The synthesis of unsymmetrically N-substituted chiral 1,4,7- triazacyclononanes

Article abstract of DOI:10.1039/b409259g

A number of chiral unsymmetrically N-substituted 1,4,7-triazacyclononane ligands have been prepared by modular methods. The key step in the synthesis centres on the macrocyclisation of three tertiary amide precursors under standard Richman-Atkins conditio

Full text of DOI:10.1039/b409259g

View Article Online / Journal Homepage / Table of Contents for this issue
A R T I C L E
The synthesis of unsymmetrically N-substituted chiral 1,4,7-
triazacyclononanes†
J. Erik W. Scheuermann,a Kevin F. Sibbons,a David M. Benoit,a,b Majid Motevallia and
Michael Watkinson*a
a
Department of Chemistry, Queen Mary, University of London, Mile End Road,
London, UK E1 4NS. E-mail: m.watkinson@qmul.ac.uk; Fax: +44 (0)20 7882 7427;
Tel: +44 (0)20 7882 3263
Department of Chemistry, University College London, Christopher Ingold Laboratories,
b
20 Gower Street, London, UK WC1H 0AJ
Received 18th June 2004, Accepted 23rd July 2004
First published as an Advance Article on the web 24th August 2004
A number of chiral unsymmetrically N-substituted 1,4,7-triazacyclononane ligands have been prepared by modular
methods. The key step in the synthesis centres on the macrocyclisation of three tertiary amide precursors under
standard Richman–Atkins conditions which allows for subsequent N-functionalisation.
Introduction
There continues to be great interest in macrocyclic polyamines
because of their rich and robust coordination chemistry,1
resulting in many applications of their complexes as biomimetics,
in medicine and in catalysis. In particular, those derived from
1,4,7-triazacyclononane (TACN), 1a (Fig. 1) (e.g. its N-alkyl
derivatives such as 1b) constitute a privileged class of ligand for
a variety of cations. Transition metal complexes of 1 have found
application as sensors,2 metalloenzyme biosite models (e.g. of
manganese containing enzymes3 and of dioxygen activation in
iron4 and copper enzymes5) as well as hydrolytic agents capable
of the non-oxidative cleavage of a range of substrates, including
activated esters,6 RNA7 and even DNA.8 Arguably greatest
interest has been generated by the activity of manganese
complexes of 1b in oxidative catalysis. This followed the initial
disclosure by Hage et al.9 that a range of manganese complexes
of 1b, including the remarkable complex 2 first reported by
Wieghardt et al.,10 were potent low-temperature bleaching
catalysts for domestic laundry applications. Subsequent
Fig. 1
reports detailing the application of manganese complexes in
the catalytic oxidation of alcohols,11 sulfides,12 alkanes13 and
alkenes14 have appeared, although it is alkene epoxidation; the
first reports of which were also presented in the seminal study
of Hage et al.,9 that has attracted greatest interest. Given this
interest, and the continued requirement for a generic catalytic
asymmetric epoxidation system, it is somewhat surprising that
examples of applications of enantiomerically pure analogues
of 1,4,7-triazacyclononanes in the epoxidation of alkenes are
limited to reports from Beller et al.,15 Bolm et al.,16 and Gibson
and co-workers.17 However, the apparently simple macrocyclic
structures, like 3–5, belie the underlying synthetic challenge,
as recently noted by Kopac and Hall18 as well as Gibson and
co-workers,17b and there remain very few examples of chiral
analogues of 1 in which the stereochemistry is included within
the carbon skeleton of the macrocyclic ring.19
to applying them in asymmetric catalysis. Our investigations
have followed broadly similar lines to those of Kim et al.21 as
well as Gibson and co-workers,17,22 in contrast to these studies,
however, a principal goal for us has been to develop convenient
routes towards unsymmetrically N-substituted enantiomerically
pure ligand systems like 5b (R1 ≠ R2). We believe that such
frameworks will be of interest in catalysis because of the efficacy
of binuclear metal complexes in certain catalytic applications7a
and also the uncertainty surrounding the active catalytic species
in the manganese oxidation systems.9 Herein we present the first
example of a concise route towards a number of such ligands.
Results and discussion
Unfortunately the conventional synthetic routes that are used to
prepare unsymmetrically N-substituted derivatives of 1,23 such
as statistical alkylation of 1 or the selective derivitisation of its
orthoamide,24 are not applicable to chiral analogues, as complex
mixtures of products would result. It is therefore necessary to
incorporate the desymmeterisation of the N-substituents prior
to (route A), or during (route B), the macrocyclisation step
(Scheme 1).
We,20 along with others,17,21,22 are currently engaged
in
a programme developing efficient routes to 1,4,7-
triazacyclononane ligands bearing two stereocentres (C-2,6)
derived from chiral pool amino acids, like 5a, with a view
† Electronic supplementary information (ESI) available: Molecular
modelling methodology. Figs. S1–S4: Lowest energy conformation
calculated for the protonated form of 6b, 6b·HOAc, the protonated form
of 6a and 6a·HOAc. Figs. S5 and S6: Charge distribution calculated for
the protonated forms of 6a and 6b. See http://www.rsc.org/suppdata/
ob/b4/b409259g/
We have previously successfully adopted the latter approach in
the direct synthesis of unsymmetrically N-substituted analogues
of 1 (from 8: R = H, R2 = Ts, R1 = Bn)23 but subsequently
found it impossible to apply this procedure to the synthesis of
unsymmetrically N-substituted analogues of 4.19j Unfortunately
2 6 6 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

View Article Online
Scheme 1
both ourselves20 and Gibson and co-workers,17a have previously
demonstrated that for the former approach (route A), the
presence of the synthetically convenient benzylic tertiary amine
in 6 (R1 = Bn, R2 = Ts) is not compatible with the formation
of the desired nine-membered macrocyclic ring 5b (R1 = Bn,
R2 = Ts). The approach that we both adopted towards the
first-generation macrocycles was thus to reveal the secondary
amines 6 (R1 = H, R2 = Ts) by catalytic hydrogenation and
then to re-protect them as their sulfonamides 6 (R1 = R2 = Ts)
which then underwent facile macrocyclisation under standard
Richman–Atkins conditions. Whilst Gibson and co-workers
have subsequently moved away from this approach due to
solubility issues during the debenzylations,22 we have continued
to use this method and, in one case, were intrigued by the regular
isolation of 11a under these reaction conditions for some time
(Scheme 2). We assumed that 11a had formed as a result of the
in situ reaction of the secondary amine 6a with anhydride 10,
following reaction of TsCl with a stoichiometric quantity of
the acetate anion, and were able to support this postulate by
a control experiment on the free amine 6a which also yielded
amide 11a (see Experimental section).
Fig. 2 ORTEP plot of the single crystal X-ray structure of 6b with
50% probability ellipsoids.
delighted to find that 11a underwent macrocyclisation cleanly
under conventional Richman–Atkins conditions to yield 12a
(Scheme 3).
As a result of this successful outcome we were able to
develop this procedure (now using acetic anhydride to prepare
acetamides 11, see Experimental section) towards the synthesis
of other related azamacrocyclic precursors 12, the structure
of 12b being corroborated by single crystal X-ray diffraction
(Fig. 3).
The single-crystal X-ray structure of 12b is comparable
to other closely related structures that have been recently
reported.17b,19j,20 The triazamacrocyclic ring adopts a chair-
boat-like conformation with the sulfonamide groups pseudo-
equatorial, situated on the opposite face of the ring to the
isopropyl groups adjacent to them. The two sulfonamide groups,
N(1)andN(2), aresimilarwithcomparablenitrogen–sulfurbond
lengths (S(1)–N(1) = 1.6272(18) Å, S(2)–N(2) = 1.6292(18) Å).
Although both sulfonamide nitrogen atoms deviate from
planarity, N(1) 0.0940 and N(2) −0.0556, this deviation is
smaller than that observed by Gibson and co-workers in the
related (2S)-2-isopropyl-1,4,7-tris[(4-methylphenyl)sulfonyl]-
1,4,7-triazacyclononane.17b In contrast the acetamide group
lies parallel to the ring system, with oxygen O(5), nitrogen N(3)
and carbon C(24) along with the adjacent carbon atoms C(16),
C(17) and C(25) forming a plane (the distances of these atoms
from a calculated plane of least squares are: C(16) −0.0135(21);
C(17) −0.0766(23); C(24) 0.0066(23); C(25) −0.0652(27); N(3)
0.0766(19) and O(5) 0.0079(17)). The single-crystal X-ray
structure also reveals significant differences in the environments
of the Pri side chains. Whilst the Pri group attached to C(18) is
situated underneath the p-system of the sulfonamide group, that
attached to C(15) is considerably further away from the p-system
of the other sulfonamide group. The conformation observed
in the crystal structure accounts for the loss of C2-symmetry
Scheme 2
This was rather puzzling, as the standard work-up used in all
hydrogenation reactions in this series involved neutralisation
with KOH to liberate the secondary amine; moreover, we never
observed this phenomenon in the other cases (6b: R = Pri,
R1 = H, R2 = Ts; 6c: R = Bus, R1 = H, R2 = Ts). We thus
postulated that 6a formed a particularly stable ammonium salt in
the presence of acetic acid as a result of a major conformational
change predicted by molecular modelling (see also ESI†).
Our attempts to substantiate this by NMR titration proved
fruitless, although they did result in our isolation of single
crystals of free amine 6b whose structure appeared consistent
with the modelling (Fig. 2). A subsequent reinvestigation of the
procedure revealed nothing untoward as free amine 6a could be
routinely isolated. Nonetheless this proved to be a fortuitous
result as we were aware that benzamides had previously been
employed by Bulkowski and co-workers25 and Parker and co-
workers19e,26 in the synthesis of selectively N-functionalised
polyamine macrocyclic ligands under standard Richman–Atkins
conditions, including derivatives of 1; furthermore, the selective
removal of the benzamide group to generate unsymmetrically
N-substituted macrocycles was demonstrated. We viewed the
procedure of Parker and co-workers,19e,26 in which detosylation
could be accomplished using concentrated sulfuric acid whilst
leaving the benzamide intact, as a particularly appealing strategy
and speculated whether this would be applicable to acetamide
11a, as this would provide a direct route towards our target
generic unsymmetrically N-substituted ligand 5b. We were
1
observed in the 13C and H NMR spectra, particularly the
differences observed for the Pri signals, which appear to indicate
that the solid and solution state structures of 12b are the same.
With extra confidence in the structural integrity of 12b we
embarked upon the application of Parker’s conditions for the
selective removal of the sulfonamide groups. To our delight this
could be effected cleanly and in high yield using concentrated
sulfuric acid to yield unsymmetrically N-substituted macrocycle
13. Similarly an ethanolic solution of hydrochloric acid led to
the facile removal of the acetamide group to furnish macrocycle
14;21 we believe this route to provide a superior synthetic
procedure as it provides greater synthetic flexibility in protecting
group chemistry allowing selective removal of either group.
Subsequent removal of the remaining protecting groups in 13
and 14 could then be readily achieved, using the appropriate
conditions (see Scheme 3) to yield 15,21,22 although we have
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0
2 6 6 5

View Article Online
Scheme 3 Reagents and conditions: i, 7, Cs2CO3, CH3CN, D; ii, H2SO4 (conc.), D; iii, EtOH, HCl, D, 2 d.; iv, LiAlH4, THF, D; v, 1,3-
bis(bromomethyl)benzene, Cs2CO3, CH3CN, D, 3 d.
anhydrous were dried as follows: Acetonitrile was refluxed for
5 h with calcium hydride in an atmosphere of nitrogen and
then distilled from calcium hydride. THF was distilled from
sodium and benzophenone ketyl in an atmosphere of nitrogen.
Nitrogen for inert atmosphere use was purified by passing it
through anhydrous manganese(II) oxide, 3 Å molecular sieves
and highly reduced chromium adsorbed onto a silica support.
Thin layer chromatography (TLC) was performed on silica gel
60 F254 plates (Merck). Melting points were determined using an
Electrothermal melting point apparatus and are uncorrected.
Optical rotations were determined using an Optical Activity
LTD, AA-1000 polarimeter and concentrations are reported
in g/100 cm3. Elemental analyses were obtained using a Carlo
Fig. 3 ORTEP plot of the single-crystal X-ray structure of 12b with
50% probability displacement ellipsoids.
1
Erba 1106 elemental analyser. H and 13C NMR spectra were
recorded as CDCl3 solutions, unless otherwise stated, on a JEOL
JNM-EX270 spectrometer at 270 and at 67.9 MHz, respectively,
and were referenced to residual chloroform as the internal
standard; J values are given in Hertz. IR spectra were recorded
on a Perkin-Elmer 1720X FT-IR spectrometer with a solid-state
ATR attachment, with the exception of 16a and 16b which were
recorded as dichloromethane solutions using KBr discs on a
Shimadzu FTIR 8300 spectrometer. Mass spectra were either
recorded on a VG Instruments ZAB-SE using xenon gas at
8 kV in a matrix of 3-nitrobenzyl alcohol (mNBA) and sodium
iodide (FAB) (University of London Research Instruments
Service, School of Pharmacy, University of London) or a
Waters ZQ4000 or a MAT 900XLT (ESI) (EPSRC National
Mass Spectrometry Service Centre, Chemistry Department,
University of Wales, Swansea).
found that the yield and purity of 15 to be superior when the
acetamide is removed first i.e. via 14.
We have also been able to develop this synthetic strategy
further to provide reliable routes towards new ligands of this
type. Firstly we were readily able to effect the reduction of the
tertiary amide 12b using LiAlH4 to yield the ethyl substituted
macrocyclic tertiary amine 16a. Although the selective
N-alkylation of 1 is known, the reported methods are not readily
applicable to these chiral analogues. We therefore believe that
this approach will prove particularly useful in the development
of active catalysts, as it provides an expedient means for
steric and electronic fine-tuning of ligand frameworks to be
undertaken through the incorporation of alternative tertiary
amides prior to the macrocyclisation step. We have also been
able to use the unsymmetrically N-substituted intermediate
14 to produce the novel binucleating ligand 17b, albeit in low
yield. Similarly achiral binucleating ligands like 17 derived from
1 are well known, and of considerable current interest, but the
synthetic routes towards them are again inappropriate to the
preparation of chiral analogues.27
Tertiary amides 11a–c were all prepared in an identical
manner as exemplified by the synthesis of 11b.
Synthesis of (2S,6S)-4-acetyl-1,7-di-p-toluenesulfonyl-2,6-
dibenzyl-1,4,7-triazaheptane 11a
Amide 11a was initially isolated due to the adventitious
formation of anhydride 10 in situ. To support this postulate,
amide 11a was prepared as outlined below; however, it can be
routinely prepared on a large scale in the same manner as that
detailed for 11b.
In summary, we have developed an efficient and modular
synthetic route towards unsymmetrically N-substituted chiral
1,4,7-triazacyclononane ligands. In addition this route allows
us to access potentially important binucleating ligand structures
like 17b. To the best of our knowledge this represents the first
report of ligand systems like 12, 13, 16 and 17.
Glacial acetic acid (0.134 g, 2.24 mmol) and (2S,6S)-1,7-
di-p-toluenesulfonyl-2,6-dibenzyl-1,4,7-triazaheptane,
6a
(1.02 g, 1.72 mmol) were dissolved in CH2Cl2 (9 cm3). DMAP
(0.042 g, 0.344 mmol), triethylamine (0.520 g, 5.15 mmol) and p-
toluenesulfonyl chloride (0.390 g, 2.05 mmol) were added and the
reaction mixture was stirred under nitrogen for 18 h. The solvent
was removed under reduced pressure and the remaining slightly
yellow oil was stirred with water (9 cm3) for 30 min. The water was
decanted off and the remaining off-white solid was recrystallised
from ethanol to yield 11a (750 mg, 69%) as colourless crystals,
Experimental
General remarks
All reagents were purchased from either Aldrich, Lancaster
or Avocado and were used without further purification unless
otherwise stated. Starting materials 6 were prepared according
to the reported procedures.28 Solvents that were required to be
2 6 6 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0

View Article Online
mp 198–200 °C; [a]2D5 +2.4 (c 0.5, CHCl3). Found C, 64.6; H, 6.3;
(from acetonitrile); [a]2D5 −41.2 (c 0.5, CHCl3); νmax/cm−1 2927,
1647, 1597, 1494, 1450, 1420, 1333, 1286, 1152, 1088, 1033,
1011, 955, 910, 861, 815, 730, 713, 695, 668, 654, 602, 543, 521,
493; dH 1.98 (3H, s, NCOCH3), 2.18–2.50 (4H, m, ArCH2CH),
2.39 (3H, s, ArCH3), 2.42 (3H, s, ArCH3), 3.41–3.93 (6H, m,
tacn-H), 4.07–4.16 (1H, m, tacn-H), 4.19–4.48 (3H, m, tacn-H),
6.94–6.98 (2H, m, Ar-H), 7.07–7.35 (12H, m, Ar-H), 7.64 (2H, d,
J 8.3, Ar-H), 7.79 (2H, d, J 8.3, Ar-H), dC 21.6, 21.8, 36.3, 36.6,
45.2, 46.2, 46.4, 48.3, 58.1, 59.7, 126.6, 127.1, 127.2, 127.2, 128.6,
128.9, 129.0, 130.0, 130.2, 136.9, 143.8, 144.3, 171.5; m/z (FAB):
682 (12%, MNa+), 660 (100%, MH+), 568 (25%, M − (CH3Ar)),
504 (13%, M − Ts), 463 (17%, M − (Ts and CH2CO)); (HRMS
Found: (MH+) 660.2540. C36H42N3O5S2 requires 660.2566).

N, 6.6. C34H39N3O5S2 requires C, 64.4; H 6.2; N, 6.5%; νmax/cm−1

3259, 2915, 1606, 1493, 1446, 1416, 1314, 1257, 1150, 1096,
807, 743, 695; dH 1.81 (3H, s, CH3CON), 2.30 (1H, dd, J 13.9
and 7.3, ArCH2CH), 2.37 (6H, s, ArCH3), 2.52 (1H, dd, J 13.9
and 6.3, ArCH2CH), 2.62 (1H, dd, J 13.3 and 7.6, ArCH2CH),
2.79–2.85 (3H, m, ArCH2CH and NCH2CH(CH2)), 3.10–3.31
(2H, m, NCH2CH(CH2) and CH2CH(CH2)N), 3.45–3.66
(2H, m, NCH2CH(CH2) and CH2CH(CH2)N), 4.82 (1H, d, J
7.2, CH(CH2)NHSO2), 5.60 (1H, d, J 6.1, CH(CH2)NHSO2),
6.74–6.77 (2H, m, Ar-H), 7.01–7.24 (12H, m, Ar-H), 7.37 (2H,
d, J 8.3, Ar-H), 7.55 (2H, d, J 8.3, Ar-H); dC 21.6, 39.2, 40.8,
48.8, 52.4, 54.0, 54.5, 126.7, 126.8, 126.9, 128.6, 128.9, 129.3,
129.7, 135.9, 137.0, 137.2, 137.9, 143.1, 143.4, 173.0; m/z (FAB):
656 (31%, MNa+), 634 (73, MH+), 592 (66); (HRMS Found:
(MH+) 634.2430. C34H40N3O5S2 requires 634.2409).
Synthesis of (2S,6S)-4-acetyl-2,6-di(1-methylethyl)-1,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononane 12b
Amide 11b (5.00 g, 9.30 mmol), 725 (4.48 g, 12.09 mmol) and
caesium carbonate (9.09 g, 27.90 mmol) were dissolved in
dry acetonitrile (100 cm3) and heated at reflux under nitrogen
for 6 d. The resulting white solid was filtered off and washed
with acetonitrile (100 cm3). The solvent was removed from
the combined filtrates and the resulting yellow semi-solid was
recrystallised from acetonitrile to yield macrocycle 12b (3.86 g,
Synthesis of (2S,6S)-4-acetyl-1,7-di-p-toluenesulfonyl-2,6-di(1-
methylethyl)-1,4,7-triazaheptane 11b
Acetic anhydride (0.65 g, 6.32 mmol) was added to (2S,6S)-1,5-
di-p-toluenesulfonyl-2,6-di(methylethyl)-1,4,7-triazaheptane 6b
(2.85 g, 5.75 mmol) and the resultant solution heated at reflux
for 4 h. The dark red–brown solid was then recrystallised from
hot methanol to yield 11b (2.40 g, 78%) as a white crystalline
74%) as colourless crystals, mp 173–175 °C (from acetonitrile);
25
solid, mp 176–178 °C; [a]D −27.6 (c 0.5, CHCl3); νmax/cm−1 3247,
25

[a]D +147.8 (c 0.5, CHCl3); νmax/cm−1 2965, 1650, 1434, 1419,

2959, 1453, 1417, 1320, 1288, 1159, 1092, 812; dH 0.69 (3H, d, J
6.9, (CH3)2CH), 0.73–0.81 (9H, m, (CH3)2CH), 1.61–1.82 (2H,
m, (CH3)2CH), 1.88 (3H, s, CH3CON), 2.40 (6H, s, ArCH3), 2.57
(1H, dd, J 14.0 and 2.9, NCH2CH(CH)), 2.91 (1H, dd, J 15.1 and
6.6,NCH2CH(CH)),3.05(1H,dd,J15.1and7.7,NCH2CH(CH))
3.13–3.22 (2H, m, CH2CH(CH)NHSO2), 3.50–3.60 (1H, m,
NCH2CH(CH)), 4.68 (1H, d, J 9.1, CH(CH)NHSO2), 5.43 (1H,
d, J 6.9, CH(CH)NHSO2), 7.26 (2H, d, J 8.0, Ar-H), 7.28 (2H, d,
J 8.0, Ar-H), 7.67 (2H, d, J 8.2, Ar-H) 7.68 (2H, d, J 8.2, Ar-H);
dC 16.8, 17.6, 18.4, 19.0, 21.6, 45.6, 50.1, 57.3, 58.0, 127.0, 129.6,
129.9, 137.6, 138.6, 143.2, 143.8, 173.1; m/z (FAB): 560 (44%,
MNa+), 538 (100, MH+), 496 (69), 367 (42); (HRMS Found:
(MH+) 538.2395. C22H40N3O5S2 requires 538.2409).
1386, 1335, 1284, 1144, 1089, 814, 714; dH 0.24 (3H, d, J 6.7,
(CH3)2CH), 0.64 (3H, d, J 6.9, (CH3)2CH), 0.79–0.83 (6H, m,
(CH3)2CH), 1.41–1.49 (1H, m, (CH3)2CH), 1.72–1.79 (1H, m,
(CH3)2CH), 2.18 (3H, s, CH3CO), 2.40 (3H, s, ArCH3), 2.41 (3H,
s, ArCH3), 3.26 (1H, dd, J 15.1 and 10.6, tacn-H), 3.41–3.97
(8H, m, tacn-H), 4.42 (1H, dd, J 15.1 and 2.7, tacn-H) 7.25–7.30
(4H, m, Ar-H), 7.65–7.71 (4H, m, Ar-H); dC 18.3, 19.3, 20.3,
20.8, 21.6, 22.5, 29.7, 30.7, 42.2, 45.3, 46.4, 46.9, 62.3, 63.1,
127.3, 127.4, 129.7, 129.8, 137.8, 138.0, 143.6, 143.8, 171.4; m/z
(FAB): 564 (100%, MH+), 522 (41), 408 (51), 366 (20); (HRMS
Found: (MH+) 564.2588. C28H42N3O5S2 requires 564.2566).
Synthesis of (2S,6S)-4-acetyl-2,6-di(1-methylpropyl)-1,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononane 12c
Synthesis of (2S,6S)-4-acetyl-1,7-di-p-toluenesulfonyl-2,6-
di(1-methylpropyl)-1,4,7-triazaheptane 11c
Macrocycle 12c was prepared from 11c in an identical
manner to 12b to yield colourless crystals (2.62 g, 71%), mp
198–200 °C (from acetonitrile); [a]2D5 +152.0 (c 0.5, CHCl3);
Amide 11c was prepared from (2S,6S)-1,7-di-p-toluenesulfonyl-
2,6-di(1-methylpropyl)-1,4,7-triazaheptane 6c in an identical
manner to 11b and was isolated as colourless crystals (6.76 g,
70%), mp 182–184 °C (from ethanol); [a]2D5 +12.4 (c 0.5, CHCl3);
max/cm−1 1648, 1449, 1333, 1220, 1180, 1034, 714; dH 0.27–0.42

ν
(1H, m, CH(CH3)CH2), 0.51–0.94 (11H, m, CH(CH3)CH2),
CHCH2CH3, CH2CH3) 0.58 (3H, t, J 6.9, CH2CH3), 0.97–1.16
(2H, m, CHCH2CH3), 1.38–1.45 (1H, m, CH(CH3)CH2), 2.15
(3H, s, NCOCH3), 2.39 (3H, s, ArCH3), 2.40 (3H, s, ArCH3),
3.23 (1H, dd, J 15.1 and 10.7, tacn-H), 3.34–4.05 (8H, m,
tacn-H), 4.39 (1H, dd, J 15.1 and 2.6, tacn-H), 7.25 (2H, d, J
8.0, Ar-H), 7.27 (2H, d, J 8.0, Ar-H), 7.64 (2H, d, J 8.3, Ar-H),
7.69 (2H, d, J 8.3, Ar-H); dC 11.8, 11.9, 14.8, 15.5, 21.6, 22.5,
26.5, 27.6, 36.6, 37.8, 42.0, 45.1, 46.7, 61.3, 62.0, 127.3, 127.4,
129.6, 129.8, 137.8, 138.0, 143.7, 143.9, 171.1; m/z (FAB): 614
(12%, MNa+), 592 (100, MH+), 436 (49); (HRMS Found: (MH+)
592–2887. C30H46N3O5S2 requires 592.2879).
max/cm−1 3297, 2967, 2885, 1614, 1441, 1417, 1324, 1288, 1158,

ν
1092, 809; dH 0.69 (3H, d, J 6.9, CH3CH(CH2)), 0.76–0.85
(9H, m, CH3CH(CH2) and CH3CH2CH(CH)), 0.92–1.05 (2H,
m, CH3CH2CH(CH)), 1.17–1.24 (2H, m, CH3CH2CH(CH)),
1.26–1.36 (1H, m, CH2CH(CH)), 1.44–1.53 (1H, m,
CH2CH(CH)), 1.87 (3H, s, CH3CON), 2.39 (6H, s, ArCH3),
2.39–2.45 (1H, m, NCH2CH(CH)), 2.75 (1H, dd, J 15.3 and 4.8,
NCH2CH(CH)), 2.94 (1H, dd, J 15.4 and 9.4, NCH2CH(CH)),
3.19–3.32 (2H, m, CH2CH(CH)NH), 3.66–3.73 (1H, m,
NCH2CH(CH)), 5.51 (1H, d, J 8.8, CH(CH)NHSO2), 5.76
(1H, m, J 6.6, CH(CH)NHSO2), 7.26 (2H, d, J 8.3, Ar-H), 7.26
(2H, d, J 8.3, Ar-H), 7.66 (2H, d, J 8.3, Ar-H), 7.67 (2H, d, J
8.3, Ar-H); dC 12.0, 12.1, 13.8, 21.6, 25.0, 26.1, 37.4, 38.9, 44.4,
48.6, 56.3, 56.5, 129.6, 127.0, 129.6, 129.8, 137.9, 138.4, 143.2,
143.6, 173.0; m/z (FAB): 588 (48%, MNa+), 566 (100, MH+),
524 (73), 395 (51), 283 (55); (HRMS Found: (MH+) 566.2745.
C28H44N3O5S2 requires 566.2722).
Synthesis of (2S,6S)-4-acetyl-2,6-di(1-methylethyl)-1,4,7-
triazacyclononane 13
Macrocycle 12b (600 mg, 1.07 mmol) was suspended in
concentrated sulfuric acid (5 cm3) and stirred at 95 °C for 16 h.
The dark brown solution was cooled on ice and slowly added
to ice-cold diethyl ether (250 cm3). The resulting light brown
precipitate was collected, redissolved in water (10 cm3) and
carefully neutralised with solid potassium hydroxide pellets. The
resulting aqueous solution was extracted with dichloromethane
(3 × 50 cm3). The organic phases were combined dried over
anhydrous magnesium sulfate and the solvents removed under
Macrocycles 13a–c were prepared in an identical manner
which is exemplified by the synthesis of 12b.
Synthesis of (2S,6S)-4-acetyl-2,6-diphenyl-1,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononane 12a
Macrocycle 12a was prepared in an identical manner to 12b from
11a to yield colourless crystals (8.37 g, 62%), mp 125–126 °C
reduced pressure to give 13 (80 mg, 52%) as a colourless oil,
25
[a]D +13.2 (c 0.65, CHCl3), νmax/cm−1 2955, 2871, 1630, 1467,

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0
2 6 6 7

View Article Online
49.1, 50.4, 58.0, 58.7, 127.8, 127.9, 130.0, 130.1, 135.6, 137.7,
1416, 1361, 1292, 1038, 732; dH 0.63–0.72 (12H, m, (CH3)2CH),
1.32–1.44 (2H, m, CH(CH3)2), 1.90 (3H, s, NCOCH3), 2.09–2.31
(3H, m, tacn-H), 2.52–2.80 (3H, m, tacn-H), 2.94–3.14 (3H, m,
tacn-H), 3.33 (1H, dd, J 2.5 and 12.9, tacn-H); dC18.3, 18.4,
19.4, 19.6, 22.7, 31.9, 32.5, 50.3, 51.4, 53.5, 55.5, 60.2, 60.6,
172.0; m/z (ES): 256.1 (100%, MH+); (HRMS Found: (MH+)
256.2379. C14H30N3O requires 256.2389).
144.3, 144.9; m/z (ES): 550.4 (100% MH+), 584.5 (50); (HRMS
Found: (MH+) 550.2762. C28H44N3O4S2 requires 550.2768).
Synthesis of (2S,6S)-2,6-di(1-methylethyl)-4-ethyl-1,4,7-
triazacyclononane 16b
Macrocycle 16a (250 mg, 0.45 mmol) was suspended in
concentrated sulfuric acid (4 cm3) and stirred at 95 °C for
18 h. The dark brown solution was cooled in ice before being
added dropwise to ice-cold diethyl ether (250 cm3). The ether
was decanted off and more ice-cold diethyl ether added to the
off-white precipitate. The precipitate was filtered off and the
solid obtained dissolved in the minimum amount of distilled
water (10 cm3) before being cooled on ice and basified with
solid KOH. The light yellow solution was then extracted with
dichloromethane (5 × 20 cm3), the organic extracts being dried
over anhydrous magnesium sulfate before being concentrated
under reduced pressure. NMR analysis of this material indicated
that incomplete detosylation had occurred, and therefore the
Synthesis of (2S,6S)-2,6-di(1-methylethyl)-1,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononane 14
To a solution of macrocycle 12b (3.00 g, 5.33 mmol) in
ethanol (40 cm3) was added concentrated hydrochloric acid
solution (40 cm3) and the mixture was heated under reflux
for 4 d. The solution was cooled on ice and neutralised using
solid potassium hydroxide pellets. The volume was reduced
by half under reduced pressure and the remaining solution
was extracted with dichloromethane (3 × 30 cm3). The organic
phases were combined, dried over anhydrous magnesium sulfate
and the solvents removed under reduced pressure to leave 14
(1.76 g, 63%) as a colourless solid. All spectroscopic data were
consistent with those previously reported.21 In addition the
cycle was repeated as outlined above to yield 16b (29.5 mg, 27%)
31
as a light yellow oil, [a]D +56.3 (c 0.59, CH2Cl2), νmax/cm−1: due

to the hygroscopic nature of the product IR spectra obtained
proved to be meaningless; dH 0.76–1.08 (15H, m, (CH3)2CH and
CH3CH2), 1.43–1.55 (2H, m, (CH3)2CH), 2.24–2.64 (10H, m,
NCH2), 2.72–2.85 (2H, m, (CH3)CHCH); dC 12.9, 20.0, 32.2,
44.0, 51.2, 54.7, 59.8; m/z (ES): 242.2 (100%, MH+); (HRMS
Found (MH+) 242.2589. C14H32N3 requires 242.2591).
following data are reported: νmax/cm−1 2963, 2874, 1465, 1324,

1291, 1148, 1089, 814; dH 0.29 (6H, d, J 6.6, (CH3)2CH), 0.75
(6H, d, J 6.3, (CH3)2CH), 1.34–1.47 (2H, m, CH(CH3)2), 2.37
(6H, s, ArCH3), 2.93 (2H, dd, J 14.0 and 6.9, NCH2CH(CH)),
3.11 (2H, dd, J 14.0 and 3.9, HNCH2CH(CH)), 3.28–3.34 (2H,
m, CH2CH(CH)NSO2), 3.42 (2H, d, J 14.6, NCH2CH2N), 3.61
(2H, d, J 14.9, NCH2CH2N), 7.23 (4H, d, J 8.0, Ar-H), 7.65 (4H,
d, J 8.3, Ar-H); m/z (FAB): 522 (100%, MH+), 366 (38); (HRMS
Found: (MH+) 522.2441. C26H40N3O4S2 requires 522.2460).
Synthesis of 1,3-di((3S,8S)-3,8-di(methylethyl)-4,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononan-1-ylmethyl)benzene 17a
To
a solution of 14 (3.00 g, 5.75 mmol) and 1,3-
bis(bromomethyl)benzene (683 mg, 2.59 mmol) in dry
acetonitrile (100 cm3) was added caesium carbonate (2.38 g,
17.25 mmol) and the mixture was heated at reflux for 3 d under
nitrogen. The white solid was removed by filtration and washed
with acetonitrile (50 cm3). The organic phases were combined
and the solvents removed under reduced pressure giving a
yellow solid. This solid was redissolved in ethanol (30 cm3),
poured into ice-cold water (150 cm3) and the resulting white
precipitate collected by suction filtration. The resulting solid
was further purified by recrystallisation from ethanol to yield
Synthesis of (2S,6S)-2,6-di(1-methylethyl)-1,4,7-
triazacyclononane 15
Macrocycle 15 could be prepared from 13 in an identical fashion
to 14 or from 14 in an identical fashion to 13 and isolated
routinely in 60–70% yield. All spectroscopic and experimental
data were consistent with those previously reported;21,22 (HRMS
Found: (MH+) 214.2275. C12H28N3 requires 214.2283).
Synthesis of (2S,6S)-2,6-di(1-methylethyl)-4-ethyl-1,7-di-p-
toluenesulfonyl-1,4,7-triazacyclononane 16a
17a (1.28 g, 43%) as colourless crystals, mp 108–110 °C (from
25
ethanol); [a] +91.4 (c 0.5, CHCl3); νmax/cm−1 2967, 2847, 1463,

1391, 1330, D1243, 1088, 814, 777, 698; dH 0.21 (12H, d, J 6.3,
(CH3)2CH), 0.54 (12H, d, J 6.3, (CH3)2CH), 1.46–1.53 (4H, m,
(CH3)2CH), 2.38 (12H, s, ArCH3), 2.78 (4H, dd, J 14.1 and 2.8,
tacn-H), 2.99 (4H, dd, J 14.6 and 6.6, tacn-H), 3.47–3.66 (14H,
m, tacn-H and ArCH2), 3.93 (2H, d, J 12.9, tacn-H or ArCH2)
7.23–7.26 (10H, m, Ar-H), 7.40–7.43 (2H, m, Ar-H), 7.67 (8H,
d, J 8.0, Ar-H); dC 20.4, 20.8, 21.6, 28.6, 46.8, 56.1, 59.3, 63.5,
127.4, 129.1, 129.5, 129.8, 137.6, 138.4, 143.1; m/z (FAB): 1146
(79%, MH+), 990 (100); (HRMS Found: (MH+) 1145.5260.
C60H85N6O8S4 requires 1145.5312).
To a stirred suspension of lithium aluminium hydride (0.63 g,
15.96 mmol) in dry tetrahydrofuran (60 cm3) was added dropwise
a solution of 12b (3.00 g, 5.32 mmol) in dry tetrahydrofuran
(150 cm3). The resultant solution was heated at reflux for
18 h under nitrogen and then cooled on ice before potassium
hydroxide (1 M, 30 cm3) was added dropwise causing the
previously grey solution to become white. The white gelatinous
precipitate was filtered through Celite and then washed with
ethyl acetate (100 cm3). The filtrate was then acidified with
10% hydrochloric acid and the resultant organic layer removed.
The aqueous layer was washed with ethyl acetate (3 × 50 cm3)
and the organic layers were combined and washed with brine
(3 × 50 cm3) before being dried over anhydrous magnesium
sulfate and concentrated under reduced pressure yielding a
dark brown-orange oil (2.37 g, 81%) which was purified upon
crystallisation from hot ethanol, yielding 16a (1.14 g, 39%) as
a white crystalline solid. Further yield could be obtained upon
Synthesis of 1,3-di((3S,8S)-3,8-di(methylethyl)-1,4,7-
triazacyclononan-1-ylmethyl)benzene 17b
This was prepared from 17a in an identical fashion to 13 and
recovered as a brown oil (21 mg, 9%). νmax/cm−1 3397, 2960,

1471, 1368, 1160, 1023, 729, 670, 646, 624, 552, 428; dH 0.81
(12H, d, J 6.1, (CH3)2CH), 0.92 (12H, d, J 4.4, (CH3)2CH),
1.46–1.68 (4H, m, (CH3)2CH), 2.06–3.87 (24H, m, tacn-H and
ArCH2), 6.97 (1H, s, Ar-H), 7.05–7.25 (3H, m, Ar-H); dC 20.0,
20.2, 31.9, 53.5, 54.5, 54.5, 61.7, 128.1, 128.6, 138.5, 139.1;
m/z (ES): 529.5 (61%, MH+), 265.2 (100%, (M2H+)/2); (HRMS
Found: (MH+) 529.4943. C32H60N6 requires 529.4958).
concentration of the filtrate (0.36 g, 12%), mp 218–220 °C (from
29
ethanol); [a] +95.5 (c 1.0, CH2Cl2); νmax/cm−1 1430, 1392, 1335,

1292, 1151, D1087, 714, 695; dH 0.22 (3H, d, J 6.9, (CH3)2CH),
0.74 (3H, d, J 6.9, (CH3)2CH), 0.81–0.85 (6H, m, (CH3)2CH),
1.19–1.28 (1H, m, (CH3)2CH), 1.42–1.51 (4H, m, CH3CH2N and
(CH3)2CH), 2.38 (3H, s, ArCH3), 2.41 (3H, s, ArCH3), 3.04–3.98
(11H, m, NCH2CHNTs, TsNCH2CH2NTs, NCH2CH3 and
(CH3)2CHCH), 4.81–4.87 (1H, m, (CH3)2CHCH), 7.28–7.32
(4H, m, Ar-H), 7.63 (2H, d, J 8.2, Ar-H), 7.80 (2H, d, J 8.2,
Ar-H); dC 10.0, 18.6, 21.1, 21.6, 21.7, 29.9, 32.0, 45.9, 46.1, 46.3,
X-Ray crystallography
The intensity data for 6b were collected on a CAD4
diffractometer at 160 K. Graphite-monochromated Mo-Ka
2 6 6 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0

View Article Online
and J. Chin, J. Am. Chem. Soc., 1998, 120, 8079–8087; (d) P. Rossi,
radiation (k = 0.71069 Å) was used with x–2h scans. The unit
cell parameters were determined by least-squares refinement of
25 automatically centred reflections 9.55  h  11.98. All data
were corrected for absorption by empirical methods (w scan)29
and for Lorentz-polarization effects by XCAD4. The structure
was solved by direct methods using SHELXS-9730 and refined
anisotropically (non-hydrogen atoms) by full-matrix least-
squares on F2 using SHELXL-97.30 All H-atoms were calculated
geometrically and refined using a riding model.
F. Felluga, P. Tecilla, F. Formaggio, M. Crisma, C. Toniolo and
P. Scrimin, J. Am. Chem. Soc., 1999, 121, 6948–6949; (e) E. L. Hegg,
S. H. Mortimore, C. Li Cheung, J. E. Huyett, D. R. Powell and
J. N. Burstyn, Inorg. Chem., 1999, 38, 2961–2968; (f) B. R. Bodsgard
and J. N. Burstyn, Chem. Commun., 2001, 647–648.
7 (a) M. J. Young and J. Chin, J. Am. Chem. Soc., 1995, 117,
10577–10578; (b) K. P. McCue, D. A. Voss, Jr., C. Marks and
J. R. Morrow, J. Chem. Soc., Dalton Trans., 1998, 2691–2963;
(c) K. P. McCue and J. R. Morrow, Inorg. Chem., 1999, 38,
6136–6142.
Crystaldatafor6b:C24H37N3O4S2, M = 495.69, orthorhombic,
8 (a) E. L. Hegg and J. D. Burstyn, Inorg. Chem., 1996, 35, 7474–7481;
(b) K. M. Deck, T. A. Tseng and J. N. Burstyn, Inorg. Chem., 2002,
41, 669–677.
space
group
P212121,
a = 10.752(4),
b = 11.183(5),
c = 21.829(10) Å, U = 2624.6(19) Å3, T = 160(2) K, Z = 4,
l(Mo-Ka) = 0.237 mm−1, 2679 reflections measured, 2622
unique (Rint = 0.0053) which were used in all calculations. The
final wR [I > 2r(I)] was 0.0887 (all data).
9 R. Hage, J. E. Iburg, J. Kerschner, J. H. Koek, E. L. M. Lempers,
R. J. Martens,
U. S. Racherla,
S. W. Russell,
T. Swathoff,
M. R. P. van Vlet, J. B. Warnaar, L. van der Wolf and B. Krijnen,
Nature, 1994, 369, 637–638.
The intensity data for 12b were collected using an Enraf-
Nonius Kappa CCD area detector on an Enraf Nonius FR591
rotating anode generator at 120(2) K. Graphite-monochromated
Mo-Ka radiation (k = 0.71073 Å) was used with φ and x to fill
the Ewald sphere. Data collection, cell refinement and data
reduction were carried out using the DENZO31 and COLLECT32
packages. A preliminary absorption corrections was carried out
by multiple scans using SORTAV.33 The structures were solved
by the heavy-atom method using the program SHELXS-9730
and refined anisotropically (non-hydrogen atoms) by full-matrix
least-squares on F2 using SHELXL-97.30 The H-atom positions
were calculated geometrically and refined with a riding model.
Data were corrected for absorption using an isotropic non-
hydrogen model with the program XABS2.34
Crystal data for 12b: C28H41N3O5S2, M = 563.76, ortho-
rhombic, space group P212121, a = 7.47600(10), b = 14.3100(2),
c = 26.3880(4) Å, U = 2823.03(7) Å3, T = 120(2) K, Z = 4,
l(Mo-Ka) = 0.231 mm−1, 25309 reflections measured, 6397
unique (Rint = 0.0654) which were used in all calculations. The
final wR [I > 2r(I)] was 0.0619 (all data).
10 K. Wieghardt, U. Bossek, B. Nuber, J. Weiss, J. Bonvoisin,
M. Corbella, S. E. Vitols and J. J. Girerd, J. Am. Chem. Soc., 1988,
110, 7398–7411.
11 C. Zondervan, R. Hage and B. L. Ferringa, Chem. Commun., 1997,
419–420.
12 (a) D. H. R. Barton, W. Li and J. A. Smith, Tetrahedron Lett.,
1998, 39, 7055–7058; (b) J. Brinksma, R. La Crois, B. L. Feringa,
M. I. Donnoli and C. Rosini, Tetrahedron Lett., 2001, 42,
4049–4052.
13 (a) J. R. Lindsay Smith and G. B. Shul’pin, Tetrahedron Lett., 1998,
39, 4909–4912; (b) G. B. Shul’pin, G. Suss-Fink and J. R. Lindsay
Smith, Tetrahedron, 1999, 55, 5345–5358; (c) T. H. Bennur, S. Sabne,
S. S. Deshpande, D. Srinivas and S. Sivasanker, J. Mol. Catal.
A: Chem., 2002, 185, 71–80.
14 (a) D. De Vos and T. Bein, Chem. Commun., 1996, 917–918;
(b) D. E. De Vos, J. L. Meinershagen and T. Bein, Angew. Chem.,
Int. Ed. Engl., 1996, 35, 2211–2213; (c) D. E. De Vos and T. Bein,
J. Organomet. Chem., 1996, 520, 195–200; (d) D. E. De Vos,
B. F. Sels, M. Reynaers, Y. V. S. Rao and P. A. Jacobs, Tetrahedron
Lett., 1998, 39, 3221–3224; (e) D. E. De Vos, S. de Wildeman,
B. F. Sels, P. J. Grobet and P. A. Jacobs, Angew. Chem., Int. Ed.,
1999, 38, 980–983; (f) A. Berkessel and C. A. Sklorz, Tetrahedron
Lett., 1999, 40, 7965–7968; (g) A. Grenz, S. Ceccarelli and C. Bolm,
Chem. Commun., 2001, 1726–1727; (h) J. Brinksma, L. Scmieder,
G. van Vliet, R. Boaron, R. Hage, D. E. De Vos, P. L. Alsters and
B. L. Ferringa, Tetrahedron Lett., 2002, 43, 2619–2622.
15 M. Beller, A. Tafesh, R. W. Fischer and B. Scharbert, Ger. Pat., Ger.
DE 195 23 890, 1996 (Chem. Abstr.,1997, 126, 74725g.).
16 (a) C. Bolm, D. Kadereit and M. Valacchi, Synlett, 1997, 687–688;
(b) C. Bolm, N. Meyer, G. Raabe, T. Weyhermüller and E. Bothe,
Chem. Commun., 2000, 2435–2436.
The program ORTEP-3,35 was used for graphical
representations and WINGX36 was used to prepare material for
publication for both structures.
CCDC reference numbers 214709 and 220376.
See http://www.rsc.org/suppdata/ob/b4/b409259g/ for crystal-
lographic data in CIF or other electronic format.
17 (a) G. Argouarch, C. L. Gibson, G. Stones and D. C. Sherrington,
Tetrahedron Lett., 2002, 43, 3795–3798; (b) G. Stones, G. Argouarch,
A. R. Kennedy, D. C. Sherrington and C. L. Gibson, Org. Biomol.
Chem., 2003, 1, 2357–2363.
Acknowledgements
We are grateful to Queen Mary, University of London for a
studentship (J. E. W. S.) to the EPSRC for support (K. F. S., GR/
R19182/01) and to The Royal Society for financial support. We
are indebted to The University of London Research Instruments
Service (ULRIS) (London School of Pharmacy) and also the
EPSRC National Mass Spectrometry service (University of
Wales Swansea) for mass spectra and to the EPSRC National
X-ray Crystallography Service (University of Southampton)
for the collection of data for 13b. In addition we are grateful to
Dr P. A. Gale and Dr J. W. Steed for help and advice with our
(attempted) binding studies.
18 D. S. Kopac and D. G. Hall, J. Comb. Chem., 2002, 4, 251–254.
19 (a) S. F. Mason and R. D. Peacock, Inorg. Chim. Acta, 1976,
19, 75–77; (b) A. F. Drake, R. Kuroda and S. F. Mason,
J. Chem. Soc., Dalton Trans., 1979, 1095–1100; (c) M. Nonoyama,
Transition Met. Chem., 1980, 5, 269–271; (d) P. G. Graham
and D. C. Weatherburn, Aust. J. Chem., 1983, 36, 2349–2354;
(e) J. P. L. Cox, A. S. Craig, I. M. Helps, K. J. Jankowski, D. Parker,
M. A. W. Eaton, A. T. Millican, K. Millar, N. R. A. Beeley and
B. A. Boyce, J. Chem. Soc., Perkin Trans. 1, 1990, 2567–2576;
(f) J. H. Koek, E. W. M. J. Kohlen, S. W. Russell, L. van der Wolf,
P. F. ter Steeg and J. C. Hellemons, Inorg. Chim. Acta, 1999, 295,
189–199; (g) L. J. Charnonnière, N. Wiebel and R. F. Ziessel,
J. Org. Chem., 2002, 67, 3933–3936; (h) M. Beller, A. Tafesh,
R. W. Fischer and B. Scharbert, Ger. Pat, Ger. DE 195 23 891, 1995
(Chem Abstr., 1997, 126, 69346e.); (i) S. W. Golding, T. W. Hambley,
G. A. Lawrance, S. M. Luther, M. Maeder and P. Turner,
J. Chem. Soc., Dalton Trans., 1999, 1975–1980; (j) S. Pulacchini,
K. F. Sibbons, K. Shastri, M. Motevalli, M. Watkinson, H. Wan,
A. Whiting and A. P. Lightfoot, Dalton Trans., 2003, 2043–2052;
References
1 See, for example: K. P. Wainwright, Coord. Chem. Rev., 1997, 166,
35–90.
2 A. Singh, Q. Yao, L. Tong, W. C. Still and D. Sames, Tetrahedron
Lett., 2000, 41, 9601–9605.
3 (a) K. Wieghardt, Angew. Chem., Int. Ed. Engl., 1989, 28, 1153–1172;
(b) A. J. Wu, J. E. Penner-Hahn and V. L. Pecoraro, Chem. Rev.,
2004, 104, 903–938.
4 M. Costas, M. P. Mehn, M. P. Jensen and L. Que, Jr., Chem. Rev.,
2004, 104, 939–986.
5 (a) L. M. Mirica, X. Ottenwaelder and T. D. P. Stack, Chem. Rev.,
2004, 104, 1013–1046; (b) E. A. Lewis and W. B. Tolman, Chem.
Rev., 2004, 104, 1047–1076.
6 See, for example: (a) J. D. Burstyn and K. A. Deal, Inorg. Chem.,
1993, 32, 3585–3586; (b) E. L. Hegg and J. N. Burstyn, Coord.
Chem. Rev., 1998, 173, 133–165; (c) N. H. Williams, W. Cheung
(k) S. Pulacchini,
K. F. Sibbons,
R. Nasser,
G. E. Hawkes,
M. Motevalli, R. T. Kroemer, E. S. Bento and M. Watkinson, Org.
Biomol. Chem., 2003, 1, 4058–4063.
20 J. E. W. Scheuermann, F. Ronketti, M. Motevalli, D. V. Griffiths
and M. Watkinson, New. J. Chem., 2002, 26, 1054–1059.
21 B. M. Kim, S. M. So and H. J. Choi, Org. Lett., 2002, 4, 949–952.
22 G. Argouarch, G. Stones, C. L. Gibson, A. R. Kennedy and
D. C. Sherrington, Org. Biomol. Chem., 2003, 1, 4408–4417.
23 S. Pulacchini and M. Watkinson, Eur. J. Org. Chem., 2001,
4233–4238.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0
2 6 6 9

View Article Online
24 T. J. Atkins, J. Am. Chem. Soc., 1980, 102, 6364–6365.
25 A. E. Martin, T. M. Ford and J. E. Bulkowski, J. Org. Chem., 1982,
47, 412–415.
26 D. Parker, Macrocycle Synthesis A Practical Approach, Oxford
University Press, Oxford, 1996, ch. 1.
27 S. Pulacchini, K. Shastri, N. C. Dixon and M. Watkinson, Synthesis,
2001, 2381–2383.
31 DENZO Data collection and processing software; Z. Otwinowski and
W. Minor, Methods Enzymol., 1997, 276, 307–326.
32 COLLECT Data collection and processing user interface: Collect:
Data collection software, R. Hooft, Nonius B.V., 1998.
33 SORTAV absorption correction software package: R. H. Blessing,
Acta Crystallogr., Sect. A., 1995, 51, 33–37; R. H. Blessing, J. Appl.
Crystallogr., 1997, 30, 421–426.
28 J. E. W. Scheuermann,
G. Ilyashenko,
D. V. Griffiths
and
34 S. Parkin, B. Moezzi and H. Hope, J. Appl. Crystallogr., 1995, 28,
53–56.
M. Watkinson, Tetrahedron: Asymmetry, 2002, 13, 269–272.
29 A. C. T. North, D. C. Phillips and F. S. Mathews, Acta Crystallogr.,
Sect. A, 1968, 42, 351–359.
30 G. M. Sheldrick, 1997, SHELX-97. Program for solution and
Refinement of Crystal Structures, Univ. of Göttingen, Germany.
35 L. J. Farrugia, ORTEP-3 for Windows, J. Appl. Crystallogr., 1997,
30, 565.
36 L. J. Farrugia, WINGX-A Windows Program for Crystal Structure
Analysis, University of Glasgow, Glasgow, 1998.
2 6 7 0
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 6 4 – 2 6 7 0