Pd(0)-catalyzed PMHS reductions of aromatic acid chlorides to aldehydes

Article abstract of DOI:10.1021/ol060463v

Contrary to previous reports, polymethylhydrosiloxane (PMHS) under Pd(0) catalysis can efficiently reduce aryl acid chlorides to their corresponding aldehydes without requiring an additional reductant, provided the reactions are run in the presence of fluoride.

Full text of DOI:10.1021/ol060463v

ORGANIC
LETTERS
2
006
Vol. 8, No. 9
887-1888
Pd(0)-Catalyzed PMHS Reductions of
Aromatic Acid Chlorides to Aldehydes
1
Kyoungsoo Lee and Robert E. Maleczka, Jr.*
Department of Chemistry, Michigan State UniVersity, East Lansing, Michigan 48824
maleczka@chemistry.msu.edu
Received February 22, 2006
ABSTRACT
Contrary to previous reports, polymethylhydrosiloxane (PMHS) under Pd(0) catalysis can efficiently reduce aryl acid chlorides to their
corresponding aldehydes without requiring an additional reductant, provided the reactions are run in the presence of fluoride.
The reduction of acid chlorides to aldehydes is a basic
functional group transformation. While reductions under
3 3
of Me SnH that was generated in situ by the reaction of Me -
SnCl with PMHS in the presence of aqueous KF (Table 1,
6
3
Rosenmund conditions or by Li(t-BuO) AlH are classic
1
means for effecting the reaction, the quest for ever greater
selectivity and efficiency has long prompted the search for
alternative methods. Among these, the palladium-mediated
Table 1. Pd-Mediated Reduction of Benzoyl Chloride to
Benzaldehyde with in Situ Generated Me SnH
3
1
organotin hydride reductions invented by Guib e´ have proven
particularly popular.2
Of course, organotin reagents carry the baggage of being
3
relatively toxic, expensive, unstable, etc. Thus, mindful of
Pd(0)
(mol %)
Me3SnCl
(equiv)
KF
(equiv)
time
(h)
yield
(%)
prior reactions made catalytic in tin through the use of
polymethylhydrosiloxane (PMHS) as the stoichiometric
entry
4
reductant and our recent report of a one-pot Pd-mediated
1
2
3
4
5
6
1
1
1
1
1
1.0
0.3
0.1
1.5
1.5
1.5
1.5
0.5
0.5
1.0
1.0
24
100
100
100
100
12
5
hydrostannation/Stille coupling of acid chlorides, we con-
templated a tin-catalyzed version of Guib e´ ’s method for
reducing acid chlorides to aldehydes.
As a prelude to that goal, we examined the Pd-catalyzed
reduction of benzoyl chloride with a stoichiometric amount
1.5
24
0
(
1) Larock, R. C. ComprehensiVe Organic Transformations: A Guide
entry 1). Despite the potential for hydrolysis and unwanted
reactions, this combination rapidly and quantitatively af-
forded benzaldehyde. We next looked to make the reaction
catalytic in tin. Needless to say, we were pleased when
reactions with 30 mol % and then 10 mol % tin worked
nearly as well as the stoichiometric variant (entries 2-3).
That satisfaction turned to surprise when, after 1 h, a tin-
free control experiment (entry 4) also gave 100% benzal-
dehyde!
to Functional Group Preparation, 2nd ed.; Wiley-VCH: New York, 1999;
pp 1265-1266 and references therein.
(
2) Four, P.; Guibe, F. J. Org. Chem. 1981, 46, 4439-4445.
(3) (a) Smith, P. J., Ed. Chemistry of Tin; Blackie Academic &
Professional: New York, 1998. (b) Davies, A. G. Organotin Chemistry;
VCH: New York, 1997.
(4) (a) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc.,
Perkin Trans. 1 1999, 3381-3391 and references therein. (b) Lavis, J. M.;
Maleczka, R. E., Jr. Polymethylhydrosiloxane (PMHS). In eEROS-Electronic
Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Crich,
D., Fuchs, P. L., Wipf, P., Eds.; Wiley: New York 2003; [Online] and
references therein.
(5) Lee, K.; Gallagher, W. P.; Toskey, E. A.; Chong, W.; Maleczka, R.
E., Jr. J. Organomet. Chem. 2006, 691, 1462-1465.
(6) Terstiege, I.; Maleczka, R. E., Jr. J. Org. Chem. 1999, 64, 342-343.
1
0.1021/ol060463v CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/07/2006

We were caught unawares by this result because, while
organosilanes have long been used to convert acid chlorides
to aldehydes,1 it has been over 20 years since Keinan and
Greenspoon reported that acid chlorides “cannot be reduced
Table 2
,7
”
8,9
just with PMHS/Pd(PPh
supported by Crabtree, who found that collidal Pd formed
from Pd(hfacac) and PMHS required the presence of H
3
)
4
.
Their observation was later
2
2
1
0
gas to reduce benzoyl chloride to benzaldehyde. In our
system, it appeared that the presence of KF heightened the
reactivity of the PMHS to where the acid chlorides can be
converted to their aldehydes without the need for an
additional reductant. This was supported by our own KF-
free experiment (entry 5), which only gave 12% benzalde-
hyde after 24 h. That said, activation by KF is not sufficient
to abolish the need for Pd catalysis (entry 6).
We presume the fluoride activates PMHS by making it
hypercoordinate.11 Nonetheless, unlike acid chlorides, acid
12
fluorides can be reduced by just PMHS/Pd(0). Therefore,
we had to consider if benzoyl chloride was first converted
to benzoyl fluoride13 and then reduced to benzaldehyde.
However, GC monitoring never indicated the presence of
benzoyl fluoride. Furthermore subjecting benzoyl fluoride
to our reaction conditions failed to afford any benzaldehyde.
14
With an acid fluoride intermediate ruled highly unlikely,
this reduction represents a noteworthy refinement of the
literature. Moreover, given that PMHS is mild, safe, and
4
cheap, these conditions may be attractive as a general way
to convert acid chlorides to aldehydes.
To assess this prospect, we tested a series of acid chlorides
against the PMHS/KF/Pd(0) conditions (Table 2). We soon
saw that not all substrates underwent complete reaction with
1.5 equiv of PMHS (e.g., 7). In contrast, 3.0 equiv of PMHS
and aqueous KF in the company of substoichiometric
1
5
amounts of Pd(0), trifurylphosphine (TFP), and TBAF
a
uniformly reduced a variety of electron-rich and neutral aryl
acid chlorides (entries 1-8), including heterocyclic 2-thio-
phenoyl chloride (entry 9), to their aldehydes within 1 h at
room temperature.16 Despite the ability of PMHS/Pd(0) to
reduce aryl halides,17 4-bromobenzoyl chloride was selec-
Average isolated yields over two runs.
Unfortunately, the reductions were not universally ap-
plicable. Water in the reaction hydrolyzed electron-poor
benzoyl chloride derivatives and aliphatic acid chlorides too
1
8
tively reduced to 4-bromobenzaldehyde (entry 10).
19
fast to allow for their reductions.
In summary, the presence of fluoride allows Pd(0)-
catalyzed PMHS reductions of electron-rich and neutral aryl
acid chlorides. Yields are generally high and reaction times
short. Perhaps most importantly, these results amend the
existing literature.
(
7) Corriu, R. J. P.; Lanneau, G. F. Perrot, M. Tetrahedron Lett. 1988,
2
9, 1271-1274 and references therein.
(
8) Keinan, E.; Greenspoon, N. J. Org. Chem. 1983, 48, 3545-3548.
(9) Rh-catalyzed PMHS reductions have been modestly successful.
See: Blum, J.; Pri-bar, I.; Alper, H. J. Mol. Catal. 1986, 37, 359-367.
10) Fowley, L. A.; Michos, D.; Luo, X.-L.; Crabtree, R. H. Tetrahedron
Lett. 1993, 34, 3075-3078.
11) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. ReV. 1993,
3, 1371-1448.
12) Braden, R.; Himmler, T. J. Organomet. Chem. 1989, 367, C12-
C14.
(
(
Acknowledgment. We thank the NIH, NSF, and the
Astellas USA Foundation for generous support.
9
(
(
13) Cuomo, J.; Olofson, R. A. J. Org. Chem. 1979, 44, 1016-1017.
Supporting Information Available: Experimental details
and product characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) We cannot rule out fluoride converting a RCO-Pd(II)-Cl species to
RCO-Pd(II)-F.
(
(
15) TBAF presumably facilitates phase transfer.
16) Typical procedure: Pd2dba3 (0.01 mmol, 9.2 mg) and trifurylphos-
phine (TFP) (0.04 mmol, 9.3 mg) were added to THF (5 mL), and the
resulting mixture was stirred at rt for 15 min. The acid chloride (1 mmol),
PMHS (3.0 mmol, 0.18 mL), aq KF (3.0 mmol, 174.5 mg in 1 mL of H2O),
and TBAF (1 drop of a 1 M solution in THF (∼0.008 mmol)) were then
added successively. The reaction was then stirred at rt until judged complete
by GC (∼1 h). At that time, the reaction was extracted with Et2O and the
aqueous phase back extracted with Et2O. The combined organics were dried
over MgSO4, filtered, and concentrated. Purification of the resulting residue
by silica gel chromatography afforded the aldehyde.
OL060463V
(17) Maleczka, R. E., Jr.; Rahaim, R. J., Jr.; Teixeira, R. R. Tetrahedron
Lett. 2002, 43, 7087-7090.
(18) No benzaldehyde was detected by GC.
(19) Reactions run under anhydrous conditions have met with mixed
results. We will disclose the details of these experiments once they are
suitably understood.
1888
Org. Lett., Vol. 8, No. 9, 2006