Studies of reactions of o-xylylene-α,α′-dihalides with palladium complexes and the catalytic synthesis of 3-isochromanone

Article abstract of DOI:10.1016/j.jorganchem.2006.01.029

Homogeneous catalysis by palladium complexes with phosphorus(III) ligands of the carbonylation of o-xylylene dihalides in the presence of water to form 3-isochromanone has been studied. Triphenylphosphine was found to provide the most effective catalyst, and by-products and intermediates of systems containing this ligand have been investigated. 2-Indanone is one by-product but is unstable to decomposition under catalytic conditions. Excess PPh₃ is necessary to prolong activity of the catalyst but is also transformed to bis-phosphonium compound [o-C₆H₄(CH₂PPh₃)₂]X₂ (X = Cl or Br); this quaternization has been investigated and the structure of the bromide salt determined by X-ray diffraction. An unstable oxidative addition product of Pd(PPh₃)₄ was detected as a probable intermediate and related to the previously reported but catalytically-inactive complex trans-Pd(o-CH₂C₆H₄CH₂Cl)Cl(PMe₃)₂, which has been structurally characterized by X-ray diffraction in this work.

Full text of DOI:10.1016/j.jorganchem.2006.01.029

Journal of Organometallic Chemistry 691 (2006) 2378–2385
www.elsevier.com/locate/jorganchem
Studies of reactions of o-xylylene-a,a0-dihalides with
palladium complexes and the catalytic synthesis of 3-isochromanone
b
a,
a
a
Ray V.H. Jones , W. Edward Lindsell *, Greg C. Paddon-Jones , Daniel D. Palmer ,
a,
a
b
Peter N. Preston *, Georgina M. Rosair , Alan J. Whitton
a
Department of Chemistry, School of Engineering and Physical Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, UK
b
Syngenta, Earls Road, Grangemouth, Stirlingshire FK3 8XG, UK
Received 1 December 2005; received in revised form 12 January 2006; accepted 12 January 2006
Available online 21 February 2006
Abstract
Homogeneous catalysis by palladium complexes with phosphorus(III) ligands of the carbonylation of o-xylylene dihalides in the pres-
ence of water to form 3-isochromanone has been studied. Triphenylphosphine was found to provide the most effective catalyst, and by-
products and intermediates of systems containing this ligand have been investigated. 2-Indanone is one by-product but is unstable to
decomposition under catalytic conditions. Excess PPh3 is necessary to prolong activity of the catalyst but is also transformed to bis-phos-
phonium compound [o-C6H4(CH2PPh3)2]X2 (X = Cl or Br); this quaternization has been investigated and the structure of the bromide
salt determined by X-ray diffraction. An unstable oxidative addition product of Pd(PPh3)4 was detected as a probable intermediate and
related to the previously reported but catalytically-inactive complex trans-Pd(o-CH2C6H4CH2Cl)Cl(PMe3)2, which has been structurally
characterized by X-ray diffraction in this work.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Palladium; Carbonylation; o-Xylylene dihalides; 3-Isochromanone; Phosphonium salt
1. Introduction
A similar catalytic carbonylation of o-benzenedimethanol
in the presence of HI(aq) affords 1 in 88% yield (56% iso-
lated) [10]. Catalytic insertion of CO into the cyclic ether
phthalan has also been reported [6], and carbonylations
of 2-(1-alkynyl)benzenemethanols under higher pressures
and temperatures are catalyzed by Rh4(CO)16 to afford
4-substituted 3-isochromanones [11]. For commercial
processes, more convenient starting materials are o-xylyl-
ene-a,a0-dihalides, 2, in particular the dichloride which is
readily obtained by radical chlorination of o-xylene, and
recent patents [1,3,4] give experimental details for the
Pd-catalyzed conversion of these substrates to 1 in up to
91% yield [1a], with high turnover numbers of >4 K being
recorded under some conditions [3].
3-Isochromanone (1,4-dihydro-3H-2-benzopyran-3-one)
1, and its substituted derivatives, are important synthetic
intermediates for products of the pharmaceutical and agro-
chemical industries, as reported in a number of recent pat-
ents [1–6]. Compound 1 and derivatives can be synthesized
in various ways using sequences of ‘classical’ organic trans-
formations from available precursors [2,7]. However, the
most convenient procedures involve metal-catalyzed car-
bonylations of o-substituted benzene derivatives. Thus,
Stille reported the synthesis of 1 in 71% yield by palla-
dium-catalyzed carbonylation of o-bromomethylbenzyl
alcohol [8] and this yield can be significantly improved
using modified conditions and Pd(PPh3)4 as catalyst [9].
Homogeneous Pd-catalysts for transformation of 2 to 1
are reported to operate efficiently at loadings of around
0.3 mol% and can be introduced as Pd(II), with procedures
described for PdCl2, Na2PdCl4, ‘H2PdCl4’ (PdCl2/HCl) or
*
Corresponding authors.
E-mail address: W.E.Lindsell@hw.ac.uk (W.E. Lindsell).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.01.029

R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
2379
PdCl2(PPh3)2 [1,3,4], or as the Pd(0) species Pd(PPh3)4 but
with lower reported yields for the latter [1b,4]; supported
catalysts, including Pd/C, Pd/CaCO3 and Pd on Montmo-
rillonite, are also reported [1]. With the exception of PdCl2
in N-methylpyrrolidone (NMP) operating at higher CO
pressure and temperature [3], all successful described pro-
cedures require the presence of triphenylphosphine (ratio
PPh3:Pd P 2.2:1) and, although alternative phosphines
are claimed in patents, no specific examples are given.
Water is required as a reagent and reported processes
involve two phase aqueous/organic systems; a satisfactory
organic solvent is a tertiary alcohol (t-butyl or t-amyl alco-
hol) but other solvents such as toluene, xylene or a higher
ether may be used; N,N-dimethylformamide (DMF) or
NMP are also suitable; phase transfer agents can be added
but with negligible improvements in reported yields. It is
necessary to remove hydrogen halide during the reaction:
a base (B) is normally added and this may be inorganic
{e.g., Ca(OH)2 or KHCO3} or a hindered amine {e.g.,
NEtPri2} but the solvent fulfils this role for reactions car-
ried out in NMP or DMF. Reaction conditions are mild:
CO pressures of 0.1–0.4 MPa and temperatures of 70–
80 ꢁC are required for most systems described [1,3,4],
although temperatures of 130–150 ꢁC and CO pressures
of 2–4 MPa were specified for reactions in NMP and
DMF [3]. A plausible general mechanism is depicted in
Scheme 1.
tions of reactions involving palladium–phosphine com-
plexes with o-xylylene-a,a0-dihalides are reported in an
attempt to throw more light on the mechanism and side
reactions of lactone formation.
2. Results and discussion
2.1. Studies of palladium-catalyzed formation of
3-isochromanone from o-xylyene-a,a0-dihalides
Adopting procedures reported in Ref. [1c], o-xylylene-
a,a0-dichloride 2a reacted completely with CO (1 atm)
within 45–60 min at 70 ꢁC in the presence of a triphenyl-
phosphine-Pd catalyst (0.2 mol% Pd), yielding 3-isochro-
manone 1 in >80% yield. A convenient method to prepare
the catalyst is to react excess PPh3 with a Pd(II) compound,
such as Na2PdCl4, in a water/t-alcohol medium. An excess
of phosphine ligand is necessary to prevent loss of catalytic
activity which can be partly ascribed to the formation of
catalytically-inactive triphenylphosphine oxide in a side-
reaction during the course of the carbonylation; a P:Pd
molar ratio of ca. 20:1 was found experimentally to be suit-
able (cf. [1c]). To assess the efficacy of alternative phospho-
rus(III) ligands in this reaction, potential catalysts were
formed as yellow solutions or suspensions by premixing
an aqueous solution of Na2PdCl4 with an excess of ligand
(ligand:Pd ratio 20:1); phosphines PMe3, PEt3, P(C6H11)3,
P(C6F5)3 and P(p-C6H4OMe)3 were tested but only tri(p-
methoxyphenyl)phosphine showed activity under condi-
tions similar to those employed for PPh3 and its reactions
were slower; the other phosphorus ligands produced inac-
tive insoluble black residues during attempted reactions.
Attempted catalyses using phosphite ligands P(OPh)3 or
P(OEt)3 under similar conditions were also unsuccessful
but in these cases it is likely that significant hydrolysis of
the ligands occurred in the aqueous-alcoholic medium. It
appears that Pd–PPh3 systems are preferred catalysts but
do produce some by-products, including triphenylphos-
phine oxide.
2-Indanone 5 was identified as a minor by-product (<5%
by GC, at termination of catalysis). However, when dis-
solved in t-amyl alcohol in the presence of water and
NEtPri2 at 70 ꢁC (i.e., under catalytic conditions [1]),
2-indanone was shown by GC analysis to decompose
completely within 2 h. Therefore, it is likely that more
significant amounts of 2-indanone are formed during the
course of a catalyzed reaction. The decomposition prod-
ucts of 5 were not identified but could be a major source
of the tarry residues observed in catalytic systems.
2-Indanone has been reported as one product of decom-
position in solution of the isolable bis-trimethylphosphine
acyl complex 4a, which is formed by CO insertion into
the corresponding o-xylyl-palladium derivative, trans-
Pd(o-CH2C6H4CH2Cl)Cl(PMe3)2 3a [12]. A mechanism
involving a Pd(IV) metallacyclic intermediate 7a has been
proposed for this reaction [12], as illustrated in Scheme 2,
but without definitive supporting evidence; it may be noted
Although the Pd-catalyzed syntheses of 1 run satisfacto-
rily giving consistent yields of >80%, by-products are also
formed, including tarry residues. In this work, investiga-
X
X
2a X = Cl;
2b X = Br
Pd0Ln
L
BH+ X-
PdXL2
X
3
CO
B
PdXL2
HPdXLn
O
4
X
H2O + B
O
BH+ X-
+
O
1
Scheme 1. (L = PPh3 or related ligand; B = base).

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R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
Cl
L Pd
L
Cl
L
stable
organic
products
Pd
Cl
L
Cl
L
8
3a L = PMe3
3b L = PPh3
6a L = PMe3
6b L = PPh3
+PdCl2L2
CO
3 atm.
- CO
Cl
Cl
L
O
O
Pd
Cl
L
L
O
5
PdCl2L2
+
Cl
4a L = PMe3
4b L = PPh3
7a L = PMe3
7b
L = PPh3
Scheme 2.
that an alternative 6-coordinate, non-ionic structure for
intermediate 7a (and also for 6a) might equally be consid-
ered. Although trimethylphosphine complexes of palla-
dium were found to be catalytically inactive for the
synthesis of 3-isochromanone from o-xylylene-a,a0-dichlo-
ride under conditions used in the present study, the forma-
tion of 2-indanone in catalytic systems containing
triphenylphosphine complexes may occur by a similar
mechanism (i.e., 3b ! 4b ! 7b ! 5; Scheme 2). The for-
mation of Pd(IV) species with PPh3 ligands will be less elec-
tronically favorable than with PMe3 but kinetic evidence
for such intermediates with the former ligand has been
reported [13].
nioalkene ligands have been isolated in reactions of vinyl
halides [17]. Related reactions are aryl/phenyl [19,20] and
methyl/phenyl [21] interchange of complexes PdRX-
(PPh3)2, although only in the former reaction was the par-
ticipation of a phosphonium salt [PR(PPh3)3]X established
[19,22].
PPh3
X
PPh3
X
PPh3
X
X
Pd
X
PPh3
PPh3
X
9a X= Cl
9b X = Br
10
11
Another by-product of the catalytic systems, identified
primarily by NMR spectroscopy, is the bis-phosphonium
compound 9a. The maximum yield of this salt is limited
by the amount of added PPh3 but its formation removes
substrate and so reduces overall conversion to lactone.
Also, formation of this salt will reduce the concentration
of PPh3, which is necessary to prolong the activity of the
palladium catalyst. It is of interest that only the dicationic
salt is observed, whereas quaternization of compounds 2 at
low PPh3:xylylene dihalide ratios normally affords mono-
cationic salt 10 and more forcing conditions are required
to form 9 [14]. The presence of Pd complexes appears to
facilitate the double quaternization and it is likely that
xylyl–palladium complexes are involved in this side-reac-
tion. A possible mechanism is the transformation of 3b,
via an intermediate Pd(IV) metallacycle 6b (or correspond-
ing neutral 6-coordinate species; see Scheme 2) followed by
reductive elimination of one benzyl–Pd bond by combina-
tion with PPh3, to form a Pd(II) complex such as 11, con-
taining a phosphoniobenzyl ligand; a second reductive
elimination, with PPh3, of Pd–C from 11 may then yield
9a. The production of phosphonium salts by a similar
mechanism has been described for triphenylphosphine–pal-
ladium complexes with aryl [15], vinyl [16,17] and alkyne
[18] ligands, and ionic Pd-complexes with g2-phospho-
Since it is known that aryl phosphonium salts can add
oxidatively to Pd(0) complexes by P–C cleavage [15] and
that this reaction is also proposed as a step in aryl group
exchange reactions [19,22], we considered the possibility
that the xylylene group of salts 9 might be reintroduced
into the catalytic cycle by Pd-activation of the benzyl–P
bond. However, an equimolar mixture of 9b and Pd(PPh3)4
in refluxing acetonitrile showed no evidence of reaction
after 6 h so it may be concluded that the cation of salts 9
is inactive in catalytic processes operating under mild reac-
tion conditions and that they do contribute to decreased
yields of lactone 1.
2.2. Stoichiometric reactions of o-xylylene-a,a0-dihalides
with palladium complexes
The first step in palladium-catalyzed carbonylations of
o-xylylene dihalides 2 to form lactone 1 is believed to be
oxidative addition to palladium(0) generating a xylyl–Pd
complex 3, followed by insertion of CO, as shown in
Scheme 1. Campora et al. [12] have established that such
a reaction does occur between o-xylylene dichloride and
the bis-trimethylphosphine–Pd(0) complex, Pd(g-CH2@

R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
2381
CHCO2Me)(PMe3)2 12, to form the mononuclear product
3a at 20 ꢁC, even when using a 1:2 ratio of reagents 2a:12;
only over a significantly longer time, or at 50 ꢁC, does a
second oxidative addition occur to form the binuclear
species 13a. However, even at a reagent ratio of 1:1, only
binuclear 13b is obtained from analogous reactions of
o-xylylene dibromide at 20 ꢁC [12]. Compounds 13 are
stable in organic solvents under nitrogen but compound
3a decomposes slowly in solution at ambient temperatures
to afford PdCl2(PMe3)2 and organic compounds derived
from o-xylylene 8, see Scheme 2. Compounds 3a and 13
undergo insertion reactions with CO (3 atm) but, whereas
diacyl products from compounds 13 are stable, the monoa-
cyl product 4a derived from 3a decomposes slowly in
organic solvents at 20 ꢁC, as mentioned in Section 2.1,
producing PdCl2(PMe3)2, 2-indanone 5 and products from
o-xylylene 8 [12]. Mechanisms proposed [12] for these
decomposition reactions are shown in Scheme 2.
PPh3
Pd
PMe3
X
Fig. 1. Molecular structure of compound 3a (ellipsoids drawn at the 50%
probability level).
Me3P
OH
X
Pd
PMe3
Pd
X
Me3P
15a X= Cl
15b X= Br
13a X= Cl
13b X = Br
Table 1
˚
Selected bond lengths (A) and angles (ꢁ) of compound 3a
Pd(1)–C(1)
Pd(1)–P(1)
Pd(1)–P(2)
Pd(1)–Cl(1)
C(1)–C(2)
Cl(2)–C(8)
2.084(3)
2.3183(7)
2.3306(7)
2.4155(7)
1.494(4)
1.815(3)
C(1)–Pd(1)–P(1)
C(1)–Pd(1)–P(2)
P(1)–Pd(1)–Cl(1)
P(2)–Pd(1)–Cl(1)
C(2)–C(1)–Pd(1)
C(7)–C(8)–Cl(2)
91.37(8)
90.59(8)
92.46(3)
85.72(3)
120.48(19)
111.9(2)
We have confirmed the observations of Campora et al.
[12] and subjected a single crystal of mononuclear 3a,
obtained from dichloromethane/hexane, to analysis by X-
ray diffraction. The molecular structure is depicted in
Fig. 1 and important geometrical parameters are listed in
Table 1. The complex is trans-square-planar with a struc-
ture similar to that reported for trans-PdBr(p-CH2C6H5Br)-
o-xylylene dihalides in attempts to gain mechanistic infor-
mation about the catalytic systems. On mixing Pd(PPh3)4,
as a source of Pd(0), with an equimolar amount of 2a or
2b at ambient temperature in an inert organic solvent such
as toluene, solutions rapidly turned bright orange but then
faded in colour over 1–2 h, precipitating poorly-soluble,
yellow PdX2(PPh3)2 (X = Cl or Br, respectively); analysis
showed the latter was produced in high yield (ca. 90%),
probably by a double oxidative mechanism via intermedi-
ates of types 3 and 6 of Scheme 2. Small amounts of bis-
phosphonium salt 9 were also formed under these condi-
tions but, as in the catalytic reactions, no mono-phospho-
nium species 10 was observed.
˚
(PMe3)2 14 [23]. The Pd–C distance, 2.084(3) A, is close to
˚
2.078(13) A of 14; the Pd–P distances are slightly longer
˚
than those of the latter complex {2.307(5) A and 2.297(6)
[23]}, although closer to those reported for trans-
˚
PdBr(Et)(PMe3)2 {2.311(2) and 2.314(2) A [24]}. In com-
plex 3a, the angle P(2)–Pd–Cl is 85.72(3)ꢁ with other
L–Pd–L0 angles in the range 90.5–92.5ꢁ and the rms devia-
tion of atoms Pd–C(1)–P(2)–P(3)–Cl(1) from the coordina-
˚
tion plane is 0.0722 A; the plane of the o-xylylene ligand is
approximately perpendicular to the coordination plane
{interplanar angle Pd–C(1)–P(2)–P(3)–Cl(1)/C(1)–(8) =
86.82ꢁ} and this compares with a related angle of 85.2ꢁ in
complex 14 [23]. The chloromethyl group of 3a is remote
from the metal centre with the Cl-atom readily available
to form binuclear product 13a. There is no interaction
1H NMR spectroscopic monitoring of these reactions
showed formation of a new small broad resonance around
d2.81 or d2.75, from reaction of 2a or 2b, respectively, as
well as the small, sharp doublet at d5.28 (JP–H = 15.5 Hz)
or d5.25 (JP–H = 14.6 Hz) assignable to the CH2 groups
of the bis-phosphonium salt, 9a or 9b. The higher field
signal is consistent with a Pd–CH2 group (cf. [9]) of a tri-
phenylphosphine–xylyl–palladium complex 3b, or the
related bromo-derivative, formed by oxidative addition; a
dipalladium species analogous to 13 is possible but less
likely at such high substrate:Pd ratios. The intensity of this
˚
between the Pd and Cl atoms (separation 4.265 A) and no
evidence for incipient intramolecular oxidative addition
but there is no steric restriction to formation of the postu-
lated metallacyclic intermediate 6a in solution.
Since trimethylphosphine complexes are catalytically
inactive for synthesis of 1, we investigated stoichiometric
reactions of triphenylphosphine–palladium complexes with

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R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
resonance remained very low (<5%) throughout formation
of PdX2(PPh3)2, and it disappeared as the limiting reagent
was consumed (e.g., within 45 min for 2b in CDCl3) indi-
cating instability at ambient temperature and probably a
steady-state existence during the reaction. Attempted isola-
tion and purification of this unstable species for further
characterization by using lower temperature reactions,
and by addition of non-solvents was unsuccessful. Also,
attempts to produce the product by reactions of 2a with
other triphenylphosphine–Pd(0) complexes, PdL(PPh3)2
(L = dimethylmaleate, maleic anhydride or p-benzoqui-
none), failed. The greater instability of 3b (and its bromine
analogue), in comparison with 3a, must be associated with
the greater steric requirements and, possibly, the poorer
donor properties of the PPh3 ligands. Note that in oxida-
tive additions of o-hydroxymethylbenzyl halides to
Pd(PPh3)4 three phosphine ligands are displaced and
monophosphine complexes 15 containing a chelated
hydroxy group are isolable [9]; an intermediate of similar
geometry, if formed in reactions of xylylene dihalides 2,
with a Pd–halogen interaction, would provide a facile path-
way for decomposition via a Pd(IV) metallacycle of type
6b.
the water molecules interact via H-bonding with bromide
anions. The structure of 9b, including a solvated H2O, is
shown in Fig. 2 and selected bond lengths and angles given
in Table 2.
The structure of neutral 1,2-bis[(diphenylphosphino)-
methyl]benzene diselenide, o-C6H4(CH2PPh2Se)2 (dpmbSe2),
has been reported [25] and has some features analogous to
9b, but the two P–CH2bonds lengths of the former are
˚
˚
˚
slightly longer {1.832(3) A/1.8303(3) A, cf. 1.793(4) A/
˚
1.806(4) A}. The two positively charged PPh3 groups in 9b
are mutually trans, with P(1)–C(1) and P(4)–C(8) bonds
lying almost in the plane of the o-phenylene ring {torsional
angles: P(1)–C(1)–C(2)–C(3) = 6.4(6)ꢁ; C(6)–C(7)–C(8)–
P(2) = 4.5(6)ꢁ}; this orientation places the H-atoms of the
methylene groups C(1)H2 and C(8)H2 in an eclipsed confor-
mation and readily available for H-bonding with the anions.
This contrasts with the structure of dpmbSe2 in which one
P–CH2 bond points out of the o-phenylene plane, placing
the two CH2 groups in an approximate gauche conforma-
tion [25]. The two Brꢀ anions of 9b interact with one H-
˚
atom of each methylene group {Br(1) ꢁ ꢁ ꢁ H(1A) 2.69 A;
˚
˚
Br(1) ꢁ ꢁ ꢁ H(8B) 2.76 A; Br(2) ꢁ ꢁ ꢁ H(1B) 2.75 A; Br(2) ꢁ ꢁ ꢁ
˚
H(8A) 2.95 A}; Br(2) also closely approaches an ortho-
˚
hydrogen of a phenyl ring {Br(2) ꢁ ꢁ ꢁ H(12) 2.81 A}. Each
2.3. Structure of o-xylylene-a,a0-bis(triphenylphosphonium-
bromide) 9b
water molecule exhibits two H-bonding interactions with
Table 2
It was of interest to determine the molecular structure of
the dicationic bis-phosphonium by-product 9. A crystal of
the dibromide salt 9b, containing one water molecule and
one methanol of solvation per molecule of 9b, was obtained
from solution in methanol and its structure was determined
by X-ray diffraction. Interactions between the disordered
methanol molecules and the salt are insignificant, whereas
˚
Selected bond lengths (A) and angles (ꢁ) of compound 9b
P(1)–C(1)
C(1)–C(2)
C(2)–C(7)
C(2)–C(3)
C(2)–C(1)–P(1)
C(2)–C(7)–C(8)
1.793(4)
1.524(6)
1.416(6)
1.389(6)
P(2)–C(8)
C(7)–C(8)
1.806(4)
1.525(6)
C(6)–C(7)
C(7)–C(8)–P(2)
C(7)–C(2)–C(1)
1.391(6)
118.3(3)
118.1(4)
119.9(3)
117.0(4)
Fig. 2. Molecular structure of compound 9b (ellipsoids drawn at the 50% probability level).

R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
2383
Brꢀ anions of adjacent salt molecules {H(2W) ꢁ ꢁ ꢁ Br(2)
(Aldrich Chemicals) and used as supplied. 1H and
13C{1H} NMR spectra were recorded on Bruker AC 200
or DPX 400 spectrometers (at ca. 25 ꢁC) using SiMe4 as
internal reference and 31P{1H} NMR spectra on the
DPX 400 instrument using 85% H3PO4 as external refer-
ence. IR spectra were recorded using a PE1600 series FTIR
spectrophotometer. GC analyses were performed with a
PE8310 gas chromatograph and GCMS with an HP6890
˚
˚
2.95(7) A; H(1W) ꢁ ꢁ ꢁ Br(1)#2 2.54(2) A}.
In the solid state, the dication is slightly asymmetric but,
as expected, NMR spectra are consistent with a symmetri-
cal system in solution (e.g., singlet 31P NMR resonance of
equivalent P-atoms at d23.7). The 1H NMR spectra of salts
9 do include distinctive chemical shifts for resonances of
the AA0BB0 grouping of o-phenylene hydrogens, {d6.96
(br s) or d6.98 (complex m) for 9a or 9b, respectively}
which are well separated, to high field, from resonances
of the phenyl groups. However, there are no unusual inter-
actions in the solid state involving these o-phenylene
hydrogens that might be related to this shift and it proba-
bly arises from inductive effects of the P+ centres and/or
other interactions in solution between halide ions and this
aromatic ring.
gas chromatograph [containing
a
HP5MS (30 m ·
0.25 mm) capillary column] coupled to an HP5973 Quadru-
pole Mass Filter (EI, high-energy dynode/electron multi-
plier detector).
4.2. Syntheses, reactions and characterization
4.2.1. General procedure for homogeneous Pd-catalysed
carbonylation of o-xylylene-a,a0-dihalide to 3-isochromanone
(cf. [1c])
3. Conclusions
A solution of Pd-catalyst was prepared by stirring
Na2PdCl4 (0.0282 mmol) in water (1 cm3) with PPh3
(0.151 g,0.576 mmol) and t-amyl alcohol (5 cm3) for
30 min under a nitrogen atmosphere. The yellow solution
of preformed catalyst was then added to o-xylylene-a,a0-
dichloride 2a (2.5 g,14.3 mmol), ethyldiisopropylamine
(5.55 g,43 mmol) and water (5 cm3) in a glass reactor fitted
with a sintered gas inlet and condenser, and CO was bub-
bled slowly through this mixture. {If required, naphthalene
(0.5 g,3.9 mmol) was also added as an inert internal GC
standard}. The reactor was then heated to 70 ꢁC for peri-
ods of 0.75–2 h. GC analysis of the reaction mixture indi-
cated complete consumption of 2a within 1 h and the
formation of 3-isochromanone (>80%), accompanied by
small amounts of 2-indanone (<5%). As described previ-
ously [1], 3-isochromanone was isolated by extraction into
aqueous base and re-extraction into an organic solvent
after acidification, followed by distillation. (Catalyst and
tertiary alcohol and amine can be recovered in this pro-
cess.) The product 1 was identified by comparison with
The carbonylation of o-xylylene-a,a0-dihalides to form
3-isochromanone 1 catalyzed by triphenylphosphine com-
plexes of palladium involves an unstable xylyl–palladium
species, probably related to the previously isolated [12]
and now structurally characterized, trimethylphosphine
derivative 3a, which is more stable but catalytically inac-
tive. Palladium complexes with a range of other phospho-
rus(III) ligands are also inactive or less effective catalysts
than complexes with PPh3 and this must be related to
their inability to cycle readily between Pd(0) and Pd(II)
states, as required in the mechanism of Scheme 1. Small
amounts of 2-indanone 5 were detected at the completion
of a catalytic reaction and probably arise from cyclization
of a monoacyl intermediate 4; the instability of 5 under
the catalytic conditions suggests that decomposition of
more significant amounts of 5, formed during the course
of reactions, is a likely source of other by-products and
the cause of reduced yields of the desired lactone. Both
triphenylphosphine oxide and o-xylylenebis(triphenylphos-
phonium) salts 9 are also by-products of the PPh3-con-
taining catalytic systems and their formation removes
phosphine ligand necessary to prolong catalyst life and,
in the latter case, also removes substrate reducing the
yield of 3-isochromanone.
1
an authentic sample (IR, H NMR, GC).
The above procedure was adapted for investigating sys-
tems with other phosphorus(III) ligands by replacing PPh3
in the catalyst mixture with PMe3, PEt3, P(C6H11)3,
P(C6F5)3, P(C6H4-p-OMe)3, P(OPh)3 or P(OEt)3. However,
except for systems with P(C6H4-p-OMe)3, negligible
amounts of 1 were produced.
4. Experimental
4.1. General
4.2.2. Reaction of o-xylylene-a,a0-dichloride 2a with
tetrakis- (triphenylphosphine)palladium
Reactions and operations involving palladium com-
pounds were conducted under an atmosphere of dry, oxy-
gen-free nitrogen or argon gas, using Schlenk techniques.
Solvents were dried and freshly distilled before use as
previously described [9]. Tetrakis(triphenylphosphine)-
palladium [26], trimethylphosphine–palladium compounds
3a, 4a and 13a/b [12] and o-xylylenebis(triphenyl-
phosphoniumbromide) 15b [14] were prepared by literature
methods; other reagents were obtained commercially
o-Xylylene-a,a0-dichloride 2a (66.5 mg,0.38 mmol) dis-
solved in toluene (10 cm3) was added to a stirred suspen-
sion of tetrakis(triphenylphosphine)palladium (437 mg,
0.38 mmol) in toluene (40 cm3) to produce a bright orange
homogeneous solution. After stirring at ambient tempera-
ture for 2 h, the colour of solution changed to yellow and
a yellow precipitate formed which was separated from solu-
tion by filtration, washed with light petroleum ether and
dried in vacuo to afford a solid (237 mg) identified as

2384
R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
PdCl2(PPh3)2: NMR (CDCl3): dH/ppm 7.26–7.5 (m, 18H,
small resonances assignable to o-xylylene-a,a0-bis(triphe-
nylphosphinebromide) 9b, see below).
PPh3), 7.63–7.71 (m, 12H, PPh3). Solvent was evaporated
1
from the filtrate in vacuo to leave a yellow residue; H
NMR (CDCl3) of the residue showed resonances assign-
able to o-xylylene-a,a0-bis(triphenylphosphoniumchloride)
9a (see below) and a small amount of unreacted starting
4.2.4. Synthesis of o-xylylene-a,a0-bis(triphenylphosphine-
chloride) 9a (cf. [14])
o-Xylylene-a,a0-dichloride 2a (0.5 g, 2.86 mmol) and tri-
phenylphosphine (3.0 g, 11.44 mmol) were dissolved in ace-
tonitrile (70 cm3) and heated under reflux for 6 h. Cooling
to rt and refrigeration at 5 ꢁC, afforded the title product as a
white, crystalline solid which was collected by filtration,
washed with diethyl ether (3 · 20 cm3) and dried in vacuo
(832 mg,42%); m.p. >300 ꢁC; NMR (CDCl3): dH/ppm
5.28 (d, JHP 15.5 Hz, 4H, CH2P), 6.96 (br s, 4H, C6H4),
7.6–7.9 (m, 30H, C6H5); NMR (CD2Cl2): dH/ppm 5.53
(d, JHP 15.3 Hz, 4H, CH2P), 6.93 (m, 4H, C6H4), 7.59–
7.87 (m, 30H, C6H5).
1
material 2a, but no other new aliphatic H resonances.
4.2.3. Reaction of o-xylylene-a,a0-dibromide 2b with
tetrakis(triphenylphosphine)palladium
o-Xylylene-a,a0-dibromide 2b (264 mg, 1.0 mmol) dis-
solved in dry, degassed toluene (20 cm3) was added to a
stirred suspension of tetrakis(triphenylphosphine)palla-
dium (1.15 g, 1.0 mmol) in toluene (70 cm3), immediately
producing a bright orange homogeneous solution. After
stirring for 15 min the solution was cooled to 0 ꢁC and
petroleum ether (b.p. 60–80 ꢁC) (70 cm3) was added. A yel-
low-orange solid precipitated from the mixture, which was
isolated by filtration and dried in vacuo. On dissolving this
solid in CDCl3, (or in deuterated benzene, toluene or ace-
tonitrile) the solution changed within 1 min from pale
4.2.5. NMR data for o-xylylene-a,a0-bis(triphenylphosphine-
bromide) 9b
NMR (CDCl3), assignments made by DEPT, HMQC,
COSY, NOESY: dH/ppm 5.25 (d, JHP 14.6 Hz, 4H,
CH2), 6.98 (m, 4H, C6H4), 7.62–7.88 (m, 30H, PPh3); dC/
ppm 28.4 (d, JCP 50 Hz, CH2), 117.9 (d, JCP 86 Hz, PPh3,
ipso-CP), 128.5 (C6H4, CH-3 or 4), 129.4 (d, JCP 8 Hz,
C6H4, quat-CCH2), 130.4 (d, JCP 13 Hz, PPh3, o- or m-
CH), 132.4 (d, JCP 4 Hz, C6H4, CH-4 or 3), 134.4 (d, JCP
10 Hz, PPh3, m- or o-CH), 135.1 (PPh3, p-CH); dP/ppm
23.7 (s, CH2P+Ph3).
1
orange to bright yellow. H NMR analysis of the yellow
solution (CDCl3) indicated the presence of PdBr2(PPh3)2:
dH/ppm 7.25–7.52 (m, 18H), 7.63–7.79 (m, 12H); also, a
broad, weak signal d2.75 but no other aliphatic resonances.
(A weak signal at d2.75 was also observed by monitoring
the 1H NMR spectra in early stages of reactions of 2b with
Pd(PPh3)4 carried out in CDCl3; spectra also contained
Table 3
Crystal and structure refinement data
Compound
3a
9b Æ H2O Æ CH3OH
Empirical formula
Formula weight
Crystal system
Space group
C
433.59
Monoclinic
P2(1)/n
a = 11.2888(14)/a = 90
b = 14.1676(9)/b = 105.244(8)
c = 12.0999(10)/c = 90
1867.1(3)
14H26Cl2P2Pd
C45H44Br2O2P2
838.57
Monoclinic
P2(1)/n
˚
Unit cell dimensions (A)/(ꢁ)
a = 11.847(2)/a = 90
b = 15.943(3)/b = 94.820(10)
c = 21.028(3)/c = 90
3957.7(11)
3
˚
Volume (A )
Z
4
2
Density (calculated) (Mg/m3)
Absorption coefficient (mmꢀ1
F(0 0 0)
1.542
1.438
880
0.18 · 0.84 · 0.36
2.20–25.00
ꢀ1 6 h 6 13,
ꢀ16 6 k 6 1,
ꢀ14 6 l 6 14
4156
1.307
1.586
1572
0.68 · 0.46 · 0.21
1.91–25.00
ꢀ1 6 h 6 14,
ꢀ18 6 k 6 1,
ꢀ25 6 l 6 25
8617
)
Crystal size (mm3)
h Range data collection (ꢁ)
Index ranges
Reflections collected
Independent reflections
3288 [R(int) = 0.0311]
99.8
0.7187 and 0.4823
3288/0/172
6926 [R(int) = 0.0649]
99.3
0.9619 and 0.5713
6926/1/473
Completeness to maximum h (%)
Maximum/minimum transmission
Data/restraints/parameters
Goodness-of-fit on F2
1.053
1.031
Final R indices [I > 2r(I)]
R indices (all data)
Largest difference in peak and hole (e A
R1 = 0.0302, wR2 = 0.0801
R1 = 0.0324, wR2 = 0.0817
0.475 and ꢀ0.657
R1 = 0.0549, wR2 = 0.1237
R1 = 0.0886, wR2 = 0.1393
1.083 and ꢀ0.752
ꢀ3
˚
)

R.V.H. Jones et al. / Journal of Organometallic Chemistry 691 (2006) 2378–2385
2385
(c) R.V.H. Jones, A.J. Whitton, J.A. White, D.J. Ritchie, K.
MacCormick, L.T. Thomson, P.R. Evans, C.J. Bennie, US Patent
6888008, 2005.
4.3. X-ray data collection and crystal structure
determinations
[2] (a) A.G. Williams, M.C.H. Standen, N.R. Foster, R.V.H. Jones, US
Patent 6008381, 1999;
Single crystals of complex 3a were grown by slow dif-
fusion of hexane into a solution in dichloromethane at
ꢀ15 ꢁC and of 9b, solvated with methanol and water,
by slow evaporation of a solution in methanol. Crystals
were mounted on a glass fibre and data collected with a
Siemens P4 diffractometer. All datasets were collected
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˚
with Mo Ka radiation (0.71073 A) at 160(2) K with cool-
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For both structures, H atoms were constrained to ideal-
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which were found in the difference Fourier map and
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˚
the O–H distances restrained to 0.90(2) A. The hydroxyl
H atom was not included in the model of the methanol
solvent, where the carbon atoms were disordered over
two sites. One carbon was assigned 2/3 occupancy and
the hydrogen atoms bound to this atom were given full
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5. Supplementary material
Crystallographic information files (CIF) have been
deposited with Cambridge Crystallographic Data Centre:
CCDC reference numbers 2283696 and 2283697 for 3a
and 9b, respectively. Copies of this information can be
obtained free of charge by application to The Director,
CCDC, 12, Union Road, Cambridge CB2 1EZ, UK (fax:
+44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk or
http://www.ccdc.cam.ac.uk).
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Acknowledgements
We thank Syngenta and Heriot-Watt University for
funding. We also thank Dr. A.S.F. Boyd for recording
some NMR spectra.
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