Catalytic dehydrogenation of o-alkylated or o-alkoxylated iodoarenes with concomitant hydrogenolysis

Article abstract of DOI:10.1002/adsc.200700562

Palladium-catalyzed dehydrogenation of suitable chains bonded to an ortho position of an iodoarene has been achieved by two methods both involving oxidative addition of the iodoarene to palladium(0) and palladacycle formation under mild conditions.

Full text of DOI:10.1002/adsc.200700562

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DOI: 10.1002/adsc.200700562
Catalytic Dehydrogenation of o-Alkylated or o-Alkoxylated
Iodoarenes with Concomitant Hydrogenolysis
Elena Mottia and Marta Catellania,*
a
Dipartimento di Chimica Organica e Industriale and CIRCC, Università di Parma, V.le G. P. Usberti 17A, 43100 Parma,
Italy
Fax : (+39)-0521-905472; e-mail: marta.catellani@unipr.it
Received: November 30, 2007; Published online: February 14, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Palladium-catalyzed dehydrogenation of
suitable chains bonded to an ortho position of an
iodoarene has been achieved by two methods both
involving oxidative addition of the iodoarene to
palladium(0) and palladacycle formation under
mild conditions.
Reaction 1: Reaction 1 readily occurs in DMF at
1058C in the presence of Pd(OAc)2 as catalyst and
AHCTREUNG
K2CO3 as a base by treatment of o,o-diethyliodoben-
zene with norbornadiene. Yields of exo-2a up to 91%
can be attained as shown in Table 1, which reports se-
lected examples. Beside product 2a another by-prod-
uct 5a (exo, diasteroisomeric mixture) is formed in a
few percent according to Scheme 2.
The presence of triphenylphosphine (TPP) as
ligand favors the formation of compound 5a which in-
creases up to 61% when TPP is used in 4:1 molar
ratio to palladium (entries 2 and 3). While no cyclic
product is observed using substrate 1b, only com-
À
Keywords: catalysis; C H activation; dehydrogena-
tion; palladium
À
In the course of our work on catalyzed C C coupling pound 2b being isolated in 74% yield (entry 4), the
via palladacycles[1] we came across the catalytic dehy- presence of a linear chain such as the butyl one leads
drogenation of a series of primary or secondary o- to both compounds (2c and 5c) in comparable
alkyl- or o-alkoxyiodoarenes. We observed that satu- amounts (entry 5). Only the cyclic product of type 5 is
rated chains in an ortho position to iodoarenes can be formed in high yield if a methyl is present in one
converted catalytically into unsaturated chains by hy- ortho position (entries 6 and 7).[2]
À
drogen transfer to a neighboring C Pd bond. The
Scheme 3 depicts the proposed reaction course re-
result was achieved by the ways shown in Scheme 1 ferred to o,o-diethyliodobenzene and norbornadiene
which reports two representative examples. for simplicity. The reaction starts with the oxidative
We shall consider the two reactions of Scheme 1 addition of o,o-diethyliodobenzene to palladium(0) to
separately.
form intermediate A. Norbornadiene insertion into
the resulting arylpalladium bond then gives rise to
complex B[3] which is stable towards b-hydrogen elim-
ination[4] and readily effects C H activation of the
À
benzylic CH2 to give palladacycle C.[5] At this point a
hydrogen atom is transferred from the methyl of the
original ethyl group to the norbornadienylpalladium
bond, likely through a palladium hydride species D,
to give the organic product 2a, containing the unsatu-
rated chain, and palladium(0). The intermediacy of
palladacycle C is clearly suggested by the formation
of condensed cyclopentene 5a which must occur from
C by reductive elimination. Chains longer than ethyl
tend to limit hydrogen transfer from the substituted
CH2 and formation of 5 is also favored (Table 1,
À
entry 5). For the aliphatic C H bond activation that
Scheme 1.
allows the dehydrogenation process, another ortho
Adv. Synth. Catal. 2008, 350, 565 – 569
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565

Elena Motti and Marta Catellani
Yield [%][b]
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Table 1. Palladium-catalyzed reaction of o,o-disubstituted iodoarenes 1 with norbornadiene.[a]
Entry
Substrate
Ligand
Yield [%][b]
TPP
1
2
3
4
5
6
7
R1 =Et; R2 =H; 1a
1a
-
R1 =Et; R2 =H; 2a, 91[c]
2a, 60
R2 =H; R3 =Me; 5a, 6
5a, 36
5a, 61
2
4
-
-
-
1a
2a, 29
R1 =i-Pr; R2 =Ph; 1b
R1 =n-Bu; R2 =Et; 1c
R1 =Me; R2 =H; 1d
R1 =Me; R2 =Ph; 1e
R1 =i-Pr; R2 =Ph; 2b, 74[c]
-
R1 =n-Bu; R2 =Et; 2c, 50
R2 =Et; R3 =n-Pr; 5c, 44
R2, R3 =H; 5d, 94[c]
R2 =Ph; R3 =H; 5e, 92[c]
-
-
-
[a]
Molar ratio of the reaction components: iodoarene, norbornadiene, K2CO3, PdACHTER(UNG OAc)2 1:1.2:2:0.1; 1058C, 24 h, DMF as
solvent, under nitrogen; 4.4”10À3 mmol Pd
GC yield on the iodoarene.
Isolated yield.
ACHTRE(UGN OAc)2/mL DMF.
[b]
[c]
to type C palladacycle formation occurs more slowly
and there is time for the first formed double bond in
6a to react with a second molecule of iodoarene
giving the Heck-type product[8] 7a (E, exo). Thus with
o,o-diethyliodobenzene (1a) the reaction carried out
in DMF at 1058C in the presence of PdACTHRE(UNG OAc)2 as cat-
alyst and K2CO3 as a base for 24 h (Scheme 4) gives
Scheme 2.
Scheme 4.
28% of 7a in addition to 31% of 6a with 65% conver-
sion of the starting 1a. By replacing K2CO3 with a
base such as KOAc, able to favor the steps leading to
palladacycle formation (through norbornene inser-
tion),[9] however, it is possible to shift this ratio to-
wards 6a (64% with 25% 7a at 99% conversion).
Reaction 2: Analogously to reaction 1, reaction 2
(Scheme 1) occurs in DMF at 80–1058C in the pres-
Scheme 3. Proposed reaction pathway for the formation of
the dehydrogenated and cyclic products (L=TPP, solvent or
any coordinating species present in the reaction mixture).
ence of PdCAHTRE(UNG OAc)2 as catalyst and a base, in particular
substituent is required, otherwise a four-membered K2CO3 or Me3CCO2Cs. In most cases the latter per-
ring closure on the free ortho position of the aromatic forms better than the former at a substrate to palladi-
ring[6] readily occurs, aromatic C H bond activation um molar ratio of 100.[10] Iodoarenes o-substituted by
À
being usually preferred to the aliphatic one.[7]
a-branched alkyl chains or by alkoxy chains have
Very subtle factors influence palladacycle forma- been found to be reactive, as shown in Table 2. Linear
tion. With norbornene in place of norbornadiene the alkyl chains are inactive.
overall reaction slows down and the yields of exo-6a
The styrene derivatives (4) thus obtained have a re-
(Scheme 4) are lower. Apparently the process leading markable tendency to give Heck-type products,[8]
566
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Catalytic Dehydrogenation of o-Alkylated or o-Alkoxylated Iodoarenes
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Table 2. Palladium-catalyzed reaction of iodoarenes o-substituted by a-branched alkyl chains or alkoxy chains (3) in the
presence of Me3CCO2Cs as a base.[a]
ArI
Dehydrogenation product 4 (yield [%][b])
4a (45)
Heck-type product (yield [%][b,c]
)
3a
8a (25)/9a (20)[d]
3b
3c
3d
4b (15, 10)
4c (2)
8b (27)/9b (15)[e]
10 (85 [E, 65; Z,
20])[f]
11 (67 [E, 60; Z,
4d (15)
7])[f]
4e (85 [E, 68; Z,
3e
17])[g]
[a]
Molar ratio of the reaction components: iodoarene, Me3CCO2Cs, Pd
nitrogen; 2.2”10À3 mmol Pd
(OAc)2/mL DMF.
GC yield.
Products formed by reaction of ArI with the dehydrogenation product.
A 6% of a product resulting from reaction of ArI with 9a was also isolated and characterized as 1-{2-phenyl-3-[2-(2-pro-
pyl)phenyl]prop-2-enyl}-2-(2-propyl)benzene.
Compound 9b was isolated in a ca. 3:1 mixture with an isomer (ca. 5%) identified as E-2-(2-butyl)-1-(3-phenylbut-1-
enyl)benzene.
ACHTRE(UNG OAc)2 1:2:0.01; 1058C, 8 h, DMF as solvent, under
AHCTREUNG
[b]
[c]
[d]
[e]
[f]
Another positional isomer not further investigated is present in the reaction mixture in small amount.
Reaction carried out at 808C.
[g]
however, by further reaction with the starting iodo picted in Scheme 5. Oxidative addition of the iodoar-
derivatives 3.[11]
ene to palladium is the first step. This is followed by
The very subtle effects involved in this reaction are formation of a palladacycle which must be five-mem-
clearly evidenced by comparing the reactivity of o- bered when the o-isopropyl chain is involved (in con-
ethyliodobenzene and o-n-propyliodobenzene, which trast to the previously shown type 1 reaction, where
do not form the double bond[12] and o-isopropyliodo- the intermediate palladacycle is likely to be six-mem-
benzene which does, owing to the presence of an ad- bered).[2] The formation of six-membered palladacy-
ditional methyl group in the alkyl chain able to favor cles, however, cannot be excluded at present for other
ring formation (Scheme 5).
substrates. Five- or six-membered palladacycles have
À
It is worth noting that if a suitable aromatic C H been proposed by Baudoin and co-workers to be in-
bond in the ortho chain is available, ring closure on termediates in the case of dehydrogenation of sub-
the aromatic carbon[13] is preferred to double bond strates containing benzylic gem-alkyl groups.[14] These
formation, thus o-(1-phenylethoxy)iodobenzene gives authors also achieved a Heck-type reaction on the de-
6-methyl-6H-benzo[c]chromene in 90% yield.
hydrogenated product, adding a second molecule of a
The reaction course appears to be clear in the case different aryl halide.[14c]
of a-branched alkyls exemplified by the reaction de-
Scheme 5. Reaction course proposal for the dehydrogenation of o-isopropyliodobenzene (L=solvent or any coordinating
species present in the reaction mixture).
Adv. Synth. Catal. 2008, 350, 565 – 569
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asc.wiley-vch.de
567

Elena Motti and Marta Catellani
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20 mL). The crude material was analyzed by GC and
1H NMR. The products were separated by flash chromatog-
raphy using hexane or mixture hexane-ethyl acetate as elu-
ents.
That palladacycles are involved in the hydrogen
transfer reactions leading to double bond formation is
further supported by the findings by Dyker[15] who
used iodoarenes containing an o-tert-butyl or an o-
methoxy group not allowing b-hydrogen elimination
to obtain the products resulting from their further re-
action with a second molecule of the iodoarene and
by Carmona[16] and Echavarren[17] who isolated the
Acknowledgements
corresponding metallacycles.
A recent paper by
This workwas financially supported by MIUR (grant No.
2006031888) and the University of Parma.
Fagnou also is worth mentioning.[18] In most cases,
however, to gain unequivocal evidence for the inter-
mediacy of five- or six-membered palladacycles an ac-
curate mechanistic investigation is required.
References
In conclusion, o-paraffinic chains in iodoarenes can
be transformed into the corresponding olefinic ones
through oxidative addition of the iodide to palladi-
um(0), palladacycle formation either with the help of
a suitable olefin or directly from alkyl chains of ap-
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propriate conformation, and hydrogen transfer to an
sp C Pd bond (Scheme 1). Since the dehydrogena-
3
À
tion products belong to the classes of styrenes and
phenyl vinyl ethers practical applications can be ex-
pected, particularly in the area of polymerization, as
already known for a-methylstyrene. Further work is
in progress to clarify the reaction scope and the
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[4] J. Sicher, Angew. Chem. 1972, 84, 177; Angew. Chem.
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Experimental Section
General Procedure for the Reaction of 2,6-
Disubstituted Aryl Iodides with Rigid and Strained
Cyclolefins
À
an aliphatic C H bond, see, for example: A. D.
Ryabov, Chem. Rev. 1990, 90, 403.
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[11] To our knowledge compounds of type 10 and 11 have
not been prepared so far under the conditions of a con-
ventional Heck reaction from aryl vinyl ethers, proba-
bly owing to the instability of the latter.
[12] Analogously, no double bond formation was obtained
under our conditions with substituents offering steric
hindrance or unsuitable conformation such as for ex-
ample o,o-diethyl and o,o-diisopropyl.
[13] For a review on intramolecular arylation of arenes, see:
L.-C. Campeau, K. Fagnou, Chem. Commun. 2006,
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[14] a) O. Baudoin, A. Herrbach, F. Guꢁritte, Angew.
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J. 2007, 13, 792; c) J. Hitce, O. Baudoin, Adv. Synth.
Catal. 2007, 349, 2054.
A DMF solution (12 mL) of the 2,6-disubstituted aryl iodide
(0.54 mmol) and the strained cyclolefin (0.64 mmol) was in-
troduced under nitrogen into a Schlenk-type flask contain-
ing PdACHTREUNG(OAc)2 (12 mg, 0.054 mmol) and the base (K2CO3,
1.1 mmol or KOAc, 2.2 mmol). The resulting mixture was
heated at 1058C under stirring for 24 h. After cooling to
room temperature, the mixture was diluted with CH2Cl2
(50 mL), washed with a 5% solution of H2SO4 (2”30 mL)
and dried over Na2SO4. The crude material was analyzed by
GC and the products were isolated by flash chromatography
using hexane as eluent.
General Procedure for the Reaction of 2-Alkyl- or
2-Alkoxy-Substituted Aryl Iodides
A
DMF solution (8 mL) of the desired aryl iodide
(1.8 mmol) was introduced under nitrogen into a Schlenk-
type flask containing Pd(OAc)2 (4 mg, 0.018 mmol) and
A
Me3CCO2Cs (842 mg, 3.6 mmol). The resulting mixture was
heated at 80–1058C under stirring for 8 h. After cooling to
room temperature, the mixture was diluted with CH2Cl2
(40 mL), washed first with a 5% solution of H2SO4 (30 mL),
then with water (30 mL) and dried over Na2SO4. In the case
of 2-ethoxyiodobenzene and 2-isopropoxyiodobenzene the
reaction mixture was washed four times only with water (4”
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Adv. Synth. Catal. 2008, 350, 565 – 569

Catalytic Dehydrogenation of o-Alkylated or o-Alkoxylated Iodoarenes
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