[1] a) A. Boudier, L. O. Bromm, M. Lotz, P. Knochel, Angew. Chem.
2000, 112, 4584; Angew. Chem. Int. Ed. 2000, 39, 4414; b) P. Knochel,
N. Millot, A. L. Rodriguez, C. A. Tucker in Organic Reactions, Vol. 58
(Ed.: L. E. Overman), 2001, p. 247.
In the case of the reaction with benzaldehyde, a sponta-
neous lactonization occurs to give the lactone 3d as a
separable mixture of two diastereoisomers in the ratio of
65:35 (entry4 of Table 1). In the presence of CuCN ¥ 2LiCl, [11]
a smooth reaction proceeds with allyl bromide and ethyl (2-
bromomethyl)acrylate[12] or benzoyl chloride (entries 5 7). A
fast Negishi cross-coupling reaction[13] takes place after trans-
metalation to the corresponding zinc reagent with ZnBr2. An
efficient cross-coupling takes place in the presence of bis-
dibenzylidenepalladium(0)[14] and tris-o-furylphosphane[15] to
give the diester 3h in 92% yield (258C, 6 h, entry8). Since
magnesium carbenoids are an important class of organo-
metallic reagents,[16] we have examined the formation of
carbenoids[17] bearing an ester group. The dibromocyclopro-
panecarboxylic acid ethyl ester 4a[18] was treated with
iPrMgCl (1.1 equiv) in THF which resulted in the formation
of a 65:35 mixture of diastereomeric carbenoids as indicated
byquenching experiments with electrophiles (Scheme 2). The
major diastereoisomer was the Grignard reagent 5a. This
ratio of diastereomers did not significantlychange with time.
However, a completelystereoselective exchange was ob-
served on performing the Br Mg exchange in diethyl ether
(À508C, 10 min). This reaction resulted in the formation of
the cis-magnesium carbenoid 5a (d.r. > 99:1) which can be
stereoselectivelytrapped byseveral electrophiles (Scheme 2
and Table 1).
¬
√
[2] a) M. Rottl‰nder, L. Boymond, L. Berillon, A. Lepretre, G. Varchi, S.
¬
Avolio, H. Laaziri, G. Queguiner, A. Ricci, G. Cahiez, P. Knochel,
¬
Chem. Eur. J. 2000, 6, 767; b) M. Abarbri, J. Thibonnet, L. Berillon, F.
Dehmel, M. Rottl‰nder, P. Knochel, J. Org. Chem. 2000, 65, 4618; c) J.
Thibonnet, P. Knochel, Tetrahedron Lett. 2000, 41, 3319; d) T.
¬
Delacroix, L. Berillon, G. Cahiez, P. Knochel, J. Org. Chem. 2000,
65, 8108; e) G. Varchi, A. E. Jensen, W. Dohle, A. Ricci, G. Cahiez, P.
Knochel, Synlett 2001, 477; f) W. Dohle, D. M. Lindsay, P. Knochel,
¬
Org. Lett. 2001, 3, 2871; g) V. Bonnet, F. Mongin, F. Trecourt, G.
¬
Queguiner, P. Knochel, Tetrahedron Lett. 2001, 42, 5717.
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[8] Interestingly, the trans-iodoester isomer of 1 gives a selective and fast
iodine magnesium exchange (THF, À408C, 15 min) which leads
after transmetalation to the copper derivative and after benzoylation
to trans-3g (65%) as the onlyisomer (no cis-3g could be detected by
1H and 13C NMR spectroscopy).
X
X
Me
X
Me
O
Me
iPrMgCl
E
-50 °C, 10 min
Et
EtO2C
E
MgCl
EtO2C
X
O
6: X = Br
7: X = I
5a: X = Br
5b: X = I
4a: X = Br
4b: X = I
[9] I. Klement, K. Lennick, C. E. Tucker, P. Knochel, Tetrahedron Lett.
1993, 34, 4623.
Scheme 2. Synthesis of carbenoids bearing an ester group.
[10] P. Knochel, N. Millot, A. L. Rodriguez, C. E. Tucker, Organic
Reactions, Vol. 58 (Ed.: L. E. Overman), Wiley, New York, 2001.
[11] P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem. 1988, 53,
2390.
Thus, the reaction of the ester-substituted carbenoid 5a
with iodine furnishes stereoselectivelythe iodobromocyclo-
propane 6a in 85% yield (entry 9). Similarly, the quenching of
6a with allyl bromide furnishes the expected allylated product
6b in 64% yield. The reaction of 5a with various aldehydes or
ketones proceeds readilyand leads to lactones 6c e in 60
61% yield. The reaction with benzaldehyde was highly
diastereoselective (d.r. 92:8) to give 6c (major isomer
depicted in entry11; its structure has been proven byX-ray
analysis[19]) in 60% yield. Interestingly, the reaction of
carbenoid 5b generated bythe reaction of iPrMgCl with the
diiodocyclopropanecarboxylic acid ethyl ester 4b[20] in diethyl
ether at À508C is also highlydiastereoselective. the isomeric
iodobromocyclopropane derivative 7a is formed in 80% yield
(compare entries 9 and 14) after quenching carbenoid 5b with
1,2-dibromotetrachloroethane.
In summary, we have reported the stereoselective prepara-
tion of functionalized cyclopropylmagnesium derivatives
including carbenoids. Under our reaction conditions they
are configurationallystable. Applications of these versatile
cyclopropylmagnesium reagents and extensions of the prep-
aration of other functionalized alkylmagnesium reagents are
currentlyunderway.
[12] J. Villieras, M. Rambaud, Synthesis 1982, 924.
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[18] M. S. Baird, A. G. W. Baxter, J. Chem. Soc. Perkin 1 1979, 2317.
[19] CCDC-171734 contains the supplementarycrystallographic data for
m.ac.uk/conts/retrieving.html (or from the Cambridge Crystallo-
graphic Data Centre, 12, Union Road, Cambridge CB21EZ, UK;
fax: (44)1223-336-033; or deposit@ccdc.cam.ac.uk).
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Received: October 15, 2001 [Z18067]
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