Regioselective iron-catalyzed decarboxylative allylic etherification

Article abstract of DOI:10.1021/ol902291z

[Chemical Equation Presented] An anionic iron complex catalyzes the decarboxylative allylation of phenols to form allylic ethers in high yield. The allylation is regioselective rather than regiospecific. This suggests that the allylation proceeds through π-allyl iron intermediates in contrast to related allylations of carbon nucleophiles that have been proposed to proceed via π-allyl complexes. Ultimately, iron catalysts have the potential to replace more expensive palladium catalysts that are typically utilized for decarboxylative couplings.

Full text of DOI:10.1021/ol902291z

ORGANIC
LETTERS
2009
Vol. 11, No. 24
5650-5652
Regioselective Iron-Catalyzed
Decarboxylative Allylic Etherification
Rushi Trivedi and Jon A. Tunge*
Department of Chemistry and Department of Medicinal Chemistry, The UniVersity of
Kansas, Lawrence, Kansas 66045
tunge@ku.edu
Received October 4, 2009
ABSTRACT
An anionic iron complex catalyzes the decarboxylative allylation of phenols to form allylic ethers in high yield. The allylation is regioselective
rather than regiospecific. This suggests that the allylation proceeds through π-allyl iron intermediates in contrast to related allylations of
carbon nucleophiles that have been proposed to proceed via σ-allyl complexes. Ultimately, iron catalysts have the potential to replace more
expensive palladium catalysts that are typically utilized for decarboxylative couplings.
Decarboxylative allylation reactions are a powerful method
for the allylation of a wide variety of nucleophiles under
Scheme 1
neutral conditions.1 A remaining issue with decarboxylative
allylations is their reliance on relatively expensive platinum
group metals. For instance, decarboxylative etherification has
been reported to occur with Pd,2 Rh,2c and more recently
Ru-based catalysts.3,4 A single example of nickel-catalyzed
decarboxylative etherification has also been reported. How-
ever, the specific reaction conditions and yield were not
included in that report.2c Herein we report that similar
transformations can be effected with simple, inexpensive
iron-based catalysts (Scheme 1).
The first palladium-catalyzed decarboxylative etherification
was reported in 1981 and Larock later generalized the
transformation into a useful method.2b Initial attempts at
enantioselective coupling were not fruitful (<23% ee);2c
however, these reactions provided the foundation for the
recent enantioselective Ru-catalyzed decarboxylative etheri-
fication.3
In looking to utilize catalysts other than standard platinum
group metals for decarboxylative etherification, we were
drawn to the seminal iron-catalyzed allylic alkylations of
Roustan5 and more recently Plietker.6 More specifically,
Plietker has used phosphine and N-heterocyclic carbene-
modified versions of the Hieber anion to form electrophilic
allyl species from allylic carbonates. However, Plietker has
(1) (a) Shimizu, I.; Yamada, T.; Tsuji, J. Tetrahedron Lett. 1980, 3199.
(b) Tsuda, T.; Chujo, Y.; Nishi, S.-i.; Tawara, K.; Saegusa, T. J. Am. Chem.
Soc. 1980, 102, 6381. (c) Rayabarapu, D. K.; Tunge, J. A. J. Am. Chem.
Soc. 2005, 127, 13510. (d) Waetzig, S. R.; Rayabarapu, D. K.; Weaver,
J. D.; Tunge, J. A. Angew. Chem., Int. Ed. 2006, 45, 4977. (e) Waetzig,
S. R.; Tunge, J. A. J. Am. Chem. Soc. 2007, 129, 4138. (f) Weaver, J. D.;
Tunge, J. A. Org. Lett. 2008, 10, 4657. (g) Mohr, J. T.; Behenna, D. C.;
Harned, A. W.; Stoltz, B. M. Angew. Chem., Int. Ed. 2005, 44, 6924. (h)
Trost, B. M.; Bream, R. N.; Xu, J. Angew. Chem., Int. Ed. 2006, 45, 3109.
(2) (a) Guibe, F.; M’Leux, Y. S. Tetrahedron Lett. 1981, 22, 3591. (b)
Larock, R. C.; Lee, N. H. Tetrahedron Lett. 1991, 32, 6315. (c) Consiglio,
G.; Scalone, M.; Rama, F. J. Mol. Catal. 1989, 50, L11. (d) Tsuji, J.; Sato,
K.; Okumoto, H. J. Org. Chem. 1984, 49, 1341. (e) Backvall, J.-E.;
Nordberg, R. E.; Vagberg, J. Tetrahedron Lett. 1983, 24, 411.
(5) (a) Roustan, J. J.; Merour, J. Y.; Houlihan, F. Tetrahedron Lett. 1979,
39, 3721. (b) Ladoulis, S. J.; Nicholas, K. M. J. Organomet. Chem. 1985,
265, C13. (c) Xu, Y.; Zhou, B. J. Org. Chem. 1987, 52, 974. (d) Zhou, B.;
Xu, Y. J. Org. Chem. 1988, 53, 4419. (e) Eberhardt, U.; Mattern, G. Chem.
Ber. 1988, 121, 1531.
(3) Austeri, M.; Linder, D.; Lacour, J. Chem.sEur. J. 2008, 14, 5737
.
(4) Other related catalytic allylations of phenols: (a) Lopez, F.; Ohmura,
T.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 3426. (b) Evans, P. A.;
Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012
.
10.1021/ol902291z  2009 American Chemical Society
Published on Web 11/18/2009

not investigated the loss of CO2 from such allylic carbonates
as a method for decarboxylative coupling reactions. Thus,
we chose to investigate the decarboxylative allylic etherifi-
cation using iron catalysts. To begin, we compared a small
variety of catalysts for their ability to effect the decarboxy-
lative allylation of phenols (Table 1). Here the qualitative
Table 2. Scope of Phenols
Table 1. Catalyst Comparison
catalyst
solv temp, °C
time
yield, %
98
10 mol % of 1, 12 mol %
of PPh3
MTBE
80
24 h
1.25 mol % of [Cp*RuCl]4,
5 mol % of bpy
5 mol % of Pd(PPh3)4
CH2Cl2
CH2Cl2
50
rt
14 h
<15 min
96
98
rate of decarboxylative allylation, as catalyzed by PPh3-
modified Bu4N[Fe(CO)3NO)] (1) in methyl tert-butyl ether
(MTBE), was compared with those of more standard Pd and
Ru catalysts.1,7 These studies show that the order of reactivity
is Pd > Ru > Fe. While the iron catalyst was not the most
active, iron is ca. 10 000 times less expensive than either
ruthenium or palladium.8 Thus, the scope of the iron-
catalyzed decarboxylative etherification was worthy of further
investigation.
As can be seen from Table 2, a variety of phenols undergo
decarboxylative allylation in high yield. In particular, the
reaction is effective for nearly any substitution pattern about
the phenol; even sterically demanding ortho-substituted
phenolates undergo allylation, albeit at a reduced rate (entries
3, 5, 8, and 9). In addition, allyl ethers of electron-rich
phenols like 3e undergo exclusive O-allylation. Related
palladium-catalyzed allylations of 3,5-dimethoxyphenol are
often plagued by the formation of C-allylated products.9
Lastly, aryl halides are tolerated (entries 2 and 10). These
functional groups have the potential to interfere with the
analogous palladium-catalyzed reactions.
electron-withdrawing groups on the phenol like CF3 and
CO2Me. To investigate the regiospecificity of the allylation,
the product of the reaction of a cinnamyl carbonate was
compared to that derived from a 1-phenylallyl carbonate
(entries 7 and 8). As can be seen, both substrates provided
the linear product exclusively as judged by 1H NMR
spectroscopy. Thus, the reaction with aryl-substituted allylic
carbonates is regioselective. Moreover, subjecting the branched
allyl phenyl ether, (1-phenoxyallyl)benzene, to the catalytic
reaction conditions resulted in no isomerization to the linear
allyl ether 3r. Thus, the observed regioselectivity is a kinetic
selectivity and not simply the result of equilibration to the
more stable linear product. Next, we investigated the coupling
of crotyl alcohol, which provided the branched allylation
product with moderate regiocontrol and high yield (entry 9).
The isomeric branched carbonate also produced the branched
allylic ether selectively (entry 10). While the regiochemical
outcome slightly depends on the regiochemistry of the
Next, the regioselectivity of the allylation was investigated
(Table 3). In all cases, the cinnamyl carbonates preferentially
formed the linear allylic ethers in good yield (entries 2-7).
Here, one can also see that the reaction is compatible with
(6) (a) Plietker, B. Angew. Chem., Int. Ed. 2006, 45, 1469. (b) Plietker,
B. Angew. Chem., Int. Ed. 2006, 45, 6053. (c) Plietker, B.; Dieskau, A.
Eur. J. Org. Chem. 2009, 775. (d) Plietker, B.; Dieskau, A.; Mows, K.;
Jatsch, A. Angew. Chem., Int. Ed. 2008, 47, 198
(7) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6, 2603. (b) Burger,
E. C.; Tunge, J. A. Chem. Commun. 2005, 2835
.
.
(8) Approximate market prices 10/2/09: Pd ($292/oz), Ru ($90/oz), Fe
($0.01/oz) .
(9) (a) Satoh, T.; Ikeda, M.; Miura, M.; Nomura, M. J. Org. Chem.
1997, 62, 4877. (b) Kuntz, E.; Amgoune, A.; Lucas, C.; Godard, G. J. Mol.
Catal. A 2006, 244, 124.
(10) He, S.; Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 2000, 122,
190.
Org. Lett., Vol. 11, No. 24, 2009
5651

Table 3. Scope of Allyl Electrophiles
Scheme 2. Decarboxylative Allylation/Claisen Rearrangement
conditions C-allylation product is produced rather than the
O-allylation product. Once again, the regiochemistry of
allylation is independent of the starting regioisomer of the
allylic ester (2t vs. 2u). Next, we were curious whether
product 3t arose from direct C-allylation of the phenolate
or via a tandem O-allylation/Claisen rearrangement reac-
tion.1d,e,10 The mechanism of the transformation appears to
be the latter, since the O-allylated product was directly
1
observed by H NMR spectroscopy of the reaction mixture
at intermediate reaction times. Moreover, the O-allylated
product was observed to convert to the C-allylated product
3t slowly as the reaction progressed.
While the yield of 3t is only moderate, our decarboxylative
allylation is more straightforward than that for some related
C-prenylations. For instance, Nicolaou has utilized propar-
gylation followed by Lindlar reduction and Claisen rear-
rangement to control the regiochemistry of formal C-ally-
lation of phenols.11 Lastly, it is noteworthy that attempts to
utilize Pd(PPh3)4 to catalyze decarboxylative etherification
of 2t led to quantitative elimination, forming 4-methoxyl
phenol and isoprene. Thus, in this instance there is both an
economic and a synthetic advantage to utilizing an iron
catalyst for decarboxylative etherification.
starting allyl ester, the reaction is not strongly regiospecific.
Thus, the decarboxylative etherfication is best referred to as
a regioselective reaction, where the position of the oxygen
nucleophile in the product is independent of the position of
the leaving group in the reactant. This is an interesting
observation since Xu5c,d and more recently Plietker6 have
shown that the analogous iron-catalyzed allylation of carbon
nucleophiles is a regiospecific process, with nucleophilic
attack occurring to preserve the regiochemistry present in
the reactant. Thus, it appears that 1 catalyzes decarboxylative
etherification through the intermediacy of π-allyl iron
complexes, while allylic alkylation occurs through σ-allyl
iron complexes.2b,3
In conclusion, an iron-catalyzed decarboxylative allylation
of phenolates was developed. The yields of the reaction are
generally high and the iron catalyst often provides chemo-
and regioselectivities that complement those of more standard
palladium catalysts. Ultimately, the results presented herein
show that decarboxylative coupling can be accomplished with
an inexpensive iron catalyst. We are currently investigating
extensions to other decarboxylative allylations.
Lastly, we investigated decarboxylative prenylation reac-
tions, since prenyl aryl ethers are excellent precursors to
biologically active chromans.11 Interestingly, the decarboxy-
lative prenylation reaction provided the 2-prenyl phenol 3t
in moderate yield (Scheme 2). Thus, under the reaction
Acknowledgment. We thank the National Science Foun-
dation (CHE-0548081) for funding.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(11) (a) Nicolaou, K. C.; Sasmal, P. K.; Xu, H.; Namoto, K.; Ritzen,
A. Angew. Chem., Int. Ed. 2003, 42, 4225. (b) Nicolaou, K. C.; Sasmal,
P. K.; Xu, H. J. Am. Chem. Soc. 2004, 126, 5493. (c) Nicolaou, K. C.; Xu,
H.; Wartmann, M. Angew. Chem., Int. Ed. 2005, 44, 756. (d) Nicolaou,
K. C.; Lister, T.; Denton, R. M.; Gelin, C. F. Tetrahedron 2008, 64, 4736.
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