Dibutyltin oxide catalyzed allyl-transfer reaction from tertiary homoallylic alcohols to aldehydes

Article abstract of DOI:10.1055/s-2006-948198

A catalytic allyl-transfer reaction from tertiary homoallylic alcohols to aldehydes was achieved using dibutyltin oxide as a catalyst in toluene under reflux conditions. Various secondary homoallylic alcohols were prepared in high yield (up to 99%). When β-alkylated tertiary homoallylic alcohols were used, branched products were exclusively obtained. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-948198

LETTER
2071
Dibutyltin Oxide Catalyzed Allyl-Transfer Reaction from Tertiary
Homoallylic Alcohols to Aldehydes
Dibutyltin
Oxide
C
k
atalyze
d
A
l
i
lyl-Tran
r
sfer Rea
a
ctions Yanagisawa,*a Takahiro Aoki,b Takayoshi Araia
a
Department of Chemistry, Faculty of Science, Chiba University, Inage, Chiba 263-8522, Japan
b
Graduate School of Science and Technology, Chiba University, Inage, Chiba 263-8522, Japan
Fax +81(43)2902789; E-mail: ayanagi@scichem.s.chiba-u.ac.jp
Received 22 May 2006
OH
O
Abstract: A catalytic allyl-transfer reaction from tertiary homo-
allylic alcohols to aldehydes was achieved using dibutyltin oxide as
a catalyst in toluene under reflux conditions. Various secondary
homoallylic alcohols were prepared in high yield (up to 99%).
When b-alkylated tertiary homoallylic alcohols were used,
branched products were exclusively obtained.
Ph
Ph
cat. Bu2SnO
toluene, reflux
OH
+
R3
H
R1 R2
O
+
R3
Ph
Ph
R1 R2
Key words: aldehydes, allylations, organometallic reagents, regio-
selectivity, tin
Scheme 1 Bu2SnO-catalyzed allyl-transfer reaction from tertiary
homoallylic alcohols to aldehydes
Allylation of aldehydes is a valuable method to prepare
secondary homoallylic alcohols.1 Since the homoallylic
alcohol moiety is not only found in many natural products
but also is able to be transformed into b-hydroxycarbonyl
compounds and other useful compounds, an efficient way
of obtaining this structure is desired for organic synthe-
sis.2 Numerous examples of Lewis acid catalyzed allyla-
tion of carbonyl compounds with allylmetals, such as
allyltributyltin, have so far been reported;3 however, the
allylation method incurs industrial and environmental
problems by requiring a stoichiometric amount of organo-
metallic reagent. One promising method to solve the prob-
lem is an allyl-transfer reaction to aldehydes using tertiary
homoallylic alcohols as allyl donors. Nokami and co-
workers have reported that tin triflate [Sn(OTf)2]
catalyzes the allyl-transfer reaction providing linear
secondary homoallylic alcohols via [3,3]-sigmatropic
rearrangement.4 This reaction has been further applied to
the asymmetric alk-2-enylation of aldehydes catalyzed by
p-toluenesulfonic acid or Sn(OTf)2.5,6 In contrast, Oshima
and co-workers have recently found that branched
secondary homoallylic alcohols are formed from similar
allyl donors under the influence of a Grignard reagent and
GaCl3 via retro-allylation.7 We report here a novel allyl-
transfer reaction to aldehydes, catalyzed by dibutyltin
oxide, that provides branched products (Scheme 1).
envisioned that this tin dimethoxide might promote the
allyl-transfer reaction from tertiary homoallylic alcohols
to aldehydes via the formation of tin alkoxides. Thus, we
initially examined the reaction of diisopropyl ketone
derived homoallylic alcohol with 4-nitrobenzaldehyde in
the presence of 10 mol% of Bu2Sn(OMe)2 under reflux
conditions for 24 h; however, the targeted product was ob-
tained only in low yield (Table 1, entry 1). Employment of
the more Lewis acidic dibutyltin dibromide and dibutyltin
dichloride also resulted in unsatisfactory results (Table 1,
entries 2 and 3). Gratifyingly, however, we found that
dibutyltin oxide (Bu2SnO) catalyzes the reaction, and
when 20 mol% of the tin oxide was used as a catalyst, the
desired homoallylic alcohol was obtained in 33% yield
(Table 1, entry 4). We then attempted the reaction
employing various amounts of the catalyst and the allyl
donor, and found that when 25 mol% of the tin oxide and
two equivalents of the tertiary homoallylic alcohol were
loaded, the chemical yield reached 70% (Table 1, entry 6).
Among the several allyl donors examined, benzophenone-
derived homoallylic alcohol was found to be effective for
the allyl-transfer reaction (Table 1, entries 8–10).
This allyl-transfer reaction was applied to diverse b-alkyl-
ated tertiary homoallylic alcohols and the results with
crotyl, prenyl, and geranyl donors are summarized in
Table 2.9 The allyl-transfer reaction of b-alkylated tertiary
homoallylic alcohols proceeded more smoothly than that
of simple tertiary homoallylic alcohols. For example, in
the reaction of the crotyl donor, not only aromatic alde-
hydes but a,b-unsaturated and aliphatic aldehydes also
afforded the corresponding branched product in high yield
(up to >99%) with moderate syn selectivity (Table 2,
entries 1–7). In the reaction with an a,b-unsaturated
aldehyde, the 1,2-adduct was formed exclusively
(Table 2, entry 6). The prenyl and geranyl donors also
indicated a similar regioselectivity in the reaction with
We have previously shown that dibutyltin dimethoxide
[Bu2Sn(OMe)2] behaves as a catalyst in the aldol reaction
of alkenyl trichloroacetates with aldehydes in the pres-
ence of methanol.8 In this reaction, nucleophilic attack of
the methoxide ion of the tin reagent to the alkenyl esters
efficiently generates the corresponding tin enolates. We
SYNLETT 2006, No. 13, pp 2071–2074
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7
.0
8
.2
0
0
6
Advanced online publication: 09.08.2006
DOI: 10.1055/s-2006-948198; Art ID: U05906ST
© Georg Thieme Verlag Stuttgart · New York

2072
A. Yanagisawa et al.
LETTER
Table 1 Optimization of the Allyl-Transfer Reaction to Aldehydes Catalyzed by Dibutyltin Catalystsa
OH
O
OH
O
R1
R1
catalyst
+
+
R2
H
R2
R1
R1
toluene, reflux, 24 h
(n equiv)
Entry
Catalyst (mol%)
Bu2Sn(OMe)2 (10)
Bu2SnBr2 (10)
Bu2SnCl2 (10)
Bu2SnO (20)
Bu2SnO (10)
Bu2SnO (25)
Bu2SnO (10)
Bu2SnO (10)
Bu2SnO (10)
Bu2SnO (10)
n
1
1
1
1
2
2
2
2
2
2
R1
R2
Yield (%)b
1
2
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Ph
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
1-Naphthyl
1-Naphthyl
1-Naphthyl
5
5
3
4
4
33
30
70
39
16
26
64
5
6
7
8
Et
9
i-Pr
Ph
10
a Unless otherwise noted, the reaction was carried out using Bu2SnX2 (10–25 mol%), tert-homoallylic alcohol (1 or 2 equiv), and aldehyde
(1 equiv) in refluxing toluene (bath temperature: 125–130 °C) for 24 h.
b Isolated yield of the corresponding homoallylic alcohol.
OH
various aldehydes, though the chemical yields were lower
than those given by the crotyl-transfer reaction (Table 2,
entries 8–15).
Ph
+
Bu2SnO
Ph
toluene, reflux, 24 h
OX
1:1
O
We further attempted a crotyl-transfer reaction to ketones
and found that 4¢-nitroacetophenone was converted to the
corresponding branched product in 99% yield under the
standard reaction conditions used for aldehydes
(Scheme 2).
SnBu2
+
Ph
Ph
X = H or Sn
(as detected by 1H NMR)
Scheme 3 Reaction of benzophenone-derived prenyl donor with
Bu2SnO for 1H NMR studies
OH
O
Ph
Ph
Bu2SnO (10 mol%)
+
toluene, reflux, 24 h
O
OH
Bu
Sn
Bu
Sn
O2N
Bu
O
OH
Bu
OH
OH
+
Ph
Ph
Ph
Ph
Bu2SnO
O
Ph
Ph
R1
Ph
R2
O2N
R1 R2
Ph
99% yield
syn:anti = 72:28
R1 R2
O
OH
R3
Ph
H
Scheme 2 Bu2SnO-catalyzed crotyl-transfer reaction from a tertiary
homoallylic alcohol to a ketone
R3
R1 R2
product
O
OH
To elucidate the catalytic mechanism of the present reac-
Ph
Ph
1
Ph
tion, we performed H NMR studies on a reaction of
Bu
Bu
Bu
OH
Bu
OH
R1 R2
benzophenone-derived prenyl donor with an equimolar
amount of Bu2SnO in refluxing toluene for 24 h, and
found that a prenyltin compound was formed (Scheme 3).
Sn
Sn
O
O
R1
H
R3
R3
R1 R2
Scheme 4 provides a plausible catalytic mechanism of the
allyl-transfer reaction of an allyl donor to an aldehyde.
Initially, the allyl donor reacts with Bu2SnO, forming the
tin alkoxide of the tertiary homoallylic alcohol. The
alkoxide then undergoes ‘retro-allylation’4,7 to provide an
R2
Scheme 4 Plausible reaction mechanism for the allyl-transfer
reaction catalyzed by Bu2SnO
Synlett 2006, No. 13, 2071–2074 © Thieme Stuttgart · New York

LETTER
Dibutyltin Oxide Catalyzed Allyl-Transfer Reactions
2073
Table 2 Crotyl-, Prenyl-, and Geranyl-Transfer Reactions to Various Aldehydesa
OH
R1
O
OH
R1
Ph
Ph
Bu2SnO (10 mol%)
toluene, reflux, 24 h
+
R3
H
R3
R2
R2
(2 equiv)
Entry
1
R1
R2
H
R3
Yield (%)b
60
syn:antic
73:27
83:17
80:20
73:27
68:32
65:35
63:37
–
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
2
H
4-NO2C6H4
4-BrC6H4
4-MeOC6H4
2-Naphthyl
(E)-PhCH=CH
Ph(CH2)2
Ph
93
3
H
75
4
H
>99
>99
91d
62
5
H
6
H
7
H
8
Me
Me
Me
Me
Me
Me
57
9
4-NO2C6H4
4-BrC6H4
4-MeOC6H4
(E)-PhCH=CH
Ph(CH2)2
Ph
84
–
10
11
12
13
14
15
65
–
73
–
81d
71
–
–
Me2C=CH(CH2)2
Me2C=CH(CH2)2
Me
Me
63
43:57
48:52
Ph(CH2)2
70
a Unless otherwise noted, the reaction was carried out using Bu2SnO (10 mol%), tert-homoallylic alcohol (2 equiv), and aldehyde (1 equiv) in
refluxing toluene (bath temperature: 125–130 °C) for 24 h.
b Isolated yield.
c The syn:anti ratio was determined by 1H NMR analysis.
d The 1,2:1,4 ratio was >99:1.
allylic tin compound and benzophenone. Subsequently,
the allylic tin is allowed to add to the aldehyde. Finally,
reaction of the resulting tin alkoxide with the allyl donor
completes the catalytic cycle, yielding the secondary
homoallylic alcohol (branched product) and regenerating
the tin alkoxide of the allyl donor.
References and Notes
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(2) For reviews, see: (a) Roush, W. R. In Comprehensive
Organic Synthesis, Vol. 2; Trost, B. M.; Fleming, I.;
Heathcock, C. H., Eds.; Pergamon: Oxford, 1991, 1.
(b) Hoppe, D. In Houben-Weyl: Methods of Organic
Chemistry, Vol. E21; Helmchen, G.; Hoffmann, R. W.;
Mulzer, J.; Schaumann, E., Eds.; Georg Thieme Verlag:
Stuttgart, 1995, 1357. (c) Chemler, S. R.; Roush, W. R. In
Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000, Chap. 11, 403.
(3) For reviews, see: (a) Yanagisawa, A. In Comprehensive
Asymmetric Catalysis, Vol. II; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: Heidelberg, 1999, 965.
(b) Denmark, S. E.; Almstead, N. G. In Modern Carbonyl
Chemistry; Otera, J., Ed.; Wiley-VCH: Weinheim, 2000,
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Chem. Int. Ed. 2003, 42, 4732. (d) Denmark, S. E.; Fu, J.
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Comprehensive Asymmetric Catalysis, Suppl. 2; Jacobsen,
E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: Heidelberg,
2004, 97.
In conclusion, we have developed a novel, catalytic allyl-
transfer reaction. By using dibutyltin oxide as a catalyst
and tertiary homoallylic alcohols as allyl donors, various
aldehydes were allylated with high regioselectivity.
Further studies on application of the present reaction to
other substrates are currently underway.
Acknowledgment
We gratefully acknowledge financial support from the Ministry of
Education, Science, Sports, Culture and Technology of the Japanese
Government.
Synlett 2006, No. 13, 2071–2074 © Thieme Stuttgart · New York

2074
A. Yanagisawa et al.
LETTER
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(9) Typical experimental procedure for crotyl-transfer reaction
to aldehydes catalyzed by dibutyltin oxide (Table 2, Entry
4). Under an argon atmosphere, 4-methoxybenzaldehyde
(68.1 mg, 0.50 mmol) was added to a solution of dibutyltin
oxide (12.4 mg, 0.05 mmol) and crotyl donor (238 mg, 1.00
mmol) in dry toluene (2 mL) at r.t. After stirring for 30 min
the mixture was heated at reflux (oil bath temperature: 125–
130 °C) for 24 h and then treated with MeOH (2 mL), brine
(2 mL), and solid KF (ca. 2 g) at r.t. for 2 h. The resulting
precipitate was filtered off and the filtrate diluted with H2O
(30 mL) and extracted with Et2O (3 × 30 mL). The combined
organic extracts were washed with brine (20 mL), dried over
anhydrous Na2SO4, and concentrated in vacuo after
filtration. The residual crude product was purified by column
chromatography on silica gel to give a syn/anti mixture of
the corresponding homoallylic alcohol (96.0 mg, >99%
yield). The syn/anti ratio was determined to be 73:27 by 1H
NMR analysis. Spectral data of a 73:27 mixture of the syn
and anti isomers: TLC Rf = 0.17 (hexane–EtOAc, 7:1); 1H
NMR (400 MHz, CDCl3): d = 0.82 (d, J = 7.0 Hz, 0.81 H),
0.99 (d, J = 6.8 Hz, 2.19 H), 2.31 (br s, 1 H), 2.42 (m, 0.27
H), 2.51 (m, 0.73 H), 3.76 (s, 3 H), 4.26 (d, J = 8.0 Hz, 0.27
H), 4.46 (d, J = 5.8 Hz, 0.73 H), 4.97–5.01 (m, 1.46 H),
5.12–5.18 (m, 0.54 H), 5.64–5.74 (m, 0.73 H), 5.74–5.85 (m,
0.27 H), 6.83 (d, J = 8.7 Hz, 1.46 H), 6.85 (d, J = 8.5 Hz,
0.54 H), 7.17 (d, J = 8.7 Hz, 1.46 H), 7.21 (d, J = 8.5 Hz,
0.54 H); 13C NMR (100 MHz, CDCl3): d = 14.4, 16.4, 44.5,
46.1, 55.0, 55.0, 76.9, 77.3, 113.2, 113.4, 115.1, 116.3,
127.6, 127.8, 134.5, 134.7, 140.2, 140.8, 158.6, 158.9.
Spectral data (1H and 13C NMR) of the mixture of the syn and
anti isomers indicated good agreement with reported data.10
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Synlett 2006, No. 13, 2071–2074 © Thieme Stuttgart · New York