Direct platination as a route to conformationally restricted enantiopure C2-symmetric bisoxazoline pincer complexes

Article abstract of DOI:10.1016/j.tetasy.2004.05.032

(S)-3-Amino-4-cyclohexyl-2-methylbutan-2-ol 10 was synthesised in four-steps from (S)-2-amino-3-cyclohexanepropanoic acid (47% overall yield). Reaction of 10 with 1,3-bis(ethyl carboximidate)benzene gave (S,S)-1,3-bis(4^′-cyclohexylmethyl-5

Full text of DOI:10.1016/j.tetasy.2004.05.032

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2067–2073
Direct platination as a route to conformationally restricted
enantiopure C2-symmetric bisoxazoline pincer complexes
John S. Fossey,a Geraint Jones,b Majid Motevalli,a Huy V. Nguyen,a
Christopher J. Richards,a,* Mark A. Starkb and Helen V. Taylora
aDepartment of Chemistry, Queen Mary, University of London, Mile End Road, E1 4NS, UK
bDepartment of Chemistry, CardiffUniversity, PO Box 912, CardiffCF10 3TB, UK
Received 13 May 2004; accepted 21 May 2004
Available online
Abstract—(S)-3-Amino-4-cyclohexyl-2-methylbutan-2-ol 10 was synthesised in four-steps from (S)-2-amino-3-cyclohexanepropa-
noic acid (47% overall yield). Reaction of 10 with 1,3-bis(ethyl carboximidate)benzene gave (S,S)-1,3-bis(40-cyclohexylmethyl-50,50-
dimethyl-20-oxazolinyl)benzene 13 in 53% yield. Heating 13 at reflux in acetic acid with K2PtCl4 gave (S,S)-chloro[2,6-bis(50,50-
dimethyl-40-methylenecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]platinum(II) 5 (22% yield). Similarly prepared were (S,S)-chloro[2,6-
bis(40-methylenecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]platinum(II) 6 (9%) and (S,S)-chloro[2,6-bis(40-methylethyl-20-oxazolinyl)-
4-nitrophenyl-N,C1,N0]platinum(II) 18 (21%). Chloride abstraction from 5 with AgOTf and 6 with AgOTf or AgSbF6, resulted in
isolation of the corresponding salts of (S,S)-aqua[2,6-bis(50,50-dimethyl-40-methylenecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]plat-
inum(II) or (S,S)-aqua[2,6-bis(40-methylenecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]platinum(II), respectively. The X-ray crystal
structures of 5 and 6 are reported and compared.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
4 have been used as catalysts for the aldol reaction of
isocyanides and aldehydes (up to 75% ee)1f and as
stoichiometric controllers of aldimine alkylation (up to
82% ee).1d In all of these cases the 5-positions of the
oxazoline rings were substituted with hydrogen
(R1 ¼ H). Part of our contribution to this previous work
was on the asymmetric Michael reaction between a-cy-
anocarboxylates and methyl vinyl ketone, where the
highest ee of 34% was obtained with the relatively long
and conformationally flexible R ¼ CH2Cy substituent.
Group 10 C2-symmetric bisoxazoline pincer complexes
of general structures 1 and 2 have recently been the
subject of several investigations.1 Following halide
abstraction (Scheme 1), the resulting cationic palladium
complexes 3 have been applied as catalysts for cyclo-
propanation (62% ee),1a Michael reactions (up to 34%
ee)1c;e and silylcyanation (0% ee).1g Platinum complexes
We reasoned that restriction of the conformational
freedom of this group by the introduction of gem-di-
methyl groups at position 5 (R1 ¼ Me) may lead to
higher enantioselectivities in the catalysis of this and
other reactions. Furthermore, we have also recently
found that cationic platinum bisoxazoline complexes
give faster rates of reaction than their palladium con-
geners when employed as catalysts for the Michael and
Diels–Alder reactions of nitriles.2 We therefore set about
to synthesise the conformationally restricted C2-sym-
metric platinum bisoxazoline pincer complex 5 with the
successful outcome of this investigation reported herein.
In addition, the X-ray crystal structure of this complex
is reported and compared to that of related complex 6.
_ Y
R1 R1
R1 R1
+
O
O
R
X
R
R
N
M
N
N
M
N
AgY/H2O
(-AgX)
OH2
R
O
R1 R1
O
R1 R1
1 M = Pd
2 M = Pt
3 M = Pd
4 M = Pt
X = halogen
Scheme 1.
*Corresponding author. Tel.: +44-020-7882-3271; fax: +44-020-7882-
7427; e-mail: c.j.richards@qmul.ac.uk
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.032

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J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
Me Me
Me Me
O
N
EtO
Cy
O
N
O
CN
CN
NH
Cy
Cy
Cy
Cy
N
i) K2CO3
HCl
.2HCl
NH
Pt
N
Pt
N
Cl
Cl
EtOH
ii) 10, PhCl
∆
N
O
5
6
Cy
EtO
O
O
13 53%
Me Me
11
12
Me Me
Scheme 3.
new complex 6 was similarly prepared from 15, and the
methodology further applied to the 5-nitro substituted
bisoxazoline 16, which gave the functionalised pincer
complex 18 (Scheme 4).
2. Results and discussion
Platinum bisoxazoline complexes have previously been
synthesised by either: (a) transmetallation of a 2-tri-
methylstannyl substituent employing Zeise’s salt
K[PtCl3(C2H4)](H2O) as the source of platinum,1d or (b)
direct cycloplatination with K2PtCl4 of precursor 1,3-
bis(2-oxazolinyl)benzenes containing only hydrogen at
position 2.2 Although the yields of the achiral bisoxazo-
line pincer complexes resulting from the latter approach
were modest (up to 49%), the simplicity of this method
was ideal for rapidly testing the viability of synthesising
target complex 5.
We have previously identified that the other reaction
occurring in this metallation protocol is the ring-open-
ing of the oxazolines under acidic conditions.2 As a
consequence, the pincer complexes are formed in rather
modest yield, but in its favour the method leads directly
to the platanacycles from 1,3-bisoxazolines, which in
turn are available in one- or two-steps from commer-
cially available starting materials. In contrast, higher
yields were reported for the introduction of platinum by
transmetallation of a 2-trimethylstannyl substituent.1f
However, these organometallics must be synthesised
from precursor 2-bromo-1,3-bisoxazolines, for which
the aromatic starting material, 2-bromoisophthalic acid,
is not commercially available and must be synthesised.5
In our hands we found the direct route described herein
is significantly more practical, especially for the syn-
thesis of functionalised complexes exemplified by 18.
The amino alcohol 10 required for this oxazoline was
synthesised as outlined in Scheme 2. Using methodology
related to the synthesis of other enantiopure amino
tertiary alcohols,1a;3 (S)-2-amino-3-cyclohexanepropa-
noic acid was first esterified to give 7 followed by N-
protection and treatment of the product 8 with excess
methylmagnesium bromide. Hydrolysis of the trifluoro-
acetamide functionality of 9 gave 10 as a colourless
crystalline solid after purification by Kugelrohr distil-
lation. Conversion of 1,3-dicyanobenzene 11 into the
imidate hydrogen chloride salt 12 was carried out as
previously described.4 Following neutralisation with
potassium carbonate, the free base was combined with
10 and the resulting mixture heated at reflux in chloro-
benzene for 16 h to give the desired bisoxazoline 13
(Scheme 3).
Satisfyingly, we also found that the methodology was
applicable to the platination of 13 resulting in the iso-
lation of 5, the first bisoxazoline pincer complex
substituted at the 5-position of the oxazoline rings
(Scheme 5). It is noteworthy that attempts to generate a
R
O
O
R
Cl
R
N
N
N
Prior to the attempted platination of 13, we first applied
the metallation methodology to the synthesis of other
C2-symmetric bisoxazoline platinum complexes. Thus
using the conditions previously developed,2 bisoxazoline
14 was heated with potassium tetrachloroplatinate in
acetic acid for 48 h resulting in the formation of complex
17, the physical and spectral characteristics of which
essentially identical to those previously reported.1f The
K2PtCl4
Pt
N
X
X
AcOH
∆
O
O
R
14 R = tBu, X = H
17 R = tBu, X = H 35%
6 R = CH2Cy, X = H 9%
18 R = iPr, X = NO2 21%
15 R = CH2Cy, X = H
16 R = iPr, X = NO2
Scheme 4.
Cy
Cy
O
TFAA, NEt3
CH2Cl2
Me Me
HCl.H2N
CO2Me
F3C
N
H
CO2Me
O
Cy
5 22%
Cy
8 94%
7
N
K2PtCl4
Cy
OH
Pt
N
Cl
Cy
13
O
MeMgBr
Et2O
AcOH
∆
KOH
OH
H2N
F3C
N
H
MeOH
O
9 73%
10 71%
Me Me
Scheme 2.
Scheme 5.

J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
2069
palladium pincer complex from 13 via regioselective
2-lithiation and transmetallation with PdBr2(COD)
proved unsuccessful. In contrast, this lithiation/trans-
metallation methodology is applicable to the synthesis
of a palladium congener of 6.1e The identity of 5 was
confirmed by X-ray crystal structure analysis (Fig. 1),
and to enable comparison of the structural and con-
formational properties of this molecule we also per-
formed an X-ray analysis of related complex 6 (Fig. 2,
Table 1).6
for which the changes on comparing 5 (R ¼ Me) to 6
(R ¼ H) are represented in Figure 3. In particular, the
averaged rotation of 77° to orientate the cyclohexyl
methine towards the R ¼ Me substituents, results in a
significant increase in the size of the ‘walls’ that define
the C2-symmetric cleft containing the exchangeable
coordination site. This was quantified by measuring the
angle from the C2-axis to the outermost edge of the van
der Waals surface of the cyclohexyl groups (Fig. 3).
Finally we wished to confirm that the chloride ligands of
both complexes could be replaced by an exchangeable
neutral ligand such as H2O. This has previously been a
requirement of the use of related systems in catalysis.1
Treatment of 6 with silver triflate or silver hexafluoro-
antiminate in wet acetone resulted in clean conversion
to the corresponding cationic complexes 19 and 20
(Scheme 6). The triflate salt was stored for several weeks
The two complexes display very similar bond lengths
and angles for the distorted square planar platinum
centres. The only significant difference is the shorter
Pt–C bond of 5 and a reduction in N–CH–CH2 bond
angles in 5 (e.g., 109.2° vs 110.9°). As anticipated, the
main differences lie in the conformation of the meth-
ylenecyclohexyl groups attached to the oxazoline rings,
Figure 1. Representations of the two independent crystal structures of 5.
Figure 2. Representations of the crystal structure of 6.
(b)
(a)
(c)
N
N
R O
N
-6o
Pt
Pt
Pt
Cl
R
θ = 54o
θ = 38o
H
N
N
77o
R = H
= exchangable coordination site
R = Me
Figure 3. (a) Average changes in the conformation of the methylenecyclohexyl groups on changing from R ¼ H to R ¼ Me, and a cartoon of the
environment about the exchangeable coordination site in (b) 6 and (c) 5.

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J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
ꢀ
Table 1. Key bond distances (A), angles (°) and torsions (°) for complexes 5 and 6
Complex 5
Complex 6
Space group
Pt(1)–C(7)
P21
Space group
Pt(1)–C(1)
C2
1.947(9)
1.843(4)
[1.893(4)]a
2.3834(11)
[2.3846(10)]
2.057(4)
[2.017(3)]
2.023(4)
[2.023(3)]
80.29(18)
[78.29(15)]
77.25(17)
[81.18(16)]
109.6(4)
[109.2(3)]
109.8(4)
[109.2(4)]
À168.4
Pt(1)–Cl(1)
Pt(1)–Cl(1)
Pt(1)–N(1)
––
2.381(2)
2.022(4)
––
Pt(1)–N(1)
Pt(1)–N(2)
C(7)–Pt(1)–N(1)
C(1)–Pt(1)–N(1)
––
79.22(10)
––
C(7)–Pt(1)–N(2)
N(1)–C(9)–C(17)
N(2)–C(13)–C(24)
N(1)–C(9)–C(17)–C(18)
N(2)–C(13)–C(24)–C(25)
C(9)–C(17)–C(18)–C(19)
C(13)–C(24)–C(25)–C(30)
N(1)–C(7)–C(8)
110.9(4)
N(1)–C(7)–C(8)–C(9)
––
À160.8
––
[166.6]
À167.6
[À163.6]
À167.1
C(7)–C(8)–C(9)–C(14)
––
69.9
––
[À179.8]
À177.5
[À167.8]
a For complex 5 the corresponding values of the second structure are given in parenthesis.
_X
cyclohexyl bond, significantly increases the height of the
‘walls’ of 5 that define the C2-symmetric cleft about the
exchangeable coordination site. That substitution reac-
tions can be performed at this position was confirmed by
chloride abstraction from both 5 and 6 to provide iso-
lable cationic complexes in excellent yield. The appli-
cation of these as catalysts in asymmetric synthesis will
be reported shortly.
+
R
R
O
Cy
OH2
Cy
N
19 R = H, X = OTf 98%
20 R = H, X = SbF6 94%
21 R = Me, X = OTf 75%
AgX
Pt
N
5 or 6
acetone
O
R
R
Scheme 6.
4. Experimental
exposed to the atmosphere without noticeable decom-
position. In contrast, the hexafluoroantiminate salt dis-
coloured after several hours exposure. Thus 5 was
treated with only silver triflate resulting in the isolation
of 21 as a pale yellow crystalline solid that darkened on
prolonged exposure to the atmosphere. This may be
avoided by storage under a nitrogen atmosphere.
Tetrahydrofuran was distilled from sodium benzophe-
none ketal; dichloromethane was distilled from calcium
hydride and glacial acetic acid was distilled from P2O5
and acetic anhydride, all under a nitrogen atmosphere.
Petroleum ether refers to the fraction boiling in the
40–60 °C range and column chromatography was per-
formed on SiO2 (40–63 lm). (S)-2-Amino-3-cyclohex-
anepropionic acid hydrate was obtained from Aldrich.
3. Conclusions
Direct platination of 1,3-bisoxazolines provides a con-
venient route to C2-symmetric bisoxazoline pincer
complexes. Systems unsubstituted at the 5-position of
the oxazolines are available in two- or three-steps from
commercially available starting materials. The platina-
tion method is also applicable to the synthesis of novel
complex 5 containing gem-dimethyl substituents at
position 5. The changes in the conformational properties
of 5, compared to its unsubstituted analogue 6, were
determined by X-ray crystal structure analyses. The
major change, an average 77° rotation about the CH2–
4.1. (S)-Methyl 2-amino-3-cyclohexylpropanoate hydro-
chloride 77
To a suspension of (S)-2-amino-3-cyclohexanepropa-
noic acid hydrate (5.44 g, 28.7 mmol) in dry methanol
(100 mL) was added TMSCl (17.26 g, 0.16 mol) and the
mixture heated at reflux overnight. After removal of the
solvent in vacuo 7 was isolated as a colourless solid
(6.20 g, 97%). mmax/cmÀ1 1749 (C@O); dH (CDCl3) 0.83
(13H, m, CH2Cy), 3.75 (3H, s, CH3), 4.00–4.04 (1H, m,
CHN), 8.79 (3H, br s, NH3).

J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
2071
4.2. (S)-Methyl 2-(trifluoroacetyl)amino-3-cyclohexyl-
propanoate 8
(CDCl3) 0.78–1.79 (13H, m, CH2Cy), 1.04 (3H, s, CH3),
1.16 (3H, s, CH3), 2.57 (1H, dd, J 11, 2, CHN); dC
(CDCl3){1H} 23.4 (CH3), 26.5 (CH2), 26.8 (CH2), 26.9
(CH2), 27.2 (CH3), 32.4 (CH2), 35.1 (CH2), 35.4
(CH2CH), 41.3 (CH2Cy), 57.4 (CHN), 72.0
(C(CH3)2OH); m=z (EI) 186 (MHþ, 6), 170 (3), 126 (71),
55 (100).
Trifluoroacetic anhydride (5.69 g, 27.1 mmol) was added
dropwise to
a suspension/solution of 7 (5.00 g,
22.6 mmol) and triethylamine (5.02 g, 49.6 mmol) in dry
dichloromethane (100 mL) at À78 °C, with stirring
continued at this temperature for 2.5 h. The reaction
mixture was then allowed to warm to room temperature
and stirred for a further 2 h. The resulting mixture was
washed with 0.1 M HCl (2 Â 20 mL), dried over Na2SO4,
filtered and concentrated in vacuo. The resulting pale
yellow oil was then purified by column chromatography
(EtOAc) to give 8 as a pale yellow oil, which solidified
on standing (5.96 g, 94%). Mp 64–65 °C (Found: C,
4.5. (S,S)-1,3-Bis(40-cyclohexylmethyl-50,50-dimethyl-20-
oxazolinyl)benzene 13
To a solution of 1,3-bis(ethyl carboximidate)benzene
dihydrochloride 124 (0.12 g, 0.41 mmol) in CH2Cl2
(10 mL) was added satd K2CO3ðaqÞ (5 mL) and the bi-
phasic mixture stirred vigorously for 10 min. The or-
ganic layer was separated, dried over Na2SO4, filtered
and the solvent removed in vacuo. The resultant mate-
rial combined directly with 10 (0.23 g, 1.2 mmol) in
chlorobenzene (10 mL) and the mixture heated at reflux
under a nitrogen atmosphere for 16 h. After cooling, the
solvent was removed in vacuo and the residue purified
by column chromatography (1:1 petroleum ether/
51.23; H, 6.50; N, 4.74. C12H18F3NO3 requires C, 51.25;
20
H, 6.45; N, 4.98%); ½aŠ ¼ þ35 (c 0.99, CHCl3); mmax
/
D
cmÀ1 (Nujol) 1750 (C@O), 1704 (C@O), 1567; dH
(CDCl3) 0.85–1.80 (13H, m, CH2Cy), 3.79 (3H, s, CH3),
4.69 (1H, td, J 8.5, 5.4, CHN), 6.84 (1H, d, J 7.3, NH);
dC (CDCl3){1H} 26.2 (CH2), 26.3 (CH2), 26.5 (CH2),
32.8 (CH2), 33.6 (CH2), 34.3 (CH2CH), 40.2 (CH2Cy),
50.9 (CHN), 53.2 (OCH3), 116.0 (q, J 286, CF3), 157.1
(q, J 37, C@O), 172.4 (CO2CH3); m=z (EI) 282 (MHþ,
37), 222 (57), 109 (56), 69 (100).
EtOAc) to yield 13 as a waxy orange solid (0.10 g, 53%):
20
D
½aŠ ¼ À12 (c 0.54, CHCl3); mmax/cmÀ1 (liquid film) 1643
(C@N); dH (CDCl3) 0.81–1.87 (26H, m, CH2Cy), 1.24
(6H, s, CH3), 1.41 (6H, s, CH3), 3.82 (2H, dd, J 9.8, 5.0,
CHN), 7.41 (1H, t, J 7.8, 5-H), 8.05 (2H, d, J 7.8, 4- & 6-
H), 8.40 (1H, s, 2-H); dC (CDCl3){1H} 26.3 (CH3), 26.5
(CH2), 26.7 (CH2), 26.9 (CH2), 28.0 (CH3), 32.6 (CH2),
33.2 (CH2), 34.8 (CH2CH), 37.4 (CH2Cy), 56.0 (CHN),
73.6 (OC(CH3)2), 126.1 (Ar, 2-C), 128.9 (Ar, 5-C), 130.3
(Ar, 4- & 6-C), 135.0 (Ar, 1- & 3-C), 167.9 (C@N); m=z
(APCI) 465 (Mþ, 100). HRMS (APCI) m=z found
465.3475; calcd for C30H45N2O2 465.3481.
4.3. (S)-4-Cyclohexyl-2-methyl-3-(trifluoroacetyl)amino-
butan-2-ol 9
A solution of 8 (8.20 g, 29.2 mmol) in dry THF (100 mL)
was cooled under an atmosphere of nitrogen to À78 °C
and to this was added dropwise an Et2O solution of
methylmagnesium bromide (48.7 mL, 146 mmol). The
reaction mixture was then allowed to warm to room
temperature, stirred for 3 h and quenched by careful
4.6. (S,S)-Chloro[2,6-bis(40-dimethylethyl-20-oxazolin-
yl)phenyl-N,C1,N0]platinum(II) 171f
dropwise addition of satd NH4Cl
(40 mL). The
ðaqÞ
organic layer was separated, dried over MgSO4, filtered
and the solvent removed in vacuo to give 9 as a
colourless crystalline solid (5.99 g, 73%). Mp 73–75 °C
(S,S)-1,3-Bis(40-dimethylethyl-20-oxazolinyl)benzene 141e
(0.045 g, 0.14 mmol) and K2PtCl4 (0.187 g, 0.45 mmol)
were heated at reflux in distilled acetic acid (15 mL)
under a nitrogen atmosphere for 48 h. The solvent was
removed in vacuo and the residue triturated with
petroleum ether and purified by column chromatogra-
phy (CH2Cl2). Removal of the solvent in vacuo gave 16
as a yellow crystalline solid (0.027 g, 35% yield, based on
14): mmax/cmÀ1 (CH2Cl2) 1607 (C@N); dH (CDCl3) 0.98
(18H, s, CH3), 4.05 (2H, dd, J 8.3, 2.2, NCH), 4.61 (2H,
t, J 8.8, OCHH), 4.89 (2H, dd, J 9.2, 2.2, OCHH), 7.12
(1H, t, J 7.6, Ar 4-H), 7.31 (2H, (66%) d, J 7.8, (34%)
(Found: C, 55.30; H, 7.92; N, 4.80. C13H22F3NO2 re-
20
quires C, 55.50; H, 7.88; N, 4.98%); ½aŠ ¼ À39
D
(c 0.89, CHCl3); mmax/cmÀ1 (Nujol) 3415 (OH, NH), 1705
(C@O); dH (CDCl3) 0.77–1.90 (13H, m, CH2Cy), 1.21
(3H, s, CH3), 1.24 (3H, s, CH3), 3.91–3.97 (1H, m,
CHN), 6.47 (1H, d, J 9.5, NH); dC (CDCl3){1H} 26.4
(CH2), 26.8 (CH2), 26.9 (CH2), 27.1 (CH3), 28.1 (CH3),
32.6 (CH2), 34.8 (CH2), 35.0 (CH2CH), 37.3 (CH2Cy),
55.9 (CHN), 73.2 (C(CH3)2OH), 116.6 (q, J 290, CF3),
158.0 (q, J 40, C@O); m=z (APCI) 282 (MHþ, 13), 264
(100), 112 (87), 87 (52).
4
app t, JPtH 7.1, Ar 3- & 5-H); dC (CDCl3){1H} 26.4
2
(CH3), 35.4 (CCH3), 70.2 ((34%) d, JPtC 25.3, NCH),
4.4. (S)-3-Amino-4-cyclohexyl-2-methylbutan-2-ol 10
122.1 (Ar, 4-C), 127.3 ((34%) d, 3JPtC 45.6, 3- & 5-C), 1-,
2- & 6-C not observed; m=z (FAB) 557 (Mþ, 6), 522
(MþÀCl, 100).
Potassium hydroxide (4.27 g, 76.1 mmol) was added to a
solution of 9 (10.70 g, 38.0 mmol) in dry methanol
(100 mL) and the resulting solution stirred overnight.
The solvent was then removed in vacuo and the resul-
tant yellow oil purified by Kugelrohr distillation to give
10 as fine colourless needles (5.00 g, 71%): Mp 61–
4.7. (S,S)-Chloro[2,6-bis(40-methylenecyclohexyl-20-oxaz-
olinyl)phenyl-N,C1,N0]platinum(II) 6
63 °C (Found: C, 71.23; H, 12.17; N, 7.30. C11H23NO
(S,S)-1,3-Bis(40-methylenecyclohexyl-20-oxazolinyl)benz-
ene 151e (2.1 g, 5.14 mmol) and K2PtCl4 (2.6 g,
6.26 mmol) were heated at reflux in distilled acetic acid
20
requires C, 71.30; H, 12.51; N, 7.56%); ½aŠ ¼ À35 (c
D
0.32, CDCl3); mmax/cmÀ1 (liquid film) 3423 (OH/NH); dH

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J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
(180 mL) under a nitrogen atmosphere for 48 h. The
solvent was removed in vacuo and the residue passed
through silica eluting with 5% ethyl acetate/CH2Cl2.
Slow evaporation of the yellow fraction gave 6 as a
vacuo. Purification by column chromatography (20%
EtOAc/CH2Cl2) gave 16 as a colourless crystalline solid
(0.240 g, 48%). Mp 66–68 °C (Found: C, 62.59;
H, 6.53; N, 12.39. C18H23N3O4 requires C, 62.59, H,
21
D
yellow crystalline solid (0.29 g, 9% yield based on 15).
6.71; N, 12.17%); ½aŠ ¼ À112 (c 0.1, EtOH); mmax/cmÀ1
20
D
Mp 279 °C (decomp.); ½aŠ ¼ þ136 (c 0.03, CHCl3);
(Nujol) 1659 (C@N); dH (CDCl3) 0.98 (6H, d, J 6.9,
CH3), 1.03 (6H, d, J 6.8, CH3), 1.76–1.85 (2H, m,
CH(CH3)2), 4.04–4.16 (4H, m, CHN & OCHH); 4.40
(2H, app t, J 7.9, OCHH), 8.75 (1H, s, Ar 2-H), 8.79
(2H, s, Ar 4- & 6-H); dC (d6-acetone){1H} 18.3 (CH3),
18.5 (CH3), 33.2. (CH(CH3)2), 71.4 (OCH2), 73.3
(CHN), 124.9 (Ar 4- & 6-C), 130.6 (Ar 1- & 3-C), 132.8
(Ar 2-C), 148.8 (Ar 5-C), 160.6 (C@N); m=z (EI) 345
(Mþ, 1), 302 (100), 258 (8), 214 (5), 189 (26), 149 (58), 57
(35).
m
max/cmÀ1 (thin film) 1610 (C@N); dH (CDCl3) 0.98–1.41
(12H, m, Cy), 1.46–1.80 (10H, m, Cy), 2.55 (2H, app t,
J 9.8, CHHCy), 3.72 (2H, app t, J 9.8, CHHCy), 4.38–
4.40 (2H, m, NCH), 4.58 (2H, dd J 8.5, 6.1, OCHH),
4.94 (2H, app t, J 9.0, OCHH), 7.08 (1H, t, J 7.6, Ar
4-H), 7.28 (2H, (66%) d, J 7.7, (34%) app t, 4JPtH 7.2, Ar
3- & 5-H); dC (CDCl3){1H} 26.0 (CH2), 26.2 (CH2), 26.4
(CH2), 32.2, 34.2, 34.9, 42.3 (CH2Cy), 60.9 ((34%)
2
d, JPtC 36.2, CHN), 77.4 (OCH2), 122.0 (Ar, 4-C),
126.8 ((34%) d, 3JPtC 40.0, Ar, 3- & 5-C), 128.0 ((34%) d,
1
2JPtC 38.1, Ar, 2- & 6-C), 161.4 (Ar, 1-C, JPtC not
2
observed), 178.7 ((34%) d, JPtC 170.0, C@N); m=z
4.9. (S,S)-Chloro[2,6-bis(40-methylethyl-20-oxazolinyl)-4-
nitrophenyl-N,C1,N0]platinum(II) 18
(FAB) 602 (MþÀCl, 100). HRMS (FAB) m=z
found for MþÀCl 602.2330; calcd for C26H35N2O2Pt
602.2346.
(S,S)-1,3-Bis(40-methylethyl-20-oxazolinyl)-5-nitrobenz-
ene 16 (0.028 g, 0.081 mmol) and K2PtCl4 (0.06 g,
0.14 mmol) were refluxed in glacial acetic acid (35 mL)
under nitrogen for 48 h. Following removal of the sol-
vent in vacuo, the resulting dark brown residue was
purified by column chromatography (CH2Cl2) to give 18
4.8. (S,S)-1,3-Bis(40-methylethyl-20-oxazolinyl)-5-nitro-
benzene 16
A solution of 5-nitroisophthaloyl dichloride (3.00 g,
12.1 mmol––prepared from commercially available 5-
nitro-1,3-benzenedicarboxylic acid) in CHCl3 (15 mL)
was added to a solution of (S)-2-amino-3-methylbutan-
1-ol (5.00 g, 48 mmol) in CHCl3 (125 mL) cooled to 0 °C.
The reaction mixture was allowed to warm to room
temperature and stirring continued for 24 h. Isolation of
the resulting solid by filtration, washing with CHCl3
(3 Â 100 mL) and recrystallisation from MeOH gave
(S,S)-N,N0-di(1-hydroxy-3-methyl-2-butyl)-5-nitro-1,3-
benzenedicarboxamide as a colourless powder (3.79 g,
82%). Mp 230–232 °C (Found: C, 56.42; H, 7.31; N,
as a yellow crystalline solid (0.0096 g, 0.017 mmol, 21%,
20
based on 16. Mp 252 °C (decomp.); ½aŠ ¼ þ72 (c 0.1,
D
CHCl3); mmax/cmÀ1 (thin film) 1611 (C@N) cmÀ1; dH
(CDCl3) 0.77 (6H, d, J 6.9, CH3), 0.97 (6H, d, J 7.1,
CH3), 2.88–2.90 (2H, m, CH(CH3)2), 4.47–4.50 (2H, m,
CHN), 4.82 (4H, app d, J 8.3, OCH2), 8.28 (2H (66%) s,
4
(34%) d, JPtH 6.9, Ar 3- & 5-H); dC (CDCl3){1H} 13.9
(CH3), 18.8 (CH3), 29.0 (CH(CH3)2), 67.4 ((34%) d, 2JPtC
3
33.3, CHN), 72.6 ((34%) d, JPtC 29.1, OCH2), 123.1
3
2
((34%) d, JPtC 42.6, Ar 3- & 5-C), 128.1 ((34%) d, JPtC
1
42.8, Ar 2- & 6-C), 143.3 (Ar 4-C), 168.7 (Ar, 1-C, JPtC
3
coupling not observed), 178.0 ((34%) d, JPtC 171.2,
11.27. C18H27N3O6 requires C, 56.68; H, 7.13;
C@N); m=z (TOF ES) 574.2 (Mþ, 18), 571
(MþÀClþMeOH, 100), 539 (MþÀCl, 83); HRMS (TOF
ES) m=z found for Mþ 574.1552; calcd for
C18H22ClN3O4Pt 574.0947.
20
D
N, 11.02%); ½aŠ ¼ À12 (c 0.1, EtOH); mmax/cmÀ1 (Nu-
jol) 3299, 3264 (NH), 3085 (OH), 1645 (C@O); dH (d6-
DMSO) 0.93 (6H, d, J 6.8, CH3), 0.97 (6H, d, J 6.8,
CH3), 1.93–2.02 (2H, m, CH(CH3)2), 3.54–3.63 (4H, m,
CHN & OCHH), 3.85–3.92 (2H, m, OCHH), 4.70 (2H,
t, J 5.5, OH), 8.60 (2H, d, J 8.8, NH), 8.80 (1H, s, Ar 2-
H), 8.86 (2H, s, Ar 4- & 6-H); dC (d6-DMSO){1H} 19.7
(CH3), 20.5 (CH3), 29.5 (CH(CH3)2), 58.2 (CHN), 62.0
(OCH2), 125.0 (Ar 4- & 6-C), 133.7 (Ar 2-C), 137.5 (Ar
1- & 3-C), 148.4 (Ar 5-C), 165.0 (C@O); m=z (CI) 382
(MHþ, 15), 147 (100).
4.10. (S,S)-Chloro[2,6-bis(50,50-dimethyl-40-methyl-
enecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]plati-
num(II) 5
(S,S)-1,3-Bis(40-cyclohexylmethyl-50,50-dimethyl-20-ox-
azolinyl)benzene 13 (0.387 g, 0.83 mmol) and K2PtCl4
(0.311 g, 0.75 mmol) were heated at reflux in distilled
acetic acid (20 mL) under a nitrogen atmosphere for
48 h. The solvent was removed in vacuo and the residue
dissolved in CH2Cl2, filtered through Celite, and col-
umn chromatographed (CH2Cl2) to give 5 as a bright
To a suspension of (S,S)-N,N0-di(1-hydroxy-3-methyl-2-
butyl)-5-nitro-1,3-benzenedicarboxamide (0.550 g, 1.44
mmol) in CH3CN (22 mL) containing NEt3 (1.03 g,
10.2 mmol) and CCl4 (1.55 g, 10.08 mmol) was added,
dropwise at room temperature, a solution of PPh3
(2.27 g, 8.65 mmol) in pyridine (25 mL) and acetonitrile
(25 mL). The resulting yellow solution was stirred at
room temperature overnight after which time it dark-
ened to brown. After concentration in vacuo, the
resulting mixture was redissolved in EtOAc (100 mL),
washed with water (2 Â 75 mL) and the organic phase
dried over MgSO4, filtered and the solvent removed in
yellow crystalline solid (0.13 g, 22%). Mp >250 °C;
22
½aŠ ¼ þ150 (c 0.1, CH2Cl2); mmax/cmÀ1 (CDCl3) 1609
D
(C@N); dH (CDCl3) 1.00–1.80 (22H, m, Cy), 1.56 (12H,
s, CH3), 1.90–1.97 (2H, m, CHHCy), 2.35–2.46 (2H, m,
CHHCy), 4.02 (2H, d, J 11, CHN), 7.10 (1H, t, J 7, Ar
4-H), 7.25–7.30 (2H, m, Ar 3- & 5-H); dC (CDCl3){1H}
22.4, 26.2, 26.4, 26.6, 29.6, 32.1, 34.6, 35.6, 37.8, 67.9
(CHN), 93.0 (OC(CH3)2), 121.9, 126.7, 128.7, 176.9

J. S. Fossey et al. / Tetrahedron: Asymmetry 15 (2004) 2067–2073
2073
(C@N); HRMS (ES) m=z found for MþÀCl 657.2939;
N,C1,N0]platinum(II) 5 (0.100 g, 0.14 mmol) and silver
triflate (0.064 g, 0.25 mmol) were stirred in acetone
(10 mL) for 24 h. The resulting precipitate of silver
chloride was removed by repeated (Â 4) filtration
through Celite, eluting with acetone, followed by re-
calcd for C30H43N2O2 194Pt 657.2946.
4.11. (S,S)-Aqua[2,6-bis(40-methylenecyclohexyl-20-oxaz-
olinyl)phenyl-N,C1,N0]platinum(II) triflate 19
moval of the solvent in vacuo to give 21 as a dark yellow
20
D
In a flask protected from light, (S,S)-chloro[2,6-bis(40-
methylenecyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]plat-
inum(II) 6 (0.130 g, 0.20 mmol) and silver triflate
(0.051 g, 0.20 mmol) were stirred in acetone (10 mL) for
24 h. The resulting grey precipitate of silver chloride was
removed by filtration through Celite, eluting with ace-
tone. Removal of the solvent in vacuo gave 18 as a dark
solid (0.087, 75% yield). Mp >250 °C; ½aŠ ¼ þ30 (c 0.2,
acetone);
m
max/cmÀ1 (thin film) 1609 (C@N); dH
(270 MHz, d6-acetone) 0.80–01.08 (4H, m, Cy), 1.08–
1.48 (6H, m, Cy), 1.52–2.20 (28H, m, Cy, 4 Â –CH3, 2Â
–CH2–), 4.06 (2H, dd, J 11.0, 2.6, CHN), 7.32 (1H, t, J
7, Ar 4-H), 7.42 (2H, d, J 7, Ar 3- & 5-H); dC (d6-ace-
tone){1H} 21.7, 25.8, 26.0, 26.1, 32.3, 34.5, 37.3, 67.9
(CHN), 94.9 (OC(CH3)2), 120.8, 120.9 (q, J 319, –CF3)
124.1, 127.7, 129.5, 178.9 (C@N) HRMS (ES) m=z found
for MþÀOTfÀH2O 658.2977; calcd for C30H43N2O2Pt
658.2972.
yellow sticky solid (0.154 g, 0.20 mmol, 98% yield). Mp
20
D
78 °C; ½aŠ ¼ þ97 (c 0.01, acetone); mmax/cmÀ1 (thin film)
1610 (C@N); dH (d6-acetone) 0.80–2.20 (26H, m,
CH2Cy), 3.85 (2H, br s, OH2) 4.47–4.48 (2H, m, CHN),
4.85 (2H, dd, J 8.0, 6.0, OCHH), 5.24 (2H, dd, J 8.5, 6.9,
OCHH), 7.32 (1H, t, J 6.4, Ar 4-H), 7.44 (2H, d, J 6.4,
Ar 3- & 5-H) no 195Pt coupling observed; dC (d6-acetone)
{1H} 24.3 (CH2), 27.2 (CH2), 33.9 (CH2), 35.1 (CH2),
Acknowledgements
2
44.9 (CH2), 61.8 ((34%) d, JPtC 27, CHN), 79.0 ((34%)
d, 3JPtC 20, OCH2), 124.9 (Ar 4-C), 129.0 (Ar 3- & 5-C),
130.1 (Ar 2- & 6-C), 131.2 (Ar 1-C), 177.2 ((34%) d, 2JPtC
169, C@N); m=z; (TOF ES) 602.2 (MþÀOH2ÀOTf,
100). HRMS (TOF ES) m=z: found for MþÀOH2ÀOTf
602.2349; calcd for C26H35N2O2Pt 602.2346.
We thank the EPSRC for support (J.S.F., G.J., H.V.N.,
M.A.S.) and the EPSRC National Mass Spectrometry
Service Centre, University of Wales, Swansea.
4.12. (S,S)-Aqua[2,6-bis(40-methylenecyclohexyl-20-oxaz-
olinyl)phenyl-N,C1,N0]platinum(II) hexafluoroantimonate
20
References and notes
1. (a) Denmark, S. E.; Stavenger, R. A.; Faucher, A.-M.;
Edwards, J. P. J. Org. Chem. 1997, 62, 3375; (b) Motoy-
ama, Y.; Makihara, N.; Mikami, Y.; Aoki, K.; Nishiyama,
H. Chem. Lett. 1997, 951; (c) Stark, M. A.; Richards, C. J.
Tetrahedron Lett. 1997, 38, 5881; (d) Motoyama, Y.;
Mikami, Y.; Kawakami, H.; Aoki, K.; Nishiyama, H.
Organometallics 1999, 18, 3584; (e) Stark, M. A.; Jones, G.;
Richards, C. J. Organometallics 2000, 19, 1282; (f) Motoy-
ama, Y.; Kawakami, H.; Shimozono, K.; Aoki, K.;
Nishiyama, H. Organometallics 2002, 21, 3408; (g)
Fossey, J. S.; Richards, C. J. Tetrahedron Lett 2003, 44,
8773.
2. Fossey, J. S.; Richards, C. J. Organometallics 2004, 23,
367.
3. (a) Bennett, S.; Brown, S. M.; Conole, G.; Kessler, M.;
Rowling, S.; Sinn, E.; Woodward, S. J. Chem. Soc., Dalton
Trans 1995, 367; (b) Davies, S. G.; Sanganee, H. J.
Tetrahedron: Asymmetry 1995, 6, 671.
In a flask protected from light, (S,S)-chloro[2,6-bis[40-
methylenecyclohexyl-20-oxazolinyl]pheny-N,C1,N0]plati-
num(II) 6 (0.034 g, 0.05 mmol) and silver hexafluoro-
antimonate (0.017 g, 0.05 mmol) were stirred in acetone
(10 mL) for 24 h. The resulting grey precipitate of silver
chloride was removed by filtration through Celite,
eluting with acetone. Removal of the solvent in vacuo
gave 19 as a dark yellow solid (0.043 g, 0.05 mmol, 94%
20
yield). Mp 119 °C; ½aŠ ¼ þ61 (c 0.1, acetone); mmax
/
D
cmÀ1 (thin film) 1609 (C@N); dH (400 MHz, d6-acetone)
0.62–2.00 (26H, m, Cy), 2.79 (2H, br s, OH2), 4.24–4.40
(2H, m, CHN), 4.87 (2H, dd, J 8.0, 6.1, OCHH), 5.12
(2H, dd, J 8.5, 7.0, OCHH), 7.20 (1H, t, J 6.9, Ar 4-H),
7.40 (2H, d, J 6.9, Ar 3- & 5-H), no 195Pt coupling ob-
served; dC (d6-acetone){1H} 23.2 (CH2), 27.3 (CH2), 33.7
(CH2), 35.2 (CH2), 43.5 (CH2), 62.0 (CHN), 79.1
(OCH2), 125.8 (Ar 4-C), 129.0 (Ar 3- & 5-C), 130.0 (Ar
2- & 6-C), 131.5 (Ar 1-C), 179.5 (C@N), no 195Pt cou-
pling observed; m=z (ES) 602 (MþÀSbF6ÀH2O, 67).
HRMS (ES) m=z found for MþÀSbF6ÀH2O 602.2339;
calcd for C26H35N2O2Pt 602.2346.
4. Zuev, P. S.; Sheridan, R. S. J. Org. Chem 1994, 59,
2267.
5. (a) Miyano, S.; Fukushima, H.; Inagawa, H.; Hashimoto,
H. Bull. Chem. Soc. Jp 1986, 59, 3285; (b) Padwa, A.;
Krumpe, K. E.; Kassir, J. M. J. Org. Chem 1992, 57, 4940.
6. Crystallographic data (excluding structure factors) for the
structures in this paper, have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 238166 (5) and 238165 (6).
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (Fax: +44(0)-1223-336033 or e-mail: deposit@
ccdc.com.ac.uk).
4.13. (S,S)-Aqua[2,6-bis(50,50-dimethyl-40-methylene-
cyclohexyl-20-oxazolinyl)phenyl-N,C1,N0]platinum(II)
triflate 21
In a flask protected from light, (S,S)-chloro[2,6-bis(50,50-
dimethyl-40-methylenecyclohexyl-20-oxazolinyl)phenyl-
7. Bonova, G. M.; Toniolo, C. Gazz. Chim. It. 1977, 107,
195.