ORGANIC
LETTERS
2007
Vol. 9, No. 25
5159-5162
Radical Reactions in Aqueous Medium
Using (Me3Si)3SiH
Al Postigo,† Sergey Kopsov,‡ Carla Ferreri, and Chryssostomos Chatgilialoglu*
ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy
Received August 28, 2007
ABSTRACT
(Me3Si)3SiH was used as a successful reagent in a variety of radical-based transformations in water. The system comprising substrate, silane,
and initiator (ACCN) mixed in aqueous medium at 100 C worked well for both hydrophilic and hydrophobic substrates, with the only variation
that an amphiphilic thiol was also needed in case of the water-soluble compounds.
°
The motivation to use water as solvent for organic reactions
is not only because it is a cheap, safe, and an environmentally
friendly substitute for organic solvents but also because it
often increases reaction rate and selectivity.1-3 Indeed, a
further encouragement for the use of this solvent came from
the concept of the reactivity “on water”, introduced by
Sharpless and co-workers to describe reactions of organic
substances that are not water soluble but yet react well or
even considerably faster in the presence of water than in
organic solvents.4 Another advantage is connected to the
workup, with the organic and aqueous phases that separate,
thus eliminating the need for complex isolation steps to
obtain the product.
categories: (i) Et3B-induced halogen atom transfer radical
additions (intra- or intermolecular),7 (ii) water-soluble reduc-
ing agents,6b,c such as R2P(O)H or ad hoc synthesized group
14 hydride,8 and (iii) water-insoluble reducing agents that
are stable to hydrolysis.9,10 For example, some water-
compatible reagents have been proposed, such as tri-2-
(5) For a review, see: Yorimitsu, H.; Shinokubo, H.; Oshima, K. Synlett
2002, 674-686. Also see: Renaud, P., Sibi, M. P., Eds. Radicals in Organic
Synthesis; Wiley-VCH: Weinheim, 2001; Vol. 1.
(6) For recent selected papers, see: (a) Campan˜a, A. G.; Este´vez, R. E.;
Fuentes, N.; Robles, R.; Cuerva, J. M.; Bun˜uel, E.; Ca´rdenas, D. J.; Oltra,
J. E. Org. Lett. 2007, 9, 2195-2198. (b) Cuerva, J. M.; Campan˜a, A. G.;
Justicia, J.; Rosales, A.; Oller-Lo´pez, J. L.; Robles, R.; Ca´rdenas, D. J.;
Bun˜uel, E.; Oltra, J. E. Angew. Chem., Int. Ed. 2006, 45, 5522-5526. (c)
Cho, D. H.; Jang, D. O. Synlett 2005, 59-62. (d) Khan, T. A.; Tripoli, R.;
Crawford, J. J.; Martin, C. G.; Murphy, J. A. Org. Lett. 2003, 5, 2971-
2974. (e) Sua´rez, R. M.; Sestelo, J. P.; Sarandeses, L. A. Chem. Eur. J.
2003, 9, 4179-4187.
(7) (a) Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K.; Omoto,
K.; Fujimoto, H. J. Am. Chem. Soc. 2000, 122, 11041-11047. (b) Yorimitsu,
H.; Shinokubo, H.; Matsubara, S.; Oshima, K. J. Org. Chem. 2001, 66,
7776-7785.
(8) (a) Light, J.; Breslow, R. Tetrahedron Lett. 1990, 31, 2957-2960.
(b) Rai, R.; Collum, D. B. Tetrahedron Lett. 1994, 35, 6221-6224. (c)
Yamazaki, O.; Togo, H.; Matsubayashi, S.; Yokoyama, M. Tetrahedron
1999, 55, 3735-3747.
(9) (a) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Bull.
Chem. Soc. Jpn. 2002, 74, 747-752. (b) Yorimitsu, H.; Oshima, K. Inorg.
Chem. Commun. 2005, 8, 131-142.
(10) Postigo, A.; Ferreri, C.; Navacchia, M. L.; Chatgilialoglu, C. Synlett
2005, 2854-2856.
Radical chemistry was also performed in water with some
success in functional group transformations and C-C bond
formation.5,6 These reactions can be divided into three
† Visiting Scientist. Permanent address: Faculty of Science, University
of Belgrano, Villanueva 1324, 1426 Buenos Aires, Argentina.
‡ Visiting Student. Present address: Department of Chemistry, Ufa State
Petroleum Thechnological University, 450062 Ufa, Russia.
(1) Li, C.-J. Chem. ReV. 2005, 105, 3095-3165.
(2) Lindstro¨m, U. M. Chem. ReV. 2002, 102, 2751-2772.
(3) Grieco, P. A., Ed. Organic Synthesis in Water; Blackie Academic
and Professional: London, 1998.
(4) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2005, 44, 3275-3279.
10.1021/ol7020803 CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/13/2007