Facile syntheses of four-membered aurathietane dioxide [Au-CHR-SO 2-CHR] ring systems, and the first isonitrile insertion reaction into a gold(III)-carbon bond

Article abstract of DOI:10.1016/j.jorganchem.2005.08.021

Cyclometallated gold(III) complexes derived from 2-benzylpyridine, 2-anilinopyridine [AuCl₂(C₅H₄N-X-C ₆H₄)] [X = CH₂ (2-bp) or NH (2-anp)] or 2-p-tolylpyridine (tolpy) [AuCl₂(C₅H₄NC ₆H₃CH₃)] react with the sulfones RCH ₂SO₂CH₂R (R = CN or COPh) in hot methanol with added trimethylamine base to give new aurathietanedioxide complexes containing the Au(CHRSO₂CHR) four-membered ring system. The previously reported cyclo-aurated dimethylbenzylamine (MeO-damp) complex [Au{CH(COPh)SO ₂CH(COPh)}(Me₂NCH₂C₆H ₃OMe)] was also synthesised by this method, and found to exist as a mixture of major (trans) and minor (cis) isomers with respect to the orientation of the COPh substituents across the four-membered ring. The reaction of one complex with ^tBuNC in refluxing dichloromethane results in insertion of the isonitrile into the Au-C bond trans to the phenyl ring, followed by proton transfer. An X-ray crystal structure determination on this product was carried out.

Full text of DOI:10.1016/j.jorganchem.2005.08.021

Journal of Organometallic Chemistry 690 (2005) 4971–4977
www.elsevier.com/locate/jorganchem
Facile syntheses of four-membered aurathietane dioxide
[Au–CHR-SO2-CHR] ring systems, and the first isonitrile
insertion reaction into a gold(III)–carbon bond
*
William Henderson , Brian K. Nicholson, Alistair L. Wilkins
Department of Chemistry, University of Waikato, Private Bag 3105, Hamilton, New Zealand
Received 27 June 2005; received in revised form 12 August 2005; accepted 12 August 2005
Available online 22 September 2005
Abstract
Cyclometallated gold(III) complexes derived from 2-benzylpyridine, 2-anilinopyridine [AuCl2(C5H4N-X-C6H4)] [X = CH2 (2-bp) or
NH (2-anp)] or 2-p-tolylpyridine (tolpy) [AuCl2(C5H4NC6H3CH3)] react with the sulfones RCH2SO2CH2R (R = CN or COPh) in hot
methanol with added trimethylamine base to give new aurathietanedioxide complexes containing the Au(CHRSO2CHR) four-membered
ring system. The previously reported cyclo-aurated dimethylbenzylamine (MeO-damp) complex [Au{CH(COPh)SO2CH(COPh)}-
(Me2NCH2C6H3OMe)] was also synthesised by this method, and found to exist as a mixture of major (trans) and minor (cis) isomers
t
with respect to the orientation of the COPh substituents across the four-membered ring. The reaction of one complex with BuNC in
refluxing dichloromethane results in insertion of the isonitrile into the Au–C bond trans to the phenyl ring, followed by proton transfer.
An X-ray crystal structure determination on this product was carried out.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Gold; Metallacyclic complexes; Sulfones; Isonitrile; Insertion reaction
1. Introduction
this methodology, products can be easily isolated in high
yields and purities. We also report that a gold(III) complex,
like its platinum(II) counterparts, undergoes isonitrile
insertion into a metal–carbon bond.
Complexes containing the metallathietane-3,3-dioxide
ring system 1 are rare in the literature. Platinum(II), palla-
dium(II) and nickel(II) complexes have been known for
some time [1,2], and insertion reactions with alkyl isonitr-
iles have been studied for some of these complexes [3]. Re-
cently, we have been carrying out studies into metallacyclic
complexes of gold(III) [4,5]. Gold(III) is isoelectronic (d8)
with platinum(II), and is expected to show similar chemis-
try. Reaction of the gold(III) dichloride complex 2 with
PhCOCH2SO2CH2COPh and Ag2O in refluxing dichloro-
methane gave the first example of an aurathietane-3,3-diox-
ide complex 3 [6]. In this paper, we report a convenient
synthetic route to a range of new aurathietane-3,3-dioxide
complexes, which uses trimethylamine as the base. Using
2. Results and discussion
Reaction of the gold(III) complex 2 with an excess of
diphenacylsulfone (PhCOCH2SO2CH2COPh) and excess
trimethylamine base in refluxing methanol gave the previ-
ously reported [6] aurathietane dioxide complex 3 as a
white solid in good yield. The complex is only slightly sol-
uble in the methanol solvent used, and is isolated in an ana-
lytically pure state directly from the reaction mixture.
Previously, this complex has been synthesised by the use
of silver(I) oxide as the base [6], but in our hands, this re-
agent often leads to the formation of products which are
apparently contaminated with traces of gold-containing
impurities and/or silver salts, as they are often more
*
Corresponding author. Fax: +64 7 838 4219.
E-mail address: w.henderson@waikato.ac.nz (W. Henderson).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.08.021

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W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
coloured, and light-sensitive, than the same product pre-
pared by the use of a tertiary amine as the base. We there-
fore prefer the use of a tertiary amine base for the synthesis
of such metallacycles, wherever it is successful.
tempt to dissolve the complexes for ESI MS analysis) were
also observed. The relative intensities of the [M + Na]+
ions varied depending on the solvent quality and instru-
ment cleanliness; for example, on some occasions the
[M + Na]+ ion for 7 dominated the spectrum whereas on
other occasions it was a relatively low intensity ion. The cy-
ano-substituted complex 10 showed rather different behav-
iour, with the [M + pyH]+ ion (m/z 588) and [M + Na]+
(m/z 531) the most intense peaks in the spectrum. Complex
11 had a very low solubility, even in pyridine, such that
it was difficult to obtain strong ion signals, but the
[M + Na]+ ion was the most intense for this compound.
We have investigated the behaviour of one of these com-
plexes (7) towards cone voltage-induced fragmentation,
where it shows appreciable stability. Thus, the spectrum
at a cone voltage of 200 V (the maximum for the instru-
ment used) has no observed fragment ions. Gold(III) com-
plexes with two ring systems typically show this extremely
high stability [4].
3. NMR spectroscopic characterisation
Detailed NMR spectroscopic characterisation of com-
plex 3 has been previously reported [6]. The 1H NMR spec-
trum of the sample of 3 reported herein (prepared by the
tertiary amine method) showed a major product species
with identical NMR spectroscopic properties to those pre-
viously reported, together with an additional set of signals
with approximately 10% relative intensity. With minor dif-
ferences, discussed below, the number and types of reso-
nances is consistent with the presence of an isomer of this
complex. A previous X-ray structure determination on 3
revealed it to have a trans disposition of COPh substituents
across the four-membered ring [6] and this is also the iso-
mer previously observed in platinum(II) analogues [1,2].
The minor component is therefore tentatively assigned as
the cis isomer, with the COPh substituents in a syn arrange-
ment with respect to the four-membered ring. Close inspec-
tion of the previously reported 1H NMR data for the
structurally characterised trans isomer also reveals a very
small trace of the cis isomer in this sample [6]. The cis iso-
mer of 3 shows ring CH protons at ca. d 5.4 and 4.8, which
are shielded relative to values of d 5.68 and 5.11 in the trans
isomer. Importantly, while the AuCH protons of the major
trans isomer appear as singlets, those of the minor cis iso-
In the same manner, reactions of the readily prepared
gold(III) dichloride complexes 4–6 with an excess of PhC-
OCH2SO2CH2COPh and aqueous trimethylamine in
refluxing methanol resulted in the formation of precipitates
of the aurathietane-3,3-dioxide complexes 7–9. Reactions
of 4–6 with the cyano-substituted sulfone NCCH2-
SO2CH2CN and Me3N gave the corresponding derivatives
10–12. All complexes were isolated in good yields by filtra-
tion and washing with cold methanol, and were analytically
pure without recourse to further purification. The colour-
less benzylpyridyl complex 7 is moderately soluble in
dichloromethane, DMSO and pyridine, while the cyano
derivative 10 is much less soluble; the tolylpyridyl complex
9 is only slightly soluble. The pale yellow anilinopyridyl
complexes 8 and 11 are effectively insoluble in all common
organic solvents tested.
4
mer appear as doublets. This arises as a result of J(HH)
coupling. The NCH2 protons of the cis isomer also appear
as an AB doublet of doublets, but the chemical shift differ-
ence between them is rather smaller than for the trans iso-
mer. Inspection of the crystal structure of the trans
complex 13 suggests that a cis isomer would have the two
cis protons in a distorted ÔWÕ configuration, in which long
range coupling constants are well known to be favoured.
Linking of two protons by alternative bond chains is also
known to optimise long-range couplings [7]. Heating a
1,2-dichloroethane solution of 3 did not effect any change
in the isomer ratio, suggesting that they are formed in the
The positive ion electrospray ionisation (ESI) mass spec-
trum of the benzoyl substituted aurathietane dioxide com-
plexes 7–9 gave various adduct ions, with the [M + H]+ ion
always the most intense. Adduct ions with Na+ and pyrid-
inium (pyH+) ions (formed from the pyridine used in an at-

W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
4973
synthesis process, and no interconversion occurs once
formed.
isonitrile moiety to the parent metallacycle. In contrast, no
reaction was observed between 7 and either norbornene,
CO, or CS2 after standing in dichloromethane for 5 days
at room temperature, when monitored by ESI mass spec-
trometry. In order to fully characterise the isonitrile inser-
tion product, a single-crystal X-ray diffraction study was
carried out.
The 1H NMR spectra of the benzylpyridyl and tolylpyr-
idyl complexes (7 and 9, respectively) also show the pres-
ence of major and minor isomers. For example, in
complex 9, Au–CH resonances for the major isomer (pre-
sumably trans) occur at d 5.74 and 5.21, while those for
the minor isomer occur at ca. d 5.6 and 4.9. The CH2 pro-
tons of both isomers of 7 are also inequivalent, and appear
The molecular structure of 15 is shown in Fig. 1, while
selected bond lengths and angles are given in Table 1. Com-
plex 7 has undergone an insertion reaction into the Au–C
bond trans to the cycloaurated phenyl ring, to give the
product 15. This is the isomer that would be expected on
the basis of the higher trans influence of the aryl group,
which labilises the trans Au–C bond. The insertion of the
isonitrile into the Au–C bond is followed by a transfer of
H from C(2) to N(1) giving rise to a hydrogen-bonded
3
as two AB doublets showing geminal J(HH) coupling of
14.7 Hz. The Au–CH protons are somewhat deshielded rel-
ative to the corresponding protons in the analogous plati-
num–triphenylphosphine complex 13 (d 4.86), and this
can be attributed to the higher oxidation state and electro-
negativity of gold(III) compared to platinum(II). Complex
12 was too insoluble to enable NMR spectroscopic charac-
terisation to be carried out, and indeed even characterisa-
tion of this complex by ESI MS was not possible due to
its low solubility.
˚
six-membered ring which is planar to within 0.02 A. This
feature is analogous to the behaviour observed previously
in the platinum(II) complex 14 [3]. The sums of the bond
angles around the carbon atoms C(2) and C(1) are
359.12ꢁ and 360.03ꢁ, respectively, consistent with planar
sp2 hybridisation at these carbons. However, the metallacy-
clic bond angle C(1)–C(2)–S(1) [112.10(19)ꢁ] is somewhat
smaller than the other two bond angles. The hydrogen is
˚
strongly bonded to N(1) [N(1)–H(1) 0.79 A] and weakly
˚
hydrogen-bonded to O(3) [O(3)Á Á ÁH(1) 1.88 A]. The C(4)–
O(3) [1.245(3)], C(2)–C(4) [1.426(4)], C(1)–C(2) [1.415(3)]
˚
and C(1)–N(1) [1.315(3)] bond distances (A) in the hydro-
gen-bonded ring compare reasonably with corresponding
˚
values of 1.246(17), 1.446(19), 1.396(16) and 1.333(17) A
in the related platinum complex 14, though the poorer pre-
cision in the platinum structure makes a detailed compari-
˚
son difficult [3]. Shorter C(5)–O(4) [1.208(3) A] and longer
˚
C(3)–C(5) [1.511(4) A] bond distances in the CH(COPh)
unit indicate the presence of substantial delocalisation of
the C–O, C–C and C–N bonds in the hydrogen-bonded
ring. The C(2)–S(1) and C(3)–S(1) bond distances
4. Insertion reactions of aurathietane dioxide complexes
Previous studies on platinathietane dioxide complexes
have demonstrated a facile reaction with alkylisonitriles,
whereupon insertion of an RNC molecule into a Pt–C
bond, followed by proton transfer, led to complexes of
the type 14, in which a phosphine ligand has been substi-
tuted by an RNC [3]. We thus wished to explore the
analogous insertion chemistry with the corresponding
gold(III) system. As far as we are aware, there has only
been one report in the literature of isonitrile insertion into
a gold–carbon bond, involving insertion of RNC (R =
2,6-dimethylphenyl) into the Au–C bond of the gold(I)
complex Ph3PAuCH2C(O)Ph, giving Ph3PAuC(=NR)CH2-
C(O)Ph [8].
Reaction of 7 with an excess of t-butylisonitrile in reflux-
ing dichloromethane for 10 min gave (on precipitation with
petroleum spirits) a pale yellow solid (15), for which the po-
sitive-ion ESI mass spectrum showed addition of a t-butyl-
Fig. 1. X-ray molecular structure of the t-butylisonitrile insertion product
15, showing the atom numbering scheme.

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W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
Table 1
˚
Selected bond lengths (A) and angles (ꢁ) for 15
Au(1)–C(3)
Au(1)–N(2)
2.017(2)
2.086(2)
S(1)–O(2)
1.434(2)
S(1)–C(2)
1.732(3)
O(3)–C(4)
1.245(3)
N(1)–C(1)
1.315(3)
N(2)–C(21)
1.338(3)
C(1)–C(2)
1.415(3)
C(3)–C(5)
1.511(4)
C(5)–C(41)
1.486(4)
C(17)–C(25)
1.492(4)
C(51)–C(54)
1.518(4)
Au(1)–C(11)
2.068(3)
Au(1)–C(1)
2.104(3)
S(1)–O(1)
S(1)–C(3)
1.4354(19)
1.783(3)
O(4)–C(5)
1.208(3)
N(1)–C(51)
1.476(3)
N(2)–C(25)
1.344(3)
C(2)–C(4)
1.426(4)
C(4)–C(31)
1.492(4)
C(16)–C(17)
1.507(4)
C(51)–C(53)
1.507(4)
C(51)–C(52)
1.519(4)
C(3)–Au(1)–C(11)
C(11)–Au(1)–N(2)
C(11)–Au(1)–C(1)
O(2)–S(1)–O(1)
O(1)–S(1)–C(2)
O(1)–S(1)–C(3)
C(1)–N(1)–C(51)
C(25)–N(2)–Au(1)
N(1)–C(1)–Au(1)
C(1)–C(2)–C(4)
C(4)–C(2)–S(1)
C(5)–C(3)–Au(1)
O(3)–C(4)–C(2)
C(2)–C(4)–C(31)
O(4)–C(5)–C(3)
C(12)–C(11)–Au(1)
C(25)–C(17)–C(16)
C(3)–Au(1)–N(2)
C(3)–Au(1)–C(1)
N(2)–Au(1)–C(1)
O(2)–S(1)–C(2)
O(2)–S(1)–C(3)
C(2)–S(1)–C(3)
C(21)–N(2)–Au(1)
N(1)–C(1)–C(2)
C(2)–C(1)–Au(1)
C(1)–C(2)–S(1)
C(5)–C(3)–S(1)
S(1)–C(3)–Au(1)
O(3)–C(4)–C(31)
O(4)–C(5)–C(41)
C(41)–C(5)–C(3)
C(16)–C(11)–Au(1)
92.79(10)
86.24(9)
174.78(9)
115.94(12)
111.42(12)
107.85(12)
133.3(2)
121.90(18)
126.63(19)
124.5(2)
122.52(19)
114.45(17)
121.0(2)
124.0(2)
120.9(2)
124.36(19)
111.0(2)
171.20(10)
82.71(10)
98.60(9)
111.81(13)
106.97(12)
101.67(12)
117.77(17)
117.8(2)
115.60(18)
112.10(19)
112.36(17)
104.45(12)
115.1(2)
Fig. 2. Side view of the central part of complex 15, showing the puckering
of cyclo-aurated gold-benzylpyridyl ligand, and the five-membered ring
formed by isonitrile insertion.
dihedral angle between the two rings is 65.3ꢁ; this is clearly
seen in Fig. 2. The benzoyl group on C(3) has remained
˚
fully planar (to 0.1 A) while that on C(2) is twisted so
that the aromatic plane is at 45.2ꢁ to the C(2)–C(4)–
O(3)–C(31) plane, precluding conjugation with this group.
The five-membered ring Au(1)–C(1)–C(2)–S(1)–C(3) is in
an envelope conformation with the Au atom at the apex.
5. Biological activity
In recent years there has been increasing interest in the
biological activity (particularly anticancer activity) of
gold(III) compounds [9], which are isoelectronic with the
well-known platinum(II) counterparts. Because gold(III)
is substantially more labile than platinum(II) [10], it could
be postulated that the presence of fairly strongly binding
ligands to the gold(III) may be required for an active com-
pound. We have therefore tested a selection of the aurathie-
tanedioxide complexes for their in vitro anticancer activity
against P388 murine leukemia cells; data are given in Table
2. The isonitrile insertion product 15, together with the
damp derivative 3 both showed good activity, most likely
due to the good solubility of these compounds in the sol-
vent mixture used. The solvent itself, a 2:1 mixture of meth-
anol and dichloromethane, showed little activity in the
assay. The remaining compounds showed either moder-
ately low or no activity, and no clear trends among the
121.1(3)
117.9(2)
117.43(18)
˚
[1.732(3) and 1.783(3) A, respectively] have significantly
different lengths, and compare with 1.73(2) and 1.75(2) A
in the four-membered aurathietanedioxide ring system in 3.
The Au centre is square-planar to within 0.1 A, and
the cyclometallated ligand is strongly folded so that the
˚
˚

W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
4975
age 50 V, MeOH), [M + H]+ (m/z 662, 100%), [M + Na]+
(m/z 684, 37%), [M + K]+ (m/z 700, 68%), [2M + Na]+
(m/z 1346, 19%), [2M + K]+ (m/z 1361, 17%).
Table 2
Antitumour (P388 murine leukemia) assay data for a selection of gold
complexes
Complex
IC50 (ng mLÀ1
)
IC50 (lM)
3
487
1310
4091
0.7
2.0
6.1
6.2. Synthesis of (2-bp)Au{CH(COPh)SO2CH(COPh)}
(7)
7
8
9
10
>62,500
30,456
1477
<487
>12,500
>93.9
60.1
2.9
A suspension of complex 4 (250 mg, 0.574 mmol) and
PhCOCH2SO2CH2COPh (250 mg, 0.827 mmol) in metha-
nol (30 mL) with aqueous Me3N (2 mL) was refluxed for
1 h giving a white suspension and very pale yellow superna-
tant. After cooling to room temperature the solid was fil-
tered, washed with cold methanol (5 mL) and diethyl
ether (10 mL) and dried under vacuum to give 7 (330 mg,
86%). M.p. 230–232 ꢁC. Found: C, 50.1; H, 3.3; N, 2.1.
C28H22NAuO4S requires C, 50.5; H, 3.3; N, 2.1%. ESI
MS (positive-ion, cone voltage 50 V, MeOH), [M + H]+
(m/z 666, 100%), [M + Na]+ (m/z 688, 22%), [M + pyH]+
12
15
<0.7
Solvent
a The concentration of sample in ng mLÀ1 and lM required to reduce the
cell growth of the P388 leukemia cell line by 50%.
different types of complexes could be ascertained. It is
known from previous studies that damp gold(III) deriva-
tives typically show good anticancer activity and the pres-
ent study is in concordance with this observation.
However, it is noteworthy that the isonitrile insertion prod-
uct 15 also shows promising anticancer activity, and this
suggests that more detailed studies into this type of deriva-
tive could prove fruitful.
1
(m/z 745, 5%), [2M + Na]+ (m/z 1354, 10%). H NMR, d
8.08–6.89 (m, aromatic H), 5.74 (s, Au–CH), 5.34 (s, Au–
CH), 4.32 [d, CH2, 3J(HH) 14.7] and 4.13 [d, CH2,
3J(HH) 14.7].
6. Experimental
6.3. Synthesis of (2-anp)Au{CH(COPh)SO2CH(COPh)}
(8)
General experimental procedures were as reported pre-
viously in publications from this laboratory [5,6]. Reac-
tions were carried out in LR grade methanol which was
used as supplied, without regard for the exclusion of air
or moisture. Electrospray ionisation (ESI) mass spectra
were recorded on a VG Platform II instrument, using
methanol as the solvent and mobile phase. Samples of
the gold complexes were suspended in 2 drops of pyridine,
diluted with methanol (total solids content ca.
0.1 mg mLÀ1) and centrifuged prior to analysis.
A suspension of complex 5 (260 mg, 0.596 mmol) and
PhCOCH2SO2CH2COPh (230 mg, 0.761 mmol) in metha-
nol (30 mL) with aqueous Me3N (2.5 mL) was refluxed
for 1 h giving a pale yellow suspension. After cooling to
room temperature the solid was filtered, washed with cold
methanol (5 mL) and diethyl ether (10 mL) and dried under
vacuum to give 8 (389 mg, 98%) as a pale yellow solid. M.p.
226–228 ꢁC. Found: C, 48.2; H, 3.1; N, 4.2.
C27H21N2AuO4S requires C, 48.7; H, 3.2; N, 4.2%. ESI
MS (positive-ion, cone voltage 50 V, MeOH), [M + H]+
(m/z 667, 100%), [M + Na]+ (m/z 689, 22%), [M + pyH]+
The compounds (2-bp)AuCl2 (4) [11], (2-anp)AuCl2 (5)
[12], (tolpy)AuCl2 (6) [13], (MeOdamp)AuCl2 (2) [14] and
PhCOCH2SO2CH2COPh [15] were prepared according to
minor modifications of the literature procedures. The sul-
fone NCCH2SO2CH2CN (Lancaster Synthesis) and aque-
ous trimethylamine solution (BDH, 25–30%) were used as
1
(m/z 746, 16%), [2M + Na]+ (m/z 1355, 5%). H NMR, d
8.25–6.17 (m, aromatic H), 5.51 (s, Au–CH), 4.95 (s, Au–
CH).
t
supplied. The isonitrile BuNC was prepared by the litera-
6.4. Synthesis of (tolpy)Au{CH(COPh)SO2CH(COPh)}
(9)
ture method [16].
6.1. Synthesis of (MeO-damp)Au{CH(COPh)-
SO2CH(COPh)} (3)
A suspension of complex 6 (135 mg, 0.310 mmol) and
PhCOCH2SO2CH2COPh (140 mg, 0.463 mmol) in metha-
nol (20 mL) with aqueous Me3N (2 mL) was refluxed for
1 h giving a white suspension. After cooling to room tem-
perature the solid was filtered, washed with cold methanol
(5 mL) and diethyl ether (10 mL) and dried under vacuum
to give 9 (170 mg, 82%) as a white solid. M.p. decomp.
>240 ꢁC. Found: C, 50.5; H, 3.3; N, 2.1. C27H22NAuO4S
requires C, 49.6; H, 3.4; N, 2.1%. ESI MS (positive-ion,
cone voltage 50 V, MeOH), [M + H]+ (m/z 666, 100%),
[M + Na]+ (m/z 688, 48%), [M + pyH]+ (m/z 745, 5%),
A suspension of complex 2 (200 mg, 0.463 mmol) and
PhCOCH2SO2CH2COPh (160 mg, 0.529 mmol) in ethanol
(30 mL) with aqueous Me3N (2 mL) was refluxed for
20 min giving a white suspension and very pale yellow
supernatant. After cooling to room temperature the solid
was filtered, washed with cold ethanol (5 mL) and dried un-
der vacuum to give 3 as a white solid (180 mg, 59%).
Found: C, 47.4; H, 3.9; N, 2.3. C26H26NAuO5S requires
C, 47.2; H, 4.0; N, 2.1%. ESI MS (positive-ion, cone volt-
1
[2M + Na]+ (m/z 1353, 18%). H NMR, d 8.27–6.89 (m,

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W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
aromatic H), 5.78 (s, Au–CH), 5.24 (s, Au–CH), 2.11 (s,
(10 mL), and dried under vacuum to give 15 as a pale yel-
CH3). Minor (cis) isomer, d 5.6, 4.9 (Au–CH), 2.2 (CH3).
low solid (74 mg, 66%). ESI MS (positive-ion, cone voltage
1
20 V), [M + H]+ (m/z 749, 100%). H NMR, d 12.93 (s,
6.5. Synthesis of (2-bp)Au{CH(CN)SO2CH(CN)} (10)
NH), 8.72–6.89 (m, aromatic H), 5.66 (s, Au–CH), 4.26
[d, CH2, 2J(HH) 14.6], 4.01 [d, CH2, 2J(HH) 14.6] and
1.20 (s, tBu). Recrystallisation by vapour diffusion of
diethyl ether into a dichloromethane solution at room tem-
perature gave colourless crystals of the product. M.p. par-
tial melting 170–190 ꢁC, melting 190–192 ꢁC (decomp.).
Found: C, 51.1; H, 4.1; N, 3.6. C33H31N2AuSO4 requires
C, 52.9; H, 4.2; N, 3.7.
A suspension of complex 4 (300 mg, 0.689 mmol) and
NCCH2SO2CH2CN (118 mg, 0.819 mmol) in methanol
(30 mL) with aqueous Me3N (2 mL) was refluxed for
40 min to give a white suspension. The mixture was cooled
to room temperature, water (10 mL) added, and the prod-
uct filtered, washed with water (20 mL) and diethyl ether
(20 mL) and dried to give 290 mg (83%) of 10 as a white
powder. The complex is poorly soluble in chloroform and
DMSO. M.p. decomp. >250 ꢁC. Found: C, 37.4; H, 2.1;
N, 8.2. C16H12N3AuO2S requires C, 37.9; H, 2.4; N,
8.3%. ESI MS (positive-ion, cone voltage 50 V, MeOH),
[M + Na]+ (m/z 531, 97%), [M + pyH]+ (m/z 588, 100%),
[2M + Na]+ (m/z 1039, 38%), [2M + pyH]+ (m/z 1096,
10%), [3M + Na]+ (m/z 1547, 20%), [3M + pyH]+ (m/z
1604, 5%), [4M + Na]+ (m/z 2055, 5%).
6.9. Attempted insertion reactions
Three separate portions of the complex 7 (60 mg) were
dissolved in distilled dichloromethane (5 mL), and to the
solutions were added norbornene (0.1 g), CS2 (2 drops),
or saturated with CO and sealed. The reaction mixtures
were allowed to stand for 5 days, and 1 drop of the reaction
mixture diluted with 1 mL of methanol and analysed by
ESI MS. In no case was any reaction observed.
6.6. Synthesis of (2-anp)Au{CH(CN)SO2CH(CN)} (11)
6.10. X-ray crystal structure determination on 15
A suspension of complex 5 (400 mg, 0.916 mmol) and
NCCH2SO2CH2CN (139 mg, 0.965 mmol) in methanol
(30 mL) with aqueous Me3N (2 mL) was refluxed for
40 min to give a pale yellow suspension. The mixture was
cooled to room temperature, and the product filtered,
washed with water (20 mL) and diethyl ether (20 mL) and
dried to give 385 mg (83%) of pale yellow 11. The complex
is poorly soluble in chloroform and DMSO. M.p. decomp.
>50 ꢁC. Found: C, 35.6; H, 2.1; N, 11.0. C15H11N4AuO2S
requires C, 35.4; H, 2.2; N, 11.0%. ESI MS (positive-ion,
cone voltage 50 V, MeOH), [M + Na]+ (m/z 530, 100%),
[M + K]+ (m/z 546, 40%), [M + pyH]+ (m/z 587, 35%).
The complex was too insoluble for NMR characterisation.
Colourless crystals were obtained by vapour diffusion of
diethyl ether into a dichloromethane solution of the complex
at room temperature. Unit cell parameters and intensity data
were collected using a Siemens SMART CCD diffractome-
ter, using standard collection procedures, with monochro-
matic Mo Ka X-rays (0.71073 A). Corrections for
absorption and other effects were carried out with SADABS
[17]. All other calculations used the SHELX-97 programs
˚
Table 3
Crystal data, collection and refinement details for the molecular structure
determination on 15
Empirical formula
Formula weight
C33H31AuN2O4S
748.62
6.7. Synthesis of (tolpy)Au{CH(CN)SO2CH(CN)} (12)
Temperature (K)
165(2)
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c
A suspension of complex 6 (300 mg, 0.689 mmol) and
NCCH2SO2CH2CN (118 mg, 0.919 mmol) in methanol
(30 mL) with aqueous Me3N (2 mL) was refluxed for
20 min to give a white suspension. The mixture was cooled
to room temperature, water (10 mL) added, and the prod-
uct filtered, washed with water (20 mL) and diethyl ether
(20 mL) and dried under vacuum to give 330 mg (94%) of
12 as a white powder. M.p. >280 ꢁC. Found: C, 37.7; H,
2.2; N, 8.2. C16H12N3AuSO2 requires C, 37.9; H, 2.4; N,
8.3%.
˚
a (A)
11.369(3)
15.668(4)
15.643(4)
95.410(3)
2774.0(12)
4, 1.793
5.422
1480
0.77 · 0.35 · 0.25 mm
1.80–26.59ꢁ
35,206/5730 [0.0280]
98.6%
0.3443 and 0.1028
Full-matrix least-squares
on F2
˚
b (A)
˚
c (A)
b (ꢁ)
3
˚
Volume (A )
Z, calculated density (mg mÀ3
)
)
Absorption coefficient (mmÀ1
F(000)
Crystal size
Theta range for data collection
Reflections collected/unique [Rint
Completeness to h = 26.59ꢁ
Maximum and minimum transmission
Refinement method
]
6.8. Synthesis of isonitrile insertion complex (15)
Complex 7 (100 mg, 0.150 mmol) was dissolved in
dichloromethane (20 mL) and t-butylisonitrile (3 drops, ex-
cess) added. The solution was refluxed for 10 min, and
petroleum spirits (70 mL) added to precipitate the product.
The solid was filtered off, washed with petroleum spirits
Data/restraints/parameters
Final R indices [I > 2r(I)]
R indices (all data)
5730/0/377
R1 = 0.0170, wR2 = 0.0406
R1 = 0.0198, wR2 = 0.0415
1.924 and À0.679
À3
˚
Largest difference in peak and hole (e A
)

W. Henderson et al. / Journal of Organometallic Chemistry 690 (2005) 4971–4977
4977
[18]. The structure was solved by direct methods and devel-
oped and refined routinely. Hydrogen atoms were placed
in calculated positions except for H(1) which was located
from a penultimate difference map and refined. Crystal data,
collection and refinement details are summarised in Table 3.
The assignment of N(2) to the position trans to C(3) was
unambiguously indicated by the refinement; interchanging
N(2) and C(11) gave a poorer R factor and distorted tem-
perature factors.
NMR spectra, Pat Gread for recording the electrospray
mass spectra, and Sarah Devoy and Kelly Kilpin for tech-
nical assistance. Professor Ward Robinson and Dr. Jan
Wikaira (University of Canterbury, NZ) are thanked for
collection of the X-ray data set.
References
[1] K.W. Chiu, J. Fawcett, W. Henderson, R.D.W. Kemmitt, D.R.
Russell, J. Chem. Soc., Dalton Trans. (1987) 733.
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Chem. Soc., Dalton Trans. (1989) 259.
7. Anticancer screening
Assays were carried out by the Marine Chemistry
Group, Department of Chemistry, Canterbury University,
New Zealand. Samples were dissolved or suspended in 2:1
methanol–dichloromethane prior to testing; some com-
pounds such as 3 and 15 were freely soluble whereas the
others had limited solubility in this (and other) solvents.
For these sparingly soluble compounds the observed activ-
ity therefore represents a minimum activity, and the true
activity is likely to be somewhat higher. Assays were car-
ried out by determining, by means of a twofold dilution
series, the concentration of sample in ng mLÀ1 required
to reduce the cell growth of the P388 leukemia cell line
(ATCC CCL 46) by 50%. The sample of interest was incu-
bated for 72 h with the P388 Murine Leukemia cells. IC50
values were determined by measurement of the absorbance
values when the yellow dye MTT tetrazolium is reduced by
healthy cells to the purple dye MTT formazan.
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8. Supplementary information
Crystallographic data have been deposited with the Cam-
bridge Crystallographic Data Centre, CCDC No. 276066.
Copies of this information can be obtained free of charge
from The Director, CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (Fax: +44 1223 336033; e-mail deposit@
ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk).
[15] E. Fromm, J. Flaschen, Liebigs Ann. Chem. 394 (1912) 310.
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Acknowledgements
[17] R.H. Blessing, Acta Cryst. A 51 (1995) 33.
[18] G.M. Sheldrick, SHELX-97, Program for the Solution and Refinement
of Crystal Structures, University of Go¨ttingen, Germany, 1997.
We thank the University of Waikato for financial sup-
port of this work, Dr. Ralph Thomson for recording some