COMMUNICATIONS
[
1] a) H. Sinn, W. Kaminsky, H. J. Vollmer, R. Woldt, Angew. Chem. 1980,
2, 396 ± 402; Angew. Chem. Int. Ed. Engl. 1980, 19, 390 ± 392; b) W.
BuMgNiPr : A New Base for Stoichiometric,
2
9
Position-Selective Deprotonation of
Cyclopropane Carboxamides and Other Weak
CH Acids**
Kaminsky, J. Chem. Soc. Dalton Trans. 1998, 1413 ± 1418, and refer-
ences therein.
2] a) H.-H. Brintzinger, D. Fischer, R. M¸lhaupt, B. Rieger, R. M.
Waymouth, Angew. Chem. 1995, 107, 1255 ± 1283; Angew. Chem. Int.
Ed. Engl. 1995, 34, 1143 ± 1170 (Erratum: H.-H. Brintzinger, D. Fischer,
R. M¸lhaupt, B. Rieger, R. M. Waymouth, Angew. Chem. 1995, 107,
[
Mao-Xi Zhang and Philip E. Eaton*
1
652; Angew. Chem. Int. Ed. Engl. 1995, 34, 1368); b) A. L. McKnight,
Organolithium (RLi) and -magnesium (R Mg) compounds
2
R. M. Waymouth, Chem. Rev. 1998, 98, 2587 ± 2598; c) G. J. P. Britov-
sek, V. C. Gibson, D. F. Wass, Angew. Chem. 1999, 111, 448 ± 468;
Angew. Chem. Int. Ed. 1999, 38, 428 ± 447, and references therein.
3] a) M. Ystenes, J. L. Eilertsen, J. Liu, M. Ott, E. Rytter, J. A. St˘vneng,
J. Polym. Sci. A 2000, 38, 3106 ± 3127; b) E. Zurek, T. K. Woo, T. K.
Firman, T. Ziegler, Inorg. Chem. 2001, 40, 361 ± 370; c) E. Zurek, T.
Ziegler, Inorg. Chem. 2001, 40, 3279 ± 3292; d) E. Rytter, J. A.
St˘vneng, J. L. Eilertsen, M. Ystenes, Organometallics 2001, 20,
are kineticallypoor bases for proton removal from weak
carbon acids. If an amine like N,N,N',N'-tetramethylethylendi-
amine (TMEDA) is added, the barrier is sometimes lowered,
but the nucleophilityof the organometallic compound re-
mains a problem. This can be ameliorated byusing metal
amides like lithium diisopropylamide (LDA) and bis(diiso-
[
4
466 ± 4468.
4] M. R. Mason, J. M. Smith, S. G. Bott, A. R. Barron, J. Am. Chem. Soc.
993, 115, 4971 ± 4984.
5] C. J. Harlan, S. G. Bott, A. R. Barron, J. Am. Chem. Soc. 1995, 117,
465 ± 6474.
6] Y. Koide, S. G. Bott, A. R. Barron, Organometallics 1996, 15, 5514 ±
518.
7] B. Richter, A. Meetsma, B. Hessen, J. H. Teuben, Chem. Commun.
001, 1286 ± 1287.
propylamido)magnesium (DA Mg). These poor nucleophiles
2
[
[
[
[
[
are still kineticallyeffective bases for deprotonation of weakly
1
[1]
acidic CH groups (pK ꢀ 30 ± 35). However, as the pK of the
a
a
liberated amine and that of the CH acid (e.g. 1) are similar,
6
such deprotonations are nowhere near stoichiometric (e.g.
[2]
5
Scheme 1 ). This is unsatisfactory.
2
8] Crystallographic structure determinations were performed on a Bruker
SMART Apex CCD diffractometer using MoKa radiation (l
0
.71073 ä). The structures were solved with Patterson methods and
extended bydirect methods applied to difference structure factors.
Crystallographic data for 2: C69 NO ¥ (C ), M
H
109Al
4
B
4
8
6
H
6
r
1309.91,
Scheme 1. The equilibrium reaction of LDA with amide 1.
monoclinic, space group P2
1
o
/n, a 13.8868(6), b 25.188(1), c
3
2
3.346(1) ä, b 106.805(1) , V 7817.2(6) ä , Z 4,
1
calcd
À3
À1
2
1
.113 gcm , m 1.1 cm , T 110 K. A final refinement on F con-
2
We now introduce alkylmagnesium amides, here specifi-
verged at wR(F ) 0.1789 for 13782 reflections and R(F) 0.0733 for
7
505 reflections with F
o
ꢁ 4s(F
o
) and 857 parameters. Crystallographic
callyBuMgN iPr , denoted hereafter as BuMgDA, as an
2
data for 3: [C25
H
41SZr][C65
H
107Al
4
B
4
O
8
] ¥ (C
7
H
8
)
1.5 , M
r
1770.83, mon-
[3]
effective solution to this problem. We prepare BuMgDA
oclinic, space group P2
1
/c, a 20.6291(8), b 20.3125(8), c
simply by adding 1.0 equivalent of anhydrous diisopropyl-
amine (DAH) to commercial[ dibutylmagnesium in heptane
(ca. 1.0m) at room temperature and then stirring the solution
for five minutes at 508C. BuMgDA[ in heptane is quite
reactive. Replacing heptane, all or in part, with THF (after the
3
2
6.301(1) ä, b 110.155(1)8, V 10346.0(7) ä , Z 4,
1
calcd
4]
À3
À1
2
1.137 gcm
,
m 2.11 cm
,
T 110 K.
A
final refinement on
F
2
converged at wR(F ) 0.2289 for 18278 reflections and R(F)
3b]
0
.0808 for 11143 reflections with F
o
o
ꢁ 4s(F ) and 1145 parameters
and 16 restraints. One of the toluene molecules in the lattice shows
extensive orientational disorder, resulting in unrealistic displacement
parameters when allowed to varyanisotropicall .y The other toluene
molecule is disordered over an inversion center, and was described as a
single molecule with 0.5 occupancywith geometrical restraints. CCDC-
base has been formed) increases this usefully. Unlike Bu Mg
and manyorganolithium bases, BuMgDA is stable even in
2
refluxing THF for manyhours. BuMgDA, like DA 2Mg,
1
77577 (2) and CCDC-177576 (3) contain the supplementarycr ys tallo-
[5]
deprotonates/metalates amide-activated
(
cyclopropyl-CH
graphic data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ,
UK; fax: (44)1223-336-033; or deposit@ccdc.cam.ac.uk).
9] E. A. Bijpost, M. A. Zuideveld, A. Meetsma, J. H. Teuben, J. Organo-
met. Chem. 1998, 551, 159 ± 164.
[6]
a, b, or beyond) and cubyl-CH (ortho), but the BuMgDA
deprotonations are driven to completion byirreversible
formation of butane.
It is instructive to compare the metalation of the cyclo-
[
propylcarboxamide 2 using Bu Mg solutions in heptane
2
treated first with 0, 0.5, or 1.0 equivalent of DAH. Bu Mg
2
[7]
itself reacted onlyslowl;y
mostlystarting material was
recovered. In the other two cases, when at least some
BuMgDA[ was present, the overall deprotonation/metal-
ation/carboxylation proceeded in high yield, but the final
3b]
[
*] Prof. Dr. P. E. Eaton, Dr. M.-X. Zhang
Department of Chemistry
The Universityof Chicago
5
735 South Ellis Avenue, Chicago, IL 60637 (USA)
Fax : (1)773-702-2053
E-mail: eaton@uchicago.edu
[
**] This work was supported in part byEastman Chemical. We are
grateful to Z. Hantosi and C.-H. Lee for trial experiments, to I. Steele
for the X-rayanal sy es, and to Professor S. Shuto of Hokkaido
Universityfor samples of Milnacipran precursors.
Angew. Chem. Int. Ed. 2002, 41, No. 12
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4112-2169 $ 20.00+.50/0
2169