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Journal of the American Chemical Society
Acidic work-up provides the aldehydes 7a-c in 69-84 % yield
(Scheme 3). The presence of the sulfur-containing Grignard
reagent 2l extends considerably the reaction rate and 16 h reaction
time is required to complete the cross-coupling leading to 7c.
ASSOCIATED CONTENT
1
2
3
4
5
6
7
Supporting Information
Full experimental details, 1H- and 13C-NMR spectra. This material
Thus, this cross-coupling constitutes
a simple way for
functionalizing aromatic aldehydes in the ortho-position.
AUTHOR INFORMATION
Corresponding Author
Scheme 3. Cr-catalyzed cross-coupling reactions between
imine-protected aldehyde 6 and Grignard reagents
8
9
Notes
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The authors declare no competing financial interests.
ACKNOWLEDGMENT
The research leading to these results has received funding from
the European Community’s Seventh Framework Programme
(FP7/2007-2013) ERC Grant Agreement No. 227763. We are
grateful to BASF SE, and Rockwood Lithium GmbH for the
generous gift of chemicals. O. M. K. thanks Novartis Pharma AG
for financial support.
Finally, alkenyl iodides, such as (E or Z)-8, also undergo a
stereoselective chromium-catalyzed arylation with a range of aryl
Grignard reagents (2b, 2g, 2h, 2m), affording in all cases the
functionalized styrenes 9a-e in 69-80 % yield (Scheme 4). For the
alkenyl iodide (E)-8, the reactions are completed in 15 min at 25
°C (E:Z ratio > 99:1), whereas a reaction time of 14 h is required
for the coupling of (Z)-8 (Z:E ratio = 99:1). Since no loss of
stereochemistry is observed, a single electron transfer mechanism
implying radical intermediates can be excluded, confirming the
result obtained with the radical clock substrate (1b, entry 1 of
Table 1).
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Scheme 4. Cr-catalyzed cross-coupling reactions between
alkenyl iodide (E or Z)-8 and Grignard reagents 2
In conclusion, we have reported
a
new transition
metal-catalyzed cross-coupling reaction requiring only 3 % of
chromium(II) chloride. This metal halide, as indicated in the
introduction, has
a moderate acute toxicity. Thus, major
international suppliers classify chromium(II) chloride as a low
toxic chemical, which is in the same category of toxicity like
iron(II) chloride. Its price is comparable to the price of CoCl2 or
FeCl2. Remarkably, these ligand-free cross-couplings proceed
rapidly (usually less than 2 h) at 25 °C, require only 1.2 to 1.5
equivalents of Grignard reagent and produce significantly less
homo-coupling side-products than the corresponding Fe- or Co-
catalyzed cross-coupling reactions. CrCl2 displays also a higher
reactivity compared to similar Mn-catalyzed cross-couplings.
Based on all these features, chromium(II)-catalyzed
cross-coupling should become attractive for research and
development. Further explorations are under way in our
laboratories.
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