C O M M U N I C A T I O N S
Table 1. Preparations and Reactions of Unsaturated Organozinc
Reagents of Type 2 Leading to Products of Type 3
the corresponding aldehyde 3n in 85% yield. A selective zinc
insertion occurs also with the tribromopyrimidine 1o at 25 °C within
4 h, leading to the zincated dibromopyrimidine 2o (entry 13).
Addition of ethyl (2-bromomethyl)acrylate in the presence of a
catalytic amount of CuCN‚2LiCl8 leads to the substituted dibro-
mopyrimidine 3o in 63% yield.
In summary, we have shown that the use of Zn dust in the
presence of LiCl in THF allows, for the first time, a highly
regioselective zinc insertion on poly iodo- and bromo- aryls as well
as heteroaryls allowing to prepare polyfunctional zinc reagents
otherwise difficult to obtain such as 2b, 2g, 2h, and 2o. This
exceptional regioselectivity is triggered by various DoI groups such
as an ester, a ketone, an aryl sulfonate, an acetate, a triazene, or a
carbamate, showing the generality of this approach. Further
extensions of this work are currently underway in our laboratories.
Acknowledgment. We thank the Fonds der Chemischen In-
dustrie, the DFG, Merck Research Laboratories (MSD), Chemetall
GmbH (Frankfurt), and BASF AG (Ludwigshafen) for financial
support. S.S. thanks the JSPS and P.S. thanks the Humboldt
Foundations for financial support.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds are provided. This material is
References
(1) (a) Knochel, P.; Millot, N.; Rodriguez, A. L. Org. React. 2001, 58, 417.
(b) Knochel, P.; Singer, R. D. Chem. ReV. 1993, 93, 2117. (c) Handbook
of Functionalized Organometallics; Knochel, P., Ed.; Wiley-VCH: Wein-
heim, Germany, 2005; Vol. 1, p 251.
(2) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P. Angew. Chem.,
Int. Ed. 2006, 45, 6040.
(3) (a) Anctil, E. J.-G.; Snieckus, V. J. Organomet. Chem. 2002, 653, 150.
(b) Snieckus, V. Chem. ReV. 1990, 90, 879. (c) Wagner, F. F.; Comins,
D. L. Eur. J. Org. Chem. 2006, 3562. (d) Katritzky, A. R.; Xu, Y.-J.;
Jain, R. J. Org. Chem. 2002, 67, 8234.
(4) (a) Rieke, R. D. Science 1989, 246, 1260. (b) Wu, X.; Rieke, R. D. J.
Org. Chem. 1995, 60, 6658. (c) Knochel, P.; Dohle, W.; Gommermann,
N.; Kneisel, F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew.
Chem., Int. Ed. 2003, 42, 4302.
(5) (a) Schlosser, M. Angew. Chem., Int. Ed. 2005, 44, 376. (b) Mulvey, R.
E.; Mongin, F.; Uchiyama, M.; Kondo, Y. Angew. Chem., Int. Ed. 2007,
46, 3802. (c) Mongin, F.; Que´guiner, G. Tetrahedron 2001, 57, 4489. (d)
Krasovskiy, A.; Krasovskaya, V.; Knochel, P. Angew. Chem., Int. Ed.
2006, 45, 2958.
(6) (a) For a regioselective Zn/Br-insertion, see: Chen, T.-A.; Wu, X.; Rieke,
R. D. J. Am. Chem. Soc. 1995, 117, 233. (b) For a regioselective Mg/Br
insertion, see: Lee, J.-S.; Velarde-Ortiz, R.; Guijarro, A.; Wurst, J. R.;
Rieke, R. D. J. Org. Chem. 2000, 65, 5428.
(7) Zinc was activated by treatment first with 1,2-dibromoethane (5 mol %)
and then with chlorotrimethylsilane (2 mol %); see also ref 1 and ref 2.
(8) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem. 1988,
53, 2390.
(9) (a) Piers, E.; Nagakura, I. Synth. Commun. 1975, 5, 193. (b) Piers, E.;
Griersar, J. R.; Lan, C. K.; Nagakura, I. Can. J. Chem. 1982, 60, 210. (c)
Kowalski, C. J.; Fields, K. W. J. Org. Chem. 1981, 46, 197.
(10) (a) Sapountzis, I.; Lin, W.; Fischer, M.; Knochel, P. Angew. Chem., Int.
Ed. 2004, 43, 4364. (b) Lin, W.; Sapountzis, I.; Knochel, P. Angew. Chem.,
Int. Ed. 2004, 44, 4258.
(11) Kauch, M.; Snieckus, V.; Hoppe, D. J. Org. Chem. 2005, 70, 7149.
(12) (a) Liu, C. J.; Knochel, P. Org. Lett. 2005, 7, 254. (b) Saeki, T.; Son,
E.-C.; Tamao, K. Org. Lett. 2004, 6, 617.
(13) Villieras, J.; Rambaud, M. Org. Synth. 1988, 66, 220.
(14) (a) Negishi, E.; Valente, L. F.; Kobayashi, M. J. Am. Chem. Soc. 1980,
102, 3298. (b) Kobayashi, M.; Negishi, E. J. Org. Chem. 1980, 45, 5223.
(c) Negishi, E. Acc. Chem. Res. 1982, 15, 340.
(15) Bra¨se, S. Acc. Chem. Res. 2004, 37, 805.
(16) For the preparation of tribromoaryltriazene 1h, see: Nicolaou, K. C.; Li,
H.; Boddy, C. N. C.; Ramanjulu, J. M.; Yue, T. Y.; Natarajan, S.; Chu,
X. J.; Bra¨se, S.; Ru¨bsam, F. Chem. Eur. J. 1999, 5, 2584.
(17) (a) For the preparation of 4,5-diiodo-2-methyl-1H-imidazole, see: Bell,
A. S.; Campbell, S. F.; Morris, D. S.; Roberts, D. A.; Stefaniak, M. H. J.
Med. Chem. 1989, 32, 1552. (b) Lipshutz, B. H.; Hagen, W. Tetrahedron
Lett. 1992, 33, 5865.
a X ) I‚LiCl or Br‚LiCl. b Isolated yield of analytically pure product.
c Catalytic amount of CuCN‚2LiCl was added. d A 1 equiv portion of
CuCN‚2LiCl was added. e A 1 mol % portion of Pd(Ph3P)4 was added.
f Ar ) 4-ClC6H4.
(18) Delgado, O.; Heckmann, G.; Mueller, H. M.; Bach, T. J. Org. Chem.
2006, 71, 4599.
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