The first catalytic Sakurai reaction of N-alkoxycarbonylamino sulfones with allyltrimethylsilane

Article abstract of DOI:10.1039/b613331b

The first Sakurai reaction of N-benzyloxycarbonylamino sulfones with allyltrimethysilane in the presence of a catalytic amount of Bi(OTf) ₃.4H₂O was investigated. Several solvents were screened for the Sakurai reaction and N-benzylox

Full text of DOI:10.1039/b613331b

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www.rsc.org/obc | Organic & Biomolecular Chemistry
The first catalytic Sakurai reaction of N-alkoxycarbonylamino sulfones with
allyltrimethylsilane
Thierry Ollevier* and Zhiya Li
Received 18th September 2006, Accepted 31st October 2006
First published as an Advance Article on the web 10th November 2006
DOI: 10.1039/b613331b
5
We report the first catalytic Sakurai reaction of N-alkoxy-
carbonylamino sulfones with allylsilanes. The allylation
reaction of N-alkoxycarbonylamino phenylsulfones with al-
lyltrimethylsilane proceeded smoothly with low catalyst load-
ing of bismuth triflate (2.0 mol%) to afford the corresponding
protected homoallylic amines in moderate to very good yields
1 (Scheme 1). This approach has previously been used for
6
highly enantioselective amine syntheses. We wish to report herein
the first catalytic Sakurai reaction of N-alkoxycarbonylamino
sulfones with allylsilanes. Alkoxycarbonyl protected homoallylic
amines are obtained efficiently in the presence of 2–5 mol% of
O. To the best of our knowledge, a catalytic version of
this reaction has never been reported. The only reported allylation
Bi(OTf)
3
·4H
2
(
up to 96%).
reaction from N-alkoxycarbonylamino sulfones involves a Lewis
acid like TiCl
large excess.
4
a,7
or SnCl used in a stoichiometric quantity or in
4
5
The development of new methods for the preparation of homoal-
lylic amines is an important area of synthetic efforts. Homoallylic
amines are extremely important as biologically active molecules.
Recently, several laboratories have disclosed significant ad-
vances regarding rare-earth and lanthanide triflates as catalysts
for allylation reactions. High catalytic activity, low toxicity,
1
8
Among the variety of synthetic methods so far reported, the Lewis
acid-catalyzed reaction of imines with allylsilanes provides an
efficient route for the synthesis of homoallylic amines. Catalytic
allylation reactions have been reported by several groups as
moisture and air tolerance make lanthanide triflates valuable
catalysts. Bismuth compounds provide a good alternative as they
have recently attracted attention due to their low toxicity, low
9
cost, and good stability. Bismuth salts have been reported as
2
10
11
an efficient method to prepare homoallylic amines. However,
catalysts for opening of epoxides, Mukaiyama-aldol reactions,
12
13
imines in general tend to be unstable during the purification
process. Therefore, methods involving the in situ generation of
imines are highly attractive, among which the one-pot allylation
Mannich-type reactions, formation of acetals, Friedel–Crafts
reactions, and Fries and Claisen rearrangements. Bi(OTf) is
14
15
3
particularly attractive because it is commercially available or can
3
16
of imines, have been proposed. Yet, most Lewis acids cannot
be easily prepared from commercially available compounds. We
be used in this reaction because they deactivate or decompose
in the presence of the amine and water produced during imine
formation. Very reactive N-acyliminiums, easily prepared from
stable precursors, provide an attractive alternative. Scheme 1
illustrates the preparation of the N-acylimine precursor from
recently reported the Bi(OTf) -catalyzed allylation reaction of a
3
variety of aldimines generated in situ using aldehydes, amines, and
17
allyltrimethylsilane in a three-component reaction. One draw-
back of this method could be eventual formation of homoallylic
alcohol as a trace by-product. These results encouraged us to
pursue an alternative approach using N-alkoxycarbonylamino
phenylsulfones as stable imine precursors.
4
corresponding aldehydes. N-Alkoxycarbonyl imines have been
prepared from basic treatment of the N-alkoxycarbonylamino
sulfones 1; and the corresponding N-alkoxycarbonyl iminium
derivatives have been prepared by the use of a Lewis acid with
Initially, we screened various solvents for the Sakurai reaction of
N-alkoxycarbonylamino sulfones with allyltrimethylsilane in the
presence of Bi(OTf)
sulfone 1a was chosen as model substrate for the following studies
Scheme 2). Interestingly, when 1a was treated with 2 mol%
3
·4H
2
O. N-Benzyloxycarbonylamino phenyl-
(
Bi(OTf)
3
·4H
2
O in dichloromethane (1.3 equiv. allyltrimethylsi-
◦
lane, 25 C, 5 h), the corresponding Cbz-protected homoallylic
amine 3a was isolated in moderate yield (73%) (Table 1, entry 1).
An increase of the quantity of the allyltrimethylsilane used led to
an increased yield, albeit with a lower catalyst loading (Table 1,
entry 2). Only 2 mol% of the catalyst with 1.5 equivalents of al-
lyltrimethylsilane 2 was necessary to obtain the homoallylic amine
Scheme
1
N-Alkoxycarbonylamino sulfones as precursors of
3
a in excellent yield (Table 1, entry 3). Among various solvents
N-alkoxycarbonyl imine derivatives.
tested, dichloromethane and acetonitrile furnished the expected
product in the highest yield (Table 1, entries 3–7). Because of the
poor solubility in acetonitrile of many N-alkoxycarbonylamino
sulfones 1 presented here (Table 2), dichloromethane was selected
as the solvent of choice.
D e´ partement de chimie, Universit e´ Laval, Qu e´ bec, Canada G1K 7P4. E-mail:
thierry.ollevier@chm.ulaval.ca; Fax: +1 418 6567916; Tel: +1 418 6565034
4
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Scheme 2 Bi(OTf) -catalyzed Sakurai reactions involving N-benzyloxycarbonylamino phenylsulfone 1a and allyltrimethylsilane.
3
Table 1 Allylation of N-benzyloxycarbonylamino phenylsulfone 1a with
good yields (Table 2, entries 1–9). Sulfones derived from several
electron-rich aromatic aldehydes led to the desired products
in good to very good yields (Table 2, entries 1–3), including
starting with o-substituted benzaldehyde (Table 2, entries 1 and 3).
The reaction was efficient using electron-deficient benzaldehyde-
derived sulfones and the corresponding homoallylic amines 3 were
obtained with moderate to good yields (Table 2, entries 4–9).
Benzyloxycarbonylamino sulfone 1j could be selectively prepared
from p-acetyl benzaldehyde and subsequently allylated to give 3j
with an overall complete aldehyde vs. ketone selectivity (Table 2,
entry 9). In addition, heteroaromatic aldehyde derived sulfone 1k
could also serve as a substrate in this reaction, albeit giving the
corresponding homoallylic amine in a moderate yield (Table 2,
entry 10). Aliphatic aldehydes led to a moderate to good yield of
a
allyltrimethylsilane using Bi(OTf)
3
·4H
2
O as catalyst
b
Entry x mol% Bi(OTf)
3
Allylsilane 2 (equiv.) Solvent Yield 3a (%)
1
2
3
4
5
6
7
2
1
2
2
2
2
2
1.3
1.5
1.5
1.5
1.5
1.5
1.5
CH
CH
CH
2
2
2
Cl
Cl
Cl
2
2
2
73
80
96
0
Et
2
O
THF
MeCN 94
PhMe 16
43
a
1
13
All new compounds were characterized by H NMR, C NMR
b
spectroscopy and mass spectroscopy. Isolated yields after purification
by column chromatography.
3
(Table 2, entries 11–15). For selected substrates, higher yields
were obtained when using a catalyst loading of 5 mol% instead of
2 mol% with 5 equiv. of allyltrimethylsilane in dichloromethane at
reflux (Table 2, entries 3, 10, 13, and 14).
In summary, we have found that the Sakurai reaction of
N-benzyloxycarbonylamino sulfones 1 proceeds smoothly with
allyltrimethylsilane in the presence of a catalytic amount of
Given that the same reaction does not occur in the pres-
1
1
8
8
ence of N ,N ,N ,N -tetramethylnaphthalene-1,8-diamine proton
ꢀ
R
sponge (1 equiv. of 1a, 1.5 equiv. of allyltrimethylsilane 2,
ꢀ
R
0
2
K
.02 equiv. of Bi(OTf)
3
·4H
2
O, 0.06 equiv. of proton sponge ,
◦
5
C, 28 h, 99% recovery of 1a) but still proceeds with
used as a proton scavenger (1 equiv. of 1a, 1.5 equiv. of
2
CO
3
Bi(OTf)
3
·4H
2
O. This method offers several advantages includ-
allyltrimethylsilane 2, 0.02 equiv. of Bi(OTf)
3
·4H
2
O, 0.06 equiv.
◦
ing mild reaction conditions, low catalyst loading (2–5 mol%),
and no formation of by-products. To the best of our knowl-
edge, this is the first report of a catalytic Sakurai reaction of
N-alkoxycarbonylamino sulfones with allyltrimethylsilane. More-
over, our process involves an environmentally benign, cheap, and
easy to handle catalyst. The homoallylic amine, already protected
as a Cbz derivative, is smoothly obtained under mild conditions.
K
2
CO
3
, 25 C, 19 h, 62% of 3a) does not indicate unambiguously
that triflic acid is involved in the mechanism. However, when HOTf
is used as the catalyst, the reaction proceeds to afford the expected
product 3a, indicating that HOTf is also an effective catalyst for
the transformation (1 equiv. of 1a, 1.5 equiv. of allyltrimethylsilane
◦
2
, 0.06 equiv. of HOTf, 25 C, 4 h, 67% of 3a). Also, Me
3
SiOTf
might be involved as a catalyst in our conditions since it appears
Because of its numerous benefits, the Bi(OTf)
should find utility in the synthesis of biologically active com-
pounds. Research is under way to demonstrate other significant
3
·4H
2
O protocol
to be an effective catalyst as well (1 equiv. of 1a, 1.5 equiv. of
◦
allyltrimethylsilane 2, 0.06 equiv. of Me
3
SiOTf, 25 C, 5 h, 82%
of 3a). Since the chemical yields of the 6% HOTf and Me
catalyzed reactions are lower than when using 2% Bi(OTf)
compare with Table 1, entry 3), a bismuth(III) salt is likely to
3
SiOTf-
applications of this Bi(OTf)
3
·4H
2
O-catalyzed Sakurai reaction.
3
·4H
2
O
(
be involved as a Lewis acid. More detailed investigations on the
mechanism of this transformation are in progress.
Acknowledgements
Several examples of Bi(OTf)
3
·4H
2
O-catalyzed Sakurai reac-
This work was financially supported by the Natural Sciences and
Engineering Research Council of Canada (NSERC), the Fonds
Qu e´ b e´ cois de la Recherche sur la Nature et les Technologies
(FQRNT, Qu e´ bec, Canada), the Canada Foundation for Inno-
vation, Universit e´ Laval, and Merck. We thank Rhodia (Lyon,
France) and Sidech s.a. (Tilly, Belgium) for the generous gift of
chemicals.
tions of various N-benzyloxycarbonylamino phenylsulfones 1
with allytrimethylsilane are summarized in Table 2.† N-Benzyl-
oxycarbonylamino sulfones 1 derived from differently substi-
tuted benzaldehydes were reacted with allytrimethylsilane in
dichloromethane at room temperature (Scheme 3). The corre-
sponding homoallylic amines 3 were obtained in moderate to
Scheme 3 Bi(OTf)
3
-catalyzed Sakurai reactions involving various N-benzyloxycarbonylamino phenylsulfones 1 and allyltrimethylsilane 2.
Org. Biomol. Chem., 2006, 4, 4440–4443 | 4441
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Table 2 Allylation of N-benzyloxycarbonylamino phenylsulfones 1 with 1.5 equiv. allyltrimethylsilane 2 using 2 mol% Bi(OTf)
3
·4H
2
O as catalyst
a
b
Entry
1
Reactant
Product
Time/h
23
Product
Yield (%)
3b
84
86
2
3
4
5
6
7
8
9
12
22
24
26
24
24
43
27
3c
3d
3e
3f
3g
3h
3i
c
62
74
78
73
78
58
56
3j
c
1
0
24
3k
45
1
1
1
1
1
2
3
4
24
44
22
28
3l
73
61
3m
3n
3o
c
76
c
74
1
5
26
3p
74
a
c
1
13
b
All new compounds were characterized by H NMR, C NMR spectroscopy and mass spectroscopy. Isolated yields after column chromatography.
The reaction was run with 5 mol% Bi(OTf) O and 5 equiv. allyltrimethylsilane 2 at reflux.
·4H
3
2
4
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Notes and references
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†
General procedure for the bismuth-catalyzed Sakurai reaction: Under
an inert atmosphere of argon, the allyltrimethylsilane 2 (0.75 mmol)
was added dropwise to a solution of Bi(OTf) O (0.01 mmol) and
3
·4H
2
N-alkoxycarbonylamino sulfone 1 (0.5 mmol) in dry CH
2
Cl
2
(1.5 mL)
◦
at 25 C. The mixture was stirred until the reaction was completed as
indicated by TLC. The reaction was quenched with distilled H
extracted with EtOAc. The combined organic phases were washed with
O, sat. aq. NaCl, dried over MgSO , and concentrated under vacuum
rotary evaporator). The crude product was purified by column chro-
matography (eluent hexane–EtOAc 92 : 8 to 85 : 15, or toluene). Spectral
2
O and
H
2
4
(
18a
17a
18b
3f
18c
18d
3f
18a
data for 3a,c, 3i, 3j, 3k, 3l, 3m, 3n–o, and 3p agree with
those previously reported in the literature. Benzyl 1-(4-fluorophenyl)but-
3
-enylcarbamate (3h): Reagents: benzyl (4-fluorophenyl) (phenylsulfonyl)
methyl carbamate 1h (201 mg, 0.5 mmol), allyltrimethylsilane 2 (121 ll,
1
.5 mmol), and Bi(OTf)
3
·4H
2
O (7 mg, 0.01 mmol). The reaction was
◦
stirred for 24 h at 25 C. The crude product was purified by silica gel
chromatography to afford 117 mg (78%) of 3h as a colorless crystal; mp
◦
3
1
9–41 C; R
f
= 0.90 (hexane–EtOAc = 7 : 3); IR (neat): 3421, 3326, 1698,
−
1 1
642 cm ; H NMR (400 MHz, CDCl
3
): d = 7.26–7.43 (m, 5 H), 7.14–7.26
(
(
m, 2 H), 6.96–7.04 (m, 2 H), 5.57–5.71 (m, 1 H), 5.00–5.20 (m, 5 H), 4.77
br s, 1 H), 2.40–2.57 (m, 2 H); C NMR (100 MHz, CDCl
13
3
): d = 162.1
(
J
(
d, JC–F = 245.5 Hz), 155.8, 138.0, 136.5, 133.6, 128.7, 128.4, 128.0 (d,
19
C–F = 7.7 Hz), 118.9, 115.6 (d, JC–F = 21.5 Hz), 67.0, 54.1, 41.2; F NMR
): d = −115.83; HRMS: m/z calcd for C18 [M +
376 MHz, CDCl
3
H19FNO
2
+
H ]: 300.1400, found: 300.1403.
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This journal is © The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4440–4443 | 4443