Arylation of allylic alcohols in ionic liquids catalysed by a Pd-benzothiazole carbene complex

Article abstract of DOI:10.1002/ejoc.200390194

The reaction of aryl bromides with allylic alcohols catalysed by a Pd-benzothiazole carbene complex, in tetrabutylammonium bromide as solvent, leads principally to β-arylated carbonyl compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390194

SHORT COMMUNICATION
Arylation of Allylic Alcohols in Ionic Liquids Catalysed by a
Pd-Benzothiazole Carbene Complex
[a]
[a]
[a]
[a]
´
Vincenzo Calo,* Angelo Nacci, Antonio Monopoli, and Michele Spinelli
Keywords: Carbenes / Palladium / Homogeneous catalysis / Allylic alcohols / Ionic liquids
The reaction of aryl bromides with allylic alcohols catalysed
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
by a Pd-benzothiazole carbene complex, in tetrabutylammo- Germany, 2003)
nium bromide as solvent, leads principally to β-arylated car-
bonyl compounds.
β-Aryl ketones are useful intermediates for the synthesis
of medicinal products such as a؊c[1Ϫ3] and therefore the
development of efficient synthetic methods is of signifi-
cant interest.
Scheme 1
Recently we reported[12] that the catalyst 1, with benzo-
thiazole carbenes as ligands,[13] efficiently catalyses the re-
gioselective arylation of 3-hydroxy-2-methylene alkanoates
(the BaylisϪHillman adducts) to β-aryl ketones in tetrabu-
tylammonium bromide (TBAB) as solvent.
Pd-catalysed arylation of allylic alcohols has been applied
by various authors for the synthesis of these
compounds.[4Ϫ9] However, these arylation reactions were
poorly regioselective as the reaction led to a mixture of car-
bonyl compounds and substituted allylic alcohols
(Scheme 1).[10,11]
Beside this drawback, the choice of aryl halides and bases
was limited to aryl iodides,[4,5,8] triflates,[11b] diazonium
salts[9e] and weak bases, since aryl bromides, by requiring
more harsh reaction conditions, led, in the case of arylation
of primary allylic alcohols, to aldol reaction of the formed
aldehydes. Moreover, toxic solvents as DMF or HMPA,
phosphanes, high palladium concentrations[8] and am-
monium salts as additive were found to be necessary.[7,9,10]
Beside the catalyst’s stability towards heat and moisture,
the reaction products could be extracted from the ionic
liquid, thus allowing the recycling of both catalyst and ionic
liquid. Though this reaction proved to be regioselective and
suitable from an environmentally point of view, the choice
of cheaper allylic alcohols as the olefinic reagent would be
more convenient.
We report here the application of the Pd catalyst 1 for an
efficient Heck reaction of aryl bromides and activated aryl
chlorides with allylic alcohols in molten TBAB as sol-
vent.[14]
[a]
Department of Chemistry, Istituto di Chimica dei Composti
As shown in Table 1, electron-rich and electron-poor aryl
bromides reacted smoothly and selectively at the 3-position
of the allylic alcohols to give, in the presence of 1 mol % of
Organometallici (Sezione di Bari),
Via Amendola 173, University of Bari, 70126-Bari, Italy
E-mail: calo@chimica.uniba.it
1382
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0408Ϫ1382 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1382Ϫ1385

Arylation of Allylic Alcohols in Ionic Liquids
SHORT COMMUNICATION
1 (based on aryl halide), 2 mol % of sodium formate as
reducing agent for PdII and sodium bicarbonate as base, β-
aryl ketones or aldehydes together with a small quantity
of the positional isomers — the α-aryl-substituted carbonyl
compounds. No unsaturated alcohols, aldol condensation
products or palladium black deposition were observed. The
efficiency of the reaction is much lower when replacing
TBAB with either DMA or butylmethylimidazolium bro-
mide [bmim]ϩ·BrϪ (runs 10,11).
Scheme 3
The regioselectivity decreased when β-alkyl- or -aryl-sub-
stituted allylic alcohols were used (Table 2). For example,
the reaction of cinnamic alcohol with p-bromotoluene gave
(run 6) an equal mixture of 3,3- and 2,3-diphenylpropanal.
Replacement of TBAB with [bmim]ϩ·BrϪ as solvent (run
7), in order to increase the regioselectivity, did not give bet-
ter results, as reaction of crotyl alcohol with bromobenzene
did not occur even after long reaction times.
Table 1. Arylation of terminal allylic alcohols in TBAB catalysed
by complex 1[a]
Run R1 R2
Ar
Ph
X
t (h) Conv. Yields[b] β:α[b]
(%) (%)
Table 2. Regioselectivity in the arylation of allylic alcohols in
TBAB catalysed by complex 1[a]
1
2
3
4
5
6
H
H
H
H
H
H
Me
C2H5 Ph
C2H5 p-MeC6H4
C2H5 p-MeOC6H4 Br 7
C2H5 p-MeCOC6H4 Cl 26 75
nC5H11 Ph
Br 5
Br 5
Br 7
Ͼ99 87
95:5
95:5
93:7
92:8
98:2
95:5
96:4
94:6
90:10
90:10
90:10
95
94
83
88
82
70
65
85
Br 5
Br 4
Br 5
94
7
8
9
Me H
Me H
Me H
C6H5
4-MeC6H4
4-MeOC6H4 Br 5
Ph
Ph
Ͼ99 94[c]
Ͼ99 91[c]
Ͼ99 96[c]
Run R1
Ar
Arylated carbonyl compound
Yields[b] (%)
t (h) β:α[b]
10[d]
11[e]
H
H
Me
Me
Br 24 50
Br 22 20
26[c]
12
1
2
3
4
Me C6H5
63
94
4
4
6
4
6
16
23
70:30
64:36
70:30
68:32
60:40
50:50
Ϫ
Me 4-AcC6H4
Me 6-MeO-2-naphthyl 84[c]
[a] Typical procedure: TBAB (3 g), allylic alcohol (6 mmol), catalyst
nPr 4-CNC6H4
93
92
75
n.r.
1 (1 mol %), HCO2Na (2 mol %), aryl halide (5 mmol), NaHCO3
5
Ph
Ph
C6H5
4-MeC6H4
[b]
[c]
[d]
(10 mmol), 130 °C.
Determined by GLC.
Isolated yields.
6
Solvent: [bmimϩ]·BrϪ. Solvent: DMA.
[e]
7[d]
Me C6H5
[a]
[b]
Reaction conditions as reported in Table 1.
Determined by
GLC. Isolated yield. [bmim]ϩ·BrϪ as solvent.
[c]
[d]
α-Alkyl-substituted alcohols (runs 7Ϫ9) also afforded α-
alkyl-β-aryl-substituted propanals regioselectively, together
with small quantities of α-alkyl-α-aryl-substituted propan-
als, the minor regioisomers, derived from the rearrangement
of a five-membered chelate intermediate[4,11c] (Scheme 2).
The recycling of the catalyst and ionic liquid was then
examined for the reaction of bromobenzene with 3-buten-
2-ol, adding a new batch of sodium bicarbonate for each
run. Unfortunately, the conversion dropped with each cycle
(Figure 1), probably due to an increase in the amount of
sodium bromide trapped in the ammonium salt which, by
rendering the reaction medium more and more viscous, de-
creases the solubility and efficiency of the catalyst.
The stability of 1 in TBAB in a phosphane-free environ-
ment, despite the observed beneficial effects exerted by qua-
ternary ammonium salts on the Heck reaction, cannot be
ascribed to a single effect such as the high polarity or
phase-transfer ability,[10e] but rather to a combination of
several factors. For example, Reetz et al.[15] have found that
Scheme 2
This procedure was extended to an efficient synthesis of reduction of a Pd salt in THF in the presence of tetraalkyl-
compounds a؊c by reaction of 3-buten-2-ol with the appro- ammonium acetate or formate gives Pd nanoparticles stabi-
priate aryl bromide (Scheme 3). For compound b, as p- lized by the large ammonium cation. Furthermore, Neghi-
bromophenol is unreactive, it was necessary to protect the shi et al.[16] and Amatore and Jutand,[17] have demonstrated
phenolic group by esterification with pivaloyl chloride be- that Pd0(PPh3)2, the proposed catalyst in the Heck reaction,
fore the C-C coupling process (see Exp. Sect.).
is unstable in the absence of halide or acetate ions, which
Eur. J. Org. Chem. 2003, 1382Ϫ1385
1383

´
V. Calo, A. Nacci, A. Monopoli, M. Spinelli
SHORT COMMUNICATION
dative addition with aryl bromides, which would render the
PdII complex more electrophilic for a fast olefin insertion.
This is conceivable since it has been calculated, for anal-
ogous Pd complexes with imidazol-2-ylidene carbenes as li-
gands, that the removal of bromide from the oxidative ad-
dition complex of aryl bromides is a strongly endothermic
process.[20] In addition, we believe that the better perform-
ance of TBAB compared with [bmim]ϩ·BrϪ (Table 1, run
10; Table 2, run 7) could be ascribed to the structural differ-
ences between the [NBu4]ϩ and [bmim]ϩ cations. Indeed,
the bulkiness of the tetrahedral ammonium ion, by forcing
the bromide ion away from the cation, renders the anion
more available for the catalyst activity. On the contrary, the
planar [bmim]ϩ cation, by binding the anion tightly,[21]
would decrease its availability for the Pd catalyst. Similar
behaviours were observed by us for different Heck reactions
and this will be published in due course.
In conclusion, while some aspects of the catalytic cycle
involving Pd-carbene complexes in ionic liquids are not well
understood, our results show that complex 1, in tetraalkyl-
ammonium bromide as solvent, is an efficient catalyst for
carbon-carbon coupling processes.
Figure 1. Recycling of catalytic system TBAB/1; reaction con-
ditions: TBAB (3 g), bromobenzene (5 mmol), 3-buten-2-ol
(6 mmol), NaHCO3 (10 mmol), NaHCO2 (0.1 mmol), catalyst 1
(0.05 mmol) at 130 °C; isolation of products by extraction with
diethyl ether; the same quantities of reagents and base were added
to the reaction mixture after each cycle
Experimental Section
General Procedure for Reactions of Allylic Alcohols with Aryl Hal-
ides: The aryl halide (5 mmol), the alcohol (6 mmol), NaHCO3
(10 mmol), NaHCO2 (0.1 mmol) and the catalyst (0.05 mmol) were
added, whilst stirring, to tetrabutylammonium bromide (3 g) at 130
°C. After the appropriate reaction time and product extraction with
diethyl ether, the ammonium salt and the catalyst can be recycled.
For compound b, p-bromophenol was protected by esterification
with pivaloyl chloride in pyridine under conventional conditions
before the C-C coupling process. The pivaloyl group was efficiently
removed under basic conditions [NaOH, MeOH/H2O (20:1), 23 °C,
20 h, 87%, m.p. 82Ϫ83 °C (ethanol), ref.[22] 79Ϫ81 °C]. The reac-
tion products were identified by comparison of their NMR and
MS spectra with those reported in the literature.
transform this complex into a more stable and catalytically
active 16-electron anionic complex such as [Pd(PPh3)2X]Ϫ.
The stabilization of catalytic systems by halide salts has also
been demonstrated by extension of the lifetime of the
Herrmann palladacycle.[18] To explain some of the ionic
liquid effects, we propose some considerations that could
explain our results. The addition of sodium formate re-
duces[19] 1 to the underligated L2Pd0 complex, which, by
reaction with TBAB, would afford an anionic and cata-
lytically active 16-electron complex [L2Pd Br]Ϫ·NR4ϩ. This
should not be surprising, since in TBAB the bromide ion,
being poorly solvated, should be a good nucleophile for pal-
ladium. The stabilizing effect is exerted not only by the bro-
mide ion, which is likely to enter the coordination shell of
underligated L2Pd0 to give the anionic complex, but also by
the large tetrabutylammonium cation. Indeed, the forma-
Acknowledgments
Work financially supported by Ministero dell’Universita e della
Ricerca Scientifica e Tecnologica, Rome, and the University of Bari
(National Project: ‘‘Stereoselezione in Sintesi Organica: Metodolo-
gie ed Applicazioni’’).
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