Efficient carbonylation reactions in phosphonium salt ionic liquids: Anionic effects

Article abstract of DOI:10.1021/ol702081g

(Formula Presented) Application of phosphonium salt ionic liquids in the carbonylation of aryl and vinyl halides is presented. Anionic effects were uncovered with the bromide ionic liquid emerging as the superior media. Acid bromide intermediates were detected in control experiments providing an extended view on the overall catalytic cycle involved. Solvent-free product isolation and recycling of the ionic liquid containing active Pd-catalyst are also demonstrated.

Full text of DOI:10.1021/ol702081g

ORGANIC
LETTERS
2007
Vol. 9, No. 22
4575-4578
Efficient Carbonylation Reactions in
Phosphonium Salt Ionic Liquids:
Anionic Effects
James McNulty,*,† Jerald J. Nair,† and Al Robertson‡
Department of Chemistry, McMaster UniVersity, 1280 Main Street West,
Hamilton, Ontario, L8S 4M1, Canada, and Cytec Canada Inc., P.O. Box 240,
Niagara Falls, Ontario, L2E 6T4, Canada
jmcnult@mcmaster.ca
Received August 23, 2007
ABSTRACT
Application of phosphonium salt ionic liquids in the carbonylation of aryl and vinyl halides is presented. Anionic effects were uncovered with
the bromide ionic liquid emerging as the superior media. Acid bromide intermediates were detected in control experiments providing an
extended view on the overall catalytic cycle involved. Solvent-free product isolation and recycling of the ionic liquid containing active Pd-
catalyst are also demonstrated.
The palladium-catalyzed carbonylation of aryl, vinyl, and
aliphatic halides (or halide equivalents) is established as a
useful, atom-economical method for the selective introduc-
tion of carbonyl groups into an organic molecule.1 These
reactions, originally established in the mid-70s by the
pioneering work of Heck et al.,2 have since found a number
of synthetic applications,3 and have been applied industrially,
for example, in the preparation of ibuprofen on a metric ton
scale and in a two-stage route to methyl methacrylate.4,5 In
terms of atom economy, highly efficient catalytic addition
reactions are actively sought after since they can occur
without formation of byproducts.6 Room temperature ionic
liquids (ILs) have recently attracted much attention as
versatile reaction media. Often, they are thermally stable,
nonvolatile, nonflammable, and recyclable liquids and as
such have emerged as promising green-substitutes for
conventional organic solvents.7 The combination of develop-
ing atom-economical catalytic addition reactions in poten-
tially recyclable ILs is thus a desirable goal in synthetic
chemistry.
† McMaster University.
‡ Cytec Canada Inc.
(1) (a) Tsuji, J. In Palladium Reagents and Catalysts; Wiley: Chichester,
UK, 2004; pp 265-288. (b) Skoda-Foldes, R.; Kollar, L. Curr. Org. Chem.
2002, 6, 1097-1119. (c) Mori, M. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; Vol. 2, pp 2663-2682. (d) Luh, T. Y.; Leung, M.; Wong, K.
T. Chem. ReV. 2000, 100, 3187-3204. (e) Beller, M. Applied Homogeneous
Catalysis with Organometallic Compounds, 2nd ed.; Cornils, B., Herrmann,
W. A., Eds.; Wiley-VCH: Weinheim, Germany, 2002; Vol. 1, pp 145-
156. (f) Beller, M.; Cornils, B.; Frohning, C. D.; Kohlpaintner, C. W. J.
Mol. Catal. 1995, 104, 17-85.
(2) (a) Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem. 1974,
39, 3318-3326. (b) Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39,
3327-3331. (c) Schoenberg, A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96,
7761-7764. (d) Garrou, P. E.; Heck, R. F. J. Am. Chem. Soc. 1976, 98,
4115-4127. (e) Moser, W. R.; Wang, A. W.; Kildahl, N. K. J. Am. Chem.
Soc. 1988, 110, 2816-2820.
(3) (a) Jimenez-Rodriguez, C.; Eastham, G. R.; Cole-Hamilton, D. J.
Dalton Trans. 2005, 10, 1826-1830. (b) Mizushima, E.; Hayashi, T.;
Tanaka, M. Green Chem. 2001, 3, 76-79.
(4) Zapf, A.; Beller, M. Top. Catal. 2002, 19, 101-109.
(5) New MMA Technology. European Chemical News; European
Chemical News: London, UK, 2000; Oct 30-Nov 5, p 20.
(6) (a) Trost, B. M. Science 1991, 254, 1471-1477. (b) Trost, B. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 259-281. (c) Trost, B. M. Acc.
Chem. Res. 2002, 35, 695-705.
(7) (a) Welton, T. Chem. ReV. 1999, 99, 2071-2084. (b) Wasserscheid,
P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3772-3789. (c) Sheldon,
R. Chem. Commun. 2001, 2399-2407. (d) Wilkes, J. S. Green. Chem. 2002,
4, 73-80. (e) Welton, T. Coord. Chem. ReV. 2004, 248, 2459-2477.
10.1021/ol702081g CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/27/2007

Over the past few years we have been actively involved
in the development of cross-coupling reactions in phospho-
nium salt ionic liquids (PSILs) in general and specifically
palladium-catalyzed processes. Both Suzuki and Heck cross-
coupling reactions were demonstrated by us to occur ef-
ficiently in PSILs allowing recovery and reuse of both active
Pd-catalyst and IL.8 In addition to the potential advantages
offered by ionic liquids described above, we have observed
mechanistically significant anionic and cationic effects
operable in esterification, general alkylation, and palladium-
catalyzed amination reactions carried out in PSILs.8e,f Thus,
in addition to the “green” credentials of these liquids, they
have proven to be valuable reaction media in which to probe
anionic and cationic effects and uncover fundamentally
valuable information about these reactions. Herein we
disclose the first examples of carbonylation reactions con-
ducted in a PSIL, highlight a bromide effect, and establish
acyl halides as viable intermediates in the catalytic cycle.
A few reports9 on the use of imidazolium- and ammonium-
based ILs in the carbonylation process have appeared. Of
note, Nacci and co-workers9d reported tetrabutylammonium
bromide (TBAB) to be a superior media to a range of other
quaternary nitrogen-based systems. This was attributed to
the involvement of a reactive anionic palladium species of
type L2PdBr-, in accord with previous studies of Amatore
and Jutand.10 The use of a soluble bromide ion source now
appears to be a tacit ploy in carbonylation reactions.10c In
the present study, we investigated carbonylative cross
coupling as a further probe of ionic effects exhibited in
PSILs. In the initial screening, a range of PSILs consisting
of the trihexyl(tetradecyl)phosphonium cation with a range
of common ions were screened in the reaction of 4-iodo-
toluene and 1-butanol with a Pd(OAc)2/dppf catalyst sys-
tem,11 and the results of the study are reported in Table 1.
The reactions were conducted at atmospheric pressure of CO
for 6 h. In contrast, most literature carbonylations9 are
conducted under pressure (10-30 atm).12 The results reveal
most of these PSIL media to be effective; however, the
Table 1. Alkoxycarbonylation of 4-iodotoluene in Various
PSILs
2 isolated
yield (%)
entry
anion (X-)
1
2
3
4
5
6
7
8
9
tosylate
chloride
dicyanamide
bis(triflimide)
bromide
PF6
decanoate
BF4
phosphate
sulfate
0
60
65
75
93
73
70
55
33
28
10
superiority of the bromide-containing media is readily
apparent (Table 1, entry 5). This reaction proceeded to
completion in the bromide PSIL under mild conditions (1
atm of CO at 60 °C containing 2 equiv of 1-butanol), giving
the product in 93% isolated yield. While other anions were
not as effective, the significant difference observed between
bromide and chloride counteranions with all other parameters
unchanged also draws attention, given that anionic complexes
LPdX- or L2PdX- are the assumed reactive catalyst. That
chloride-doped Pd-catalysts have proven to be very effective
in a range of cross-coupling reactions10a raises the possibility
that bromide anion plays a more specific role in the present
and other9d carbonylation reactions. Overall, the anionic
effects (Table 1) demonstrate that a viable catalytic cycle is
operative with coordinating chloride as well as noncoordi-
nating anions such as dicyanamide and bistriflimide, with
an accelerating effect being observed only with bromide.
These results are therefore not consistent simply with the
involvement of an anionic L2PdX- species and led us to
suspect that the bromide-anionic effect may be exerted
through a completely different pathway.
(8) (a) McNulty, J.; Capretta, A.; Wilson, J.; Dyck, J.; Adjabeng, G.;
Robertson, A. J. J. Chem. Soc., Chem. Commun. 2002, 1986-1987. (b)
Gerritsma, D. A.; Robertson, A. J.; McNulty, J.; Capretta, A. Tetrahedron
Lett. 2004, 45, 7629-7632. (c) McNulty, J.; Capretta, A.; Cheekoori, S.;
Clyburne, J. A. C.; Robertson, A. J. Chemica Oggi 2004, 22, 13. (d)
McNulty, J.; Cheekoori, S.; Nair, J. J.; Larichev, V.; Capretta, A.; Robertson,
A. J. Tetrahedron Lett. 2005, 46, 3641-3644. (e) McNulty, J.; Nair, J. J.;
Cheekoori, S.; Larichev, V.; Capretta, A.; Robertson, A. J. Chem. Eur. J.
2006, 12, 9314-9322. (f) McNulty, J.; Cheekoori, S.; Bender, T. P.; Coggan,
J. A. Eur. J. Org. Chem. 2007, 9, 1423-1428.
(9) (a) Li, Y.; Yu, Z.; Alper, H. Org. Lett. 2007, 9, 1647-1649. (b) Li,
Y.; Alper, H.; Yu, Z. Org. Lett. 2006, 8, 5199-5201. (c) Zhao, X.; Alper,
H.; Yu, Z. J. Org. Chem. 2006, 71, 3988-3990. (d) Calo, V.; Giannoccaro,
P.; Nacci, A.; Monopoli, A. J. Organomet. Chem. 2002, 645, 152-157.
(e) Mizushima, E.; Hayashi, T.; Tanaka, M. Green Chem. 2001, 3, 76-79.
(f) Calo, V.; Nacci, A.; Monopoli, A. Eur. J. Org. Chem. 2006, 3791-
3802. (g) Fukuyama, T.; Inouye, T.; Ryu, I. J. Organomet. Chem. 2007,
692, 685-690.
In considering the generally accepted catalytic cycle
invoved (Figure 1, path a), one possible hypothesis that might
explain the bromide effect would be the intervention of the
intermediate acyl-palladium species A with the nucleophilic
bromide anion yielding a reactive acid bromide intermediate.
Acid halides were postulated by both Heck2a and Moser,2e
but discounted as significant contributors on kinetic grounds.13
Under typical carbonylation reaction conditions (nucleophile,
base) rapid ester or amide formation would be expected from
any acid bromide formed, and excess bromide would simply
(10) (a) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314-321.
(b) Fagnou, K.; Lautens, M. Angew. Chem., Int. Ed. 2002, 41, 26-47. (c)
Peng, C.; Cheng, J.; Wang, J. J. Am. Chem. Soc. 2007, 129, 8708-8709.
(11) Choice of Pd-source [Pd(OAc)2, Pd2(dba)3, Pd(PPh3)4, PdCl2(PPh3)2]
and ligand [BINAP, Ph3P, DPPE, DPPP, DPPB, DPPF] was not critical;
however, the 1:2 ratio of Pd(OAc)2:DPPF proved to be a general and optimal
choice.
(13) The reductive elimination of acyl halide intermediates is a key step
in the Rh- or Ir-mediated carbonylation of alcohols, see: Haynes, A.;
Maitilis, P. M.; Morris, G. E.; Sunley, G. J.; Adams, H.; Badger, P. W.;
Bowers, C. M.; Cook, D. B.; Elliot, P. I. P.; Ghaffar, T.; Green, H.; Griffin,
T. R.; Payne, M.; Pearson, J. M.; Taylor, M. J.; Vickers, P. W.; Watt, R.
J. J. Am. Chem. Soc. 2004, 126, 2847-2861.
(12) Attempts to measure the saturation solubility of CO in the IL media
by mass transfer indicated only low solubility.
4576
Org. Lett., Vol. 9, No. 22, 2007

and vinyl halides reacting with a range of alcohols (primary,
secondary, tertiary) providing the ester products in good to
excellent yields, Table 2. In general, aryl bromides and
Table 2. Generality of the Carbonylation Reaction in
Trihexyl(tetradecyl)phosphonium Bromide PSIL
Figure 1. General catalytic cycle (path a) and bromide-mediated
exit opening path b via the acylbromide intermediate. Details of
the ligand exchange step in path a are removed for clarity.
provide an exit from the catalytic cycle opening an alternative
path (path b) to the product and catalyst regeneration as
shown.
The oxidative addition of Pd complexes to acyl halides is
well documented providing acyl-palladium intermediates.1a
The present hypothesis simply implies that this latter reaction
is reversible and given the PSIL conditions (i.e., high
concentration of soluble bromide) the acid halide intermedi-
ate may previously have been overlooked.
Control experiments were run to test this acid bromide
hypothesis. Under standard carbonylation conditions in the
bromide PSIL but absence of alcohol or other nucleophile,
4-bromotoluene (4 mol % of Pd(OAc)2, 8 mol % of dppf,
60 °C) remained essentially unchanged; however, GC and
GCMS analysis from this reaction readily showed the
formation of 4-methylbenzoyl bromide. A more detailed
GCMS analysis of a similar blank control run with bromo-
benzene in the bromide-containing PSIL also showed low
conversion after 8 h, but confirmed the presence of benzoyl
bromide as well as traces of benzene and benzaldehyde as
minor hydride elimination products and a trace of the
homocoupled product biphenyl. This result confirms the
existence of the acid bromide exit from the catalytic cycle:
the low yield of acid bromide is attributable to the revers-
ibility of this reaction via the well-known acyl-bromide Pd
insertion pathway. Consumption of the acid bromide in the
presence of a nucleophile (e.g., alcohol, water, or amine)
under typical conditions would make the acid bromide path
a more productive pathway, in addition to product emanating
from the standard catalytic cycle (path a), thus explaining
the observed effects. Attempts to prepare bromobenzene
through reaction of benzoyl bromide under the same control
conditions (parging with argon) failed, indicating the ir-
reversibility of the CO insertion step under these conditions
in accord with previous reports.2e
iodides are effective partners with considerably lower
reactivity being observed with aryl chlorides and triflates
under these conditions. Electron-withdrawing groups enhance
the reactivity as expected and yields drop as the steric bulk
of the alcohol increases, and slightly with the introduction
of an ortho-substituent on the ring. 2-Arylbromoethylene
The scope of the carbonylative cross-coupling reaction in
the bromide PSIL was extended by screening a series of aryl
Org. Lett., Vol. 9, No. 22, 2007
4577

gave good yields (entries 8, 11, 14, and 18) of cinnamic ester
derivatives with essentially complete (E)-geometry, similar
to results recently described by Alper et al.9c A range of
carboxylic acids and amides could be similarly obtained
through the introduction of water or a secondary amine as
the nucleophile.
recyclable catalyst is present in the PSIL. The full scope of
catalyst reprocessing remains to be investigated.
In conclusion, the phosphonium salt ionic liquid trihexyl-
(tetradecyl)phosphonium bromide has proven to be a par-
ticularly effective general reaction media for carbonylation
reactions under mild conditions, including atmospheric
pressure of CO. An interesting bromide effect was uncovered
through screening a range of ionic liquids with differing
counteranions. Control experiments showed that carboxylic
acid bromides are reaction intermediates providing a mecha-
nistic rationale for this effect and allowing an expanded view
of the overall reaction mechanism that implies a slow ligand
exchange step with the incoming nucleophile. Recyclability
of the IL and active Pd-catalyst was demonstrated. Finally,
the use of ILs as valuable reaction media in which to probe
anionic effects8f is again highlighted as a fundamental
rationale for their continued development.7
In addition to replacing volatile organic solvents, the
recyclability of IL’s is perhaps one of their greatest potentials,
in particular where this can be linked to recycling an active
IL-soluble catalyst.7,8 While the chemical yields reported in
Table 2 involve solvent-mediated product extraction, solvent-
free product isolation and recyclability of active catalyst in
the carbonylation reaction of 4-iodotoluene (Table 2, entry
1) with n-butanol were also investigated. The ester could be
directly distilled (90% isolated yield, see experimental details
in the Supporting Information) from the PSIL at this point
without the use of any volatile organic solvent. Catalyst reuse
was also investigated with this system. After the reaction,
the ionic liquid was partitioned with methanol/water (3/2)
and the ester product extracted into hexane. The initial run
gave complete conversion and buty(4-methyl)benzoate was
isolated in 93% yield from the hexane phase by using this
workup process. The IL phase containing active Pd-catalyst
was dried under vacuum and recharged with starting materi-
als with the exception of fresh Pd(OAc)2 and ligand. High
conversion of the aryl iodide was again observed and the
ester was isolated in 85% yield proving that a viable,
Acknowledgment. We thank NSERC, Cytec Canada Inc.,
and McMaster University for financial support of this work.
Supporting Information Available: Experimental pro-
cedures, characterization data, and copies of NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL702081G
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Org. Lett., Vol. 9, No. 22, 2007