Oyamada, H. Synlett 1999, 138.
(b) Manabe, K.; Oyamada, H.; Sugita, K.; Kobayashi, S. J.
Org. Chem. 1999, 64, 8054. Cf. (c) Kobayashi, S.;
Hirabayashi, R. J. Am. Chem. Soc. 1999, 121, 6942.
(7) For example: Burk, M. J.; Feaster, J. E. J. Am. Chem. Soc.
1992, 114, 6266.
(8) (a) Oyamada, H.; Kobayashi, S. Synlett 1998, 249.
(b) Kobayashi, S.; Furuta, T.; Sugita, K.; Oyamada, H. Synlett
1998, 1019. (c) Kobayashi, S.; Furuta, T.; Okitsu, O.;
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(9) (a) Kobayashi, S.; Hachiya, I.; Araki, M.; Ishitani, H.
Tetrahedron Lett. 1993, 34, 3755. (b) Kobayashi, S. Eur. J.
Org. Chem. 1999, 15.
(10) Proton was also found to catalyze the reaction, but the yield
was lower. It was already confirmed that no hydrolysis
occurred in a Sc(OTf)3-water solution. See: (a) Kobayashi, S.;
Nagayama, S.; Busujima, T. J. Am. Chem. Soc. 1998, 120,
8287. (b) Kobayashi, S.; Hamada, T.; Nagayama, S.; Manabe,
K. Org. Lett. 2001, 3, 165.
Acknowledgement
This work was partially supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and Cul-
ture, Japan.
(11) For recent examples of multi-component reactions, see:
(a) Ebert, B. M.; Ugi, I. K.; Grosche, M.; Herdtweck, E.;
Herrmann, W. A. Tetrahedron 1998, 54, 11887. (b) Patel, S.;
Saroglou, L.; Floyd, C. D.; Miller, A.; Whittaker, M.
Tetrahedron Lett. 1998, 39, 8333. (c) Nemoto, H.; Ma, R.;
Suzuki, I.; Shibuya, M. Org. Lett. 2000, 2, 4245. See also:
(d) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem. Lett.
1995, 423. (e) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc.
1996, 118, 8977. (f) Kobayashi, S. Chem. Soc. Rev. 1999, 28,
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(12) NaHCO3 was used to introduce a CO2 unit in the synthesis of
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Article Identifier:
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Synlett 2001, No. 7, 1140–1142 ISSN 0936-5214 © Thieme Stuttgart · New York