Catalytic performance of symmetrical and unsymmetrical sulfur-containing pincer complexes: Synthesis and tandem catalytic activity of the first PCS-pincer palladium complex

Article abstract of DOI:10.1002/chem.200800350

The synthesis and catalytic applications of a new aryl-based unsymmetrical PCS-pincer complex are reported. Preparation of the robust air- and moisture-stable PCS-pincer palladium complex 5[X] started from the symmetrical α,α′-dibromo-meta-xylene and involved the selective substitution of one bromide by PPh₂(BH₃), followed by substitution of the second bromide by SPh and subsequent introduction of the palladium. The new PCS complexes (5[X]) were employed as catalysts in two important organic transformations. Firstly, complex 5[Cl] displays high catalytic activity in aldol reactions but enters the catalytic cycle as a precatalyst. Secondly, complex 5- [BF₄] displays tandem catalytic activity in the coupling of allyl chlorides with aldehydes and imines in the presence of hexamethylditin. In these tandem catalytic reactions the first process is the conversion of allyl chlorides into trimethylallyltin (and trimethyltin chloride) with Sn₂Me₆, which is followed by catalytic allylation of aldehyde and sulfonimine substrates. In addition, we present a new catalytic process for the one-pot allylation of 4-nitrobenzalde-hyde with vinyloxirane. The catalytic performance of the novel PCS-pincer palladium complex was compared to those of its symmetrical PCP- and SCS-pincer complex analogues. It was concluded that the unsymmetrical PCS complex advantageously unifies the attractive catalytic features of the corresponding symmetrical pincer complexes including both (π-) electron-withdrawing (such as phosphorus) or (σ-) electron-donating (such as sulfur and nitrogen) heteroatoms. Thus, in the aldol reaction the PCS-pincer palladium complex 5[X] provides a high turnover frequency, while in the tandem process both reactions are catalysed with sufficiently high activity.

Full text of DOI:10.1002/chem.200800350

DOI: 10.1002/chem.200800350
Catalytic Performance of Symmetrical and Unsymmetrical Sulfur-Containing
Pincer Complexes: Synthesis and Tandem Catalytic Activity of the First PCS-
Pincer Palladium Complex
Marcella Gagliardo,[a] Nicklas Selander,[b] Nilesh C. Mehendale,[a] Gerard van Koten,[a]
Robertus J. M. Klein Gebbink,*[a] and Kµlmµn J. Szabó*[b]
4800
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4800 – 4809

FULL PAPER
Abstract: The synthesis andcatalytic
applications of a new aryl-basedun-
symmetrical PCS-pincer complex are
reported. Preparation of the robust air-
andmoisture-stable PCS-pincer palla-
dium complex 5[X] startedfrom the
symmetrical a,a’-dibromo-meta-xylene
andinvolvedthe selective substitution
N
performance of the novel PCS-pincer
palladium complex was compared to
those of its symmetrical PCP- andSCS-
pincer complex analogues. It was con-
cluded that the unsymmetrical PCS
complex advantageously unifies the at-
tractive catalytic features of the corre-
sponding symmetrical pincer com-
plexes including both (p-) electron-
withdrawing (such as phosphorus) or
(s-) electron-donating (such as sulfur
andnitrogen) heteroatoms. Thus, in the
aldol reaction the PCS-pincer palladi-
um complex 5[X] provides a high turn-
over frequency, while in the tandem
process both reactions are catalysed
with sufficiently high activity.
of one bromide by PPh2ACHTREU(GN BH3), fol-
lowedby substitution of the second
bromide by SPh and subsequent intro-
duction of the palladium. The new PCS
complexes (5[X]) were employedas
catalysts in two important organic
transformations. Firstly, complex 5[Cl]
displays high catalytic activity in aldol
reactions but enters the catalytic cycle
as a precatalyst. Secondly, complex 5-
Introduction
stable species that are easy to immobilize, these complexes
can be appliedas the core units of robust andsustainable
catalysts. Design of such economically andenvironmentally
benign reusable catalytic systems represents one of the
greatest challenges in modern organic synthesis.
Aryl-basedmonoanionic, ECE-pincer ligasn—d[C
6H3-
ACHTREUNG
(CH2E)2-2,6]ꢀ, where E=NR2, PR2, AsR2, OR, SR or SeR
(Scheme 1a)—are a versatile class of organic species, thanks
to their unique properties in binding a metal ion through a
ꢀ
strong M C s-bondandin forming two metallacycles, repre-
[1]
ꢀ
senting M E coordination, with this bond in common. The
properties of the metal centre in an ECE-pincer complex
can be controlledboth by the nature of the E-donor andby
the various substituents R on the E-group, as well as by the
nature of the para-substituent on the aryl ring of the pincer
itself.[2] A variety of ECE-pincer metal complexes display in-
teresting activities as catalysts in various synthetically impor-
Scheme 1. General formula for aryl-baseda) symmetrical andb) unsym-
metrical pincer complexes.
ꢀ
ꢀ
tant organic reactions including C C andC X bond-forma-
tion reactions.[2,3] The fact that the aryl-basedECE-pincer
metal complexes can be easily para-functionalized(Z in
Scheme 1) has allowedexploration of their use as immobi-
lizedcatalysts on various soluble andinsoluble supports, in-
cluding silica,[4] polymers,[5] functionalized dendrimers,[6] por-
phyrins,[7] Buckminsterfullerenes,[8] peptides[9] anden-
zymes.[10] Because aryl-basedpincer complexes are highly
ECE-pincer palladium complex catalysis[4,11–14] has recent-
ly been focusedon two particularly important application
areas: aldol reactions[4e,12] andtransformations involving al-
lylmetal compounds.[13] Symmetrical aryl ECE-pincer metal
catalysts (Scheme 1a) have been appliedexclusively in these
catalytic transformations, because of the stability, modularity
andrelatively simple availability of these species. It was
found[11–14] that the electronic properties of the heteroatoms
in the side arms have a particularly powerful influence on
the selectivities andreactivities of the pincer palladium cata-
lysts in the above reactions. However, previous studies on
aldol reactions have also indicated that there are considera-
ble mechanistic differences between complexes, depending
on the s-donor/p-acceptor properties of the heteroatom-
s.[11,12i–j,14] In various cases, this leads to catalysts with differ-
ent selectivities andactivities. Allylations of aldehydes and
imines, for example, are readily catalysed by PCP-pincer
palladium complexes, whereas complexes with s-donating
[a] Dr. M. Gagliardo, Dr. N. C. Mehendale, Prof. Dr. G. van Koten,
Prof. Dr. R. J. M. Klein Gebbink
Chemical Biology & Organic Chemistry, Faculty of Science
Utrecht University, Padualaan 8, 3584 CH Utrecht (The Netherlands)
Fax : (+31)302523615
E-mail: r.j.m.kleingebbink@uu.nl
[b] N. Selander, Prof. K. J. Szabó
Department of Organic Chemistry, Arrhenius Laboratory Stockholm
University, 10691 Stockholm (Sweden)
Fax : (+46)8154908
E-mail: kalman@organ.su.se
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2008, 14, 4800 – 4809
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4801

K. J. Szabó, R. J. M. Klein Gebbink et al.
heteroatoms (NCN andSeCSe) have idsplayedlower (if
any) catalytic activity.[13a–d] Interestingly, formation of allyl-
metal species proceeds smoothly with NCN, SCS and SeCSe
complexes, but PCP complexes display very low activi-
ty.[13d,f–k]
These observations promptedus to synthesise andexplore
the catalytic activities of a novel class of pincer palladium
catalysts using combinations of s-donor/p-acceptor effects in
the pincer ligands. A possible way to accomplish this goal is
to use the unsymmetrical ECE’-pincer complexes shown in
Scheme 1b.
Results and Discussion
Synthesis of the unsymmetrical PC(H)S-pincer pro-ligand:
The synthesis of symmetrical pincer arene ligands typically
starts from a,a’-dibromo-meta-xylene (1, Scheme 2) by nu-
cleophilic displacement of the benzylic bromines. By appli-
cation of excesses of NR2-, PR2-, SR- or other nucleophiles
the corresponding symmetrical ECE-pincer ligand can be
[1–3]
obtainedin usually excellent yields.
As the two bromines
in 1 are symmetrically equivalent, synthesis of unsymmetri-
cal ECE’-pincer ligands requires selective and sequential nu-
cleophilic substitution of the benzylic leaving groups, which
is obviously a more challenging task.
The first unsymmetrical PCN-pincer palladium complexes
[3b,15a]
were reportedby Dupont, Monteiro andco-workers
These complexes, generatedby chloropalladation of hetero-
substitutedalkynes, provedto be highly reactive catalyst
.
precursors in coupling of arylboronic acids with aryl chlor-
ides. Aryl-based unsymmetrical (PCN) pincer metal (i.e.,
rhodium) complexes have also been reported by Milstein
[15b–d]
andco-workers,
andudring the preparation of this
paper an excellent methodfor the synthesis of PCN-pincer
palladium complexes was reported by Song and co-work-
ers.[15e]
In order to study the composite effects of electron-with-
drawing and -donating side arms in palladium-catalysed
aldol reactions[12] andtransformations involving allylmetal
compounds,[13] we have designed a new aryl-based pincer
complex catalyst. Considering the synthetic aspects of ob-
taining such a complex (see below), we chose phosphorus as
p-acceptor heteroatom andsulfur as the s-donor one to
make up a PCS-pincer complex (Scheme 1b, E=SPh, E’=
PPh2). We employed the corresponding palladium complex
as catalyst in the aldol condensation of methyl isocyanoace-
tate with benzaldehyde, as well as in tandem catalytic trans-
formations of allyl chloride or vinyloxirane substrates with
aldehyde and sulfonimine reagents. The major focus of this
study is on the mechanistic aspects of having two electroni-
cally different donor atoms (phosphorus and sulfur) present
in the pincer ligand. Moreover, it was also of interest to see
whether the PCS-pincer palladium complex would combine
the different activities andselectivities of PCP- andSCS-
Scheme 2. Synthesis of the PCHSꢀpincer arene 4.
Pro-ligand 4 was preparedin three steps from commer-
cially available a,a’-dibromo-meta-xylene (1, Scheme 2).
ꢀ
pincer palladium complexes in the corresponding C Sn and
ꢀ
C C coupling reactions discussed and could thus lead to a
Treatment of 1 with one equivalent of Li-PPh
paredin situ) yieldeda mixture containing monophosphine
(63%) andipdhosphine [C 6H4A{CH2P(BH3)Ph2}2-1,3]
2ACHTRE(UNG BH3) (pre-
catalytic tandem reaction. This latter aspect is particularly
interesting because previous attempts to perform tandem
catalytic reactions with a single, symmetrical ECE-pincer
complex failed, and synthetically useful procedures could
2
C
ACHTREUNG
(12%), together with unreacted 1 (25%). This mixture of
compounds was used without further purification. Full con-
version of the benzylic bromides into thioethers was ach-
ievedby treatment of the mixture with an excess of thiophe-
nol in the presence of K2CO3. Separation of the resulting
borane-protectedPC(H)S pro-ligand 3 from the symmetri-
cal SCHS- andPCHP-pincer arenes was carriedout by
column chromatography. Subsequent deprotection of the di-
phenylphosphino-BH3 moiety in 3 with HBF4·OEt2, fol-
only be performedby the simultaneous use of two different
[13d]
(NCN andPCP) complexes.
In the reference reactions,
we employedsymmetrical SCS- (Scheme 1a, E =S) andin
some cases PCP-catalysts under the same reaction condi-
tions as the PCS-pincer palladium catalyst. As the perfor-
mance of the SCS-complexes in many relatedcatalytic trans-
formations have not yet been explored, we have also been
able to present some new interesting applications with this
system.
lowedby a basic workup, gave the PC(H)S-pincer arene
4
as an air- andmoisture-sensitive white solid. In the 1H NMR
spectrum of 4, recorded in CDCl3, the benzylic protons are
foundas a singlet at 4.02 ppm (SCH ) andas a singlet at
2
4802
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4800 – 4809

Catalytic Activity of the First PCS-Pincer Palladium Complex
FULL PAPER
3.39 ppm (PCH2). The 31P{1H} NMR spectrum shows a sin-
glet at ꢀ7.23 ppm (PPh2), whereas the 13C NMR spectrum
of 4 (in CDCl3) shows a doublet at 35.99 ppm (1JC,P
=
15.9 Hz) for the benzylic PCH2 carbon.
Synthesis of neutral and cationic PCS-pincer PdII com-
plexes: The cationic PCS–PdII complex 5
ACHTRE[UNG BF4] was prepared
ꢀ
by electrophilic C H activation upon treatment of 4 with
[16]
[Pd
G
G
(Scheme 3). Complex 5ACHTRE[UNG BF4] was
Scheme 4. Aldol condensation reaction between benzaldehyde (8a) and
methyl isocyanoacetate (9). Turnover frequency (TOF) is given as mol of
product per mol of catalyst in the first hour.
[BF4] andneutral 5[Cl] PCS–PdII com-
Scheme 3. Synthesis of ionic 5CAHTREUNG
plexes.
as such is indeed the catalyst for this reaction, whereas the
SCS-pincer palladium complex 6[Cl] is in fact a pre-cata-
lyst.[4e] Thus, complex 6[Cl][4e] andthe PCS-complex 5[Cl]—
but not 7[Cl]—are convertedby the methyl isocyanoacetate
substrate 9 into the corresponding 1:1 isocyanide insertion
products 11a and 11b (Scheme 5).
readily converted into the neutral 5[Cl] by treatment with
excess NaCl in an acetonitrile/water mixture (Scheme 3).
Both complexes were isolatedas air-stable, yellow solids,
which can be storedwithout change for months in air at am-
1
bient temperature. The H and 31P NMR data for 5
A
5[Cl] are similar andconsistent with binding of the PCS-
pincer ligand in a terdentate fashion. The downfield shift of
the single resonance for the benzylic SCH2-protons in the
1H NMR spectrum of 5
ACHTREU[NG BF4], relative to that in the free
arene 4, confirms coordination of the S-donor atom to the
palladium centre. This resonance is broadened as a result of
fluxional behaviour attributedto various processes such as
ꢀ
reversible Pd S bondbreaking andformation, andpyrami-
dal inversion at the sulfur atom. These processes lead to iso-
mers in which the phenyl group coordinated to the S-centre
occupies either an axial or equatorial position.[17] The pres-
ence of an apparent molecular symmetry plane (the palladi-
um coordination plane) is reflected in the enantiotopicity of
the benzylic PCH2 protons. These appear as a doublet in the
1H NMR spectrum, due to coupling with the phosphorus
centre. The 31P NMR spectrum shows only one resonance at
ꢀ
Scheme 5. Insertion of methyl isocyanoacetate into the Pd C bondof the
neutral [PdCl
A
ꢀ
Insertion of an isocyanide into the M C bondof a cyclo-
[4e,11,12i–j]
metallatedcompoundhas been extensively studied
and has also been documented for ECE-pincer palladium-d8
complexes (NCN[12i–j] andSCS [4e,14]). The fact that PCP-
pincer complex 7[Cl] appears to be stable towards inser-
49.7 ppm for 5
ACHTREUNG
tion[12j] has been ascribedto the stronger P Pdcoordination
ꢀ
A
G
U
G
of the two ortho-(diphenylphosphino)methyl substituents
ꢀ
ꢀ
Catalytic performance of 5[Cl] as pre-catalyst in an aldol
condensation: The catalytic activities of the new PCS-pincer
complex andthose of the known SCS- andPCP-pincer com-
plexes 5[Cl], 6[Cl][14] and 7[Cl][18] were comparedas Lewis
acid pre-catalysts in the aldol condensation reaction be-
tween methyl isocyanoacetate (9) and benzaldehyde (8a,
Scheme 4). The data reported in Scheme 4 show that PCS
complex 5[Cl] is the fastest catalyst (entry 1), with a trans/
cis ratio of the product comparable to that obtained when
the reaction is carriedout with SCS-pincer palladium com-
plex 6[Cl] (entry 2). In contrast with these results, the PCP-
catalyst is the slowest, also giving a different cis/trans ratio
of the products. Previous studies[4e,12j] have shown that 7[Cl]
relative to the Pd N and Pd S bonding in the correspond-
ing NCN- andSCS-pincer palladium(II) complexes. Recent-
ly we have shown[4e,12i–j] that a likely reaction mechanism for
this insertion reaction involves coordination of the isocya-
nide as a ligand cis to the aryl C atom in the symmetrical
ECE-pincer palladium complex (E=NMe2 or SPh), which
may only occur through prior decoordination of one or both
of the ortho-ligands. These findings prompted us also to
study the reactivity of PCS complex 5[Cl] towards alkyl iso-
cyanide 9 in CH2Cl2. It was foundthat PCS complex 5[Cl]
readily reacted with isocyanide 9 to afforda quantitative
yieldof complex 11a (Scheme 5), incorporating two isocya-
noacetate molecules. One of the isocyanoacetates has insert-
Chem. Eur. J. 2008, 14, 4800 – 4809
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4803

K. J. Szabó, R. J. M. Klein Gebbink et al.
1
ꢀ
edinto the Pd C bond, whereas the second one is h -C-co-
ordinated to the palladium centre.
cesses. On the contrary, allylation of aldehydes and imines
(Scheme 6, 14a ! 16/17) can be performedwith much more
efficiency with PCP-catalysts than with the corresponding
NCN- or SeCSe-catalysts.[13d] Accordingly, we anticipated
Complex 11a was characterisedby elemental analysis and
by IR andNMR spectroscopy. The 1H NMR spectrum of a
solution of 11a in CD2Cl2 showedpatterns pointing to the
presence of both insertedandcoordinatedmethyl isocya-
noacetate. The singlet methylene hydrogen signal at
3.52 ppm is indicative of a non-coordinated CH2SPh group,
whereas the doublet (2JH,P =10.8 Hz) of the methylene hy-
that with PCS-pincer palladium catalyst 5CAHTRE[UGN BF4] it shouldbe
possible to perform both catalytic processes in a tandem se-
quence. Indeed, a tandem catalytic coupling of allyl chlor-
ides (12a and 12b) andvinyloxirane ( 18) with aldehyde 8b
or sulfonimine 15 reagents couldbe achievedwith hexame-
thylditin (13) in the presence of catalytic amounts (5 mol%)
1
drogen at 4.25 ppm for the CH2PPh2 group in the H NMR
spectrum, as well as the downfield singlet resonance at
47.8 ppm (cf. ꢀ7.2 ppm for the free PCHS-pincer arene 4) in
the 31P{1H} NMR spectrum, are consistent with a coordinat-
of 5ACHTRE[UNG BF4] (Schemes 6, 7, Table 1). These reactions resulted
edCH PPh2 group. Further confirmation of the formation
2
of a 1:1 insertion complex was provided by solution IR spec-
tra, which showedabsorptions for a C-coordinated isocya-
ꢀ1
ꢁ
nide [n˜
for the imidoyl moiety [n˜
(C N)] at 2230 cm (vs. 2166 cmꢀ1 for free 10) and
(C=N) at 1627 cmꢀ1.
ꢀ
The rapidinsertion of 9 into the Pd C bondof complex
5[Cl] contrasts with the stability of 7[Cl] towards this re-
agent andhas been ascribedto the more labile coordination
ꢀ
ꢀ
of the Pd S bondin 6[Cl] relative to that of the Pd P one.
As a consequence, in 11a it is the S-donor ligand that is the
non-coordinated one.
Scheme 6. Tandem catalytic approach for stannylation of allyl chlorides
followed by allylation of aldehyde and imine substrates 8b and 15. The
catalyst employedin this process, [Pd] cat, is either complex 5
plex 6[BF4].
ACHTRE[UNG BF4] or com-
With regard to the mechanistic details of the aldol reac-
AHCTREUNG
ꢀ
tion catalysedby 5[Cl] it seems likely that prior Pd S bond
cleavage occurs with h1-coordination of the incoming methyl
isocyanoacetate (9). This is followedby insertion of the iso-
1
ꢀ
cyanide into the Pd C bond, which is followed by h -coordi-
nation of the secondmolecule of 9 to give 11a (cf. reaction
in Scheme 5). Subsequently, it is the h1-coordinated isocya-
noacetate (9) molecule that then undergoes the aldol reac-
tion. Consequently, the resulting isocyanoacetate (9) inser-
tion compounds (11a–b) are the active catalysts in the aldol
reaction in the cases of PCS (5[Cl]) andSCS ( 6[Cl]) which
in fact are true pre-catalysts. In contrast, the PCP-pincer
complex 7[Cl] follows a different reaction coordinate involv-
ing halide displacement and h1-C coordination of a methyl
isocyanoacetate (9).[12j]
The catalytic results obtainedwith complexes 5[Cl], 6[Cl]
and 7[Cl] in this aldol condensation show how changes in
the nature of the pincer liganddonor arms can affect the re-
activity of the corresponding metal complexes. In this specif-
ic case, changing the arms from symmetrical sulfur heteroa-
toms (6[Cl]) to symmetrical phosphorus heteroatoms (7[Cl])
alters the direct interaction/reaction of these complexes with
9, andas a result alters the mechanism of the catalysedreac-
tion, resulting in different activities (TOFs and product se-
lectivities).
Scheme 7. Tandem catalytic allylation of 8b with vinyloxirane (18) in the
presence of 5[BF4] or 6[BF4] as catalyst.
A
ACHTREUNG
in formation of homoallyl alcohols (16a–c) andhomoallyl
amines (17a–b) via intermediate formation of allylstannanes
(14a). These processes couldbe performedunder mildcon-
ditions (408C) as genuine one-pot reactions in a single op-
erational step. Accordingly, all reagents (12, 13, 8b/15 and
ionic catalyst 5ACHTRE[UNG BF4]) were mixedtogether at the beginning
of the reaction, andafter the allottedreaction time (16 h)
the products (16 or 17) were isolated. The reactions with
allyl chloride (12a) proceeded cleanly and with relatively
high isolatedyields of 63–78% (entries 1 and3). When a
substituted allyl chloride (such as cinnamyl chloride, 12b)
was used, the yields dropped slightly (59–60%), but they
still remained respectable, considering that the product is
formedin a tandem catalytic process (entries 5 and7).
SCS- and the PCS-pincer complexes as catalysts for tandem
catalysis: Recent reports showed[13d,f–i] that NCN- and
SeCSe-pincer palladium complexes (Scheme 1a, E=N, Se)
are excellent catalysts for preparation of allylmetal species,
such as allylstannanes (Scheme 6, 12 ! 14a) andallylboro-
nates, whereas the PCP-pincer palladium complexes
(Scheme 1a, E=P) are less efficient catalysts in these pro-
The diastereoselectivity of the reaction is poor in the case
of allylation of 4-nitrobenzaldehyde (8b, entry 5), but it is
rather promising for allylation of sulfonimine 15 (entry 7).
The major diastereomer obtained is the anti form in the
case of allylation of 8b andthe syn form in that of allylation
of 15. Previously, we have studied[13b,l] the roles of steric and
electronic interactions in determining the stereoselectivity in
4804
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4800 – 4809

Catalytic Activity of the First PCS-Pincer Palladium Complex
FULL PAPER
Table 1. Tandem catalytic reactions in the presence of symmetrical (6ACHTERU[NG BF4]) andunsymmetrical ( 5ACHTRE[UGN BF4])
pincer complexes as catalysts.
the SCS-pincer complex 6ACHTREUNG[BF4]
are particularly high for allyla-
tion of aldehyde 8b, while the
stereoselectivity obtainedwith
12b as allyl substrate is even
higher than with the PCS-
Entry
Allyl
Electro
phile
Cat.
[8C]/[h][b]
Product
Yield [%][c]
dr[d]
reagent
1
2
3
5
6
5
N
40/16
40/16
40/16
63
80
78
–
–
–
pincer
complex
5ACHTREUNG[BF4]
(entry 6). However, in the ally-
lation reaction of sulfonimine
15 the PCS-pincer complex 5-
12a
12a
12a
8b
16a
AHCTREUNG
AHCTREUNG
17a and 17b (entries 3–4 and
7–8) are formedin higher yields
4
5
6
8b
8b
8b
6
5
6
40/16
40/16
40/16
17a
16b
73
59
74
–
with PCS catalyst 5
and60%) than with the SCS
catalyst 6[BF4] (73 and48%).
ACHTREU[NG BF4] (78
AHCTREUNG
3:1
9:1
In particular, when the tandem
reaction of 12b and 15 was cat-
alysedwith SCS catalyst 6ACHTREUNG[BF4]
12b
12b
12b
(entry 8), a substantial amount
of cinnamylstannane (14a, R=
Ph) was present in the crude re-
action mixture. This finding in-
dicates that the allylation pro-
cess (Scheme 6, 14 ! 16) of the
imine by cinnamyl stannane
proceeds very slowly in the
7
15
5
40/16
60
1:5
8
15
8b
8b
6
5
6
40/16
20/16
20/16
17b
16c
48
46
57
1:4
5:3
3:1
9[e]
10[e]
18
presence of 6
We have also succeeded in
performing (Scheme 7)
ACHTRE[UNG BF4] as catalyst.
[a] In a typical reaction 5 mol% catalyst was employedin THF solvent. [b] Reaction conditions: reaction tem-
perature/time. [c] Isolated yield. [d] Diastereomeric ratio: anti/syn. [e] LiOAc (10 mol%) andwater (2 equiv)
were also added to the reaction mixture.
a
tandem catalytic coupling reac-
tion of vinyloxirane (18) with
pincer-complex-catalysedallylation reactions. These studies
have clearly shown that the allylation of aldehydes (such as
8b) proceeds with anti selectivity, while the opposite regio-
selectivity (syn selectivity) occurs for the corresponding pro-
cess with imine substrates (such as 15). These previous ob-
servations[13b,l] are in perfect agreement with the stereoselec-
8b (entries 9 and 10). This reaction proceeds under reaction
conditions similar to those used for the allylation with allyl
chlorides, except that catalytic amounts of LiOAc and water
were added to the reaction mixture. Without this addition of
LiOAc andwater, vinyloxirane ( 18) is decomposed by the
catalysts, probably through opening of the epoxy functional-
ity. The coupling reaction of aldehyde 8b with vinyloxirane
(18) leads to formation of an unprotected homoallyl diol
(16c), which is a useful synthetic intermediate. As far as we
know, this reaction represents the first example of a palladi-
um-catalysedcoupling of a vinyloxirane with an aldehyde to
affordhomoallyl alcohol 16c.
tivity observedin the presentedprocesses catalysedby
[BF4] and 6[BF4] (Table 1).
As reportedpreviously
5-
A
ACHTREUNG
[3f,13d]
symmetrical PCP-pincer pal-
ladium complexes do not catalyse the formation of the inter-
mediate allylstannanes (Scheme 6, 12 ! 14), andso these
complexes alone cannot be employedas catalysts for cou-
pling of allyl chlorides and aldehydes in the presence of hex-
amethylstannane (13). Therefore, reactions with PCP com-
plex 7 as reference catalyst were not performedin this
study. On the other hand we also studied the catalytic per-
Mechanistic considerations of the tandem coupling reaction:
On the basis of the above results andour previous mecha-
nistic and modelling studies,[13b,k,l] it is possible to propose a
ꢀ
formance of SCS-pincer complex 6
complex showeda high catalytic activity, comparable to that
of the PCS-pincer complex 5[BF4] (entries 2, 4, 6 and8).
The high activity of SCS complex 6[BF4] in the tandem cata-
lytic reactions is surprising, because symmetrical ECE-
pincer complexes with s-donor heteroatoms (e.g., NCN)
usually perform poorly[13a–b,l] in the allylation step
(Scheme 6, 14 ! 16/17). The isolatedyields obtainedwith
A
plausible catalytic cycle for the presentedtandem C Sn and
ꢀ
C C processes (Scheme 8). The first catalytic process is the
A
formation of the allylstannane intermediate 14 from allyl
chloride 12 (or vinyloxirane (18)) andhexamethylstannane
(13). This catalytic reaction is initiatedby transmetallation
of catalyst 5[L] with 12 to affordcomplex 5CATHRE[UGN SnMe3] andtri-
metyltin chloride. Formation of trimethyltin-palladium
pincer complexes under similar reaction conditions has been
Chem. Eur. J. 2008, 14, 4800 – 4809
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4805

K. J. Szabó, R. J. M. Klein Gebbink et al.
cates that the catalytic genera-
tion of the allylstannane (14) is
complete before significant
progress in the allylation reac-
tion has taken place.
Conclusion
Aryl-basedunsymmetrical PCS-
pincer palladium complexes 5-
AHCTRE[UNG BF4] and 5[Cl] couldbe pre-
paredin relatively simple four-
andfive-step synthesis sequen-
ces, respectively. These PCS-
pincer complexes, as well as the
Scheme 8. Proposedcatalytic cycle of the auto-tandem reaction. The employedpincer complex 5[L] catalyses
both the stannylation andthe allylation processes.
SCS-pincer
complex
6[Cl],
provedto be efficient catalysts
in the aldol reaction between
[13k]
observedfor NCN-pincer palladium complexes.
Complex
benzaldehyde and methyl isocyanoacetate, but are obviously
pre-catalysts because the methyl isocyanoacetate reactant
converts the pincer catalyst into a ketimine-palladium cata-
lyst. In the aldol condensation reaction (Scheme 4) the PCS
complex gave higher turnover numbers than its PCP and
SCS counterparts. The combination of a sulfur anda phos-
phorus heteroatom in the side arms, such as in complex 5-
5ACHTREUNG
AHCTREUNG
The regeneratedcatalyst 5[L] is able to undergo transme-
tallation with allylstannane 14 to give h1-allylpalladium com-
plex 19. Similar transmetallation reactions were previously
[13b]
reportedfor PCP-pincer complexes andallylstannanes.
ACHTRE[UNG BF4], results in a synergetic effect. This effect involves two
In those studies it was concluded[13a–b] that complexes with
heteroatoms exhibiting p-accepting properties in the ortho-
substituents (such as symmetrical PCP-pincer complexes)
undergo more facile transmetallation than the correspond-
ing analogues with strongly s-electron donating ortho-li-
gands ligands (such as NCN). Considering this, the presence
major components: a weak coordination of the sulfur atom
allowing insertion of 9, as well as a strong coordination of
the phosphorus atom, which increases the rate of the cata-
lytic process.
In the tandem catalytic coupling of allyl chlorides or vi-
nyloxirane with aldehyde or sulfonimine substrates, both 5-
of at least one phosphorus atom in 5
an efficient transmetallation. On the other hand, the rela-
tively low catalytic activity of 6[BF4] in the allylation step
A
ACHRTUNEG[BF4] and 6ACHTRE[UGN BF4] are the true catalytic species. Comparative
studies using symmetrical PCP- and SCS-pincer palladium
complexes show that a strong synergistic effect is also opera-
tive in these catalytic reactions. In the tandem catalytic stan-
nylation andallylation of allyl chlorides (Scheme 6, Table 1)
the PCS complex performs much better than the PCP ana-
logue.[13d] Although the SCS complex has a surprisingly high
catalytic activity, the PCS complex is more efficient in allyla-
tion of sulfonimines. In these processes, the PCS catalyst
unifies the attractive catalytic features of the symmetrical
analogues: firstly, a high catalytic activity in the stannylation
reaction (Scheme 6, 12 ! 14), in which symmetrical com-
plexes with electron-donating heteroatoms and a weaker co-
ordination interaction to the palladium centre (e.g., NCN or
SCS) perform well, andsecondly, the more efficiently cata-
lysedallylation of the electrophile (Scheme 6, 14 ! 16/17)
by less electron-rich pincer complexes in which the heteroa-
tom has a stronger interaction with palladium (i.e., as in
PCP).
AHCTREUNG
(entry 8) may be due to a slow transmetallation of the stan-
nane intermediate 14 to the palladium atom, which is at-
tached to an electron-rich SCS-pincer ligand. According to
our mechanistic and modelling studies[13b,l] these h1-allylpal-
ladium complexes readily react with aldehyde or imine elec-
trophiles (8b or 15). Thus, electrophilic substitution by com-
plex 19 gives 20, which subsequently undergoes decomplexa-
tion to provide the homoallyl alcohol or homoallyl amine
products (16 or 17) andto regenerate catalyst 5[L] once
again. In this way complex 5[L] performs as an auto-tandem
catalyst controlling two bondformation processes: the stan-
ꢀ
nylation (Sn C bondformation) of the allyl chloride and
ꢀ
the electrophilic substitution (C C bondformation) of the
allylstannane intermediate. Our studies show that the stan-
nylation process (12 ! 14) in the presence of the PCS cata-
lyst 5
G
16/17). It was foundthat in the presence of 5
G
The above study on PCS-complexes has at least three im-
portant implications for reactions catalysedby ECE ’-pincer
palladium complexes. 1) It has been demonstrated that elec-
tronic fine-tuning andedsymmetrization of pincer-com-
plexes allows development of catalytic auto-tandem proto-
appliedreaction conditions (entry 1), but in the absence of
an electrophile (e.g., 8b), allyl chloride (12a) was converted
into allylstannane (14a) in 30 min, while the full reaction
time requiredfor coupling of 12a with 8b is 16 h. This indi-
4806
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4800 – 4809

Catalytic Activity of the First PCS-Pincer Palladium Complex
FULL PAPER
AHCTREUNG
cols, in which a single complex is able to catalyse several cat-
alytic events with different mechanisms. 2) New types of
PCS-basedchiral catalysis can be designedfor asymmetric
allylation[13e,m] of sulfonimines with allyl chlorides. These re-
actions are suitable for synthesis of homoallyl amines (such
as 17a–b), which are important motifs in bioactive natural
products and pharmaceuticals.[19] 3) Unsymmetrical aryl-
basedPCS-pincer palladium complexes are particularly suit-
able catalytic platforms as recyclable, robust catalysts, as
these complexes have considerable thermal and kinetic sta-
bility andcan easily be connectedto both soluble andin-
soluble supports of various length scales, making these
(tandem) catalysts suitable for separation by (nano)filtration
1H NMR (CDCl3, 258C): d=1.2 (brs, 3H; BH3), 3.61 (d, 2JH,P =12.0 Hz,
2H; ArCH2P), 3.98 (s, 2H; ArCH2S), 6.8–7.7 ppm (m, 19H; ArH);
13C NMR (CDCl3, 258C): d=33.95 (d, 1JC,P =31.8 Hz; ArCH2PBH3),
38.64 (s; ArCH2S), 126.23, 127.42 (d, JC,P =3 Hz), 128.16 (d, JC,P =2.4 Hz),
128.64, 128.77, 128.84, 129.16 (d, JC,P =4.9 Hz), 129.57, 130.87 (d, JC,P
4.3 Hz), 131.32 (d, JC,P =2.5 Hz), 132.21 (d, JC,P =4.3 Hz), 132.64 (d, JC,P
9 Hz), 136.39, 137.25 ppm (d,
=
=
J
C,P =2.5 Hz; ArC); 31P NMR (CDCl3,
258C): d=19.35 ppm (brs); elemental analysis calcd(%) for C 26H26BPS
(412.33): C 75.73, H 6.36, P 7.51, S 7.78; found: C 75.66, H 6.35, P 7.64, S
7.73.
ACHETRGNU[C6H3HCATRE(UGN CH2PPh2)-2-(CH2SPh)-6] (4): HBF4·Et2O (0.9 mL, 5.9 mmol) was
added at 08C under nitrogen to a stirred solution of 3 (0.5 g, 1.2 mmol)
in CH2Cl2. The mixture was then allowedto warm to room temperature,
andthe stirring was continuedfor another 18 h. A saturatedaqueous
NaHCO3 solution was added dropwise at 08C, resulting in considerable
gas evolution. When the addition was complete, the mixture was stirred
at room temperature for another 30 min. The organic layer was collected
anddriedover MgSO 4. After evaporation of all the volatiles, 4 was ob-
tainedas an air- andmoisture-sensitive, white, sticky solid(0.35 g, 74%).
1H NMR (CDCl3, 258C): d=3.39 (s, 2H; ArCH2P), 4.02 (s, 2H;
ArCH2S), 6.8–7.8 ppm (m, 19H; ArH); 13C NMR (CDCl3, 258C): d=
35.99 (d, 1JC,P =15.9 Hz; ArCH2P), 39.0 (s; ArCH2S), 126.23, 127.42 (d,
[4–9]
andre-use.
Experimental Section
General: All reactions were performed under dry oxygen-free nitrogen
with use of Schlenk techniques. THF andEt 2O were dried over Na/ben-
zophenone. MeCN andCH 2Cl2 were dried over CaH2, andall solvents
were freshly distilled under nitrogen prior to use. CD2Cl2 was purchased
from Cambridge Isotopes, dried over CaH2, distilled prior to use and
storedin a Schlenk flask over 4 Š molecular sieves under nitrogen. All
standards reagents were purchased from Acros Organics and Aldrich
J
J
C,P =3 Hz), 128.16 (d, JC,P =2.4 Hz), 128.64, 128.77, 128.84, 129.16 (d,
C,P =4.9 Hz), 129.57, 130.87 (d, JC,P =4.3 Hz), 131.32 (d, JC,P =2.5 Hz),
132.21 (d, JC,P =4.3 Hz), 132.64 (d, JC,P =9 Hz), 136.39, 137.25 ppm (d,
J
C,P =2.5 Hz; ArCipso); 31P NMR (CDCl3, 258C): d=ꢀ7.23 ppm; elemen-
Chemical Co., Inc, andwere usedas received. Imine
plexes [Pd(MeCN)4] {C6H3A(CH2SPh2)2-2,6}
[BF4]2,[16] [Pd
[BF4])[5b] and[PdCl (CH2PPh2)2-2,6}] (7[Cl])[18] were synthesizedby
{C6H3A
15[20] andthe com-
(MeCN)](BF4) (6-
tal analysis calcd(%) for C 26H23PS (398.5): C 78.36, H 5.82; found: C
78.26, H 5.71.
G
R
A
N
G
ACHTREUNG
U
A
CHTREUNG
[Pd
of 4 (0.35 g, 0.8 mmol) in dry MeCN (25 mL) was added to a solution of
[Pd(MeCN)4](BF4)2 (0.39 g, 0.8 mmol) in dry MeCN (25 mL). The result-
ACHTER(UGN NCMe)AHTCER{UNG C6H3ACHERT(UGN CH2PPh2)-2-(CH2SPh)-6}]ACHTREG(UN BF4) (5ACHTRE[UGN BF4]): A solution
literature procedures. 1H NMR (1H (300.1/400.0 MHz), 13C NMR (75.5/
100.6 MHz) and 31P{1H} NMR (121.5 MHz)) spectra were recorded on a
Varian INOVA 300 MHz spectrometer anda Bruker 400 MHz spectrom-
eter. Chemical shift values are reportedin ppm ( d) relative to (CH3)4Si
(1H and 13C NMR) anda capillary containing 85% H 3PO4 in D2O,
(31P{1H} NMR). FT-IR spectra were recorded on a Mattson Instruments
Galaxy Series FTIR 5000. Gas chromatographic analyses were performed
with a Perkin–Elmer Autosystem XL GC with use of a 30 m, PE-17 capil-
lary column with an FID detector. High-resolution electron spray ioniza-
tion (ESI) mass spectra were recorded with a Micromass LC-TOF mass
anda Bruker MicrOTOF spectrometer. Elemental analyses were per-
formedby H. Kolbe Microanalysis Laboratories, Mülheim, Germany. For
column chromatography, Merck silica gel 60 (230–400 mesh) was used.
A
ACHTREUNG
ing yellow solution was stirredfor one hour at room temperature. The
solvent was removedin vacuo until a small amount remainedin the
flask. Dry Et2O was added, causing the precipitation of 5CATHRE[UNG BF4] as a light
yellow powder that was collected by centrifugation, washed with Et2O
anddriedin vacuo (0.55 g, 70%).
1H NMR (CD3CN, 258C): d=4.15 (d,
3
2JH,P =12.3 Hz, 2H; ArCH2P), 4.65 (s, 2H; ArCH2S), 7.06 (d, JH,H
=
3.9 Hz, 2H; ArH), 7.13 (t, 3JH,H =4.7 Hz, 1H; ArH), 7.46–7.64 (m, 9H;
ArH), 7.72–7.84 ppm (m, 6H; ArH); 13C NMR (CD3CN, 258C): d=42.37
(d, 1JC,P =36.6 Hz; ArCH2P), 48.70 (s; ArCH2S), 124.39, 125.32 (d, JC,P
=
2
25 Hz), 127.89, 130.31, 130.46, 131.01, 131.10, 132.34 (d, JC,P =1.8 Hz),
133.14 (d,
C,P =3.02 Hz), 133.73, 133.88, 148.02 (d, 3JC,P =17.06 Hz),
J
ACHTREUNG[C6H4ACHTREUNG(CH2Br)-1-(CH2PACHTREUNG(BH3)Ph2)-3] (2): nBuLi (4.5 mL, 7.1 mmol) was
151.81, 156.75 ppm (d, JC,P =2.49 Hz; ArCipso); 31P NMR (CD3CN, 258C):
d=49.7 ppm (s); IR (ATR): n˜ =3058, 2976, 2935, 2317, 2287, 1579, 1484,
1437, 1049, 1023, 743, 689 cmꢀ1; MS (ES) (70 eV): m/z (%): 544.19 (100)
[MꢀBF4]+, 503.16 (70) [MꢀMeCNꢀBF4]+; elemental analysis calcd(%)
for C28H25BF4NPPdS (631.77): C 53.23, H 3.99, N 2.22; found: C 53.09, H
4.06, N 2.14.
added at ꢀ788C to HPPh2·BH3 (1.29 g, 7.1 mmol) in dry THF (40 mL).
The temperature was allowedto rise to room temperature andstirring
was continuedfor 15 h. Next, a solution of 1 (1.87 g, 7.1 mmol) in dry
THF (20 mL) was added at ꢀ788C. The mixture was allowedto warm to
room temperature andstirredfor 20 h. All volatiles were then removed
in vacuo, and the obtained residue was dissolved in CH2Cl2. The organic
A
ACHTREU{NG C6H3AHCRTE(UGN CH2PPh2)-2-(CH2SPh)-6}] (5[Cl]): An excess of NaCl
layer was washedwith water andbrine anddriedover MgSO
4. After fil-
tration andevaporation of CH 2Cl2 a white, sticky solidwas obtained.
Analysis by H NMR in CDCl3 showed the presence of the desired prod-
1
AHCTREUNG
was stirredat room temperature for 3 h. The solvent was removedin
vacuo, and the obtained yellow residue was dissolved in CH2Cl2 (5 mL).
Subsequently, the organic layer was washedwith H 2O (2”15 mL) and
dried in vacuo, yielding 5[Cl] as a yellow powder, which was washed with
uct 2 (63%), [C6H4ACHTREUNG{CH2PCAHTREU(GN BH3)Ph2}2–1,3] (12%) andunreacted 1 (25%).
Compound 2 was usedin the next reaction without further purification.
Because of its toxicity, elemental andESI analyses were not carriedout.
CAUTION: Substituted benzyl bromides can be powerful lachrymators
and should be used with adequate ventilation and precaution against skin
contact or ingestion.
Et2O anddriedin vacuo (0.14 g, 95%). 1H NMR (CDCl3, 258C): d=3.99
3
(d, 2JH,P =12.2 Hz, 2H; ArCH2P), 4.48 (s, 2H; ArCH2S), 6.99 (d, JH,H
=
4.2 Hz, 2H; ArH), 7.09 (t, 3JH,H =4.8, 3.6 Hz, 1H; ArH), 7.24–7.46 (m,
9H; ArH), 7.74–7.92 ppm (m, 6H; ArH); 13C NMR (CDCl3, 258C): d=
ACHTREUNG[C6H4ACHTREUNG(CH2PACHTREUNG(BH3)Ph2)-1-(CH2SPh)-3] (3): K2CO3 (2.0 g, 15 mmol), 18-
crown-6 (0.4 g, 15 mmol) and PhSH (2.2 g, 20 mmol) were added to a
THF (40 mL) solution of ligand 2. The resultant mixture was stirredat
room temperature for 15 h. After filtration andevaporation of the sol-
vent, the residue, a colourless oil, was purified by silica gel chromatogra-
phy with Et2O/hexane 1:9, to afford 3 as a white solid. The other prod-
ucts of the reaction were characterizedby 1H, 13C and 31P{1H} NMR spec-
1
43.94 (d, JC,P =36.07 Hz; ArCH2P), 49.01 (s; ArCH2S), 122.52, 123.30 (d,
J
C,P =24.38 Hz), 125.56, 128.80, 128.94, 129.01, 129.48, 131.04, 131.07,
132.85, 133.0, 147.02 (d, JC,P =18.34 Hz), 150.32, 160.67 ppm (ArCipso);
31P NMR (CDCl3, 258C): d=45.02 ppm (s); IR (ATR): n˜ =3051, 2972,
2864, 1579, 1482, 1435, 1103, 1055, 1025, 740, 688 cmꢀ1; MS (ES) (70 eV):
m/z (%): 503.2 (100) [MꢀCl]+; elemental analysis calcd(%) for
troscopy as the pincer ligands [C6H4ACHTREU{NG CH2SPh}2-1,3] and[C 6H4ACHTRE{UGN CH2P-
Chem. Eur. J. 2008, 14, 4800 – 4809
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4807

K. J. Szabó, R. J. M. Klein Gebbink et al.
C26H22ClPPdS (539.36): C 57.90, H 4.11, P 5.74, S 5.94; found: C 57.83, H
4.19, P 5.84, S 5.86.
1-(4-Nitrophenyl)-2-vinylpropane-1,3-diol (16c): For the preparation of
16c, the standard protocol was slightly modified. The catalyst 5ACHTREUNG[BF4]
(0.008 mmol, 5 mol% [Pd]) was dissolved in THF, followed by addition
of LiOAc·2H2O (0.016 mmol, 10 mol%) andwater (0.32 mmol, 2 equiv).
The mixture was stirredfor 10 minutes at room temperature, followedby
addition of the vinyloxirane (18) (0.192 mmol), aldehyde 8b (0.16 mmol)
and 15 (0.192 mmol). The workup procedure was the same as described
in the standard protocol. The diastereoselectivity was assigned on the
basis of 1H NMR data given in the literature[23] for an analogous stereo-
defined compound. 1H NMR for anti-16c (CDCl3, 258C): d=1.89 (br,
1H), 2.58 (m, 1H), 3.02 (br, 1H), 3.79 (d, 3JH,H =5.5 Hz, 2H), 5.05 (d,
3JH,H =17.3 Hz, 1H), 5.09 (d, 3JH,H =4.4 Hz, 1H), 5.21 (d, 3JH,H =10.4 Hz,
1H), 5.80 (ddd, 3JH,H =8.7, 10.4, 17.3 Hz, 1H), 7.51 (d, 3JH,H =8.8 Hz,
Methyl isocyanoacetate insertion complex (11a): Compound 9 (36 mL,
0.4 mmol) was added to a solution of 5[Cl] (0.1 g, 0.18 mmol) in CH2Cl2
(5 mL). The resulting solution was stirredat room temperature for 20 mi-
nutes. Subsequently, the solvent was evaporateduntil a small amount re-
mained. Addition of pentane (10 mL) caused the precipitation of 11a as
a yellow solid, which was collected by centrifugation and dried under
vacuo (0.07 g, 50%). 1H NMR (CD2Cl2, 258C): d=3.52 (s, 2H; SCH2),
3.78 (brs, 6H; OMe), 4.1 (brs, 2H; C(O)CH2), 4.25 (d, 2JH,P =10.8 Hz,
2H; PCH2), 4.85 (s, 2H; C(O)CH2), 6.89 (1H; ArH), 7.05–7.24 (m, 3H;
ArH), 7.3–7.6 (m, 10H; ArH), 7.7–7.94 (m, 3H; ArH), 8.0–8.1 ppm (m,
1H; ArH); 13C NMR (CD2Cl2, 258C): d=30.8 (s; ArCH2S), 44.0 (d,
1JC,P =36 Hz; ArCH2P), 46.0 (s; C(O)CH2), 49.5 (s; OCH3), 51.0 (s;
CCH3), 62.0 (s; C(O)CH2), 122.8, 123.0, 125.0, 125.8, 126.5, 127.5, 127.8,
129.2, 129.7, 131.1, 131.5, 131.9, 133.1, 138.2, 150.5, 163.0, 171.0,
186.0 ppm; 31P NMR (CD2Cl2, 258C): d=47.76 ppm; IR (CH2Cl2 solu-
tion): n˜ =3053, 2953, 2230, 1750, 1627, 1582, 1482, 1436, 1219, 1179, 1102,
2H), 8.19 ppm (d, 3JH,H =8.8 Hz, 2H); 1H NMR for syn-16c (CDCl3,
3
258C): d=1.89 (br, 1H), 2.58 (m, 1H), 3.02 (br, 1H), 3.85 (d, JH,H
=
5.6 Hz, 2H), 4.93 (d, 3JH,H =7.5 Hz, 1H), 5.02 (d, 3JH,H =17.3 Hz, 1H),
5.09 (d, 3JH,H =10.4 Hz, 1H), 5.60 (ddd, 3JH,H =8.6, 10.4, 17.3 Hz, 1H),
7.50 (d, 3JH,H =8.8 Hz, 2H), 8.19 ppm (d, 3JH,H =8.8 Hz, 2H); 13C NMR
for both diastereomers (CDCl3, 258C): d=52.19, 52.74, 64.19, 64.79,
74.08, 119.11, 120.08, 123.38, 123.47, 127.09, 127.51, 133.38, 134.35, 147.21,
149.85, 149.98 ppm; HRMS (ESI): m/z: calcdfor [C 11H13NO4+Na]+:
246.0737; found: 246.0739.
1055, 1025, 999, 742, 690 cmꢀ1
; elemental analysis calcd(%) for
C34H32ClN2O4PPdS (737.54): C 55.37, H 4.37, N 3.80; found: C 55.26, H
4.44, N 3.69.
Standard protocol for the aldol condensation reaction: In a typical ex-
periment, the catalyst 5[Cl] (0.016 mmol, 1 mol% [Pd]) was added to a
solution of methyl isocyanoacetate (9, 1.6 mmol), benzaldehyde
(1.6 mmol) and pentadecane (internal standard, 0.4 mmol) in distilled
CH2Cl2 (5 mL). iPr2EtN (Hunigꢁs base, 0.16 mmol, 10 mol%) was added
to this mixture at room temperature at the time notedas 0 h. Samples of
the reaction mixtures were taken with an airtight syringe at regular inter-
vals. The degrees of conversion relative to benzaldehyde were monitored
over time by GC analysis.
N-[1-(4-Nitrophenyl)but-3-enyl]benzenesulfonamide (17a): This com-
pound was prepared by the standard protocol for the tandem coupling re-
1
3
actions with 12a and 15. H NMR (CDCl3, 258C): d=2.43 (dd, JH,H =7.0,
7.0 Hz, 2H), 4.50 (dt, 3JH,H =6.5, 6.5 Hz, 1H), 5.04–5.14 (m, 3H), 5.45
(ddt, 3JH,H =7.2, 10.2, 17.3 Hz, 1H), 7.29 (d, JH,H =8.7 Hz, 2H), 7.36–7.41
3
(m, 2H), 7.48–7.53 (m, 1H), 7.68 (d, 3JH,H =8.7 Hz, 2H), 8.04 ppm (d,
3JH,H =8.7 Hz, 2H); 13C NMR (CDCl3, 258C): d=41.60, 56.39, 120.60,
123.59, 127.07, 127.51, 128.93, 131.78, 132.83, 139.89, 147.20, 147.76 ppm;
HRMS (ESI): m/z: calcdfor [C 16H16N2SO4+Na]+: 355.0723; found:
355.0724.
Standard protocol for the tandem coupling reactions (Table 1): In a typi-
cal experiment, the catalyst
5ACHTREU[NG BF4] (0.008 mmol, 5 mol% [Pd]) was
N-[1-(4-Nitrophenyl)-2-phenylbut-3-enyl]benzenesulfonamide (17b): This
compoundwas preparedby the standardprotocol for the tandem cou-
pling reactions with 16b and 18. The diastereoselectivity was assigned on
added to a solution of the allylic substrate 12 (0.192 mmol) and aldehyde
8b or sulfonimine 15 (0.16 mmol) in distilled THF (0.7 mL). In the allyla-
tion of sulfonimine, molecular sieves (0.025 g) were also added. Hexame-
tylditin (13, 0.192 mmol) was added to this mixture by airtight syringe
under inert atmosphere. This reaction mixture was stirred for the allotted
temperatures andtimes listedin Table 1 andwas then quenchedwith
water and extracted with diethyl ether. After drying and evaporation of
the ether phase, the products were purified by silica gel column chroma-
tography. The ratios of diastereomers were determined from the crude
1H NMR spectra.
1
the basis of H NMR data given in the literature[22] for an analogous ster-
eodefined compound. Only the major isomer was isolated and character-
ized: 1H NMR for syn-17b (CDCl3, 258C): d=3.50 (brt, 3JH,H =8.4 Hz,
1H), 4.60 (dd, 3JH,H =4.9, 8.2 Hz, 1H), 4.85 (d, 3JH,H =4.9 Hz, 1H), 4.87
3
(d, 3JH,H =17.0 Hz, 1H), 5.02 (d, 3JH,H =10.2 Hz, 1H), 5.71 (ddd, JH,H
=
8.7, 10.2, 17.0 Hz, 1H), 6.92–6.96 (m, 2H), 7.15 (d, 3JH,H =8.8 Hz, 2H),
7.24–7.35 (m, 5H), 7.48–7.51 (m, 3H), 7.99 ppm (d, 3JH,H =8.8 Hz, 2H);
13C NMR for syn-17b (CDCl3, 258C): d=56.39, 61.04, 119.27, 123.10,
127.08, 127.96, 128.03, 128.74, 128.84, 129.27, 132.72, 135.25, 137.88,
139.40, 146.14, 147.25 ppm; HRMS (ESI): m/z: calcdfor
[C22H20N2SO4+Na]+: 431.1036; found: 431.1030.
1-(4-Nitrophenyl)but-3-en-1-ol (16a): This compoundwas preparedby
the standard protocol for the tandem coupling reactions with 12a and 8b.
The NMR data obtained for 16a are identical with the literature[21]
1
3
values. H NMR (CDCl3, 258C): d=2.21 (d, JH,H =3.3 Hz, 1H), 2.41–2.50
(m, 1H), 2.53–2.61 (m, 1H), 4.87 (m, 1H), 5.16–5.23 (m, 2H), 5.79 (dddd,
3JH,H =6.5, 7.8, 10.4, 16.9 Hz, 1H), 7.54 (d, 3JH,H =8.8 Hz, 2H), 8.21 ppm
(d, 3JH,H =8.8 Hz, 2H); 13C NMR (CDCl3, 258C): d=43.92, 72.13, 119.72,
123.65, 126.55, 133.17, 147.30, 151.03 ppm; HRMS (ESI): m/z: calcdfor
[C10H11NO3+Na]+: 216.0631; found: 216.0632.
Acknowledgements
This collaborative study was supported by the IDECAT Network of Ex-
cellence of the European Community under contract: NMP3-CT-2005-
011730. Additional grants from the Swedish Natural Science Research
Council (V.R.) andUtrecht University are gratefully acknowledged.
1-(4-Nitrophenyl)-2-phenylbut-3-en-1-ol (16b): This compoundwas pre-
paredby the standardprotocol for the tandem coupling reactions with
12b and 8b. The diastereoselectivity was assigned on the basis of
1H NMR data given in the literature[22] for 16b. 1H NMR for anti-16b
(CDCl3, 258C): d=2.51 (d, 3JH,H =2.3 Hz, 1H), 3.48 (brt, 3JH,H =8.5 Hz,
1H), 4.93 (dd, 3JH,H =2.3, 7.8 Hz, 1H), 5.27 (d, 3JH,H =17.0 Hz, 1H), 5.32
[1] G. van Koten, Pure Appl. Chem. 1989, 61, 1681.
[2] M. Albrecht, G. van Koten, Angew. Chem. 2001, 113, 3866; Angew.
Chem. Int. Ed. 2001, 40, 3750.
3
3
(d, JH,H =10.1 Hz, 1H), 6.23 (ddd, JH,H =9.1, 10.1, 17.0 Hz, 1H), 7.04 (m,
2H), 7.18–7.25 (m, 3H), 7.28 (d, 3JH,H =8.8 Hz, 2H), 8.05 ppm (d, JH,H
=
3
8.8 Hz, 2H); 1H NMR for syn-16b (CDCl3, 258C): d=2.12 (d, JH,H
=
3
[3] For reviews see: a) C. M. Jensen, Chem. Commun. 1999, 2443; b) J.
Dupont, M. Pfeffer, J. Spencer, Eur. J. Inorg. Chem. 2001, 1917; c) J.
Dupont, C. S. Consorti, J. Spencer, Chem. Rev. 2005, 105, 2527;
d) J. T. Singleton, Tetrahedron 2003, 59, 1837; e) M. E. van der
Boom, D. Milstein, Chem. Rev. 2003, 103, 1759; f) K. J. Szabo, Syn-
lett 2006, 811; g) The Chemistry of Pincer Compounds (Eds.: D. Mo-
rales-Morales, C. Jensen), Elsevier, Amsterdam, 2007; h) G. Zanoni,
A. Pontiroli, A. Marchetti, G. Vidari, Eur. J. Org. Chem. 2007, 3599.
3.2 Hz, 1H), 3.59 (brt, 3JH,H =8.0 Hz, 1H), 4.91 (m, 1H), 5.05 (m, 2H),
5.94 (ddd, 3JH,H =8.2, 10.3, 17.0 Hz, 1H), 7.17–7.45 (m, 7H), 8.16 ppm (d,
3JH,H =8.8 Hz, 2H); 13C NMR for both diastereomers (CDCl3, 258C): d=
58.70, 59.51, 76.37, 118.20, 119.48, 123.05, 123.21, 127.16, 127.44, 127.50,
127.80, 128.12, 128.64, 128.70, 128.93, 136.62, 136.79, 139.48, 147.16,
149.12 ppm; HRMS (ESI): m/z: calcdfor [C 16H15NO3+Na]+: 292.0944;
found: 292.0942.
4808
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4800 – 4809

Catalytic Activity of the First PCS-Pincer Palladium Complex
FULL PAPER
[4] a) R. Chanthateyanonth, H. Alper, Adv. Synth. Catal. 2004, 346,
1375; b) R. Chanthateyanonth, H. Alper, J. Mol. Catal. A 2003, 201,
23; c) R. Gimenez, T. M. Swager, J. Mol. Catal. A 2001, 166, 265;
d) N. C. Mehendale, C. Bezemer, C. A. van Walree, R. J. M. Klein
Gebbink, G. van Koten, J. Mol. Catal. A 2006, 257, 167; e) N. C. Me-
hendale, J. R. A. Sietsma, K. P. de Jong, C. A. van Walree, R. J. M.
Klein Gebink, G. van Koten, Adv. Synth. Catal. 2007, 349, 2619.
[5] a) D. E. Bergbreiter, P. L. Osburn, A. Wilson, E. M. Sink, J. Am.
Chem. Soc. 2000, 122, 9058; b) D. E. Bergbreiter, P. L. Osburn, Y.-S.
Liu, J. Am. Chem. Soc. 1999, 121, 9531; c) D. E. Bergbreiter, P. L.
Osburn, J. D. Frels, J. Am. Chem. Soc. 2001, 123, 11105; d) D. E.
Bergbreiter, S. Furyk, Green Chem. 2004, 6, 280; e) D. E. Bergbreit-
er, J. D. Frels, P. L. Osburn, Polym. Prepr. 2000, 41, 1360; f) D. E.
Bergbreiter, Chem. Rev. 2002, 102, 3345; g) M. Q. Slagt, S.-E. Stiri-
ba, H. Kautz, R. J. M. Klein Gebbink, H. Frey, G. van Koten, Orga-
nometallics 2004, 23, 1525; h) M. Q. Slagt, S.-E. Stiriba, R. J. M.
Klein Gebbink, H. Kautz, H. Frey, G. van Koten, Macromolecules
2002, 35, 5734.
[6] a) R. van de Coevering, A. P. Alfers, J. D. Meeldijk, E. Martinez-
Viviente, P. S. Pregosin, R. J. M. Klein Gebbink, G. van Koten, J.
Am. Chem. Soc. 2006, 128, 12700; b) P. A. Chase, R. J. M. Klein
Gebbink, G. van Koten, J. Organomet. Chem. 2004, 689, 4016;
c) M. Q. Slagt, Don A. P. van Zwieten, A. J. C. M. Moerkerk,
R. J. M. Klein Gebbink, G. van Koten, Coord. Chem. Rev. 2004, 248,
2275; d) B. M. J. M. Suijkerbuijk, L. Shu, R. J. M. Klein Gebbink,
A. D. Schlueter, G. van Koten, Organometallics 2003, 22, 4175;
e) H. P. Dijkstra, N. Ronde, G. P. M. van Klink, D. Vogt, G. van Ko-
ten, Adv. Synth. Catal. 2003, 345, 364; f) J. W. J. Knapen, A. W. van
der Made, J. C. de Wilde, P. W. N. M. van Leeuwen, P. Wijkens,
D. M. Grove, G. van Koten, Nature 1994, 372, 659.
17, 4374; c) Y. Motoyama, H. Kawakami, K. Shimozono, K. Aoki,
H. Nishiyama, Organometallics 2002, 21, 3408; d) M. A. Stark, C. J.
Richards, Tetrahedron Lett. 1997, 38, 5881; e) M. A. Stark, G. Jones,
C. J. Richards Organometallics 2000, 19, 1282; f) S. Gosiewska, M.
Huis in ’t Veld, J. J. M. de Pater, P. C. A. Bruijnincx, M. Lutz, A. L.
Spek, G. van Koten, R. J. M. Klein Gebbink, Tetrahedron: Asymme-
try 2006, 17, 674; g) J. G. Donkervoort, J. L. Vicario, E. Rijnberg,
J. T. B. H. Jastrzebski, H. Kooijman, A. L. Spek, G. van Koten, J. Or-
ganomet. Chem. 1998, 550, 463; h) R. Gimꢃnez, T. M. Swager, J.
Mol. Catal. A 2001, 166, 265; i) A. Zografidis, K. Polborn, W. Beck,
B. A. Markies, G. van Koten, Z. Naturforsch. B 1994, 49, 1494;
j) N. C. Mehendale, PhD Thesis: Silica Immobilized Pincer-Metal
Complexes. Catalysis, Recycling, and Retrospect on Active Species,
2007, University Utrecht (The Netherlands), Chapters 5–6; k) J.
Aydin, K. S. Kumar, L. Eriksson, K. J. Szabó, Adv. Synth. Catal.
2007, 349, 2585.
[13] a) N. Solin, J. Kjellgren, K. J. Szabó, Angew. Chem. 2003, 115, 3784;
Angew. Chem. Int. Ed. 2003, 42, 3656; b) N. Solin, J. Kjellgren, K. J.
Szabó, J. Am. Chem. Soc. 2004, 126, 7026; c) N. Solin, O. A. Wallner,
K. J. Szabó, Org. Lett. 2005, 7, 689; d) O. A. Wallner, K. J. Szabó,
Org. Lett. 2004, 6, 1829; e) O. A. Wallner, V. J. Olsson, L. Eriksson,
K. J. Szabó, Inorg. Chim. Acta 2006, 359, 1767; f) S. Sebelius, V. J.
Olsson, K. J. Szabó, J. Am. Chem. Soc. 2005, 127, 10478; g) S. Sebe-
lius, V. J. Olsson, O. A. Wallner, K. J. Szabó, J. Am. Chem. Soc.
2006, 128, 8150; h) V. J. Olsson, S. Sebelius, N. Selander, K. J. Szabó,
J. Am. Chem. Soc. 2006, 128, 4588; i) N. Selander, S. Sebelius, C.
Estay, K. J. Szabó, Eur. J. Org. Chem. 2006, 4085; j) J. Kjellgren, H.
Sundꢃn, K. J. Szabó, J. Am. Chem. Soc. 2004, 126, 474; k) J. Kjellg-
ren, H. Sundꢃn, K. J. Szabó, J. Am. Chem. Soc. 2005, 127, 1787;
l) O. A. Wallner, K. J. Szabó, Chem. Eur. J. 2006, 12, 6983; m) J. A.
Aydin, K. S. Kumar, M. J. Sayah, O. A. Wallner, K. J. Szabó, J. Org.
Chem. 2007, 72, 4689.
[7] a) B. M. J. M. Suijkerbuijk, S. D. Herreras Martꢂnez, G. van Koten,
R. J. M.
Klein Gebbink,
Organometallics
2008,
27,
534;
b) B. M. J. M. Suijkerbuijk, M. Lutz, A. L. Spek, G. Van Koten,
R. J. M. Klein Gebbink, Org. Lett. 2004, 6, 3023.
[8] M. D. Meijer, N. Ronde, D. Vogt, G. P. M. van Klink, G. van Koten,
Organometallics 2001, 20, 3993.
[9] a) D. Beccati, K. M. Halkes, G. D. Batema, G. Guillena, A. Carvalho
de Souza, G. van Koten, J. P. Karmeling, ChemBioChem 2005, 6,
1196; b) G. Guillena, K. M. Halkes, G. Rodrꢂguez, G. D. Batema, G.
van Koten, J. P. Karmeling, Org. Lett. 2003, 5, 2021.
[10] C. A. Kruithof, M. A. Casado, G. Guillena, M. R. Egmond, A. van
der Kerk-van Hoof, A. J. R. Heck, R. J. M. Klein Gebbink, G.
van Koten, Chem. Eur. J. 2005, 11, 6869.
[14] a) J. Dupont, M. Pfeffer, J. C. Daran, Y. Jeannin, Organometallics
1987, 6, 899; b) J. Dupont, M. Pfeffer, J. Chem. Soc. Dalton Trans.
1990, 3193.
[15] a) G. R. Rosa, G. Ebeling, J. Dupont, A. L. Monterio, Synthesis
2003, 2894; b) M. Gandelman, A. Vigalok, L. J. W. Shimon, D. Mil-
stein, Organometallics 1997, 16, 3981; c) A. Sundermann, O. Uzan,
J. M. L. Martin, Organometallics 2001, 20, 1783; d) M. Gandelman,
L. Konstantinovski, H. Rozenberg, D. Milstein, Chem. Eur. J. 2003,
9, 2595; e) J.-F. Gong, Y.-H. Zhang, M.-P. Song, C. Xu, Organome-
tallics 2007, 26, 6487.
[16] J.-C. Yuan, S.-J. Lu, Organometallics 2001, 20, 2697.
[11] a) Y. Yamamoto, H. Yamazaki, Coord. Chem. Rev. 1972, 8, 225;
b) Y. Yamamoto, H. Yamazaki, Inorg. Chem. 1974, 13, 438; c) J. F.
van Baar, J. M. Klerks, O. P. , D. J. Stufkens, K. Vrieze, J. Organo-
met. Chem. 1976, 112, 95; d) Y. Yamamoto, H. Yamazaki, Synthesis
1976, 750; e) Y. Yamamoto, H. Yamazaki, Inorg. Chim. Acta 1980,
41, 229; f) A. D. Ryabov, Synthesis 1985, 233; g) J. Vincente, I.
Saura-Llamas, J. Turpꢂn, M. C. R. de Arellano, P. G. Jones, Organo-
metallics 1999, 18, 2683; h) J. Vincente, I. Saura-Llamas, C. Grün-
wald, C. Alcaraz, P. G. Jones, D. Bautista, Organometallics 2002, 21,
3587; i) Y.-J. Kim, X. Chang, J.-T. Han, M. S. Lim, S. W. Lee, Dalton
Trans. 2004, 3699.
[17] J. Dupont, N. Beydoun, M. Pfeffer, J. Chem. Soc. Dalton Trans.
1989, 1715.
[18] F. Gorla, L. M. Venanzi, A. Albinati, Organometallics 1994, 13, 43.
[19] H. Ding, G. K. Friestad, Synthesis 2005, 2815.
[20] K. Y. Lee, C. G. Lee, J. N. Kim, Tetrahedron Lett. 2003, 44, 1231.
[21] T. Akiyama, J. Iwai, M. Sugano, Tetrahedron 1999, 55, 7499.
[22] O. A. Wallner, K. J. Szabó, J. Org. Chem. 2003, 68, 2934.
[23] S. Sebelius, K. J. Szabó, Eur. J. Org. Chem. 2005, 2539.
[12] a) F. Gorla, A. Togni, L. M. Venanzi, Organometallics 1994, 13,
1607; b) J. M. Longmire, X. Zhang, M. Shang, Organometallics 1998,
Received: February 25, 2008
Publishedonline: April 23, 2008
Chem. Eur. J. 2008, 14, 4800 – 4809
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4809