ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
The Design, Synthesis and Validation of
Recoverable and Readily Reusable
Siloxane Transfer Agents for Pd-Catalyzed
Cross-Coupling Reactions
Dionicio Martinez-Solorio, Adam T. Hoye,† Minh H. Nguyen, and Amos B. Smith, III*
Department of Chemistry, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, United States
Received April 4, 2013
ABSTRACT
The development of competent, recoverable and reusable 1-oxa-2-silacyclopentene (siloxane) transfer agents for Pd-catalyzed cross-coupling
reactions (CCRs) of organolithium reagents with aryl and alkenyl iodides has been achieved. Drawbacks of the first-generation siloxane-transfer
agent (1), relating to facile recovery for potential recycling, have been addressed.
Transition-metal catalyzed cross-coupling reactions
(CCRs) comprise one of the most studied1 and celebrated
classes of transformations in chemistry, as noted by the
2010 Nobel Prize in chemistry to Heck, Negishi, and
Suzuki.2 Silicon being more abundant, stable, and
environmentally benign holds the promise as a potential
alternative to tin, boron, and zinc for “green” cross-
coupling reactions. Indeed, Hiyama3 and Denmark4 have
independently reported significant advancements in silicon-
based CCRs.5 However, a major drawback is the need
to construct the individual silane cross-coupling partners,
frequently accessed via the corresponding organolithium
species. Additional issues include the use of stoichiometric
amounts of base or fluoride and/or elevated temperatures,
which may be incompatible with common functional
groups and/or lead to substrate decomposition. On the
other hand, palladium-catalyzed CCRs of organolithium
reagents have been limited to the early examples pioneered
by Murahashi6 where slow addition of the aryllithium is
required to avoid homocoupled products resulting from
competitive lithiumÀhalogen exchange. In this Letter, we
report the rational design, synthesis, and validation of a
† Current address: Avid Radiopharmaceuticals, 3711 Market St. Fl. 7,
Philadelphia, PA 19104.
(1) (a) Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; 1st ed., Wiley-VCH, Weinheim, 1998. (b) Metal-catalyzed
Cross-coupling Reactions; A. de Meijere, Diederich, F., Eds.; 2nd ed.,
Wiley-VCH, Weinheim, 2004. (c) Special Issue on Cross-Coupling, Acc.
Chem. Res. 2008, 41 (11).
(2) (a) Seechurn, C. C. J.; Kitching, M. O.; Colacot, T. J.; Snieckus,
V. Angew. Chem., Int. Ed. 2012, 51, 5062.
(3) (a) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918. (b)
Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. (c) Hiyama, T.; Hatanaka,
T. Pure Appl. Chem. 1994, 66, 1471. (d) Hiyama, T. J. Organomet. Chem.
2002, 653, 58. (e) Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.;
Hiyama, T. J. Am. Chem. Soc. 2005, 127, 6952. (f) Chen, J.; Tanaka, M.;
Sahoo, A. K.; Takeda, M.; Yada, A.; Nakao, Y.; Hiyama, T. Bull. Chem.
Soc. Jpn. 2010, 83, 554. (g) Nakao, Y.; Takeda, M.; Matsumoto, T.;
Hiyama, T. Angew. Chem., Int. Ed. 2010, 49, 4447. (h) Nakao, Y.;
Hiyama, T. Chem. Soc. Rev. 2011, 40, 4893. (i) Tang, S.; Takeda, M.;
Nakao, Y.; Hiyama, T. Chem. Commun. 2011, 47, 307.
(4) (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821. (b)
Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2004, 126, 4876. For reviews,
see: (c) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835. (d)
Denmark, S. E.; Ober, M. H. Aldrichimica Acta 2003, 36, 75. (e) Denmark,
S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486. (f) Chang, W.-T. T.;
Smith, R. C.; Regens, C. S.; Bailey, A. D.; Werner, N. S.; Denmark, S. E.
Chapter 3, Organic Reactions, Inc. 2011, John Wiley & Sons, Inc.
(5) For recent contributions to proximial alkoxide-activated silicon
based CCRs, see: (a) Rooke, D. A.; Ferreira, E. M. Org. Lett. 2012, 14,
3328. (b) Tang, S.; Li, S.-H.; Yan, W.-B. Tetrahedron Lett. 2012, 53,
6743.
(6) (a) Murahashi, S.-I.; Tanba, Y.; Yamamura, M.; Moritani, I.
Tetrahedron Lett. 1974, 15, 3749. (b) Murahashi, S.-I.; Tanba, Y.;
Yamamura, M.; Yoshimura, N. J. Org. Chem. 1978, 43, 4099. (c)
Murahashi, S.-I. J. Organomet. Chem. 2002, 653, 27.
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10.1021/ol400922j
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