Surfactant-type Bronsted acid catalyzed dehydrative nucleophilic substitutions of alcohols in water

Article abstract of DOI:10.1021/ol062813j

(Chemical Equation Presented) A protocol for the dehydrative nucleophilic substitution of benzyl alcohols with a variety of carbon- and heteroatom-centered nucleophiles using dodecylbenzenesulfonic acid (DBSA) as a surfactant-type Bronsted acid catalyst i

Full text of DOI:10.1021/ol062813j

ORGANIC
LETTERS
2007
Vol. 9, No. 2
311-314
Surfactant-Type Brønsted Acid
Catalyzed Dehydrative Nucleophilic
Substitutions of Alcohols in Water
Seiji Shirakawa and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo,
The HFRE DiVision, ERATO, Japan Science and Technology Agency (JST),
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
skobayas@mol.f.u-tokyo.ac.jp
Received November 19, 2006
ABSTRACT
A protocol for the dehydrative nucleophilic substitution of benzyl alcohols with a variety of carbon- and heteroatom-centered nucleophiles
using dodecylbenzenesulfonic acid (DBSA) as a surfactant-type Brønsted acid catalyst in water has been developed. The reaction system can
be applied to the stereoselective C-glycosylation of 1-hydroxy sugars in water.
Coupling reactions of alkyl halides with nucleophiles are
among the most useful protocols for carbon-carbon bond
formation in organic synthesis. The reaction may be further
enhanced from the viewpoint of atom efficiency, when
alcohols are used as substrates instead of alkyl halides, as
in this case where water is generated as the sole byproduct
for the reactions. However, the catalytic activation of alcohols
is difficult due to the poor leaving ability of the hydroxyl
group, and as a result, an excess amount of a Brønsted acid
or a stoichiometric amount of a Lewis acid is often required
to promote the reactions.1 Therefore, the development of a
procedure for the nucleophilic substitutions of alcohols using
catalytic amounts of Brønsted or Lewis acids is highly
desirable and, accordingly, a number of catalytic methods
for the promotion of this process in organic solvent systems
have recently been reported.2
The use of water as a reaction medium has received
considerable attention in organic synthesis due to its many
advantages from economical, environmental, and safety
standpoints.3 In addition, it has been found that reactions in
water can facilitate access to different reactivity and selectiv-
ity patterns compared with those observed in common
organic solvents due to its unique physical and chemical
properties.4 Although various efficient catalytic systems in
water have been developed to date, execution of dehydration
reactions in water is one of the most challenging research
(2) For a recent example, see: (a) Motokura, K.; Fujita, N.; Mori, K.;
Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew. Chem., Int. Ed. 2006, 45,
2605. (b) Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006,
45, 793. (c) Zhan, Z.-P.; Yang, W.-Z.; Yang, R.-F.; Yu, J.-L.; Li, J.-P.;
Liu, H.-J. Chem. Commun. 2006, 3352. (d) Sanz, R.; Mart´ınez, A.; Miguel,
D.; AÄ lvarez-Gutie´rrez, J. M.; Rodr´ıguez, F. AdV. Synth. Catal. 2006, 348,
1841. (e) Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W. AdV. Synth. Catal.
2006, 348, 1033. (f) Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M.
Angew. Chem., Int. Ed. 2005, 44, 3913. (g) Noji, M.; Ohno, T.; Fuji, K.;
Futaba, N.; Tajima, H.; Ishii, K. J. Org. Chem. 2003, 68, 9340.
(3) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media;
Wiley: New York, 1997. (b) Organic Synthesis in Water; Grieco, P. A.,
Ed.; Blackie Academic and Professional: London, 1998. (c) Li, C.-J. Chem.
ReV. 2005, 105, 3095.
(1) For example: (a) Gullickson, G. C.; Lewis, D. E. Aust. J. Chem.
2003, 56, 385. (b) Bisaro, F.; Prestat, G.; Vitale, M.; Poli, G. Synlett 2002,
1823. (c) Coote, S. J.; Davies, S. G.; Middlemiss, D.; Naylor, A. Tetrahedron
Lett. 1989, 30, 3581. (d) Khalaf, A. A.; Roberts, R. M. J. Org. Chem. 1972,
37, 4227.
10.1021/ol062813j CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/21/2006

topics. In the course of our investigation of organic reactions
in water,5 we recently reported that dodecylbenzenesulfonic
acid (DBSA) efficiently catalyzes dehydrative esterifications
of carboxylic acids with alcohols and etherification of
alcohols in water.6 In this context, we have been interested
in the DBSA-catalyzed dehydrative carbon-carbon bond-
forming reactions in water.7 We herein report the catalytic
nucleophilic substitution of benzyl alcohols with various
carbon nucleophiles in water and describe its application to
the dehydrative C-glycosylation of 1-hydroxy sugars.8
Initially, we examined various Brønsted acids as catalysts
in the Friedel-Crafts-type substitution reaction of benzhydrol
with 1-methylindole as model substrates in water (Table 1).
tutions of alcohols using a variety of nucleophiles. Initially,
we selected benzhydrol derivatives as the alcohol component
because the resulting products 1 obtained from the reaction
contain a diarylmethane motif that is an integral part of a
number of biologically active and pharmaceutical compounds
(Figure 1). Friedel-Crafts-type substitution reactions of
Table 1. Effect of Catalysts
Figure 1. Biologically active compounds.
entry
catalyst
yield (%)a
1
2
3
4
5
6
7
none
AcOH
TFA
0
0
3
8
3
benzhydrols containing electron-donating or -withdrawing
groups occurred cleanly on treatment with electron-rich
heteroaromatic or aromatic compounds to afford the desired
triarylmethanes 1a-e (entries 1-5 in Table 2). Substitution
reactions using active methylene compounds also proceeded
smoothly to give the products 1f-h in high yields (entries
6-8). Furthermore, it was shown that even a simple
enolizable ketone could be used as the nucleophile giving
the corresponding product 1i in good yield (entry 9). The
present reaction system could also be applied to carbon-
nitrogen10 and carbon-sulfur11 bond formations, and the
desired compounds 1j-l were obtained in good yields
(entries 10-12).
Next, we examined the substrate generality with respect
to the alcohol substrate, and a variety of benzyl alcohols were
subjected to Friedel-Crafts-type substitutions with 1-meth-
ylindole (Table 3). Pleasingly, it was found that primary,
secondary, and tertiary alcohols could be applied to this
reaction and that the desired 3-substituted indoles 2a-g were
obtained in moderate to good yields.12 Substrates containing
heteroaromatic and allylic alcohols also worked well in this
reaction (entries 4 and 5).
TfOH
TsOH (4-CH3-C6H4-SO3H)
DBSA (C12H25-C6H4-SO3H)
C9H19COOH
85
0
a
Isolated yield.
Common Brønsted acids such as AcOH, TFA, TfOH, and
TsOH were not effective for this reaction (entries 2-5).
Gratifyingly, however, a surfactant-type Brønsted acid such
as DBSA was found to catalyze the reaction efficiently to
give the product 1a in good yield (entry 6). It is interesting
that use of a long-chain carboxylic acid, which is known to
be an effective catalyst for the three-component aza-Friedel-
Crafts reaction in water,9 was not effective for the reaction
(entry 7), suggesting that both the surfactant property and
the strong Brønsted acidity of DBSA are essential to promote
the reaction efficiently.
With this information in hand, we investigated the
substrate generality of DBSA-catalyzed nucleophilic substi-
To expand the utility and applicability of the present
system, we next focused on its application to the stereo-
selective dehydrative C-glycosylations of 1-hydroxy sugars13
in water. Because of the biological and synthetic importance
of C-glycosides and C-nucleosides, the development of
(4) (a) Lindstro¨m, U. M.; Andersson, F. Angew. Chem., Int. Ed. 2006,
45, 548. (b) Pirrung, M. C. Chem.-Eur. J. 2006, 12, 1312. (c) Li, C.-J.;
Chen, L. Chem. Soc. ReV. 2006, 35, 68. (d) Otto, S.; Engberts, J. B. F. N.
Org. Biomol. Chem. 2003, 1, 2809. (e) Breslow, R. Acc. Chem. Res. 1991,
24, 159.
(5) (a) Kobayashi, S.; Ogawa, C. Chem.-Eur. J. 2006, 12, 5954. (b)
Manabe, K.; Kobayashi, S. Chem.-Eur. J. 2002, 8, 4095. (c) Kobayashi,
S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209.
(6) (a) Manabe, K.; Iimura, S.; Sun, X.-M.; Kobayashi, S. J. Am. Chem.
Soc. 2002, 124, 11971. (b) Kobayashi, S.; Iimura, S.; Manabe, K. Chem.
Lett. 2002, 10. (c) Manabe, K.; Sun, X.-M.; Kobayashi, S. J. Am. Chem.
Soc. 2001, 123, 10101.
(7) For DBSA-catalyzed three-component Mannich-type reactions in
water, see: Manabe, K.; Mori, Y.; Kobayashi, S. Tetrahedron 2001, 57,
2537.
(10) For C-N bond formation with alcohols in organic slovent, see: (a)
Motokura, K.; Nakagiri, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Jitsukawa,
K.; Kaneda, K. Org. Lett. 2006, 8, 4617. (b) Terrasson, V.; Marque, S.;
Georgy, M.; Campagne, J.-M.; Prim, D. AdV. Synth. Catal. 2006, 348, 2063.
(11) C-S bond formation of alcohols was also described in ref 6.
(12) For reviews for the synthesis of 3-substituted indoles, see: (a)
Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A. Synlett 2005,
1199. (b) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew. Chem., Int.
Ed. 2004, 43, 550.
(8) For DBSA-catalyzed O-glycosylation in water, see: Aoyama, N.;
Kobayashi, S. Chem. Lett. 2006, 35, 238.
(9) Shirakawa, S.; Kobayashi, S. Org. Lett. 2006, 8, 4939.
(13) For a review, see: Gin, D. J. Carbohydr. Chem. 2002, 21, 645.
312
Org. Lett., Vol. 9, No. 2, 2007

Table 2. Nucleophilic Substitution Reactions of Benzhydrols
Table 3. Nucleophilic Substitution Reactions of Benzyl
in Water
Alcohols in Water
a
Isolated yield.
the viability of our methodology, we selected the reaction
of 1-hydroxy-D-ribofuranose with electron-rich hetero-
Scheme 1. C-Glycosylations of 1-Hydroxy Sugar in Water
aromatic or aromatic compounds as a model of C-glycosy-
lation and were delighted to discover that the reactions
proceeded smoothly to afford the corresponding C-nucleo-
sides 3a16 and 3b17 in good yields with excellent â-selectivity
a
Isolated yield. b Nu-H (2 equiv). c Nu-H (3 equiv). d Nu-H (5 equiv).
e
Isomerization product 1j’ was obtained in 24% yield.
(14) For reviews, see: (a) Wu, Q.; Simons, C. Synthesis 2004, 1533.
(b) Du, Y.; Linhardt, R. J. Tetrahedron 1998, 54, 9913.
(15) (a) Saito, T.; Nishimoto, Y.; Yasuda, M.; Baba, A. J. Org. Chem.
2006, 71, 8516. (b) Mukaiyama, T.; Matsubara, K.; Hora, M. Synthesis
1994, 1368.
(16) Yokoyama, M.; Nomura, M.; Togo, H.; Seki, H. J. Chem. Soc.,
Perkin Trans. 1 1996, 2145.
methods for their stereoselective generation has been exten-
sively studied.14 However, methods for the synthesis of
C-glycosides via the conversion of 1-hydroxy sugars using
a catalytic amount of an activator are still limited.15 To test
Org. Lett., Vol. 9, No. 2, 2007
313

(Scheme 1). The synthesis of C-nucleoside 3b is of particular
note as it is a key intermediate in the total synthesis of
showdomycin.18
In summary, we have developed a method for surfactant-
type Brønsted acid catalyzed dehydrative nucleophilic sub-
stitutions of benzyl alcohols in water. It is noteworthy that
the present reaction proceeded under nonmetallic conditions
in water and that a variety of diarylmethanes and 3-substi-
tuted indoles bearing a biologically interesting structure could
be prepared using the procedure. Furthermore, this reaction
system could be applied to stereoselective C-glycosylations
of 1-hydroxy sugars. This simple system offers an efficient
method for the synthesis of various biologically interesting
compounds.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research from the Japan Society
of the Promotion of Science (JSPS). S.S. thanks JSPS for a
postdoctoral research fellowship.
Supporting Information Available: Experimental pro-
cedures and product characterization. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(17) He, W.; Togo, H.; Waki, Y.; Yokoyama, M. J. Chem. Soc., Perkin
Trans. 1 1998, 2425.
(18) (a) Stewart, A. O.; Williams, R. M. J. Am. Chem. Soc. 1985, 107,
4289. (b) Kalvoda, L.; Farkas, J.; Sorm, F. Tetrahedron Lett. 1970, 2297.
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