Reductive olefination of aldehydes via chromium brook rearrangement

Article abstract of DOI:10.1021/ol0607140

The combination of CrCl₂ and silyl chlorides converts aryl and conjugated aldehydes into olefinic adducts in good to excellent yields. When constrained by structural features, the intermediate vic-diol can be isolated. Available data are consistent with a novel chromium Brook rearrangement.

Full text of DOI:10.1021/ol0607140

ORGANIC
LETTERS
2006
Vol. 8, No. 14
2949-2951
Reductive Olefination of Aldehydes via
Chromium Brook Rearrangement
Rachid Baati,† Charles Mioskowski,*,† Deb Barma,‡ Rajashaker Kache,‡ and
J. R. Falck*,‡
Laboratoire de Synthe`se Bio-Organique, UMR 7175/LC1-CNRS,
Faculte´ de Pharmacie, UniVersite´ Louis Pasteur de Strasbourg, 74 Route du Rhin,
BP 60024, 67 401 Illkirch, France, and Department of Biochemistry,
UniVersity of Texas Southwestern Medical Center, Dallas, Texas 75390
Mioskow@aspirine.u-strasbg.fr; j.falck@utsouthwestern.edu
Received March 23, 2006
ABSTRACT
The combination of CrCl2 and silyl chlorides converts aryl and conjugated aldehydes into olefinic adducts in good to excellent yields. When
constrained by structural features, the intermediate vic-diol can be isolated. Available data are consistent with a novel chromium Brook
rearrangement.
The inter- and intramolecular reductive coupling of carbonyls
to generate olefins is popularly known as the McMurry
reaction.1 It is most often conducted using low-valent
titanium, although other metals have been utilized.2 Mecha-
nistically, the carbonyl forms a transient ketyl that dimerizes
on or near the metal surface.3 The resultant metallopinacolate
undergoes stepwise cleavage of the C-O bonds resulting in
formation of an alkene. Carbenoid intermediates may also
be involved depending upon the reaction conditions and/or
structural features.4 The geometry of the newly formed
double bond is controlled principally by thermodynamic
factors. Comparable reductions of carbonyls by chromium-
(II), on the other hand, typically lead to pinacols.5 In contrast,
we have observed that the combination of CrCl2 and silyl
chlorides generally converts aryl and conjugated aldehydes
into olefinic adducts in good to excellent yields.6 Conse-
quently, we initiated a study to define the scope of the
reaction and the mechanistic reason for the differences in
outcomes.
The olefination was optimized using benzaldehyde (1)
which furnished trans-stilbene (2) (Table 1).7 The best yield
and fastest reaction time were obtained with trichlorosilane
and CrCl2 in THF at reflux (entry 1). EtOAc was also
satisfactory (entry 2), whereas THF/DMF (1:1) generated
threo-dihydrobenzoin (58%) and benzyl alcohol (36%) only.8
Repetition of the reaction described in entry 1, but utilizing
catalytic CrCl2 (10 mol %) regenerated by Mn9 (4 equiv),
also led to a mixture of threo-dihydrobenzoin and benzyl
alcohol. Control experiments confirmed that both trichlo-
rosilane and CrCl2 were necessary for olefin formation.
(6) Contrast with the reductive deoxygenations observed with chlorot-
rimethylsilane and zinc: Banerjee, A. K.; Sulbaran De Carrasco, M. C.;
Frydrych-Houge, C. S. V.; Motherwell, W. B. J. Chem. Soc., Chem.
Commun. 1986, 1803.
† Universite´ Louis Pasteur de Strasbourg.
(7) General procedure: The aldehyde (1 mmol) and silyl chloride (5
mmol) were added to a stirring suspension of anhydrous CrCl2 (3-4 mmol)
under an argon atmosphere in the solvent (15 mL) (indicated in Table 1).
After heating under reflux for the indicated time, the reaction mixture was
cooled to room temperature, quenched with water (10 mL), and extracted
with ether (3 × 10 mL), and the combined organic extracts were washed
with brine, dried, and evaporated. The residue was purified by SiO2 column
chromatography to furnish adducts in the yields stated (Table 1).
(8) Satisfactory spectral data consistent with the literature values or by
comparison with commercial samples were obtained for all products using
chromatographically homogeneous material.
‡ University of Texas Southwestern Medical Center.
(1) Reviews: (a) Moser, W. H. Tetrahedron 2001, 57, 2065. (b)
McMurry, J. E. Chem. ReV. 1989, 89, 1513.
(2) Fu¨rstner, A. In Transition Metals for Organic Synthesis, 2nd ed.;
Beller, M., Bolm, C., Eds.; Wiley-VCH Verlag: Weinheim, 2004; Vol. 1,
p 449.
(3) Hodgson, D. M.; Boulton, L. T. In Preparation of Alkenes; Williams,
J. M. J., Ed.; Oxford University Press: Oxford, 1996; p 81.
(4) Ephritikhine, M. Chem. Commun. 1998, 2549.
(5) (a) Svatos, A.; Boland, W. Synlett 1998, 549. (b) Fu¨rstner, A.; Shi,
N. J. Am. Chem. Soc. 1996, 118, 12349 and references cited therein.
(9) Alois Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 1239.
10.1021/ol0607140 CCC: $33.50
© 2006 American Chemical Society
Published on Web 06/09/2006

Table 1. Reductive Olefination of Aldehydes Using CrCl2/Silyl Chlorides
a 8:92 cis/trans by GC analysis. b 35:65 cis/trans by GC analysis.
A variety of other chlorosilanes in THF likewise afforded
olefinated adducts, inter alia, such as methyl trichlorosilane
(entry 3), ethyl trichlorosilane (entry 4), phenyl trichlorosilane
(entry 5), dimethyl dichlorosilane (entries 6 and 7), trimethyl
chlorosilane (entry 8), and 1,3-dichloro-1,1,3,3-tetraisopro-
pyldisiloxane (entry 9). The outcomes of these reactions
broadly followed the overall reactivity of the chlorosilanes
toward chromium.
Aldehydes bearing an electron-withdrawing substituent (3,
entry 10),10,11 an electron-donating group (5, entry 11),12 and
a fused aromatic (7, entry 12)13 gave generally similar results.
Importantly, many functional groups were well tolerated, e.g.,
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Org. Lett., Vol. 8, No. 14, 2006

Although the details must be confirmed, we favor a
mechanism whereby the silyl anion, formed via successive
one-electron transfers from Cr(II),21 adds to the aldehyde to
give R-hydroxysilane 21 which undergoes chromium Brook
rearrangement to organochromium 22 (Figure 1). Numerous
other metals and nonmetals are known to undergo similar
transformations.22 Subsequent addition of 22 to a second
equivalent of aldehyde furnishes pinacol 23. The isolation
of trans-diol 20 as the sole product in entry 18 suggests that
cyclic chromate ester 24, which cannot form in this case, is
the obligate intermediate for elimination to olefin 25. As
would be anticipated from this mechanistic hypothesis,
heating the aldehyde and CrCl2 or silyl chloride together for
several hours prior to addition of the remaining ingredients
does not yield olefinic adducts. However, good yields of
adduct are obtained when the silyl chloride and CrCl2 are
heated together for several hours followed by addition of
the aldehyde.
Figure 1. Proposed chromium Brook rearrangement.
bromide (9, entry 13),14 methylenedioxy (11, entry 14),15,16
benzyl/methyl ethers (13, entry 15),17 and, surprisingly, an
unprotected phenol (15, entry 16).18 The conjugated aldehyde
cinnamaldehyde (17) was also well behaved and led to triene
18 (entry 17).19 However, aliphatic aldehydes and unhindered
ketones principally afforded aldol products under the same
reaction conditions. The intramolecular condensation of
dialdehyde 19 gave rise unexpectedly to trans-diol 20 (entry
18),20 presumably because it could not close to form the
cyclic chromium diester necessary for elimination (vide
infra).
These data reveal a novel entry into an otherwise unat-
tainable class of functionalized chromium anions. Efforts to
exploit them as reagents for organic synthesis will be detailed
elsewhere.
Acknowledgment. Financial support from the CNRS,
Ministe`re de la Jeunesse, de l’Education Nationale et de la
Recherche, the Robert A. Welch Foundation, and NIH
(GM31278, DK38226) is gratefully acknowledged.
(10) 2,2′-(E)-Difluorostilbene: Dunne, E. C.; Coyne, E. J.; Crowley, P.
B.; Gilheany, D. G. Tetrahedron Lett. 2002, 43, 2449.
(11) 2,2′-(Z)-Difluorostilbene: Aitken, R. A.; Hodgson, P. K. G.;
Morrison, J J.; Oyewale, A. O. J. Chem. Soc., Perkin Trans. 1 2002, 402.
(12) 4,4′-(E)-Dimethylstilbene: Grasa, G. A.; Singh, R.; Stevens, E. D.;
Nolan, S. P. J. Organomet. Chem. 2003, 687, 269.
Supporting Information Available: Spectra and/or gas
chromatograms of 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(13) 1,1′-(E)-1,2-Ethenediylbisnaphthalene: Satoh, T.; Hanaki, N.; Ya-
mada, N.; Asano, T. Tetrahedron 2000, 56, 6223.
(14) 2,2′-(E)-Dibromostilbene: Barman, D. C.; Thakur, A. J.; Prajapati,
D.; Sandhu, J. S. Synlett 2001, 515.
OL0607140
(15) 1,1′-Bis(3,4-methylenedioxy)-(E)-stilbene: Ali, R. S.; Jagtap, P. G.
Synth. Commun. 1991, 21, 841.
(16) 1,1′-Bis(3,4-methylenedioxy)-(Z)-stilbene: Jiang, Q.; He, L.; He,
G.; Zheng, S.-l. Hecheng Huaxue 2004, 12, 267.
(17) 1,1′-Bis(3-methoxy-4-benzyloxy)-(E)-stilbene: Brezny, R.; Puffle-
rova, A. Collect. Czech. Chem. Commun. 1978, 43, 3263.
(18) 4,4′-(E)-Dihydroxystilbene: Ali, M. A.; Kondo, K.; Tsuda, Y. Chem.
Pharm. Bull. 1992, 40, 1130.
(19) 1,6-Diphenyl-(E,E,E)-1,3,5-hexatriene: Doyle, M. P.; Yan, M. J.
Org. Chem. 2002, 67, 602.
(20) trans-9,10-Dihydro-9,10-phenanthrenediol: Mori, K.; Ohtaka, S.;
Uemura, S. Bull. Chem. Soc. Jpn. 2001, 74, 1497.
(21) (a) Kochi, J. K.; Davis, D. D. J. Am. Chem. Soc. 1964, 86, 5264.
(b) Kochi, J. K.; Singleton, D. M. J. Am. Chem. Soc. 1968, 90, 1582.
(22) (a) Stanna Brook: Paleo, M. R.; Calaza, M. I.; Grana, P.; Sardina,
F. Org. Lett. 2004, 6, 1061. (b) Phospha Brook: El Kaim, L.; Gaultier, L.;
Grimaud, L.; Dos Santos, A. Synlett 2005, 15, 2335. (c) Lithium Brook:
Nakazaki, A.; Nakai, T.; Tomooka, K. Angew. Chem., Int. Ed. 2006, 45,
2235.
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