New recoverable poly(ethylene glycol)-supported C1-diamino- oligothiophene ligands for palladium-promoted asymmetric allylic alkylation (AAA) reactions

Article abstract of DOI:10.1002/adsc.200606125

A new class of chiral C₁-symmetrical diamino-oligothiophene ligands easy-grafted on a soluble polymeric support (MeOPEG₅₀₀₀) is described. The diamines were found to be effective promoting agents for the [Pd(0)]-catalysed asymmetric

Full text of DOI:10.1002/adsc.200606125

COMMUNICATIONS
DOI: 10.1002/adsc.200606125
New Recoverable Poly(ethylene glycol)-Supported C1-Diamino-
oligothiophene Ligands for Palladium-Promoted Asymmetric
Allylic Alkylation (AAA)Reactions
Marco Bandini,a,* Maurizio Benaglia,b,* Tommaso Quinto,a Simona Tommasi,a
and Achille Umani-Ronchia
a
Dipartimento di Chimica “G. Ciamician”, Università di Bologna, via Selmi 2, 40126, Bologna, Italy
Fax : (+39)-051-209-9456; e-mail: marco.bandini@unibo.it
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via Golgi 19, 20133 Milano, Italy
b
Fax : (+39)-02-5031-4159; e-mail: maurizio.benaglia@unimi.it
Received: March 22, 2006; Accepted: June 2, 2006
Dedicated to Professor Mauro Cinquini on occasion of his 65th birthday.
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A new class of chiral C1-symmetrical di-
amino-oligothiophene ligands easy-grafted on a
soluble polymeric support (MeOPEG5000) is de-
scribed. The diamines were found to be effective
promoting agents for the [Pd(0)]-catalysed asym-
metric allylic alkylation (AAA) of dimethyl malo-
nate in high yields and excellent enantioselectivity
(ee up to 99%). The supported chiral ligand was
readily recovered by precipitation and filtration was
recycled up to three times without an appreciable
loss in activity. The recycle of the organometallic
catalytic system was also investigated.
In many instances, the main goal of the immobilisa-
tion was the simplification of the reaction work-up,
the separation of the product being simpler in the
case of a supported rather than a non-supported cata-
lyst. However, with the continuing discovery of more
and more sophisticated chiral catalytic species, also
recovery and recycling will surely become an impor-
tant issue in justifying catalyst immobilisation. Immo-
bilisation is obviously convenient if the catalyst is ex-
pensive, or has been obtained after a complex synthe-
sis, or is employed in a relatively large amount. A cat-
alystꢀs instability can be another reason for immobili-
sation. Chiral catalysts do exist that slowly
decompose under the reaction conditions and release
trace amounts of by-products that must be separated
from the products. If decomposition is slow and the
catalyst is very chemically active, this phenomenon
does not markedly affect the efficiency of the catalyst
and its recycling, but product purification remains a
Keywords: asymmetric synthesis; palladium; PEG;
supported catalysts; thiophene
The design and application of new chiral catalysts for problem. Last but definitely not least, immobilisation
the synthesis of enantiomerically enriched molecules of a chiral catalyst can be used in a combinatorial ap-
have gained an ever-growing attention in the field of proach to facilitate the process of catalyst discovery
the chemical research over the last three decades.[1,2] and/or optimisation.
In this context, although the major developments in
Despite this interest, the use of chiral catalysts im-
this field have mainly concerned processes in which a mobilised on heterogeneous supports is often charac-
catalytic stereoselective system is solubilised in the re- terised by some problems; for example, they com-
action media, homogeneous catalysis suffers from a monly promote the reaction with a chemical and ste-
limited use on an industrial scale, because of the lack reochemical efficiency lower than those of the non-
of easy separation and recycling of the undesired supported catalytic systems. The immobilisation of an
components of the final product and environmental organometallic catalyst, generally obtained by anchor-
concerns.[3] The grafting of chiral ligands as well as or- ing an organic ligand on the support followed by
ganometallic complexes onto solid insoluble supports metal addition, may also suffer from the serious draw-
(heterogeneous catalysis)[4] is commonly accepted as back of metal leaching.
a promising route for the diffusion of asymmetric cat-
alytic transformations at the industry level.
To overcome these limitations, soluble organic
polymers were introduced as a valuable alternative;
Adv. Synth. Catal. 2006, 348, 1521 – 1527
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1521

Marco Bandini et al.
COMMUNICATIONS
thus a reaction promoted by soluble polymer-support- ed starting from commercially available precursors,[7a]
ed catalysts can be run under homogeneous (and the isolation of variously functionalised analogous
likely best performing) conditions while the catalyst (i.e., 1b) required a multi-step sequence[7b] and the
itself can be easily precipitated and then recovered by possibility to recover them at the end of each reaction
filtration as if it was bound to an insoluble polymer. is strongly desirable.
Among the different polymeric matrixes, poly(ethy-
In this paper, we describe a novel synthetic route
lene glycols) (PEGs) occupy a prominent position be- for the grafting of 1 to the monomethyl ether of
cause of their easy functionalisation, inexpensiveness PEG5000 (MeOPEG) and applications of the products
and unique property of being soluble in most organic in [Pd(0)]-catalysed asymmetric allylic alkylation
solvents but insoluble in a few common ones, like (AAA). Triggered by the physical properties of PEG,
Et2O or hexanes.[5]
it was possible to accomplish the asymmetric transfor-
Recently, we reported on the effectiveness of di- mations both under homogeneous and heterogeneous
amino-oligothiophene compounds (DATs, 1, Figure 1) conditions simply by choosing the proper reaction
as valuable ligands for Pd-catalysed nucleophilic allyl- media (CH2Cl2 where the ligands are completely solu-
ic alkylations.[6] Although the synthesis of unsubstitut- ble or THF for the heterogeneous version). It is
ed ligands (i.e., DAT2, 1a) can be readily accomplish- worthy of note that, to the best of our knowledge, a
PEG-supported catalyst has never been used under
heterogeneous phase conditions.
The synthetic plan involved the replacement of one
outer thiophene by a 4’-phenol ring suitable for the
anchoring to the organic polymer (2, Figure 1). Here,
to evaluate the effect of the thienyl/phenol substitu-
tion on the catalytic performances of the ligands we
prepared the C1-symmetrical 2c bearing a butoxy
group mimicking the pattern introduced by the link-
age of the PEG. Firstly we performed the desymmetr-
isation of the enantiopure scaffold by transforming
(R,R)-1,2-cyclohexandiamine (DACH) into the corre-
sponding monochlorohydrate salt (4, Scheme 1).[8]
Subsequently, the condensation of 4 with commercial-
ly available 2,2’-bithiophene-5-carbaldehyde (3a) fur-
nished the corresponding mono-imine 5a in high
1
purity (judged >95% by H NMR).
Figure 1. Damino-oligothiophene compounds (DATs).
Scheme 1. Multistep synthesis of 1c. Reagents and conditions: a) (R,R)-4/MeOH/EtOH 1/1, room temperature; b) 3c/TEA/
MgSO4/DCM; c) NaBH4/MeOH, 08C ! room temperature, 16 h.
1522
www.asc.wiley-vch.de
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1521 – 1527

Poly(ethylene glycol)-Supported C1-Diamino-oligothiophene Ligands
COMMUNICATIONS
The introduction of the 4-n-BuO-phenyl ring facili- edly increases the catalytic properties of the whole
tates the final reductive amination with aldehyde 3c, catalyst. In the light of these findings we decided to
easily obtainable through Suzuki cross-coupling (yield evaluate this peculiar electronic effect also in the
89%, see Experimental Section). The present synthet- analogous supported catalysis by synthesizing the C1
ic approach gave rise to 2c in 43% yield (2 steps).
precursor 2b.
The catalytic performance of 2c was tested by using
The syntheses of 2a and 2b were carried out follow-
the [Pd(0)]-catalysed AAA of dimethyl malonate 9 ing the synthetic plan highlighted in Scheme 1 for 2c.
with 1,3-diphenylallyl carbonate (8) as the probe reac- Here, the chemoselective condensation of (R,R)-4 to
tion (Scheme 2). Under optimal conditions, compara- commercially available 2,2’-bithiophene-5-carbalde-
ble results for 1a in terms of isolated yield and enan- hyde 3a or (2-EDOT-2’-thienyl)-5-carbaldehyde 3b[7b]
tiomeric excess (yield 99%, ee 93%) were obtained, furnished the corresponding mono-imines 5a, 5b
proving the reliability of our approach.
(90% and>90%, respectively) that were subsequent-
Recent investigations addressed toward the possi- ly transformed to the bis-imines 6a/6b in the presence
bility of fine-tuning the features of these chiral Pd- of the phenol-thienylaldehyde 3d (see Supporting In-
complexes by molecular remote control (MRC)[7b] formation for details). The final ligands were easily
pointed out that the introduction of electron-donating obtained by reduction of 6a/6b with NaBH4 in 40%
groups both on the outer and inner thienyl unit mark- and 60% yield, respectively (Scheme 3, reaction a).
Following the well-developed methodology em-
ployed in the synthesis of poly(ethylene glycol)-sup-
ported chiral organic[9] as well as organometallic cata-
lysts[10], C1 DAT ligands were anchored to a properly
modified PEG derivative. The reaction of 1.1 mol
equivs. of ligands 2a/2b with 1 mol equiv. of the readi-
ly available mesylate 11[11] in the presence of Cs2CO3
(DMF, 558C, 48 h) afforded the PEG-supported li-
gands 7a and 7b in quantitative yield (Scheme 3, reac-
tion b).
In analogy with the homogeneous DATs applica-
tions,[7] we chose to test the new PEG-C1-DATs 7a
and 7b in the model reaction depicted in Scheme 2,
and we examined the generality of the protocol by ap-
plying the supported catalysts to different linear hin-
dered and unhindered allyl carbonates (8a–c).
Scheme 2. Asymmetric allylic alkylation: model reaction.
Scheme 3. Synthesis of 2a,b and their grafting to MeOPEG5000. Reagents and conditions: a) (R,R)-4/MgSO4/EtOH:MeOH,
room temperature, 48 h; b) 3c/TEA/MgSO4/DCM; c) NaBH4/MeOH, 08C ! room temperature, 16 h; d) Cs2CO3, DMF,
558C, 48 h.
Adv. Synth. Catal. 2006, 348, 1521 – 1527
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1523

Marco Bandini et al.
COMMUNICATIONS
Table 1. Optimization of reaction conditions for allylic sub-
stitution with supported Pd(II)-7a and 7b.[a]
Moreover, the supported catalyst displayed the gen-
erality in scope of homogeneous DATs with particular
regard to acyclic allyl carbonates. Here, hindered aro-
matic substrate 8b underwent smoothly the allylic al-
kylation in 80% yield and 99% ee (entry 8), and also
in the case of the more challenging aliphatic carbon-
ate 8c comparable enantioselectivity with respect to
1a was recorded (ee 78% vs. 77%).[7a]
Finally, inferior results in terms of chemical and op-
tical outcomes were obtained with 7b that proved to
be less effective than 7a for both aromatic as well as
aliphatic substrates (entries 5 and 10). We tentatively
ascribed the drop in catalytic performace to deleteri-
ous interactions involving the EDOT pendage and
the bulk of the PEG structure that significantly limits
the necessary conformational flexibility of the anch-
ored chiral unit.
Entry L* Solvent Base
10 Yield
ee
[%][b]
[%][c]
1[d]
1a THF
BSA/
10a 96
99
KOAc
2
3
4
5
7a CH2Cl2 K2CO3
7a CH2Cl2[e] Cs2CO3
7a CH2Cl2 NaH
7b CH2Cl2 Cs2CO3
10a 80
10a 90
10a 99
10a 58
10a 98
10a 99
10b 80
10c 50
10c 41
86
95
97
82
99
97
99
78
38
Next, attempts to recover and reuse the ligand
were carried out and the results over three consecu-
tive runs are summarised in Table 2. An optimised re-
6
7
7a THF
7a THF
Cs2CO3
NaH
8
9
10
7a CH2Cl2 Cs2CO3
7a CH2Cl2 Cs2CO3
7b CH2Cl2 Cs2CO3
Table 2. Recycling of (R,R)-7a in the Pd-catalysed allylic
substitution with carbonate 8a.[a]
[a]
All the reactions were carried out at room temperature
by using a 1:1 L:Pd ratio (24 h).
Yield [%][b]
ee [%][c]
[b] Isolated yields after flash chromatography.
Entry
Time [h]
[c]
Determined by chiral HPLC (10a, 10b) and by chiral GC
1
2
3
24
24
24
90
91
84
95 (S)
92 (S)
92 (S)
for 10c. The absolute configuration was assigned by com-
parison with the known optical rotation value.
[d] [Pd2
(dba)3]·CHCl3 was used as the palladium source.
N
[e]
[a]
Sodium malonate was prepared in THF and then added
to the CH2Cl2 reaction mixture (CH2Cl2:THF, 3:1).
All the reactions were carried out in CH2Cl2 at room tem-
perature, [Pd(II)]:7a = 1:1 and Cs2CO3 as the base. [Pd-
(h3-C3H5)Cl]2 (5 mol%) was added for each consecutive
run.
[b] Isolated yields after flash chromatography.
Determined by HPLC analysis with chiral column (Chir-
[c]
In Table 1 we summarise a collection of results ob-
tained during the survey of reaction conditions. To
ensure truly homogeneous conditions we initially
tested the in situ formed catalyst[12] [Pd(II)-7a]
CH2Cl2 with a range of base systems (entries 2–4). To
alcel AD). The absolute configuration was assigned by
comparison with the known optical rotation value.
our delight, no loss of activity was recorded with the action work-up that involves removal of the insolu-
structurally modified 7a (10 mol%) respect to the bles (Cs2CO3 and [Pd(0)] species) by filtration on
non-supported ligand 1a (entry 1). In particular, the celite, allowed 7a to be recovered (65–70%) after
employment of Cs2CO3 and NaH furnished 10a in> each run and effectively reused in the AAA of 8a
90% yield with enantiomeric excesses up to 97% (en- with 9 without appreciable loss of activity.
tries 3 and 4). Noteworthy, these values are among
the highest reported to date for AAA in the presence by comparing the H NMR spectrum (CD3CN, room
of PEG-supported catalysts.[13] temperature) of the isolated cationic [Pd(h3-
Then, the coordination mode of 7a was investigated
1
Due to the fact that THF resulted to be the solvent Ph2C3H3)]-7a complex (see Experimental Section)
of choice for the protocol with ligand 1a/b, we investi- with that of [Pd(h3-Ph2C3H3)]-1a. The comparable
gated the possibility to employ [Pd(II)]-7a in such a chemical shifts of the diagnostic allyl unit {supported
reaction medium (heterogeneous catalysis). Remarka- complex: d=4.68 (d, J=9.2 Hz, 1H), 5.48 (d, J=
bly, the reaction was successful giving 10a with yield 9.2 Hz, 1H), 6.60–6.72 (m, 1H) to be compared with
(98%) and stereoselectivity (ee 99%) comparable to [Pd(h3-Ph2C3H3]-1a: d=4.64 (d, J=9.2 Hz, 1H), 5.46
that obtained in homogeneous conditions (entry 6 vs. (d, J=9.2 Hz, 1H), 6.64–6.71 (m, 1H)}, led us to sup-
3). To our knowledge, this is the first case in which a pose an N,N-binding mode also for the supported
catalytic system can be employed in the same trans- ligand.
formation with comparably high efficiency both under
homogeneous and heterogeneous conditions.
The possibility of recovering and successively recy-
cling the supported organometallic catalytic species
1524
www.asc.wiley-vch.de
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1521 – 1527

Poly(ethylene glycol)-Supported C1-Diamino-oligothiophene Ligands
COMMUNICATIONS
was then examined. To this purpouse, when the reac- runs. We are currently examining the scope of this
tion under the model homogeneous conditions (8a/9/ class of supported ligands in different environmental-
Cs2CO3/CH2Cl2) was judged complete by TLC, anhy- ly friendly metallo-catalysed stereoselective transfor-
drous Et2O was added to the reaction crude under an mations and the results will be reported in due
inert atmosphere with the consequent precipitation of course.
the supported Pd catalyst. The slurry was then kept at
08C (ice bath) for 10 min and the liquid removed by
syringe.
Experimental Section
The solid residue was then dried under vacuum and
reused without the addition of Pd salt. This procedure
allowed us to perform up to three consecutive runs
(Table 3) although losses in activity (from 98% to
Suzuki Cross-Coupling for the Synthesis of 3b and 3c
In a 100 mL, two-necked flask 5-bromo-2-thiophenecarbal-
dehyde (2 mmol) and PdCl2(PPh3)2 (0.1 mmol) were dis-
A
Table 3. Recycling of 7a in the Pd-catalysed allylic substitu-
tion with carbonate 8a without any addition of Pd after the
first run.[a]
solved in 8 mL of DME. Then, 4 mL of EtOH were added
followed by the corresponding boronic acid (2.6 mmol) and
6 mL of Na2CO3 (2M). The reaction mixture was refluxed
overnight, then the solution was cooled at room tempera-
ture and 10 mL of H2O were added. After elimination of
the volatiles under vacuum, the aqueous phase was extract-
ed with AcOEt, dried (Na2SO4) and concentrated under re-
duced pressure. The crude product was purified by flash
chromatography on silica gel.
Entry
Time [h]
Yield [%][b]
ee [%][c]
1
2
3
24
36
48
90
46
30
95 (S)
86(S)
66 (S)
[a]
All the reactions were carried out in CH2Cl2 at room tem-
perature, by using 5 mol% of [Pd
(h3-C3H5)Cl]2 as the Pd
AHCTREUNG
source, 7a as ligand, a 1:1 L:Pd ratio and Cs2CO3 as the
base.
Synthesis of 2a,b and 2c
[b] Isolated yields after flash chromatography.
In a 50 mL two-necked flask, mono-ammonium salt (R,R)-
4[8] (1 equiv.) and aldehyde 3 (1 equiv.) were dissolved in
20 mL of a mixture of EtOH/MeOH (1/1). After the reac-
tion mixture had been stirred at room temperature for 24 h,
the solvent was removed under reduced pressure leaving the
mono-imine compound 5.
[c]
Determined by HPLC analysis with chiral column (Chir-
alcel AD). The absolute configuration was assigned by
comparison with the known optical rotation value.
30% yield) and enantioselectivity (from 95% to 66%
ee) were observed over the three cycles. These results
Imine-mono salt intermediate 5 (1 equiv.) was dissolved
under a N2 atmosphere in 15 mL of CH2Cl2. Then, TEA
are comparable to those previously reported for (2.0. equivs.), aldehyde 3c/d (1 equiv.) and MgSO4 (2.5
equivs.) were successively added and the mixture stirred at
room temperature for 32 h. After evaporation of CH2Cl2,
the crude was washed with Et2O to separate the insoluble
ammonium salts from the desired product and the solvent
evaporated under reduced pressure. Finally, 6 (1 equiv.) was
dissolved in 5 mL of MeOH and NaBH4 (5.0 equivs.) was
added portionwise. The mixture was stirred overnight at
room temperature then, 8 mL of water were added and the
product was extracted with CH2Cl2 (3”4 mL). Evaporation
of the volatiles afforded a crude 2 product that was purified
AAA reactions promoted by chiral phosphine-based
ligands linked to soluble organic polymers.[13g,h] The
formation of black insoluble, poorly stereoselective
[Pd(0)] clusters that are retained by the PEG matrix
could be responsible for the drop in catalytic per-
formaces.[14]
In summary, we have presented our preliminary re-
sults toward the recovery and the recycle of a
“young” class of chiral ligands (DATs), obtained by
grafting two phenolic-modified derivatives to by washing with 10 mL of c-hexane.
MeOPEG5000. The anchored ligands proved to be effi-
cient in Pd-catalysed AAA under homogeneous as
well as heterogeneous conditions on various sub-
Synthesis of PEG-C1-DATs (7a,b)
strates affording yields and enantioselectivities com-
parable to those obtained with the non-immobilised
catalytic species. The present strategy allowed the
almost complete recovery of the ligand (up to three
times), that was reused without appreciable loss of
chemical and stereochemical efficiency. Then, a prop-
erly optimised reaction work-up rendered possibile
also the recycling of the whole organometallic species
even if a significant erosion in chemical and stereo-
To a solution of mesylate 11 (0.9 g, 0.17 mmol) in dry DMF
(3 mL) stirred under nitrogen at 558C, caesium carbonate
(0.180 g, 0.55 mmol), and ligand 2a or 2b (0.19 mmol) were
added. The mixture was stirred for 48 h at 558C. After filtra-
tion, the reaction mixture was cooled to room temperature
to eliminate Cs2CO3, then dichloromethane (1 mL) was
added and the solution was poured into Et2O (70 mL); the
precipitated PEG-supported ligands were recovered by fil-
chemical yields was observed over three consecutive tration and washed with Et2O (20 mL).
Adv. Synth. Catal. 2006, 348, 1521 – 1527
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1525

Marco Bandini et al.
COMMUNICATIONS
by syringe. The solid residue was dried and reused in the
same flask without any further Pd addition.
Representative Procedure for Pd-Catalysed AAA
under Homogeneous Conditions (CH2Cl2)
A flamed-dried, 25 mL, two-necked flask was charged,
under a nitrogen atmosphere with [Pd
(h3-C3H5)Cl]2 (1.8 mg,
U
Representative Procedure for Pd-Catalysed AAA
under Heterogeneous Conditions (THF)
A flame-dried, 25 mL two-necked flask was charged, under
a
nitrogen atmosphere, with [Pd
(h3-C3H5)Cl]2 (1.8 mg,
A
malonate
9
(57 mL, 0.5 mmol), and Cs2CO3 (65 mg,
5·10ꢀ3 mmol), supported diamine 7 (0.01 mmol) and 1.5 mL
of anhydrous THF. The mixture was stirred at room temper-
ature for 5 min, then 8 (0.1 mmol), dimethyl malonate 9
(57 mL, 0.25 mmol), and Cs2CO3 (65 mg, 0.2 mmol) were
added sequentially. The reaction mixture was stirred over-
night at room temperature and the liquid removed by a sy-
ringe, collected and evaporated to give the crude product
which was then purified by flash cromatography.
0.2 mmol) were added sequentially. The mixture was stirred
overnight at room temperature until the reaction was
judged complete by TLC analysis. The ligand was recovered
by solvent evaporation followed by addition of Et2O
(5 mL). The solid was recovered by filtration on a sintered
glass funnel and washed with Et2O. The filtrate was evapo-
rated under vacuum to give a crude product that was puri-
fied by flash chromatography.
Representative Procedure for the Synthesis of the
7a-[Pd(h3-Ph2C3H3)]·
[BF4] Complex
A
Acknowledgements
This work was supported by M.I.U.R. (Rome), National proj-
ect “Sintesi e stereocontrollo di molecole organiche per lo svi-
luppo di metodologie innovative di interesse applicativo”,
FIRB Project (Progettazione, preparazione e valutazione
biologica e farmacologica di nuove molecole organiche quali
potenziali farmaci innovativi) and from University of Bolo-
gna.
A flamed-dried, 25 mL flask was charged with 3 mL of an-
hydrous DCM followed by 85 mg (ꢁ 0.015 mmol) of 7a and
6.6 mg (7.5·10ꢀ3 mmol) of [Pd(h3-Ph2C3H3)Cl]2. The yellow-
orange mixture was stirred for 1 h after which 4 mg of
AgBF4 (0.015 mmol) were added at once. The mixture was
then placed in the dark and stirred overnight at room tem-
perature. The insolubles were then filtered and the filtrate
reduced to 1/3 of its original volume. Cold anhydrous Et2O
(2 mL) was then added causing precipitation of the support-
ed complex as a pale-yellow solid. The slurry was kept at
08C for 30 min then filtered to recover the complex. Yield:
62 mg (ca. 71%). 1H NMR (CD3CN, 300 MHz, diagnostic
signals): d=4.68 (d, J=9.2 Hz, 1H), 5.48 (d, J=9.2 Hz, 1H),
6.60–6.72 (m, 1H).
References
[1] E. N. Jacobsen, A. Pfaltz, H. Yamamoto, (Eds.), Com-
prehensive Asymmetric Catalysis, Springer, Berlin,
1999.
[2] B. M. Trost, Proc. Nat. Acad. Sci. 2004, 101, 5348–5353.
[3] a) R. A. Sheldon, H. van Bekkum, Fine Chemicals
Through Heterogeneous Catalysis, Wiley-VCH, Wein-
heim, 2001; b) B. H. Lipshutz, B. A. Frieman, A. E.
Tomaso, Jr., Angew. Chem. Int. Ed. 2006, 45, 1259–
1264.
[4] a) N. E. Leadbeater, M. Marco, Chem. Rev. 2002, 102,
3217–3274; b) D. E. Bergbreiter, Chem. Rev. 2002, 102,
3345–3384; c) Q.-H. Fan, Y.-M. Li, A. S. C. Chan,
Chem. Rev. 2002, 102, 3385–3466.
[5] a) T. J. Dickerson, N. N. Reed, K. D. Janda, Chem. Rev.
2002, 102, 3325–3344; b) D. E. Bergbreiter, Chem. Rev.
2002, 102, 3345–3384. For a recent review on polymer-
supported organic catalysts, see: M. Benaglia, A. Pugli-
si, F. Cozzi, Chem. Rev. 2003, 103, 3401–3429.
[6] a) B. M. Trost, D. L. Van Vraken, Chem. Rev. 1996, 96,
395–422; b) G. Helmchen, A. Pfaltz, Acc. Chem. Res.
2000, 33, 336–345; c) B. M. Trost, M. L. Crawley,
Chem. Rev. 2003, 103, 2921–2943.
Recovery of the Ligand 7a (Table 2)
The crude reaction mixture was passed through a pad of
celite and washed with a mixture DCM:MeOH (95:5) in
order to remove the excess of Cs2CO3 and the black [Pd(0)]
particles. The pale yellow filtrate was concentrated under re-
duced pressure and the PEG-7a was finally recovered by
precipitation with an excess of Et2O. After filtration 70% of
the supported ligand was recovered and reused in the next
run without further purification.
Recovery of the Whole Pd-7a under Homogeneous
Conditions (Table 3)
[7] a) V. G. Albano, M. Bandini, M. Melucci, M. Monari,
F. Piccinelli, S. Tommasi, A. Umani-Ronchi, Adv.
Synth. Catal. 2005, 347, 1507–1512; b) V. G. Albano,
M. Bandini, G. Barbarella, M. Melucci, M. Monari, F.
Piccinelli, S. Tommasi, A. Umani-Ronchi, Chem. Eur.
J. 2006, 12, 667–675.
To isolate the reaction adduct and recover the organometal-
lic system, anhydrous diethyl ether was added to the reac-
tion mixture under an inert atmosphere to precipitate the
supported catalyst. After holding the mixture at 08C for
10 min, the solution was removed under an N2 atmosphere
1526
www.asc.wiley-vch.de
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1521 – 1527

Poly(ethylene glycol)-Supported C1-Diamino-oligothiophene Ligands
COMMUNICATIONS
[8] E. J. Campbell, S. T. Nguyen, Tetrahedron Lett. 2001,
42, 1221–1225.
[13] a) Y. Uozumi, H. Danjo, T. Hayashi, Tetrahedron Lett.
1998, 39, 8303–8306; b) M. Glos, O. Reiser, Org. Lett.
2000, 2, 2045–2048; c) C. Saluzzo, R. ter Halle, F. Tou-
chard, F. Fache, E. Schulz, M. Lemaire, J. Organomet.
Chem. 2000, 603, 30–39; d) Y. Uozumi, K. Shibatomi,
J. Am. Chem. Soc. 2001, 123, 2919–2920; e) O. Belda,
S. Lundgren, C. Moberg, Org. Lett. 2003, 5, 2275–2278;
f) D. Zhao, J. Sun, K. Ding, Chem. Eur. J. 2004, 10,
5952–5963; g) H. Nakano, K. Takahashi, Y. Suzuki, R.
Fujita, Tetrahedron: Asymmetry 2005, 16, 609–614;
h) H. Nakano, K. Takahashi, R. Fujita, Tetrahedron:
Asymmetry 2005, 16, 2133–2140.
[9] For selected references, see: a) M. Benaglia, G. Cele-
ntano, F. Cozzi, Adv. Synth. Catal. 2001, 343, 171–173;
b) M. Benaglia, M. Cinquini, G. Celentano, F. Cozzi, A.
Puglisi, Adv. Synth. Catal. 2002, 344, 533–542; c) M.
Benaglia, M. Cinquini, G. Celentano, F. Cozzi, Eur. J.
Org. Chem. 2004, 567–573 and references cited there-
in.
[10] a) R. Annunziata, M. Benaglia, M. Cinquini, F. Cozzi,
M. Pitillo, J. Org. Chem. 2001, 66, 3160–3166; b) M.
Benaglia, M. Cinquini, G. Celentano, F. Cozzi, Org.
Biomol. Chem. 2004, 2, 3401–3407.
[14] Indications for the presence of [Pd(0)] species embed-
ded into the organic polymer came from the dark grey
colour of the recovered PEG-supported catalyst.
[11] M. Benaglia, S. Guizzetti, C. Rigamonti, A. Puglisi, Tet-
rahedron 2005, 61, 12100–12106.
[12] Pd(p-C3H3)Cl]2 proved to be superior to [Pd(0)] spe-
G
cies in the present supported catalytic asymmetric
transformation.
Adv. Synth. Catal. 2006, 348, 1521 – 1527
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1527