New Efficient Procedure for the Use of Diethoxyphosphoryl as a Protecting Group in the Synthesis of Polyazamacrocycles. Preparation of Polyazacyclophanes Derived from Resorcinol

Article abstract of DOI:10.1021/jo0353381

The synthesis of polyazamacrocycles containing an electron-rich aromatic subunit derived from resorcinol is described. The reported synthetic procedure is based on the use of diethoxyphosphoryl (Dep) as an amine protecting group. The new conditions employed for the cyclization reaction allow for a generalized use of Dep in the synthesis of polyazamacrocycles.

Full text of DOI:10.1021/jo0353381

SCHEME 1. Rich m a n -Atk in s Cycliza tion
New Efficien t P r oced u r e for th e Use of
Dieth oxyp h osp h or yl a s a P r otectin g Gr ou p
in th e Syn th esis of P olya za m a cr ocycles.
P r ep a r a tion of P olya za cyclop h a n es
Der ived fr om Resor cin ol
M. Isabel Burguete,† Laura Lo´pez-Diago,†
Enrique Garc´ıa-Espan˜a,*,‡ Francisco Galindo,†
Santiago V. Luis,*,† J uan F. Miravet,*,† and
Dariusz Sroczynski§
polyamine is reacted with a bis-electrophile to yield the
macrocyclic product. The protecting group is required
both to provide enough acidity to the protected primary
amine groups so that they can be deprotonated under
mild conditions and to avoid reaction at the secondary
nitrogen atoms.
Departament de Qu´ımica Inorga`nica i Orga`nica, ESTCE,
Universitat J aume I, E-12080 Castello´n, Spain,
Departament de Qu´ımica Inorga`nica, Universitat de
Vale`ncia, E-46100 Burjassot (Vale`ncia), Spain, and
Department of General and Inorganic Chemistry,
University of Lodz, Narutowicza 68, 90-136 Lodz 1,
P.O. Box 376, Poland
The original Richman-Atkins procedure uses tosyl as
a protecting group but several alternatives have been
described during the last years. This is mainly due to
the rather harsh conditions required for the transforma-
tion of tosylamides into amines, which can be incompat-
ible with some functional groups present in the structure
of the macrocycle. Recently reported examples of substi-
tutes for the tosyl groups include nitrobenzenesulfonyl
(nosyl),3b,c,e â-trimethylsilylethanesulfonyl (SES),3f tert-
butoxyoxycarbonyl (t-BOC),3g and diethoxyphosphoryl
(Dep).3a,d
luiss@qio.uji.es; miravet@qio.uji.es
Received September 10, 2003
Abstr a ct: The synthesis of polyazamacrocycles containing
an electron-rich aromatic subunit derived from resorcinol
is described. The reported synthetic procedure is based on
the use of diethoxyphosphoryl (Dep) as an amine protecting
group. The new conditions employed for the cyclization
reaction allow for a generalized use of Dep in the synthesis
of polyazamacrocycles.
The use of Dep as a protecting group in the synthesis
of polyaazamacrocyles is appealing for several reasons.
Dep-protected polyamines are easy to prepare in multi-
gram quantities, and the cyclization products are in
general very soluble in common organic solvents, a
property that facilitates their purification if required.
Especially interesting is the fact that this protecting
group can be removed quantitatively under mild condi-
tions (HCl/dioxane, for example). However, the use of Dep
in the synthesis of polyazamacrocycles is not generalized.
Mertes and co-workers reported the cyclization of Dep-
protected polyamines using DMSO as solvent and sodium
hydride as the base.3a According to later work by Gio-
venzana, Palmisano, and co-workers with this protecting
group, those conditions are not of general applicability,
and in any case, the use of a solvent of such a high boiling
point as DMSO is a serious drawback from a practical
point of view. The alternative proposed by these authors
is exemplified with the efficient preparation of polyaza-
cyclophanes employing a biphasic toluene/water system
as the solvent, sodium hydroxide as a base, and a phase-
transfer catalyst for the cyclization reaction.3d
Polyazamacrocycles have received much attention due
to their different applications which are related to their
interesting properties as ligands.1 This type of compounds
forms complex species with metal cations and anions
which are very useful in fields such as NMR imaging,1g
medicinal chemistry,1i or analytical chemistry.1f There-
fore, the optimization or the development of new syn-
thetic procedures for the preparation of polyazamacro-
cycles is an important challenge.
Several strategies have been described for the prepara-
tion of polyazamacrocycles in order to overcome success-
fully the entropically unfavorable macrocyclization
reaction.1c,f These include the use of high dilution condi-
tions, templates, or conformationally preorganized mac-
rocycle precursors. Associated with the latter strategy,
reactions involving Richman-Atkins cyclization or re-
lated procedures are used to prepare polyazamacrocycles.
In this approach, as shown in Scheme 1, an N-protected
* To whom correspondence should be addressed.
† Universitat J aume I.
‡ Universitat de Vale`ncia.
(2) (a) Richman, J . E.; Atkins, T. J . J . Am. Chem. Soc. 1974, 96,
2268. (b) Atkins, T. J .; Richman, J . E.; Oettle, W. F. Org. Synth. 1976,
58, 86; CV6, 652.
§ University of Lodz.
(1) (a) Izatt, R. M.; Pawlak, K.; Bradshaw, J . S. Chem. Rev. 1991,
91, 1721. (b) Kimura, E. Tetrahedron 1992, 6175. (c) Bradshaw, J . S.;
Krakowiak, K. E.; Izatt, R. M. Aza-crown Macrocycles; J ohn Wiley &
Sons: New York, 1993. (d) Izatt, R. M.; Pawlak, K.; Bradsaw, J . S.
Chem. Rev. 1995, 95, 2529. (e) Supramolecular Chemistry of Anions;
Bianchi, A., Bowman-J ames, K., Garc´ıa-Espan˜a, E., Eds.; J ohn-Wiley
& Sons: Chichester, 1997. (f) Macrocyclic Compounds in Analytical
Chemisty; Zolotov, Y. A., Ed.; J ohn Wiley & Sons: New York, 1997.
(g) Caravan, P.; Ellison, J . J .; McMurry, T. J .; Lauffer, R. B. Chem.
Rev. 1999, 99, 2293. (h) Steed, J . W.; Atwood, J . L. Supramolecular
Chemistry; J ohn Wiley & Sons: Chichester, 2000. (i) Kikuta, E.; Aoki,
S.; Kimura, E. J . Am. Chem. Soc. 2001, 123, 7911.
(3) (a) Qian, L.; Sun, Z.; Mertes, M. P.; Mertes, K. B. J . Org. Chem.
1991, 56, 4904. (b) Fukuyama, T.; J ow, C.-K.; Cheung, M. Tetrahedron
Lett. 1995, 36, 6373. (c) Burguete, M. I.; Escuder, B.; Luis, S. V.;
Miravet, J . F.; Querol, M.; Garc´ıa-Espan˜a, E. Tetrahedron Lett. 1998,
39, 3799. (d) Chellini, A.; Pagliarin, R.; Giovenzana, G. B.; Palmisano,
G.; Sisti, M. Helv. Chim. Acta 2000, 83, 793. (e) Burguete, M. I.;
Escuder, B.; Garc´ıa-Espan˜a, E.; Luis, S. V.; Miravet, J . F. Tetrahedron
2002, 58, 2839. (f) Hoye, R. C.; Richman, J . E.; Dantas, G. A.;
Lightbourne, M. F.; Shinneman, L. S. J . Org. Chem. 2001, 66, 2722.
(g) Krakowiak K. E., Bradshaw, J . S. J . Heterocyclic Chem. 1995, 32,
1639.
10.1021/jo0353381 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/27/2003
J . Org. Chem. 2003, 68, 10169-10171
10169

SCHEME 2
K2CO3/CH3CN was found to be ineffective. After chro-
matographic purification of the cyclic products, the
deprotection reaction was performed quantitatively (yield
> 95%) to afford the corresponding hydrochlorides using
3 M HCl in dioxane. The yield of the cyclization reactions
after chromatographic purification was 35-45% (see
Scheme 2). These values are moderate compared, for
example, to other related cyclizations described by us
4a,b,e
using tosyl or nosyl as protecting groups
(70-90%)
and comparable to those reported previously using this
protecting group.3d However, the overall methodology
compares favorably with the use of other protecting
groups. The mild and quantitative deprotection reaction
extends the attainable structural diversity of the polyaza-
macrocycles when compared to tosyl. In the case of nosyl,
the low solubility of the pernosylated macrocyclic com-
pounds in common organic solvents can be a serious
drawback if purification of the protected polyamines is
required. The method compares well with the use of
â-trimethylsilylethanesulfonyl if the easy and cheap
preparation ofmultigram quantities ofprotected polyamine
is considered. It has also to be noted that the deprotection
under acidic conditions affords hydrochlorides that are
easy to handle and stable solids, while the methods based
on nosyland â-trimethylsilylethanesulfonylyield polyamines
in their basic form that can be rather unstable and
difficult to handle.
In summary, the new cyclization conditions reported
here for a particular case allow for a generalized use of
Dep-protected polyamines for the preparation of poly-
azamacrocycles. The new methodology constitutes an im-
portant improvement over the previous procedures that
have not achieved a broad applicability.
Keeping in mind all this information and following our
ongoing research in polyazamacrocycles and their use in
supramolecular chemistry, we targeted the preparation
of polyazacyclophanes containing electron-rich aromatic
subunits such as those shown in Scheme 2. Accordingly,
a bis-electrophile derived from resorcinol was prepared
by reaction of this aromatic compound with 2-chloro-
ethanol followed by tosylation under standard conditions.
Dep-protected polyamines were easily prepared in mul-
tigram quantities from commercially available polyamines
using the Atherton-Openshaw-Todd procedure as re-
ported recently.3d The cyclization reaction shown in
Scheme 2 was attempted according to the procedure
described by Giovenzana, Palmisano, and co-workers
using a biphasic toluene/water system. Regrettably, it
was found that the bistosylate hydrolysis was the main
reaction yielding the corresponding dialcohol. Since in
the original procedure the hydrolysis of bis-halide elec-
trophiles is not an important side reaction, it seems that
the nature of the electrophile used in the cyclization
(probably its hydrophobicity) plays an important role in
the success of the reaction, and therefore, the method is
not of general applicability.
Here we report on new improved conditions for the
cyclization of polyamines protected with Dep. We have
found that the cyclization reaction can be performed
using a common organic solvent such as THF and
potassium tert-butoxide as the base. In the experimental
procedure, the base dissolved in THF is added to a
solution of the Dep-protected polyamine, which results
in partial precipitation of the dianion formed upon
polyamine deprotonation. Fortunately, for all the studied
polyamines this dianion is partially soluble in THF and
upon addition of the corresponding bis-electrophile all
the starting material was reacted after a few hours. The
use of different reaction conditions such as NaH/THF or
Exp er im en ta l Section
Dep-protected polyamines 5 and 6 were obtained following
the procedure reported in the literature for the preparation of
compounds 3 and 4.3d
N,N′,N′′,N′′′-Tet r a k is(d iet h oxyp h osp h or yl)-1,5,8,12-t et -
r a a za d od eca n e (5). Compound 5 (11.4 g, 69%) was prepared
from commercially available N,N′-bis(aminopropyl)ethylenedi-
amine (4.00 g, 23 mmol). 1H NMR (CDCl3, δ ppm): 1.31 (m,
24H), 1.66 (m, 4H), 2.95 (m, 12H), 3.56 (m, 2H), 4.01 (m, 16H).
13C NMR (CDCl3, δ ppm): 16.5, 30.6, 38.3, 43.7, 44.8, 62.4, 62.7.
MS(ES) (m/z): M + H ) 719. IR (cm-1): 3425, 3238, 2983, 2940,
2906, 2800, 1641, 1444. Anal. Calcd for C24H58N4O12P4: C, 40.11;
H, 8.13; N, 7.80. Found: C, 40.24; H, 8.02; N, 7.77.
N,N′,N′′,N′′′-Tetr a k is(d ieth oxyp h osp h or yl)-1,5,10,14-tet-
r a a za tetr a d eca n e (6). Compound 6 (12.0 g, 81%) was prepared
from commercially available spermine (4.00 g, 19.8 mmol). 1H
NMR (CDCl3, δ ppm): 1.28 (m, 24H), 1.40 (m, 4H), 1.63 (m, 4H),
3.05 (m, 12H), 3.45 (m, 2H), 4.01 (m, 16H). 13C NMR (CDCl3, δ
ppm): 16.6, 26.1, 30.6, 38.4, 42.7, 45.6, 62.5. MS (ES) (m/z): M
+ H ) 747. IR (cm-1): 3235, 2981, 2936, 2906, 1648, 1444. Anal.
Calcd for C26H62N4O12P4: C, 41.82; H, 8.37; N, 7.50. Found: C,
41.71; H, 8.49; N, 7.38.
(4) See, for example: (a) Bencini, A.; Burguete, M. I.; Garcı´a-Espan˜a,
E.; Luis, S. V.; Miravet, J . F.; Soriano, C. J . Org. Chem. 1993, 58, 4749.
(b) Burguete, M. I.; Escuder, B.; Garcı´a-Espan˜a, E.; Luis, S. V.; Miravet,
J . F. J . Org. Chem. 1994, 59, 1067. (c) Burguete, M. I.; D´ıaz, P.; Garc´ıa-
Espan˜a, E.; Luis, S. V.; Miravet, J . F.; Querol, M.; Ram´ırez, J . A.; Chem.
Commun. 1999, 649. (d) Albelda, M. T.; Burguete, M. I.; Frias, J . C.;
Garc´ıa-Espan˜a, E.; Luis, S. V.; Miravet, J . F.; Querol, M. J . Org. Chem.
2001, 66, 7505. (e) D´ıaz, P.; Basallote, M. G.; Man˜ez, MA.; Garc´ıa-
Espan˜a, E.; Gil, L.; Latorre, J .; Soriano, C.; Verdejo, B.; Luis, S. V.
Dalton Trans. 2003, 1186.
(5) Atherton, F. R.; Openshaw, H. T.; Todd, A. R. J . Chem. Soc. 1945,
660.
10170 J . Org. Chem., Vol. 68, No. 26, 2003

Gen er a l P r oced u r e for th e Cycliza tion Rea ction . A
solution of potassium tert-butoxide (0.021 mol) in 30 mL of dry
THF was added dropwise under nitrogen and with stirring to a
solution of Dep-protected polyamine (0.01 mol) in 150 mL of dry
THF cooled in an ice bath. At that moment, a yellowish
precipitate appeared. Then, ditosylate 2 (0.01 mol) dissolved in
150 mL of THF was added dropwise (30-60 min) and the
mixture was refluxed overnight. The reaction was cooled to room
temperature, the solvent was removed under vacuum, and the
solid residue was added to a mixture of CH2Cl2 (100 mL) and
water (10 mL). The aqueous solution was extracted with
additional CH2Cl2 (2 × 30 mL), and the organic extracts were
dried (Na2SO4). After filtration, the solvent was removed under
vaccum and the residue purified by flash chromatography (silica
gel, EtOAc/MeOH 9:1).
N,N′,N′′-Tr is(dieth oxyph osph or yl)-4,8,12-tr iaza-1,5-dioxa-
[15]m eta cyclop h a n e (7). Macrocycle 7 (2.28 g, 35%) was
prepared as indicated in the general procedure from 3 (5.00 g,
9.3 mmol). 1H NMR (CDCl3, δ ppm): 1.24 (m, 18H), 1.75 (m,
4H), 2.95 (m, 8H), 3.34 (m, 4H), 4.0-3.86 (m, 12H), 4.08 (t,
J ) 5.4 Hz, 4H), 6.40 (m, 3H), 7.12 (t, J ) 7.8 Hz, 1H). 13C
NMR (CDCl3, δ ppm): 16.3, 28.3, 43.5, 45.1, 45.2 45.6, 62.3, 67.9,
101.3, 107.3, 130.7, 159.5. MS (ES) (m/z): M + H ) 702. IR
(cm-1): 3406, 2979, 2928, 2862, 1602, 1440. Anal. Calcd for
in 15 mL of 3 M HCl/dioxane and stirred overnight. The solvent
was removed, and the residue refluxed in 5 mL of absolute
ethanol for 2 h to obtain the compound as a solid that was
filtered.
4,8,12-Tr ia za -1,5-d ioxa [15]m et a cyclop h a n e t r ih yd r o-
ch lor id e (11). Macrocycle 11 (0.81 g, 95%) was prepared as
indicated in the general procedure from 7 (1.50 g, 2.1 mmol).
Mp: 234 °C. 1H NMR (D2O, δ ppm): 1.85 (m, 4H), 2.91 (t, J )
7.8 Hz,4H), 3.04 (t, J ) 7.8 Hz, 4H), 3.34 (t, J ) 5.1 Hz, 4H),
4.31 (t, J ) 5.1 Hz, 4H), 6.60 (dd, J 1 ) 2.4, J 2 ) 8.3 Hz, 2H),
6.64 (t, J ) 2.4 Hz,1H), 7.2 (t, J ) 8.3 Hz,1H). 13C NMR (D2O,
δ ppm): 21.9, 42.9, 43.8, 44.6, 62.7, 105.5, 107.6, 131.6, 158.1.
MS (ES) (m/z): M + H ) 294. Anal. Calcd for C16H36Cl3N3O2: C,
47.00; H, 8.88; N, 10.28. Found: C, 46.61; H, 8.80; N, 10.14.
4,7,10,13-Tetr a a za -1,16-d ioxa [16]m eta cyclop h a n e Tet-
r a h yd r och lor id e (12). Macrocycle 12 (0.75 g, 93%) was pre-
pared as indicated in the general procedure from 8 (1.5 g, 1.8
1
mmol). Mp: 177 °C. H NMR (D2O, δ ppm): 2.92 (s, 4H), 3.21 (t,
J ) 7.3 Hz, 4H), 3.29 (t, J ) 7.3 Hz, 4H), 3.38 (t, J ) 5.1 Hz,
4H), 4.28 (t, J ) 5.1 Hz, 4H), 6.56 (dd, J 1 ) 2.4 Hz, J 2 )8.3 Hz,
2H), 6.61 (t, J ) 2.4 Hz,1H), 7.23 (t, J ) 8.3 Hz, 1H). 13C
NMR (D2O, δ ppm): 43.1, 43.3, 43.7, 46.3, 63.3, 105.3, 107.8,
131.5, 158.2. MS (ES) (m/z): M + H ) 309. Anal. Calcd for
C16H44Cl4N4O2: C, 41.21; H, 9.51; N, 12.01. Found: C, 40.81;
H, 9.55; N, 11.90.
C
28H54N3O11P3: C, 47.93; H, 7.76; N, 5.99. Found: C, 48.36; H,
7.73; N, 5.66.
4,8,11,15-Tetr a a za -1,18-d ioxa [18]m eta cyclop h a n e Tet-
r a h yd r och lor id e (13). Macrocycle 13 (0.81 g, 96%) was pre-
pared as indicated in the general procedure from 9 (1.5 g, 1.7
N,N′,N′′,N′′′-Tetr a k is(d ieth oxyp h osp h or yl)-4,7,10,13-tet-
r a a za -1,16-d ioxa [16]m eta cyclop h a n e (8). Macrocycle 8 (1.83
g, 37%) was prepared as indicated in the general procedure from
4 (4.00 g, 5.8 mmol). 1H NMR (CDCl3, δ ppm): 1.25 (m, 24H),
3.20 (m, 12H), 3.35 (m, 4H), 4.01 (m, 16H), 4.16 (t, 4H), 6.46
(dd, J 1 ) 7.8 Hz, J 2 ) 1.4 Hz, 2H), 6.5 (t, J ) 1.4 Hz, 1H), 7.15
(t, J ) 7.8 Hz,1H). 13C NMR (CDCl3, δ ppm): 16.5, 16.6, 47.0,
47.4, 62.6, 68.2, 101.3, 107.7, 130.7, 159.6. MS (ES) (m/z): M +
H ) 853. IR (cm-1): 3448, 2981, 2929, 2899, 1596, 1444. Anal.
Calcd for C32H64N4O14P4: C, 45.07; H, 7.56; N, 6.57; Found: C,
44.69; H, 7.61; N, 6.52.
1
mmol). Mp: 243 °C. H NMR (D2O, δ ppm): 1.1 (q, J ) 7.3 Hz,
4H), 3.35 (t, J ) 7.3 Hz, 4H), 3.45 (s, 4H), 3.52 (t, J ) 5.1 Hz,
4H), 4.35 (t, J ) 5.1 Hz, 2H), 6.69 (dd,J 1 ) 2.4 Hz, J 2 ) 8.3 Hz,
2H), 6.79 (t, J ) 2.4 Hz, 1H), 7.31 (t, J ) 8.3 Hz, 1H). 13C
NMR (D2O, δ ppm): 29.4, 48.4, 48.5, 48.9, 49.6, 68.0, 103.9,
107.8, 130.2, 160.3. MS (ES) (m/z): M + H ) 337. Anal. Calcd
for C18H48Cl4N4: C, 43.73; H, 9.79; N, 11.33. Found: C, 43.65;
H, 9.83; N, 11.25.
4,8,13,17-Tetr a a za -1,20-d ioxa [20]m eta cyclop h a n e Tet-
r a h yd r och lor id e (14). Macrocycle 14 (0.83 g, 96%) was pre-
pared as indicated in the general procedure from 10 (1.5 g, 1.7
mmol). Mp: 145 °C. 1H NMR (D2O, δ ppm): 1.62 (m, 4H), 1.98
(m, 4H), 2.93 (m, 4H), 3.02 (t, J ) 7.3 Hz, 4H), 3.11 (t, J ) 7.3
Hz, 4H), 3.36 (t, J ) 5.3 Hz, 4H), 4.22 (t, J ) 5.3 Hz, 4H), 6.56
(dd, J 1 ) 2.4 Hz, J 2 ) 8.3 Hz, 2H), 6.61 (t, J ) 2.4 Hz, 1H), 7.18
(t, J ) 8.3 Hz, 1H). 13C NMR (D2O, δ ppm): 22.1, 22.5, 43.8,
43.9, 46.3, 62.7, 103.9, 107.4, 130.9, 158.5. MS (ES) (m/z): M +
H ) 365. Anal. Calcd for C20H52Cl4N4O2: C, 45.98; H, 10.03; N,
10.72. Found: C, 45.51; H, 10.08; N, 10.62.
N,N′,N′′,N′′′-Tetr a k is(d ieth oxyp h osp h or yl)-4,8,11,15-tet-
r a a za -1,18-d ioxa [18]m eta cyclop h a n e (9). Macrocycle 9 (2.06
g, 42%) was prepared as indicated in the general procedure from
5 (4.00 g, 5.6 mmol). 1H NMR (CDCl3, δ ppm): 1.20 (m, 24H),
1.88 (m, 4H), 3.20 (m, 12H), 3.45 (m, 4H), 4.01 (m, 16H), 4.08
(m, 4H), 6.45 (dd, J 1 ) 7.8 Hz, J 2 ) 1.4 Hz, 2H), 6.48 (t, J ) 1.4
Hz, 1H), 7.18 (t, J ) 7.8 Hz, 1H), 13C NMR (CDCl3, δ ppm): 16.5,
29.7, 45.4, 46.5, 46.7, 47.1, 62.4, 68.7, 103.2, 105.9, 130.5, 159.8.
MS (ES) (m/z): M + H ) 881. IR (cm-1): 3445, 2983, 2927, 2897,
1603, 1445. Anal. Calcd for C34H68N4O14P4: C, 46.36; H, 7.78;
N, 6.36. Found: C, 45.99, H, 7.89; N, 6.31.
N,N′,N′′,N′′′-Tetr a k is(d ieth oxyp h osp h or yl)-4,8,13,17-tet-
r a a za -1,20-d ioxa [20]m eta cyclop h a n e (10). Macrocycle 10
(2.19 g, 45%) was prepared as indicated in the general procedure
from 6 (4.00 g, 5.4 mmol). 1H NMR (CDCl3, δ ppm) 1.28 (m, 24H),
1.44 (m, 4H), 1.81 (q, 4H), 3.02 (m, 16H), 3.45 (m, 4H), 4.02 (m,
20H), 6.37 (t, J ) 7.8 Hz, 1H), 6.48 (dd, J 1 ) 7.8 Hz, J 2 ) 1.4
Hz, 2H), 7.18 (t, J ) 7.8 Hz, 1H). 13C NMR (CDCl3, δ ppm): 16.5,
16.6, 26.6, 28.6, 44.0, 45.9, 46.1, 46.6, 62.4, 69.0, 103.0 106.2,
130.5, 159.8. MS (ES) (m/z): M + H ) 909. IR (cm-1): 3445, 2983,
2927, 2897, 1603, 1445. Anal. Calcd for C36H72N4O14P4: C, 47.57;
H, 7.98; N, 6.16. Found: C, 47.49; H, 7.87; N, 6.25.
Ack n ow led gm en t. We thank CICYT (BQU2000-
1424-C03) and BANCAIXA (P1.1A2000-10) for financial
support. D.S. is grateful to BANCAIXA for a postdoc-
toral fellowship.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 4-14. This material is available free of
charge via the Internet at http://pubs.acs.org.
Gen er a l P r oced u r e for Dep R em ova l. Dep-protected
polyazamacrocyle (2 mmol) was dissolved at room temperature
J O0353381
J . Org. Chem, Vol. 68, No. 26, 2003 10171