9196
J. Am. Chem. Soc. 2001, 123, 9196-9197
Scheme 1
Chromium Vinylidene Carbenoids: Generation,
Characterization, and Reactivity. First Evidence for
an Internal Proton Return Phenomenon with
Vinylidene Carbenoids
Scheme 2
Rachid Baati,† D. K. Barma,‡ J. R. Falck,*,‡ and
C. Mioskowski*,†
UniVersite´ Louis Pasteur de Strasbourg
Faculte´ de Pharmacie
Laboratoire de Synthe`se Bio-Organique 74
Route du Rhin 67 401 Illkirch
Strasbourg, France
Department of Biochemistry
UniVersity of Texas Southwestern Medical Center
Dallas, Texas 75390
ReceiVed June 28, 2001
ReVised Manuscript ReceiVed August 4, 2001
Organometallic chemistry has played an influential role in the
development of organic synthesis.1 Presently, a wide variety of
organometallic species are routinely exploited for the creation of
new carbon-carbon bonds under mild conditions, often with
excellent regio- and stereocontrol.2 By comparison, organo-
chromium(III) reagents (mostly allylic3 and vinylic4) have been
relatively infrequently explored despite their demonstrated supe-
rior capabilities for some transformations compared with canonical
organometallics.5 Herein, we describe the formation and reactivity
of the first stable halovinylidene chromium(III) carbenoids 3
(Scheme 1).6 Generally, halovinylidene carbenoids7 are generated
by metal halogen exchanges between organolithium, -sodium, or
-potassium reagents and gem-dihalovinylidenes8 or by R-meta-
lation of terminal halovinyldene compounds9 at -100 to -78 °C.
Alternatively, zinc10 and zirconium11 halovinylidene carbenoids
have been prepared recently by carbometalation of metalated
alkynes followed by monohalogenation or by direct carbo-
metalation of haloalkynes below -20 °C. These reactions,
however, are plagued by drawbacks, inter alia, multistep proce-
dures at low temperatures, strictly anhydrous conditions, a
dependency upon additives (e.g., methylaluminoxane), â-elimina-
tion, low yields, and poor regioselectivities.
In sharp contrast, we have discovered that chlorovinylidene
chromium(III) carbenoids 3 can be easily prepared from readily
available12 trichloroalkanes 1 using 4 equiv of CrCl2 in THF at
room temperature. The mechanism of formation appears to
proceed through highly unstable 1-chloro-1,1-bis-chromium al-
kane carbenoids 2 generated by the reduction of two C-Cl
bonds.13 Formally, the oxidative addition of Cr(II) into a C-Cl
bond involves two consecutive single-electron transfers,14 thus
accounting for the four equiv of CrCl2 needed for the reduction
of the two C-Cl bonds. The chlorovinylidene carbenoid is
subsequently formed by a syn â-elimination of chromium hy-
dride15 (Scheme 1). As a consequence of the high steric require-
ments of the terminal bis-chromium intermediate 2, the stereo-
chemistry of the chlorovinylidene carbenoid 3 is exclusively trans.
Notably, 1,1-dichloroalkenes do not react with chromium(II)
chloride under these reaction conditions, thus excluding them as
intermediates in the overall transformation.16
The nucleophilic character of 3 is evident by its reaction with
aldehydes and water (Scheme 2, reactions a and b, respectively).
The reaction of 3 under both Grignard’s and Barbier’s conditions
with a wide variety of aldehydes gave only the (Z)-isomer of
hydroxy-chloroalkenes 5 in >90% yield. Quenching a THF
solution of 3 with water at room temperature afforded (Z)-
chloroolefins 6 as the sole product. Additionally, chlorovinylidene
carbenoids 3 could be induced to cross-couple under mild
conditions with aryl iodides (phenyl, furanyl, substituted aryl) in
the presence of Pd(0) and Cu(I), furnishing 4 in >85% yield
(reaction c). The high yields of these reactions, combined with
the ready availability12 of primary trichloroalkanes 1, makes this
methodology very attractive for the stereoselective synthesis of
* Corresponding authors addresses. E-mail: mioskow@aspirine.u-strasbg.fr;
e-mail: j.falck@utsouthwestern.edu.
‡ University of Texas Southwestern Medical Center.
† Universite´ Louis Pasteur de Strasbourg.
(1) (a) Schlosser, M. Organometallics in Synthesis, A Manual; John Wiley
& Sons: New York, 1994. (b) Tsuji, J. Transition Metal Reagents and
Catalysts, InnoVations in Organic Synthesis; John Wiley & Sons: New York,
2001.
(2) Diederich, F., Stang, P. J., Eds.; Metal-catalyzed Cross-Coupling
Reactions; Wiley-VCH: New York, 1998.
(3) Allylic Cr(III) reagents: (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki,
H. J. Am. Chem. Soc. 1977, 99, 3179. (b) Okude, Y.; Hiyama, T.; Nozaki, H.
Tetrahedron Lett. 1977, 43, 3829. (c) Hiyama, T.; Okude, Y.; Kimura, K.;
Nozaki, H. Bull. Chem. Soc. Jpn. 1982, 55, 561. (d) Cintas, P. Synthesis 1992,
248. (e) Baati, R.; Gouverneur, V.; Mioskowski, C. J. Org. Chem. 2000, 65,
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(5) (a) Furstner, A. Chem. ReV. 1999, 99, 991. (b) Wessjohan, L. A.; Scheid,
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Schlama, T. Tetrahedron lett. 1999, 40, 2091.
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10.1021/ja016515n CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/22/2001