Preparation of 15-membered unsaturated N-H containing azamacrocycles and their differential coordination with Pd(0) and Pd(II)

Article abstract of DOI:10.1016/j.tet.2005.08.013

The use of 2-(trimethylsilylethyl)sulfonamide (SES-NH₂) has permitted the selective and efficient synthesis of new triolefinic 15-membered azamacrocycles 3. Differential coordination mode with palladium has been observed when macrocycle 3aab [(

Full text of DOI:10.1016/j.tet.2005.08.013

Tetrahedron 61 (2005) 10105–10112
Preparation of 15-membered unsaturated N–H containing
azamacrocycles and their differential coordination
with Pd(0) and Pd(II)
Judit Masllorens,a Marcial Moreno-Man˜asb and Anna Roglansa,
*
aDepartment of Chemistry, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain
`
Department of Chemistry, Universitat Autonoma de Barcelona, Cerdanyola, 08193 Barcelona, Spain
b
Received 17 May 2005; revised 29 July 2005; accepted 2 August 2005
Available online 19 August 2005
Abstract—The use of 2-(trimethylsilylethyl)sulfonamide (SES-NH2) has permitted the selective and efficient synthesis of new triolefinic
15-membered azamacrocycles 3. Differential coordination mode with palladium has been observed when macrocycle 3aab [(E,E,E)-1,6-
bis(p-tolylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triene] was treated with a palladium(0) or a palladium(II) source.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
of coordinating ability due to lone pair conjugation with the
SO2 group. Palladium(0) complexes 2 were obtained by
interchange of ligand using either Pd(PPh3)4 or Pd(dba)2 as
metal source. The palladium atom perfectly fit inside of the
macrocyclic cavity being the coordination mode with the
three olefins planar trigonal.3
In the last 5 years we have studied 15-membered triolefinic
macrocycles of type 1 and their capacity to coordinate
palladium(0) giving the air- and moisture stable Pd0-
complexes of type 2 (Fig. 1).1,2 The three olefinic double
bonds in 1 are the only coordinating centers for the
palladium atom because the three nitrogen atoms are devoid
On the other hand, azamacrocycles are important and
powerful ligands in transition metal coordination chem-
istry.4–7 Special attention has been paid to the coordination
properties of cyclam8 and porphyrin9 derivatives. Since
macrocycles 1 are structurally related to macrocyclic
structures mentioned above, the preparation of N–H
macrocycles 3 and the study of their coordinative properties
was an interesting point of analysis. Unfortunately, the first
attempts in our group to prepare unsaturated triolefinic
azamacrocycles 3 by detosylation of 1 (ArZp-tolyl) proved
to be troublesome.
We present in this paper, the preparation of new unsaturated
azamacrocycles 3 by selective removal of N-sulfonamide
SE groups and their coordination with Pd0 and PdII.
Moreover, introduction of two different metals—or the
same metal in two different oxidation states—within the
framework of an organic molecule in an ordered way at
well-defined distances is a target that has interest in metal–
metal interactions studies10,11 and in metal deposition on
solid supports for heterogeneous catalysis.12–14 Our macro-
cycles 3 have the appropriate features for such an ordered
distribution of metals.
Figure 1.
Keywords: Macrocycles; Azamacrocycles; Sulfonamides; Protecting
groups; Palladium.
*
Corresponding author. Tel.: C34 972418275; fax: C34 972418150;
e-mail: anna.roglans@udg.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.013

10106
J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
Scheme 1. Synthesis of 15-membered triolefinic azamacrocycles 3bbb and 3abb.
2. Results and discussion
trifluoroacetic acid selectively removed the BOC group to
afford 8 in 100% yield. Conversion of 8 into 10 required an
excess of dichloride 9 (8 equiv). After some optimizing
work,† treatment of bis-sulfonamide 10 with one equiv of
either SES-NH2 4 or p-tolylsulfonamide 11 gave, respect-
ively, the two macrocycles 12 and 13. The SES groups in
macrocycles 12 and 13 were cleaved with cesium fluoride in
anhydrous DMF at 100 8C affording azamacrocycles 3bbb
and 3abb in 81 and 88% yield, respectively, (Scheme 1).
The use of the 2-(tri-methylsilylethyl)sulfonyl (or SES)
group as an amine protecting group has been reported in the
literature.15,16 SES-sulfonamides are easily deprotected
under mild reaction conditions tolerating sensitive function-
ality in the compound and, in addition, the deprotection
process leaves the free amine rather than the salt.17,18 The
selective and easy removal of the SES protecting group
offers us the opportunity to prepare different types of
unsaturated azamacrocycles 3 (Fig. 1). Preparation of
macrocycles 3abb, 3bbb and 3aab are outlined in
Schemes 1 and 2.
Macrocycle 3aab was prepared as outlined in Scheme 2.
Following the same pathway as for macrocycles 3bbb and
3abb, reaction of (E,E,E)-1,14-dichloro-N,N0-bis(p-tolyl-
sulfonyl)-5,10-diazatetradeca-2,7,12-triene 1419 with SES-
NH2 4 in the presence of potassium carbonate in refluxing
2-(Trimethylsilylethyl)sulfonamide (SES-NH2) 4 was pre-
pared according to the procedure described in the
literature.18 Compound 4 was converted into its N-tert-
butyloxycarbonyl (BOC) derivative 5. Reaction of 5 with
0.5 equiv of trans-1,4-dibromo-2-butene (6) afforded the
† The cyclisation step to 12 was also tried using Cs2CO3 as a base in DMF
affording 45% yield when the reaction was run at room temperature and
58% yield when the reaction was run at 80 8C. The cyclisation step to 13
was also tried using K2CO3 in refluxing CH3CN. Under these reaction
conditions 13 was obtained in 45% yield.
protected disulfonamide 7. Treatment of
7 with

J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
10107
Scheme 2. Synthesis of 15-membered triolefinic azamacrocycle 3aab.
acetonitrile afforded macrocycle 15 in 58% yield. Deprotec-
tion of SES group using cesium fluoride in anhydrous DMF
at 100 8C led to azamacrocycle 3aab in 91% yield.
potassium carbonate in refluxing acetonitrile gave the
macrocycle 13 in 72% yield. Comparing the two pathways
for the synthesis of 13 the overall yield of five steps
improves from 26% (Scheme 1) to 39% (Scheme 3).
An alternative and more efficient way to prepare protected
macrocycles, as for example 13, is outlined in Scheme 3.
The synthesis started with the BOC-protected SES-
sulfonamide 5, which was treated with an excess of
dichloride 9 (4 equiv) to afford chlorosulfonamide 16 in
79% yield. Condensation of 2 equiv of 16 with 1 equiv of
p-tolylsulfonamide 11 led to intermediate 17. Again,
treatment of 17 with trifluoroacetic acid removed selectively
and efficiently (97% yield) the two BOC-protecting groups
leaving the two SES-groups unaffected. Finally, cyclisation
of 18 with 1 equiv of dibromobutene 6 in the presence of
Once we had azamacrocycles of type 3 in hand we decided
to study their complexating ability towards palladium
metal in its different oxidation states. Macrocycle 3aab
turned out to be the most soluble compound in classical
organic solvents, therefore, it was the compound chosen
for coordination studies. The results are summarized in
Scheme 4. Owing to the high insolubility of macrocycles
containing two or three NH groups (3abb and 3bbb) no
complexation studies with palladium could be done with
them.
Scheme 3. Alternative pathway for the synthesis of protected macrocycle 13.

10108
J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
Scheme 4. Complexation ability of azamacrocycle 3aab in front of Pd0 and PdII complexes.
Palladium(0) complex 19 was prepared in 88% yield by
reaction of 3aab with bis(dibenzylideneacetone)palla-
dium(0) in refluxing THF. On the other hand, when 3aab
was treated with an alcoholic solution (EtOH–MeOH, 4:1)
of sodium tetrachloropalladate(II) at room temperature, PdII
complex 20 was obtained in 63% yield. Unfortunately, all
attempts to obtain X-ray quality crystals of complexes 19
and 20 failed. However, the structure of Pd0 complex 19
could be unequivocally assigned based on our previous
structural analysis by means of NMR spectroscopy of Pd0
complexes 2 (Fig. 1).3 Upfield shift of the 1H and 13C NMR
signals of the olefinic protons is an inequivocal proof of the
triolefinic coordination mode of 19.
elemental analysis and their molecular weight was
confirmed by Electrospray Ionization Mass Spectrometry
(ESI-MS). Compounds 19 and 20 were easily identified by
the characteristic isotope distribution of the metal. Isotope
abundance of clusters was compared with calculated values.
The ESI mass spectra of 19 showed a cluster centered at m/z
622 assigned to the [MCH]C ion. The ESI mass spectra of
20 showed a cluster centered at m/z 1173 attributed to the
cationic species [MKCl]C. Figure 2 shows the ESI-MS
spectra of complexes 19 and 20. The two insets show the
isotope distribution pattern for the m/z 621 ion correspond-
ing to [M]C of 19 and for the m/z 1173 ion corresponding to
[MKCl]C of 20, respectively.
Thus, the 1H NMR spectrum of 3aab showed a broad singlet
at d 5.69 ppm corresponding to the six olefinic protons and
the 13C NMR spectrum presented three signals at d 129.4,
130.3 and 131.0 ppm for the olefinic carbon atoms. In
contrast, the olefinic protons in Pd0-complex 19, compared
to 3aab, shifted strongly upfield (dZ1.5–4.8 ppm)
following the normal behavior observed for complexes 2,3
as well as for other Pd0-olefin complexes.20–24 13C NMR
spectrum of 19 showed the olefinic carbon atoms shifted by
DdZ50 ppm upfield as compared to the free ligand 3aab. In
contrast, this behavior is not observed for PdII-complex 20
(most probably trans-20). The 1H NMR data for the olefins
of PdII-complex 20 showed two broad signals at d 5.5 and
5.8 ppm for the twelve olefinic protons and the 13C NMR
spectrum presented three signals in the same range (d 128–
132 ppm) as for the free ligand 3aab. Furthermore, 2D
heteronuclear (1H–13C HMQC) correlation spectrum has
been done to confirm assignment of the ring protons (See
Supplementary data)
With all these data in hand, we can conclude that when
macrocycle 3aab is treated with a palladium(0) source, the
metal atom is introduced into the macrocyclic cavity, being
coordinated by the three olefins, whereas, when it is treated
with palladium(II), the nitrogen donor atoms are responsible
for the coordination.
Further studies on the complexation properties of this novel
macrocycles are in progress in our laboratories.
3. Experimental
3.1. General remarks
2-(Trimethylsilylethyl)sulfonamide 4 was prepared accord-
ing to the procedure of Robins et al.18 (E,E,E)-1,14-
dichloro-N,N0-bis(p-tolylsulfonyl)-5,10-diazatetradeca-
2,7,12-triene 14 was prepared as previously reported by us
for the 1,14-dibromo analogue.19 1,4-dibromo-2-butene, 6,
In addition, complexes 19 and 20 presented correct

J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
10109
Figure 2. ESI(C) mass spectra of (a) complex 19 and (b) complex 20 compared with theoretical isotope distribution (the inset).
1,4-dichloro-2-butene, 9, and p-tolylsulfonamide, 11, are
commercially available and were used as received.
spectrometer equipped with an electrospray ion source.
The instrument was operated in the positive-ion mode
(ESIC) at a probe tip voltage of 3 kV. Elemental analyses
1H NMR (13C NMR) spectra were recorded at 200 MHz
(50 MHz) using Me4Si as internal standard. Chemical shifts
are given in d units. ESI (electrospray ionization) mass
were determined at ‘Servei d’Analisi de la Universitat de
`
Girona’. TLC analyses were performed on silica gel 60 F
256 plates, and column chromatographies were performed
on silica gel 60 (70–230 mesh).
spectra were acquired using
a quadrupole mass

10110
J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
3.1.1. N-(tert-Butyloxycarbonyl)(2-trimethylsilylethyl)
sulfonamide (5). It was prepared according to the general
method of ref.25 Colorless solid. Mp 79–81 8C (n-hexane)
(lit.26 82–82.5 8C). IR (ATR): n 3258, 2984, 1710, 1432,
hexane to afford 10 (2.28 g, 66%) as a colorless solid. Mp
79.5–80.5 8C (n-hexane). IR (ATR): n 2951, 1321, 1247,
1
1142 cmK1. H NMR (200 MHz, CDCl3, 25 8C, TMS): d
0.09 (s, 18H), 0.98–1.07 (m, 4H), 2.88–2.97 (m, 4H), 3.87
(d, JZ4.2 Hz, 8H), 4.09 (d, JZ5.6 Hz, 4H), 5.60–5.95 (m,
6H). 13C NMR (50 MHz, CDCl3, 25 8C, TMS): d K1.4,
11.0, 44.4, 48.6, 49.1, 50.0, 130.0, 130.3, 131.0. ESI-MS
(m/z): 591–593 [MCH]C, 608–610 [MCNH4]C. Anal.
Calcd for C22H44Cl2N2O4S2Si2 (591.80): C, 44.65; H, 7.49;
N, 4.73. Found: C, 44.34 and 44.33; H, 7.85 and 7.88; N,
4.68 and 4.66.
1341, 1245, 1130 cmK1 1H NMR (200 MHz, CDCl3,
.
25 8C, TMS): d 0.06 (s, 9H), 0.99–1.08 (m, 2H), 1.50 (s,
9H), 3.27–3.36 (m, 2H), 7.66 (s, 1H). 13C NMR (50 MHz,
CDCl3, 25 8C, TMS): d K1.5, 10.8, 28.4, 49.9, 84.6, 150.6.
ESI-MS (m/z): 299 [MCNH4]C, 580 [2MCNH4]C.
3.1.2. (E)-N,N0-Bis(tert-butyloxycarbonyl)-N,N0-bis[(2-
trimethylsilylethyl)sulfonyl]-2-butene-1,4-diamine (7).
A stirred mixture of 5 (0.74 g, 2.63 mmol), (E)-1,4-
dibromo-2-butene (6) (0.28 g, 1.31 mmol), potassium
carbonate (0.66 g, 4.77 mmol), and acetonitrile (10 mL)
was refluxed for 27 h (TLC monitoring). The salts were
filtered off and the filtrate was evaporated to afford a
residue, which was purified by column chromatograpy on
silica gel (n-hexane–EtOAc, 9:1) to afford 7 (0.64 g, 79%)
as a colorless solid. A sample specially purified for
elemental analysis was obtained by digestion with n-hexane.
Mp 120–121 8C (n-hexane). IR (ATR): n 2954, 1723, 1346,
3.1.5. (E,E,E)-1-6,11-Bis[(2-trimethylsilylethyl)sulfonyl]-
1,6,11-triazacyclopentadeca-3,8,13-triene (12). A stirred
mixture of 10 (0.63 g, 1.06 mmol), 4 (0.24 g, 1.32 mmol),
potassium carbonate (0.59 g, 4.27 mmol), and acetonitrile
(50 mL) was refluxed for 24 h (TLC monitoring). The salts
were filtered off and the filtrated was evaporated. The
residue was purified by column chromatography on silica
gel (n-hexane–EtOAc, polarity from 9:1 to 8:2) to afford 12
(0.58 g, 78%) as a colorless solid. A sample specially
purified for elemental analysis was obtained by digestion
with n-hexane. Mp 150.5–151.5 8C (n-hexane). IR (ATR): n
2955, 1328, 1249, 1134 cmK1. 1H NMR (200 MHz, CDCl3,
25 8C, TMS): d 0.06 (s, 27H), 0.95–1.04 (m, 6H), 2.86–2.95
(m, 6H), 3.88 (br s, 12H), 5.76 (br s, 6H). 13C NMR
(50 MHz, CDCl3, 25 8C, TMS): d K1.3, 11.0, 48.7, 51.3,
130.9. ESI-MS (m/z): 717 [MCNH4]C. Anal. Calcd for
C27H57N3O6S3Si3 (700.21): C, 46.31; H, 8.21; N, 6.00.
Found: C, 46.44 and 46.60; H, 8.49 and 8.50; N, 5.92 and
5.91.
1
1137 cmK1. H NMR (200 MHz, CDCl3, 25 8C, TMS): d
0.07 (s, 18H), 0.93–1.02 (m, 4H), 1.52 (s, 18H), 3.35–3.44
(m, 4H), 4.24 (br abs, 4H), 5.78 (s, 2H). 13C NMR (50 MHz,
CDCl3, 25 8C, TMS): d K1.4, 10.9, 28.6, 48.0, 51.5, 85.0,
129.5, 152.0. ESI-MS (m/z): 632 [MCNH4]C. Anal. Calcd
for C24H50N2O8S2Si2 (614.96): C, 46.87; H, 8.20; N, 4.56.
Found: C, 47.03 and 47.02; H, 8.53 and 8.33; N, 4.51 and
4.50.
3.1.3. (E)-N,N0-Bis[(2-trimethylsilylethyl)sulfonyl]-2-
butene-1,4-diamine (8). A mixture of 7 (0.41 g,
0.67 mmol), trifluoroacetic acid (0.31 mL, 4.02 mmol),
and dichloromethane (6 mL) was stirred at room tempera-
ture for 24 h. Then, a second portion of trifluoroacetic acid
(0.47 mL, 6.10 mmol) was added and the mixture was
stirred 24 h more until completion of the reaction (TLC
monitoring). The solution was washed with aqueous
NaHCO3 (2!10 mL), water (2!10 mL), dried over
anhydrous sodium sulfate and evaporated. Compound 8
(0.28 g, 100%) was obtained as a colorless solid. A sample
specially purified for elemental analysis was obtained by
crystallization from CH2Cl2–n-hexane. Mp 119.5–120.5 8C
(CH2Cl2–n-hexane). IR (ATR): n 3283, 2954, 1310, 1248,
3.1.6. (E,E,E)-1-(p-Tolylsulfonyl)-6,11-bis[(2-trimethyl-
silylethyl)sulfonyl]-1,6,11-triazacyclopentadeca-3,8,13-
triene (13). A mixture of 10 (0.77 g, 1.30 mmol), 11
(0.22 g, 1.28 mmol), cesium carbonate (1.70 g, 5.20 mmol),
and DMF (50 mL) was stirred at room temperature for 24 h
(TLC monitoring). The solvent was evaporated and CH2Cl2
(50 mL) was added. The salts were filtered of through Celite
and the organic layer was dried and evaporated. The residue
was purified by column chromatography on silica gel
(n-hexane–EtOAc, polarity from 9:1 to 8:2) to afford 13
(0.49 g, 55%) as a colorless solid. A sample specially
purified for elemental analysis was obtained by digestion
with n-hexane. Mp 113–114 8C (n-hexane). IR (ATR): n
2954, 1330, 1250, 1136 cmK1. 1H NMR (200 MHz, CDCl3,
25 8C, TMS): d 0.06 (s, 18H), 0.95–1.04 (m, 4H), 2.43 (s,
3H), 2.85–2.94 (m, 4H), 3.75 (br s, 4H), 3.84 (br s, 8H), 5.70
(br s, 6H), 7.32 (d, JZ8 Hz, 2H), 7.68 (d, JZ8 Hz, 2H). 13C
NMR (50 MHz, CDCl3, 25 8C, TMS): d K1.4, 10.9, 22.1,
48.5, 51.0, 51.5, 127.7, 130.4, 130.5, 130.6, 130.7, 136.8,
144.1. ESI-MS (m/z): 690 [MCH]C, 707 [MCNH4]C.
Anal. Calcd for C29H51N3O6S3Si2$CH3OH (722.14): C,
50.47; H, 7.45; N, 6.09. Found: C, 49.84 and 49.63; H, 7.92
and 8.09; N, 5.91 and 5.92. HRMS Calcd m/z for (MCNa)
712.2370. Found: 712.2387.
1
1134 cmK1. H NMR (200 MHz, CDCl3, 25 8C, TMS): d
0.06 (s, 18H), 0.97–1.06 (m, 4H), 2.90–2.99 (m, 4H), 3.72
(br abs, 4H), 4.98 (br s, 2H), 5.78 (s, 2H). 13C NMR
(50 MHz, CDCl3, 25 8C, TMS): d K1.3, 11.2, 45.3, 49.9,
129.8. ESI-MS (m/z): 415 [MCH]C, 432 [MCNH4]C.
Anal. Calcd for C14H34N2O4S2Si2 (414.73): C, 40.54; H,
8.26; N, 6.75. Found: C, 40.56 and 40.84; H, 8.34 and 8.53;
N, 6.73 and 6.72.
3.1.4. (E,E,E)-N,N0-Bis[(2-trimethylsilylethyl)sulfonyl]-
1,14-dichloro-5,10-diazatetradeca-2,7,12-triene (10). A
stirred mixture of 8 (2.43 g, 5.86 mmol) and potassium
carbonate (3.64 g, 26.34 mmol) was heated at 70 8C in
acetonitrile (25 mL) for 10 min. Then, (E)-1,4-dichloro-2-
butene (9) (5.43 mL, 49.72 mmol) was added. The mixture
was refluxed for 18 h (TLC monitoring). The salts were
filtered off and the solvent was evaporated under vacuum.
The residue was crystallized from CH2Cl2–EtOAc–n-
3.1.7. (E,E,E)-1,6-Bis(p-tolylsulfonyl)-11-[(2-trimethyl-
silylethyl)sulfonyl]-1,6,11-triazacyclopentadeca-3,8,13-
triene (15). This was obtained as for 12. Colorless solid. Mp
118–120 8C (n-hexane–diethyl ether). IR (ATR): n 2923,
1328, 1155, 1090 cmK1 1H NMR (200 MHz, CDCl3,
.
25 8C, TMS): d 0.06 (s, 9H), 0.95–1.04 (m, 2H), 2.43 (s,

J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
10111
6H), 2.83–2.95 (m, 2H), 3.72 (br s, 8H), 3.81 (br s, 4H), 5.64
(br s, 6H), 7.32 (d, JZ7.6 Hz, 4H), 7.67 (d, JZ7.6 Hz, 4H).
13C NMR (50 MHz, CDCl3, 25 8C, TMS): d K1.4, 10.8,
22.0, 48.5, 50.8, 51.3, 51.4, 127.7, 130.1, 130.2, 130.4,
136.7, 144.1. ESI-MS (m/z): 680 [MCH]C, 697 [MC
NH4]C. Anal. Calcd for C31H45N3O6S3Si.Et2O (754.10): C,
55.74; H, 7.35; N, 5.57; S, 12.76. Found: C, 55.71 and
55.63; H, 7.42 and 7.38; N, 5.76 and 5.75; S, 12.64 and
13.06.
CDCl3, 25 8C, TMS): d K1.4, 11.2, 28.7, 44.7, 47.7, 51.5,
85.2, 130.3, 130.4, 152.0. ESI-MS (m/z): 370 [MCH]C,
387 [MCNH4]C.
3.1.12. (E,E)-1,11-Bis(tert-butyloxycarbonyl)-1,11-
bis[(2-trimethylsilylethyl)sulfonyl]-6-(p-tolylsulfonyl)-1,
6,11-triazaundeca-3,8-diene (17). A stirred mixture of 16
(2.29 g, 6.19 mmol), 11 (0.54 g, 3.15 mmol), potassium
carbonate (2.62 g, 18.96 mmol), and acetonitrile (60 mL)
was refluxed for 19 h (TLC monitoring). The salts were
filtered off and the filtrated was evaporated. The residue
was purified by column chromatography on silica gel
(n-hexane–EtOAc, 9:1) to afford 17 (2.06 g, 79%) as a
colorless oil. IR (ATR): n 2953, 1723, 1349, 1133 cmK1. 1H
NMR (200 MHz, CDCl3, 25 8C, TMS): d 0.06 (s, 18H),
0.90–0.99 (m, 4H), 1.51 (s, 18H), 2.42 (s, 3H), 3.33–3.45
(m, 4H), 3.77 (d, JZ6 Hz, 4H), 4.17 (d, JZ6 Hz, 4H), 5.45–
5.70 (m, 4H), 7.29 (d, JZ8.2 Hz, 2H), 7.67 (d, JZ8.2 Hz,
2H). 13C NMR (50 MHz, CDCl3, 25 8C, TMS): d K1.4,
11.0, 22.2, 28.6, 48.1, 48.5, 51.5, 85.0, 127.8, 128.5, 130.4,
130.7, 137.8, 143.9, 152.0. ESI-MS (m/z): 855 [MCNH4]C.
Anal. Calcd for C35H63N3O10S3Si2$2Et2O (986.49): C,
52.35; H, 8.48; N, 4.26. Found: C, 52.50 and 51.58; H, 8.62
and 8.82; N, 4.63 and 4.83.
3.1.8. General procedure for deprotection of macro-
cycles 12, 13, and 15. Preparation of (E,E,E)-1,6,11-
triazacyclopentadeca-3,8,13-triene (3bbb). A stirred mix-
ture of macrocycle 12 (0.53 g, 0.76 mmol), anhydrous
cesium fluoride (1.15 g, 7.57 mmol), and anhydrous DMF
(15 mL) was heated at 100 8C for 19 h (TLC and RMN
monitoring). Methanol (1 mL) was added and the solvents
were evaporated under vacuum. The oily residue was
purified by bulb-to-bulb distillation affording 3bbb (0.13 g,
81%) as a colorless oil. Bp 175–185 8C/3 mmHg. IR (ATR):
1
n 3293, 2907 cmK1. H NMR (200 MHz, CD3OD, 25 8C,
TMS): d 3.20–3.27 (m, 12H), 5.55–5.70 (m, 6H). 13C NMR
(50 MHz, CD3OD, 25 8C, TMS): d 51.7, 132.7. ESI-MS
(m/z): 208 [MCH]C, 249 [MCCH3CNCH]C. HRMS
Calcd m/z for (MCH) 208.1810. Found: 208.1803.
3.1.13. (E,E)-1,11-Bis[(2-trimethylsilylethyl)sulfonyl]-6-
(p-tolylsulfonyl)-1,6,11-triazaundeca-3,8-diene (18). A
mixture of 17 (1.97 g, 2.35 mmol), trifluoroacetic acid
(1.08 mL, 14.02 mmol), and dichloromethane (30 mL) was
stirred at room temperature for 24 h. Then, a second portion
of trifluoroacetic acid (1.63 mL, 21.16 mmol) was added
and the mixture was stirred 24 h more until completion of
the reaction (TLC monitoring). The crude solution was
washed with aqueous NaHCO3 (2!30 mL), water (2!
30 mL), dried over anhydrous sodium sulfate and evapo-
rated. Compound 18 (1.45 g, 97%) was obtained as a
colorless solid. A sample specially purified for elemental
analysis was obtained by digestion with n-hexane. Mp 123–
124 8C (n-hexane). IR (ATR): n 3280, 2954, 1314,
3.1.9. (E,E,E)-1-(p-Tolylsulfonyl)-1,6,11-triazacyclo-
pentadeca-3,8,13-triene (3abb). Colorless solid. Mp
91.5–92.5 8C (n-hexane). IR (ATR): n 3251, 2890, 1323,
1150, 1088 cmK1 1H NMR (200 MHz, CDCl3, 25 8C,
.
TMS): d 2.43 (s, 3H), 3.25–3.34 (m, 8H), 3.74 (d, JZ5 Hz,
4H), 5.50–5.75 (m, 6H), 7.30 (d, JZ8.2 Hz, 2H), 7.70 (d,
JZ8.2 Hz, 2H). 13C NMR (50 MHz, CDCl3, 25 8C, TMS): d
22.1, 51.0, 51.5, 51.8, 127.6, 127.8, 130.4, 131.6, 134.4,
137.2, 143.9. ESI-MS (m/z): 362 [MCH]C. HRMS Calcd
m/z for (MCH) 362.1900. Found: 362.1892.
3.1.10. (E,E,E)-1,6-Bis(p-tolylsulfonyl)-1,6,11-triaza-
cyclopentadeca-3,8,13-triene (3aab). Colorless solid. Mp
144–145 8C (n-hexane). IR (ATR): n 1331, 1154 cmK1. 1H
NMR (200 MHz, CDCl3, 25 8C, TMS): d 2.43 (s, 6H), 3.42
(br s, 4H), 3.73 (br s, 8H), 4.87 (br s, 1H), 5.69 (br s, 6H),
7.31 (d, JZ8 Hz, 4H), 7.67 (d, JZ8 Hz, 4H). 13C NMR
(50 MHz, CDCl3, 25 8C, TMS): d 22.1, 49.1, 51.4, 51.9,
127.8, 129.4, 130.3, 130.4, 131.1, 136.8, 144.1. ESI-MS
(m/z): 516 [MCH]C. Anal. Calcd for C26H33N3O4S2$
1⁄2 MeOH (531.70): C, 59.86; H, 6.63; N, 7.90; S, 12.06.
Found: C, 59.99 and 59.80; H, 6.71 and 6.83; N, 8.00 and
8.01; S, 12.00 and 11.87.
1
1134 cmK1. H NMR (200 MHz, CDCl3, 25 8C, TMS): d
0.09 (s, 18H), 0.99–1.08 (m, 4H), 2.47 (s, 3H), 2.92–3.01
(m, 4H), 3.68–3.79 (m, 8H), 4.73 (t, JZ6.2 Hz, 2H), 5.64–
5.72 (m, 4H), 7.35 (d, JZ8.0 Hz, 2H), 7.71 (d, JZ8.0 Hz,
2H). 13C NMR (50 MHz, CDCl3, 25 8C, TMS): d K1.4,
10.9, 22.0, 44.9, 49.7, 49.8, 127.7, 128.3, 130.4, 131.1,
137.1, 144.4. ESI-MS (m/z): 638 [MCH]C, 655 [MC
NH4]C. Anal. Calcd for C25H47N3O6S3Si2 (638.02): C,
47.06; H, 7.42; N, 6.59. Found: C, 46.78; H, 7.85; N, 6.33.
3.1.14. (E,E,E)-1-(p-Tolylsulfonyl)-6,11-bis(2-trimethyl-
silylethyl)sulfonyl-1,6,11-triazacyclopentadeca-3,8,13-
triene (13). A stirred mixture of 18 (1.39 g, 2.18 mmol),
dibromobutene 6 (0.48 g, 2.24 mmol), potassium carbonate
(1.51 g, 10.92 mmol), and acetonitrile (180 mL) was
refluxed for 22 h (TLC monitoring). The salts were filtered
off and the filtrated was evaporated. The residue was
purified by column chromatography on silica gel
(n-hexane–EtOAc, 8:2) to afford 13 (1.08 g, 72%) as a
colorless solid.
3.1.11. N-[(E)-4-Chloro-2-butenyl]-N-(tert-butyloxycar-
bonyl)(2-trimethylsilylethyl)sulfonamide (16). A stirred
mixture of 5 (3.32 g, 11.80 mmol), dichlorobutene 9
(5.15 mL, 47.16 mmol), potassium carbonate (8.14 g,
58.90 mmol), and acetonitrile (80 mL) was refluxed for
6 h (TLC monitoring). The salts were filtered off and the
filtrated was evaporated. The oily residue was purified by
column chromatography on silica gel (n-hexane–EtOAc,
15:1) to afford 16 (3.44 g, 79%) as a colorless oil. IR (ATR):
1
n 2955, 1727, 1355 cmK1. H NMR (200 MHz, CDCl3,
25 8C, TMS): d 0.09 (s, 9H), 0.95–1.04 (m, 2H), 1.57 (s,
9H), 3.38–3.47 (m, 2H), 4.08 (d, JZ4.5 Hz, 2H), 4.30 (d,
JZ4.5 Hz, 2H), 5.85–5.92 (m, 2H). 13C NMR (50 MHz,
3.1.15. (E,E,E)-1,6-Bis(p-tolylsulfonyl)-1,6,11-triaza-
cyclopentadeca-3,8,13-trienepalladium(0) (19). A mag-
netically stirred solution of macrocycle 3aab (0.14 g,

10112
J. Masllorens et al. / Tetrahedron 61 (2005) 10105–10112
0.27 mmol) and bis(dibenzylideneacetone)palladium(0)
(0.16 g, 0.28 mmol) in THF (14 mL) was refluxed for
3.5 h (TLC monitoring). The solvent was removed under
reduced pressure, and the residue was purified by column
chromatography on silica gel (EtOAc–CH2Cl2–methanol,
8:1:1) to afford 19 as a colorless solid (0.15 g, 88%). Mp
References and notes
´
1. Moreno-Man˜as, M.; Pleixats, R.; Roglans, A.; Sebastian,
R. M.; Vallribera, A. Arkivoc 2004, 109–129 available from
http//www.arkat-usa.org.
´
2. Moreno-Man˜as, M.; Pleixats, R.; Sebastian, R. M.; Vallribera,
150–152 8C (dec). IR (ATR): n 2918, 1329, 1156 cmK1
.
A.; Roglans, A. J. Organomet. Chem. 2004, 689, 3669–3684.
´
3. Pla-Quintana, A.; Roglans, A.; Vicente de Julian-Ortiz, J.;
1H NMR (200 MHz, CDCl3, 25 8C, TMS): d 1.55–1.95
(m, 4H), 2.39 (s, 6H), 2.80 (q, JZ11.6 Hz, 2H), 3.13 (dt, JZ
13.0, 2.8 Hz, 2H), 3.53–4.10 (m, 6H), 4.55–4.87 (m, 4H),
7.25–7.32 (m, 4H), 7.60–7.75 (m, 4H). 13C NMR (50 MHz,
CDCl3, 25 8C, TMS): d 22.0, 45.8, 46.0, 48.8, 49.1, 50.2,
50.3, 77.6, 77.7, 78.4, 81.3, 81.7, 82.5, 127.5, 127.6, 130.3,
130.4, 135.9, 136.6, 143.8, 143.9. ESI-MS (m/z): 622 [MC
H]C. Anal. Calcd for C26H33N3O4S2Pd$1⁄2 CHCl3 (681.78):
C, 46.68; H, 4.95; N, 6.16; S, 9.40. Found: C, 46.63 and
46.76; H, 5.21 and 5.26; N, 5.93 and 5.93; S, 9.17 and 9.32.
Moreno-Man˜as, M.; Parella, T.; Benet-Buchholz, J.; Solans,
X. Chem. Eur. J. 2005, 11, 2689–2697.
4. Dietrich, B.; Viout, P.; Lehn, J.-M. Aspects de la Chimie des
´
Composes Macrocycliques; InterEditions/CNRS: Paris, 1991.
5. Macrocycle Synthesis. A Practical Approach. Parker, D. Ed.;
Oxford University: Oxford, 1996.
6. Constable, E. C. Coordination Chemistry of Macrocyclic
Compounds; Oxford University Press: Oxford, 1999.
7. Melson, G. A. Coordination Chemistry of Macrocyclic
Compounds; Plenum: New York, 1979.
3.1.16. trans-(E,E,E)-Dichlorobis[1,6-bis(p-tolylsulfo-
nyl)-1,6,11-triazacyclopentadeca-3,8,13-triene]palla-
dium(II) (20). Macrocycle 3aab (0.10 g, 0.19 mmol) was
stirred in a mixture of EtOH–MeOH (20–5 mL) until
complete dissolution. Then, a solution of sodium tetra-
chloropalladate (II) (0.058 g, 0.20 mmol) in MeOH (3 mL)
was added slowly to the previous one and the mixture was
stirred 10 min until precipitation of a yellow solid. The
reaction mixture was stored in the freeze overnight to assure
the complete precipitation of the complex. Then, the solid
residue was filtered, washed with cold methanol to give
Pd(II) complex 20 (0.074 g, 63%) as a yellow solid. A
sample specially purified for elemental analysis was
obtained by crystallization from n-hexane–CHCl3. Mp
8. Hubin, T. J. Coord. Chem. Rev. 2003, 241, 27–46 and
references cited therein.
9. The Porphyrin Handbook; Kadish, K. M., Smith, K. M.,
Guilard, R., Eds.; Academia: San Diego, CA, 2000.
10. Giuffrida, G.; Campagna, S. Coord. Chem. Rev. 1994, 135/
136, 517–531.
11. Braunstein, P. New J. Chem. 1994, 18, 51–60.
12. Thomas, J. M.; Raja, R. J. Organomet. Chem. 2004, 689,
4110–4124.
13. Thomas, J. M.; Raja, R. Chem. Rec. 2001, 1, 448–466.
14. Absihalabi, M.; Stanislaus, A.; Qabazard, H. Hydrocarbon
Process., Int. Ed. 1997, 76, 45–50 pp 53–55.
15. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; p 612.
16. Kocienski, P. J. In Protecting Groups; Enders, D., Noyori, R.,
Trost, B. M., Eds.; Thieme: New York, 2000; pp 554–558.
17. Hoye, R. C.; Richman, J. E.; Dantas, G. A.; Lightbourne,
M. F.; Shinneman, L. S. J. Org. Chem. 2001, 66, 2722–2725.
18. Parker, L. L.; Gowans, N. D.; Jones, S. W.; Robins, D. J.
Tetrahedron 2003, 59, 10165–10171.
137–139 8C (dec). IR (ATR): n 1332, 1155 cmK1 1H
.
NMR (200 MHz, CDCl3, 25 8C, TMS): d 2.45 (s, 12H),
3.15–3.45 (m, 4H), 3.50–3.90 (m, 20H), 5.40–5.95 (m,
12H), 7.33 (d, JZ8 Hz, 8H), 7.68 (d, JZ8 Hz, 8H). 13C
NMR (50 MHz, CDCl3, 25 8C, TMS): d 22.2, 51.4, 51.9,
54.7, 127.9, 128.3, 130.4, 130.6, 132.3, 136.7, 144.4.
ESI-MS (m/z): 1173 [MKCl]C. Anal. Calcd for
C52H66N6O8S4Cl2Pd$CHCl3 (1328.06): C, 47.93; H, 5.08;
N, 6.33; S, 9.66. Found: C, 47.87 and 47.76; H, 5.49 and
5.46; N, 6.23 and 6.20; S, 9.36 and 9.34.
19. The related 1,14-dibromo compounds has been described:
`
Cerezo, S.; Cortes, J.; Galvan, D.; Lago, E.; Marchi, C.;
´
Molins, E.; Moreno-Man˜as, M.; Pleixats, R.; Torrejon, J.;
Vallribera, A. Eur. J. Org. Chem. 2001, 329–337.
20. Keasey, A.; Mann, B. E.; Yates, A.; Maitlis, P. M.
J. Organomet. Chem. 1978, 152, 117–123.
Acknowledgements
21. Itoh, K.; Ueda, F.; Hirai, K.; Ishii, Y. Chem. Lett. 1977,
877–880.
Financial support from MEC of Spain (Projects BQU2002-
04002 and predoctoral grant to J. M.) and ‘Generalitat de
Catalunya’ (Projects SGR2001-00291 and SGR2001-
00181) is gratefully acknowledged.
22. Krause, J.; Cestaric, G.; Haack, K.-J.; Seevogel, K.; Storm, W.;
¨
Porschke, K.-R. J. Am. Chem. Soc. 1999, 121, 9807–9823.
23. Porth, S.; Bats, J. W.; Trauner, D.; Giester, G.; Mulzer, J.
Angew. Chem., Int. Ed. 1999, 38, 2015–2016.
24. Kluwer, A. M.; Elsevier, C. J.; Bu¨hl, M.; Lutz, M.; Spek, A. L.
Angew. Chem., Int. Ed. 2003, 42, 3501–3504.
Supplementary data
25. Neustadt, B. R. Tetrahedron Lett. 1994, 35, 379–380.
26. Campbell, J. A.; Hart, D. J. J. Org. Chem. 1993, 58,
2900–2990.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.08.013
NMR spectroscopic data for macrocycle 3aab Palladium(0)
complex 19 and Palladium(II) complex 20.