Direct use of allylic alcohols in the allylation of sulfonylimidates

Article abstract of DOI:10.1039/c0cc03067h

We have developed catalytic allylation reactions of sulfonylimidates using allylic alcohols as allylating reagents. Stoichiometric amounts of neither activators nor bases are required in this reaction.

Full text of DOI:10.1039/c0cc03067h

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Direct use of allylic alcohols in the allylation of sulfonylimidatesw
Ryosuke Matsubara, Koichiro Masuda, Jyunya Nakano and Shu¯ Kobayashi*
Received 5th August 2010, Accepted 23rd September 2010
DOI: 10.1039/c0cc03067h
We have developed catalytic allylation reactions of sulfonyl-
imidates using allylic alcohols as allylating reagents. Stoichio-
metric amounts of neither activators nor bases are required in
this reaction.
Our laboratory, among others, is continuously working on the
direct use of a-alkyl ester equivalents as nucleophiles in
catalysis.1 Because simple a-alkyl esters have a higher pKa
value compared with ketones and aldehydes, the catalytic,
in situ generation and use of enolates for C–C, C–N, and other
bond formation is challenging, requiring the thoughtful design
of catalysts and nucleophiles. While there have been some
successful examples of catalytic direct addition reactions of
a-alkyl ester equivalents,2 no catalytic direct substitution reac-
tions had been achieved3 until our first report of the allylation
of sulfonylimidates using allylcarbonates as electrophiles.4
This allylation reaction of sulfonylimidates harnesses allyl-
carbonate decarboxylation for the turnover of a base, and
thus the carbonate moiety is crucial for achieving catalytic
deprotonation.5 However, from an atom economical view-
point, it would be more appealing if we could circumvent the
need of allylcarbonates and use allylic alcohols directly. In
precedents of catalytic allylic substitution reactions of carbon
nucleophiles with allylic alcohols, most examples have relied
on the intrinsic high reactivity of allylic alcohols6 or nucleo-
philes, such as indoles and highly enolizable active methylene
compounds.7 However, the catalytic allylation of sulfonylimidates
using allylic alcohols is more challenging, because the catalytic
in situ activation of both allylic alcohols and sulfonylimidates
has to be achieved in the same reaction vessel. Here, we report
on the direct use of allylic alcohols in the allylation of
sulfonylimidates. This report represents the first example of
allylic substitution of an a-alkyl ester derivative using allylic
alcohols (Fig. 1). Note that a feature of this developed reaction
is that there is no stoichiometric coproduct, only water.
Inspired by the report by Lu et al.,7o we commenced our
investigation using a combination of Pd(PPh3)4, PPh3, and
As2O38 as catalysts. To our delight, the desired product 3a was
obtained, albeit in a low yield (Table 1, entry 1). A significant
amount of by-product 4 was produced because of the forma-
tion of water, which led to the hydrolysis of sulfonylimidate
in this reaction (vide infra). While an attempt to suppress
hydrolysis using N-Ts-imidate 2b, which is less prone to
Fig. 1 A comparison of the precedents with this work.
hydrolysis, increased the product yield slightly (entry 2),9 the
addition of a desiccant (MS 3A) improved the yield markedly
(entry 3). Further optimization revealed that increasing the
loading of PPh3 had an adverse effect on the productivity
(entry 3 vs. entry 4) and that As2O3 was necessary in our system
(entry 5 vs. entry 4). After screening the solvents, 1,4-dioxane
was found to be the best solvent for this reaction (entry 6).
Satisfactory results were obtained at 90 1C with shorter
reaction times (entry 7). The amount of allylic alcohol could
be decreased to 1.5 equiv. by conducting the reaction at higher
concentration (entry 8).
Having established the optimum reaction conditions
(Table 1, entry 8), we then investigated the substrate scope
of this reaction (Table 2). Sulfonylimidate bearing no
Table 1 Optimization of the allylation of sulfonylimidate 2a with
allylic alcohol 1aa
Yield 3a Yield 4
(%)
Entry Additive Solventb
Temp./1C Time/h (%)
1
PPh3
(16 mol%)
PPh3
(16 mol%)
PPh3
THF
THF
THF
50
50
50
24
24
24
8
25
39
58
2c
3
49
34
(16 mol%)
MS 3Ad
4
MS 3Ad THF
MS 3Ad THF
50
50
8
24
8
2
6
56
29
85
86
86
26
34
6
5e
6
MS 3Ad 1,4-Dioxane 50
MS 3Ad 1,4-Dioxane 90
MS 3Ad 1,4-Dioxane 90
7
5
7
8f
a
Sulfonylimidate (1 equiv.) and allylic alcohol (2.75 equiv.) were
added to a suspension of Pd(PPh3)4 (4 mol%), As2O3 (6 mol%), and
an additive of the indicated solvent (0.43 M) under Ar. The reaction
mixture was heated, and the crude product was purified by chromato-
Department of Chemistry, School of Science and Graduate School of
Pharmaceutical Sciences, The University of Tokyo,
The HFRE Division, ERATO, Japan Science Technology Agency
(JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization of new materials. See DOI: 10.1039/
c0cc03067h
b
c
graphy on silica gel. The isolated yields are shown. 0.43 M. 2b
d
e
. No As2O3. 0.6 M, and 1a
f
(Ar = p-tolyl). 167 mg mmolÀ1
(1.5 equiv.) used.
c
8662 Chem. Commun., 2010, 46, 8662–8664
This journal is The Royal Society of Chemistry 2010

View Article Online
Table 2 Allylation of sulfonylimidates 2 with allylic alcohol 1a
substitutions at various positions of the allylic alcohol
could be accommodated. The reaction of cinnamyl alcohol
gave a mixture of a- and g-adducts in favor of the a-adduct 3fa
(entry 6). The g-alkyl substituted allylic alcohol also gave
coupled adducts, albeit in lower yields, possibly because of
the facile b-hydride elimination from the allyl-Pd intermediates
(entry 7). The a-substituted allylic alcohols demonstrated the
same trend (entries 8 and 9). Because the regio- and diastereo-
selectivity observed in the reactions of a- and g-substituted
allylic alcohols were identical, we presumed that both allylic
alcohols led to the same p-allyl Pd species.10 The reactions
with b-substituted allylic alcohols also proceeded smoothly,
affording the corresponding allylated sulfonylimidates in
excellent yields, regardless of the nature of the substituent
on the allylic alcohol (entries 10 and 11).
Entry R1
1
Yieldb (%) Product
1
Me 1a 86
3a
2c
H
1a 66
3
Et
1a Quant
The assumed reaction mechanism is shown in Fig. 2.
According to the proposed mechanism reported by Lu et al.,7o
the allylic alcohol reacts initially with As2O3 to generate an
allylic arsenite 5, which, upon oxidative addition by Pd(0),
forms the p-allyl Pd species 7. The arsinite anion 611 is
sufficiently Brønsted basic to deprotonate the a-proton
of p-nitrobenzenesulfonylimidate, leading to the formation
of the aza-enolate 8 and water, with the regeneration of
As2O3. The coupling of 7 and 8 furnishes the desired product
and completes the Pd(0)–Pd(II) catalytic cycle. At this stage, it
is unclear whether allylation takes place via an innersphere
(i.e., via a Pd–aza-enolate) or via an outersphere mechanism.10
As a side reaction, the water generated in this reaction can
hydrolyze sulfonylimidate to give p-nitrobenzenesulfonamide
10, which consumes two molecules of allylic alcohol to give the
observed by-product 4.
4d
iPr 1a 51
5
Ph 1a 91
6d
Me 1b 91
7d
Me 1c 39
We examined the conversion of the allylated sulfonylimidate
into the corresponding ester to demonstrate the versatility of
sulfonylimidate (Scheme 1).12 Gratifyingly, using a one-pot
procedure, in which 10 equivalents of water were added to the
3fa (E only) + 3fb (dr = 63 : 37)
(3fa : 3fb = 83 : 17)
3ga (E only) + 3gb (dr = 70 : 30)
(3ga : 3gb = 70 : 30)
8
Me 1d 82
Me 1e 54
9d
10
11
Me 1f 92
Me 1g 90
a
Sulfonylimidate (1 equiv.) and allylic alcohol (1.50 equiv.) were
added to a suspension of Pd(PPh3)4 (4 mol%), As2O3 (6 mol%), and
MS 3A (167 mg mmolÀ1) in 1,4-dioxane (0.6 M) under Ar. The
reaction mixture was heated to 90 1C, and the crude product was
b
purified using chromatography on silica gel. Isolated yields, or the
c
combined yields if stereoisomers were obtained. 1a (3 equiv.) used.
d
1 (2 equiv.) used.
substituent at the a-position provided diallylated products 3b.
Sulfonylimidates bearing bulkier a-substituents were also
good substrates (entries 3–5). These reactions demonstrated
a broad substrate scope with respect to the electrophile, and
Fig. 2 Assumed reaction mechanism for the allylation of sulfonyl-
imidates (upper) and byproduct formation (lower).
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 8662–8664 8663

View Article Online
Q. Peng, X.-L. Hou and Y.-D. Wu, Angew. Chem., Int. Ed.,
2008, 47, 1741.
4 S. B. J. Kan, R. Matsubara, F. Berthiol and S. Kobayashi, Chem.
Commun., 2008, 6354.
5 (a) J. Tsuji, I. Shimizu, I. Minami and Y. Ohashi, Tetrahedron
Lett., 1982, 23, 4809; (b) J. Tsuji, I. Shimizu, I. Minami,
Y. Ohashi, T. Sugiura and K. Takahashi, J. Org. Chem., 1985,
50, 1523.
Scheme
1 The one-pot allylation–hydrolysis procedure of
sulfonylimidate.
6 M. Sakakibara and A. Ogawa, Tetrahedron Lett., 1994, 35,
8013.
reaction mixture after completion of the allylation reaction,
ester 11 was obtained in 82% yield.
7 (a) A. B. Zaitsev, S. Gruber, P. A. Pluss, P. S. Pregosin,
L. F. Veiros and M. Worle, J. Am. Chem. Soc., 2008, 130,
11604; (b) I. Usui, S. Schmidt, M. Keller and B. Breit, Org. Lett.,
2008, 10, 1207; (c) A. B. Zaitsev, S. Gruber and P. S. Pregosin,
Chem. Commun., 2007, 4692; (d) I. F. Nieves, D. Schott, S. Gruber
and P. S. Pregosin, Helv. Chim. Acta, 2007, 90, 271; (e) B. Trost
and J. Quancard, J. Am. Chem. Soc., 2006, 128, 6314;
(f) M. Kimura, M. Futamata, R. Mukai and Y. Tamaru, J. Am.
Chem. Soc., 2005, 127, 4592; (g) C. Garcıa-Yebra, J. P. Janssen,
F. Rominger and G. Helmchen, Organometallics, 2004, 23, 5459;
(h) N. T. Patil and Y. Yamamoto, Tetrahedron Lett., 2004, 45,
3101; (i) K. Manabe and S. Kobayashi, Org. Lett., 2003, 5, 3241;
(j) F. Ozawa, H. Okamoto, S. Kawagishi, S. Yamamoto,
T. Minami and M. Yoshifuji, J. Am. Chem. Soc., 2002, 124,
10968; (k) R. Takeuchi and M. Kashio, J. Am. Chem. Soc., 1998,
120, 8647; (l) H. Bricout, J.-F. Carpentier and A. Mortreux,
J. Mol. Catal. A: Chem., 1998, 136, 243; (m) I. Shimizu,
M. Toyoda, T. Terashima, M. Oshima and H. Hasegawa, Synlett,
1992, 301; (n) D. E. Bergbreiter and D. A. Weatherford, J. Chem.
Soc., Chem. Commun., 1989, 883; (o) X. Lu, L. Lu and J. Sun,
J. Mol. Catal. A: Chem., 1987, 41, 245; (p) J.-P. Haudegond,
Y. Chauvin and D. Commereuc, J. Org. Chem., 1979, 44, 3063;
(q) K. E. Atkins, W. E. Walker and R. M. Manyik, Tetrahedron
Lett., 1970, 11, 3821.
In summary, we have developed a catalytic allylation reaction
of sulfonylimidates using allylic alcohols as allylating reagents.
Stoichiometric amounts of neither activators nor bases are
required in this reaction. Allylic alcohols are ubiquitous
structural elements in organic synthesis, thus conferring great
practical value on this developed allylation reaction. The
asymmetric variant of this reaction, as well as further applica-
tion of sulfonylimidates as nucleophiles, is currently under
way in our laboratory.
This work was partially supported by a Grant-in-Aid for
Science Research from JSPS and the Global COE Program,
The University of Tokyo, MEXT, Japan.
Notes and references
1 For review, see: S. Kobayashi and R. Matsubara, Chem.–Eur. J.,
2009, 15, 10694.
2 Trichloromethyl ketones: (a) H. Morimoto, S. H. Wiedemann,
A. Yamaguchi, S. Harada, Z. Chen, S. Matsunaga and
M. Shibasaki, Angew. Chem., Int. Ed., 2006, 45, 3146; N-acyl-
anilides: (b) S. Saito and S. Kobayashi, J. Am. Chem. Soc., 2006,
128, 8704; Acetonitrile: (c) N. Kumagai, S. Matsunaga and
M. Shibasaki, J. Am. Chem. Soc., 2004, 126, 13632; sulfonyl-
imidates: (d) R. Matsubara, F. Berthiol and S. Kobayashi,
J. Am. Chem. Soc., 2008, 130, 1804; Thioamide: (e) M. Iwata,
R. Yazaki, Y. Suzuki, N. Kumagai and M. Shibasaki, J. Am.
Chem. Soc., 2009, 131, 18244.
8 Investigation seeking the other catalytic activator to avoid rather
toxic As2O3 is ongoing in our laboratory.
9 The kinetic acidity of various sulfonylimidates has been studied
quantitatively: R. Matsubara, F. Berthiol, H. V. Nguyen and
S. Kobayashi, Bull. Chem. Soc. Jpn., 2009, 82, 1083.
10 B. M. Trost and D. L. Van Vranken, Chem. Rev., 1996, 96, 395.
11 Whether the arsinite ion 6 forms a covalent bond with p-allyl-Pd 7
is not clear.
3 Palladium-catalyzed allylation of a-alkyl amides using a stoichio-
metric amount of strong base was reported; see: K. Zhang,
12 For the other types of conversion of sulfonylimidates, see
ref. 2d.
c
8664 Chem. Commun., 2010, 46, 8662–8664
This journal is The Royal Society of Chemistry 2010