Synthesis of polyazamacrocyclic compounds via modified Richman-Atkins cyclization of β-trimethylsilylethanesulfonamides

Article abstract of DOI:10.1021/jo001639o

The Richman-Atkins cyclization remains one of the most widely used methods for the preparation of macrocyclic polyamines. The use of β-trimethylsilylethanesulfonamides (SES-sulfonamides) for the preparation of polyazamacrocyclic compounds is described. This expands existing Richman-Atkins sulfonamide macrocyclization methodology, and it successfully enables preparation of labile polyaza[n](1,4)naphthalenophanes and polyaza[n](9,10)anthracenophanes, not previously available in appreciable quantities.

Full text of DOI:10.1021/jo001639o

2722
J . Org. Chem. 2001, 66, 2722-2725
Syn th esis of P olya za m a cr ocyclic Com p ou n d s via Mod ified
Rich m a n -Atk in s Cycliza tion of
â-Tr im eth ylsilyleth a n esu lfon a m id es
Rebecca C. Hoye,*,† J ack E. Richman,‡ Gautam A. Dantas,† Marissa F. Lightbourne,† and
L. Scott Shinneman†
Department of Chemistry, Macalester College, St. Paul, Minnesota 55105, and University of Minnesota,
Biological Process Technology Institute, St. Paul, Minnesota 55108
hoye@macalester.edu
Received November 20, 2000
The Richman-Atkins cyclization remains one of the most widely used methods for the preparation
of macrocyclic polyamines. The use of â-trimethylsilylethanesulfonamides (SES-sulfonamides) for
the preparation of polyazamacrocyclic compounds is described. This expands existing Richman-
Atkins sulfonamide macrocyclization methodology, and it successfully enables preparation of labile
polyaza[n](1,4)naphthalenophanes and polyaza[n](9,10)anthracenophanes, not previously available
in appreciable quantities.
The Richman-Atkins cyclization (eq 1)1 remains one
or lithium aluminum hydride8 have all been used to
cleave the sulfonamides. Reduced yields of the depro-
tected polyamines result when labile benzylic C-N bonds
are present in the polyazamacrocycle, and reactive
functional groups are precluded. It has also been shown
that trifluoroacetamide derivatives,9a mesylates,9b and
the diethylphosphoryl derivatives9c can similarly be used
in a Richman-Atkins-like cyclization. These groups have
not been widely adopted for polyazamacrocyle synthesis
since they either also require deprotection under drastic
conditions, suffer from decreased yields in the macrocy-
clization, or require arduous reagent preparation.
of the most widely used methods for the preparation of
macrocyclic polyamines (polyazamacrocycles). This gen-
eral procedure is best effected by the reaction of a bis-
p-toluenesulfonamide salt with a bis-tosylate or mesylate
in anhydrous DMF.2 The bis-p-toluenesulfonamide salt
can conveniently be formed in situ when the reagents
are combined in DMF in the presence of potassium or
cesium carbonate.3 High dilution conditions often are not
required for this macrocyclization reaction, as the bulky
nature of the tosyl group contributes to preorganization
of the intermediates and favors the transition state
leading to intramolecular cyclization as opposed to
intermolecular oligomerization.
Fukuyama and co-workers have recently reported the
utilization of the nosyl group (2-and/or 4-nitrobenzene-
sulfonyl) as an amine protecting group that can be
removed under mild conditions.10 The utility of the nosyl
group in the Richman-Atkins macrocyclization was
demonstrated by Cook et al. during the preparation of
orthogonally protected polyazapyridinophane scaffolds for
solution-phase combinatorial chemistry.11
We report here our results on the use of the â-tri-
methylsilylethanesulfonamides (SES-sulfonamides) 3a
(4) (a) Lazar, I. Synth. Commun. 1995, 25, 3181. (b) Ciampolini, M.;
Micheloni, M.; Nardi, N.; Vizza, F.; Buttafava, A.; Fabbrizzi, L.; Perotti,
A. J . Chem. Soc. Chem. Commun. 1984, 998. (c) Thom, V. J .; Shaikjee,
M. S.; Hancock, R. D. Inorg. Chem. 1986, 25, 2992.
(5) (a) Snyder, H. R.; Heckert, R. E. J . Am. Chem. Soc. 1952, 74,
2006. (b) Stetter, H.; Roos, E. E. Chem Ber. 1955, 88, 1390.
(6) (a) Lehn, J .-M.; Montavon, F. Helv. Chim. Acta 1976, 59, 1566.
(b) Bottino, F.; Grazia, M. D.; Finocchiaro, P.; Fronczek, F. R.; Mamo,
A.; Pappalardo, S. J . Org. Chem. 1988, 53, 3521.
Although the macrocyclization step is generally ef-
ficient, harsh conditions are required to remove the tosyl
groups. Detosylation with liberation of the secondary
amines can be accomplished, but most of the methods
are relatively harsh. Thus, hot concentrated sulfuric
acid,1,4 HBr-AcOH in the presence or absence of phenol,5
sodium or lithium in ammonia,6 sodium naphthalenide,7
(7) Schmidtchen, F. P. Chem. Ber. 1980, 113, 864.
(8) (a) Stetter, H.; Mayer, K. H. Chem. Ber. 1961, 94, 1555. (b)
Naemura, K.; Kanda, Y.; Yamanaka, M.; Chikamatsu, H. Chem. Lett.
1989, 283.
(9) (a) Panetta, V.; Yaouanc, J . J .; Handel, H. Tetrahedron Lett.
1992, 33, 5505. (b) Pratt, J . A. E.; Sutherland, I. O.; Newton, R. F. J .
Chem. Soc., Perkin Trans. 1 1988, 13. (c) Qian, L.; Sun, Z.; Mertes, M.
P.; Mertes, K. B. J . Org. Chem. 1991, 56, 4904.
(10) (a) Fukuyama, T.; J ow, C.-K.; Cheung, M. Tetrahedron Lett.
1995, 36, 6373. (b) Fukuyama, T.; Cheung, M.; J ow, C.-K.; Hidai, Y.;
Kan, T. Tetrahedron Lett. 1997, 38, 5831.
(1) (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.
(2) (a) Macrocycle Synthesis, a Practical Approach; Parker, D., Ed.;
Oxford University Press: New York, 1996. (b) Bradshaw, J . S.;
Krakowiak, K. E.; Izatt, R. M. Aza-Crown Macrocycles. In The
Chemistry of Heterocyclic Compounds; Taylor, E. C., Ed.; J ohn Wiley
and Sons: New York, 1993; Volume 51.
(3) (a) Vriesema, B. K.; Buter, J .; Kellogg, R. M. J . Org. Chem. 1984,
49, 110. (b) Dijkstra, G.; Kruizinga, W. H.; Kellogg, R. M. J . Org. Chem.
1987, 52, 4230.
(11) An, H.; Cummins, L. L.; Griffey, R. H.; Bharadwaj, R.; Haly,
B. D.; Fraser, A. S.; Wilson-Lingardo, L.; Risen, L. M.; Wyatt, J . R.;
Cook, P. D. J . Am. Chem. Soc. 1997, 119, 3696.
10.1021/jo001639o CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/28/2001

Synthesis of Polyazamacrocyclic Compounds
J . Org. Chem., Vol. 66, No. 8, 2001 2723
Ta ble 1. Str u ctu r es of 4-6 a n d Yield s for F or m a tion of
Tr is-SES-tr ia za m a cr ocycles 5 fr om th e Alk yla tion of 3
w ith 4 a n d for SES Rem ova l in 5 To Give 6
Sch em e 1
and 3b for the preparation of macrocyclic polyamines via
the Richman-Atkins cyclization. We anticipated that the
SES group would perform the same role as the tosyl/nosyl
group: increasing the acidity of the remaining N-H
group for deprotonation by relatively weak bases, preor-
ganization of a favorable intramolecular transition state,
and protection of other secondary nitrogen atoms that
are present in the polyamine substrate. A potential
advantage of using the SES protecting group is that the
SES-sulfonamide can be easily cleaved under mild condi-
tions to generate the parent amine with cesium fluoride
in DMF,12 thereby offering potential compatibility with
a wider array of functionality.
â-Trimethylsilylethanesulfonyl chloride (SES-Cl), 1,
was prepared according to the procedure of Weinreb et
al.13 Reaction with N-(3-aminopropyl)-1,3-propanedi-
amine (2a ) or diethylenetriamine (2b) (Scheme 1) gave
the tris-SES sulfonamide derivatives 3a or 3b. Macro-
cyclization by treatment with alkyl R,ω-ditosylates or
-dibromides 4 in the presence of Cs2CO3 in DMF afforded
the N,N′,N′′ -tris(â-trimethylsilylethanesulfonyl)triaza-
macrocycles 5, as shown in Table 1.
The cyclization reactions are remarkably clean. Ex-
amination of an aliquot taken after the 48 h reaction time
by 1H NMR spectroscopy routinely reveals virtually
quantitative formation of the product. High dilution
conditions are not needed for the macrocyclization; little
or no evidence of oligomerization is seen.
Removal of the SES group occurs smoothly upon
treatment of the macrocyclic tris-sulfonamides 5 with
CsF in DMF at 95 °C for 24 h. Examination of an aliquot
1
of the crude reaction mixture by H NMR spectroscopy
shows complete, clean conversion to the parent triamine
6. Since all byproducts from fluoride-induced decomposi-
tion of the SES-sulfonamide moiety are volatile, the crude
products 6a -h are generally very pure. The parent
macrocyclic polyamines can be further purified, if desired,
by chromatography on neutral alumina.
â-Trimethylsilylethanesulfonamides are excellent sub-
strates for the construction of polyazamacrocycle skel-
etons under Richman-Atkins-like conditions. Yields are
generally comparable to tosyl- or nosylsulfonamide de-
rivatives. A distinct advantage of the mild conditions for
SES-sulfonamide cleavage is illustrated by the prepara-
tion of naphthalenophane (6e, 6f) and anthracenophane
(6g, 6h ) derivatives. The SES-sulfonamide derivatives
described here alleviate the problem of deprotection with
(12) Weinreb, S. M.; Demko, D. M.; Lessen, T. A. Tetrahedron Lett.
1986, 27, 2099.
(13) Weinreb, S. M.; Chase, C. E.; Wipf, P.; Venkatraman, S. Org.
Syn. 1997, 75, 161.

2724 J . Org. Chem., Vol. 66, No. 8, 2001
Hoye et al.
0 °C. A solution of SES chloride (1, 3.43 g, 17.2 mmol, 4.5
equiv) in 5 mL of DMF was added dropwise. The reaction
mixture was stirred at 0 °C for 1.5 h and then poured into 30
mL of water. The resulting aqueous solution was extracted
with CH2Cl2. The combined organic extracts were washed with
brine, dried (Na2SO4), filtered, and concentrated. The residue
was purified by flash chromatography (SiO2, 9:1 CH2Cl2:ethyl
acetate) to afford 3a (1.52 g, 2.4 mmol, 63%) as a colorless
solid: mp 106.5-107.5 °C; IR (neat) 3288, 3059, 2955, 1324
concomitant naphthylic and anthrylic C-N bond cleavage
as observed with the corresponding nosyl and tosyl
derivatives.14 1H NMR examination of the crude reaction
product shows clean conversion to the desired naphtha-
lenophane (6e or 6f) or anthracenophane (6g or 6h ). No
products resulting from cleavage of the naphthylic or
anthrylic C-N bonds are observed. Rapid chromatogra-
phy on neutral alumina affords the pure products in good
yields. Polyazacyclophanes, -naphthalenophanes, and
-anthracenophanes are currently of interest as synthetic
receptors and as potential molecular signals for the
detection and/or removal of metal ions and cations.15
Handling of the polyazaanthracenophanes 6g and 6h
as the free bases is complicated by their facile decomposi-
tion. Triazaanthracenophanes 6g and 6h are stable when
protected from oxygen and light.
In summary, we have demonstrated that â-trimethyl-
silylethanesulfonamides efficiently undergo macrocy-
clization with dibromides and ditosylates. Removal of the
SES-sulfonamide occurs under mild conditions to liberate
the free polyazamacrocycle in good yield. This methodol-
ogy complements and expands the existing Richman-
Atkins sulfonamide macrocyclization methodology. It
enables preparation of labile polyazamacrocyclic com-
pounds 6e-6h not previously characterized or available
in useful quantities. In addition, isolation and purifica-
tion of the parent polyazamacrocycles is greatly facili-
tated by the fact that all of the organic byproducts from
the deprotection are volatile.
;
cm-1 1H NMR (500 MHz, CDCl3) δ 4.97 (br s, 2H), 3.33 (t,
4H, J ) 6 Hz), 3.18 (t, 4H, J ) 6 Hz), 2.90 (m, 6H), 1.82 (tt,
4H, J ) 6, 6 Hz), 0.99 (m, 6H), 0.05 (s, 9H), 0.03 (s, 18H); 13
C
NMR (75 MHz, CDCl3) δ 48.6, 46.9, 46.5, 39.9, 30.4, 10.2, 9.9,
-2.3. Anal. Calcd for C21H53N3O6S3Si3: C, 40.41; H, 8.56; N,
6.73. Found: C, 40.49; H, 8.96; N, 6.49.
N,N′,N′′-Tr is(â-tr im eth ylsilyleth a n esu lfon yl)-1,4,7-tr i-
a za h ep ta n e (3b). By a similar procedure, diethylenetriamine
(2b, 1.03 g, 10 mmol, 1.0 equiv), triethylamine (7.0 mL, 5.05
g, 50 mmol, 5 equiv), and SES chloride (1, 8.00 g, 40 mmol, 4
equiv) in 20 mL of DMF afforded after purification 3b (4.03 g,
6.8 mmol, 68%) as a colorless solid.
N,N′,N′′-Tr is(â-tr im eth ylsilyleth a n esu lfon yl)-1,5,9-tr i-
a za cyclod od eca n e (5a ). Compound 3a (500 mg, 0.80 mmol,
1 equiv) and Cs2CO3 (785 mg, 2.4 mmol, 3 equiv) were
combined in 20 mL of DMF. A solution of 1, 3-propanediol di-
p-tosylate (307 mg, 0.80 mmol, 1 equiv) in 5 mL of DMF was
added dropwise. The reaction mixture was stirred at room
temperature for 48 h. The solvent was removed in vacuo, and
the residue was transferred to a separatory funnel with CH2-
Cl2 and water. The aqueous solution was extracted with CH2-
Cl2. The combined organic extracts were washed with brine,
dried (Na2SO4), filtered, and concentrated. Chromatography
(SiO2, 20:1 CH2Cl2:EtOAc) afforded the product (396 mg, 0.59
mmol, 73%) as a white solid: mp 177.6-178.7 °C; IR (KBr)
2954, 2901, 1330, 1240 cm-1 1H NMR (500 MHz, CDCl3) δ
;
Exp er im en ta l Section
3.38 (t, 12H, J ) 6 Hz), 2.86 (m, 6H), 2.03 (tt, 6H, J ) 6, 6
Hz), 0.98 (m, 6H), 0.06 (s, 27H); 13C NMR (75 MHz) δ 46.1,
45.4, 27.9, 9.8, -2.3. Anal. Calcd for C24H57N3O6S3Si3: C, 43.40;
H, 8.65; N, 6.33. Found: C, 43.32; H, 8.96; N, 6.07.
Gen er a l Exp er im en ta l Deta ils. Flash chromatography
was performed using the indicated solvent system on EM
reagent silica gel 60 (230-400 mesh).17 DMF was distilled from
CaH2 and stored over 4 Å molecular sieves. Triethylamine was
distilled from KOH and stored over 4 Å molecular sieves. CsF
was dried at 100 °C for 2 h in vacuo.18 â-Trimethylsilylethane-
sulfonyl chloride (SES-Cl) was prepared according to the
procedure of Weinreb et al.13 Air- and/or moisture-sensitive
reactions were carried out under N2 or Ar using oven-dried
glassware and standard syringe/septa techniques.
N,N′,N′′-Tr is(â-t r im et h ylsilylet h a n esu lfon yl)-1-oxa -
4,8,12-tr ia za cyclotetr a d eca n e (5b). By a similar procedure,
3a (624 mg, 1 mmol, 1 equiv) and Cs2CO3 (978 mmol, 3 equiv)
in 20 mL of DMF were treated with di(ethylene glycol) di-p-
tosylate (414 mg, 1.0 mmol, 1 equiv) in 5 mL of DMF.
Chromatography (SiO2, 7:3 hexanes/EtOAc) afforded the prod-
uct (492 mg, 0.71 mmol, 71%) as a white solid.
N,N′,N′′-Tr is(â-tr im eth ylsilyleth a n esu lfon yl)-1,4,7-tr i-
a za cyclon on a n e (5c). By a similar procedure, 3b (300 mg,
0.50 mmol, 1 equiv), Cs2CO3 (488 mg, 1.50 mmol, 3 equiv) and
ethylene glycol di-p-tosylate (185 mg, 0.50 mmol, 1 equiv) were
combined in 10 mL of DMF. Chromatography (SiO2, 40:1 CH2-
Cl2/EtOAc) afforded the product (247 mg, 0.34 mmol, 68%) as
a white solid.
3,7,11-Tr is(â-t r im et h ylsilylet h a n esu lfon yl)-3,7,11,17-
tetr a a za bicyclo[11.3.1]h ep ta d eca -1(17),13,15-tr ien e (5d ).
By a similar procedure, 3a (323 mg, 0.52 mmol, 1 equiv), Cs2-
CO3 (508 mg, 1.56 mmol, 3 equiv), and 2,6-bis(bromomethyl)-
pyridine were combined in 10 mL of DMF. Chromatography
(SiO2, 20:1 CH2Cl2/EtOAc) afforded the product (231 mg, 0.32
mmol, 61%) as a white solid.
N ,N ′,N ′′-Tr is(â-t r im e t h ylsilyle t h a n e su lfon yl-2,6,10-
tr ia za [11](1,4)n a p h th a len ecyclop h a n e (5e). By a similar
procedure, 3a (162 mg, 0.26 mmol, 1 equiv), Cs2CO3 (942 mg,
1.28 mmol, 5 equiv), and 1,4-bis(bromomethyl)naphthalene17
(100 mg, 0.26 mmol, 1 equiv) were combined in 3 mL of DMF.
Chromatography (SiO2, 100:1 CH2Cl2/CH3OH) afforded the
product (140 mg, 0.19 mmol, 74%) as a colorless solid.
N,N′,N′′-Tr is(â-tr im eth ylsilyleth an esu lfon yl-2,5,8-tr iaza-
[9](1,4)n a p h th a len ecyclop h a n e (5f). By a similar proce-
dure, 3b (154 mg, 0.26 mmol, 1 equiv), Cs2CO3 (420 mg, 1.28
mmol, 5 equiv), and 1,4-bis(bromomethyl)naphthalene19 (100
N,N′,N′′-Tr is(â-tr im eth ylsilyleth a n esu lfon yl)-1,5,9-tr ia -
za n on a n e (3a ). N-(3-Aminopropyl)-1,3-propanediamine (2a ,
0.50 g, 3.8 mmol, 1.0 equiv) and triethylamine (2.6 mL, 19.0
mmol, 5 equiv) were combined in 5 mL of DMF and cooled to
(14) (a) Altava, B.; Burguete, M. I.; Escuder, B.; Luis, S. V.; Garcia-
Espan˜a, E.; Munoz, M. C. Tetrahedron 1997, 53, 2629. (b) Bruguete,
M. I.; Escuder, B.; Luis, S. V.; Miravet, J . F.; Querol, M. Tetrahedron
Lett. 1998, 39, 3799.
(15) (a) Franke, J .; Voegtle, F. Top. Curr. Chem. 1986, 132, 135. (b)
Bianchi, A.; Escuder, B.; Garcia-Espan˜a, E.; Luis, S. V.; Marcelino,
V.; Miravet, J . F.; Ramirez, J . A. J . Chem. Soc., Perkin Trans. 2 1994,
1253. (c) Bernardo, M. A.; Parola, A. J .; Pina, F.; Garcia-Espan˜a, E.;
Marcelino, V.; Luis, S. V.; Miravet, J . F. J . Chem. Soc., Dalton Trans.
1995, 993. (d) Aguilar, J . A.; Garcia-Espan˜a, E.; Guerrero, J . A.; Luis,
S. V.; Llinares, J . M.; Miravet, J . F.; Ramirez, J . A.; Soriano, C. J .
Chem. Soc., Dalton Trans. 1995, 2995. (e) Andres, A.; Bazzicaluppi,
C.; Bianchi, A.; Garcia-Espan˜a, E.; Luis, S. V.; Miravet, J . F. J . Chem.
Soc., Dalton Trans. 1994, 2995. (f) Garcia-Espan˜a, E.; LaTorre, J .; Luis,
S. V.; Miravet, J . F.; Pozuelo, P. E.; Ramirez, J . A.; Soriano, C. Inorg.
Chem. 1996, 35, 4591. (g) Burguete, M. I.; Escuder, B.; Frias, J . C.;
Garcia-Espan˜a, E.; Luis, S. V.; Miravet, J . F. J . Org. Chem. 1998, 63,
1810. (h) Burguete, M. I.; Diaz, P.; Garcia-Espan˜a, E.; Luis, S. V.;
Miravet, J . F.; Querol, M.; Ramirez, J . A. Chem. Commun. 1999, 649.
(i) Bernardo, M. A.; Pina, F.; Escuder, B.; Garcia-Espan˜a, E.; Godino-
Salido, M. L.; LaTorre, J .; Luis, S. V.; Ramirez, J . A.; Soriano, C. J .
Chem. Soc., Dalton Trans. 1999, 915. (j) Siaugue, J .-M.; Segat-Dioury,
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2000, 41, 7443.
(16) Denny, R. W.; Nickon, A. Org. React. 1973, 20, 133.
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J . Org. Chem. 1991, 56, 1210.

Synthesis of Polyazamacrocyclic Compounds
J . Org. Chem., Vol. 66, No. 8, 2001 2725
mg, 0.26 mmol, 1 equiv) were combined in 3 mL of DMF.
Chromatography (100:1 CH2Cl2/CH3OH) gave the product (163
mg, 0.22 mmol, 84%) as a colorless solid.
N,N′,N′′-Tr is(â-t r im et h ylsilylet h a n esu lfon yl)-2,6,10-
tr ia za [11](9,10)a n th r a cen ecyclop h a n e (5g). By a similar
procedure, 3a (750 mg, 1.19 mmol, 1 equiv), Cs2CO3 (1.94 g,
5.95 mmol, 5 equiv), and 9,10-di(bromomethyl)anthracene (436
mg, 1.19 mmol, 1 equiv) were combined in 30 mL of DMF.
Chromatography (SiO2, 40:1 CH2Cl2/EtOAc) gave the product
(817 mg, 0.98 mmol, 83%) as a yellow solid.
N ,N ′,N ′′-Tr is(â-t r im e t h ylsilyle t h a n e su lfon yl)-2,5,8-
t r ia za [9](9,10)a n t h r a cen ecyclop h a n e (5h ). By a similar
procedure, 3b (600 mg, 1.01 mmol, 1 equiv), Cs2CO3 (1.63 g,
5.00 mmol, 5 equiv), and 9,10-bis(bromomethyl)anthracene
(364 mg, 1.00 mmol, 1 equiv) were combined in 30 mL of DMF.
Chromatography (SiO2, 200:1 CH2Cl2/CH3OH) yielded the
product (581 mg, 0.72 mmol, 72%) as a pale yellow solid.
Gen er a l P r oced u r e for Su lfon a m id e Clea va ge. The
tris-sulfonamide 5 (1 equiv) and CsF (10-20 equiv) were
combined in DMF (3 mL/100 mg of substrate) and heated at
95 °C for 24 h, at which time an aliquot was removed and
stripped to ascertain by 1H NMR analysis that the reaction
was complete. Methanol (1 mL) was added to the reaction
mixture and it was concentrated in vacuo. Purification by
chromatography on neutral alumina (2:1 CH2Cl2/MeOH) af-
forded the desired product.
2.9 mmol, 20 equiv) in 3 mL of DMF afforded 6e (39 mg, 0.14
mmol, 93%): IR (neat) 3305, 3045, 2925, 1265 cm-1; 1H NMR
(C6D6, 300 MHz) δ 8.19 (m, 2H), 7.37 (m, 2H), 7.00 (s, 2H),
4.54 (d, 2H, J ) 13 Hz), 3.39 (d, 2H, J ) 13 Hz), 2.56 (dt, 2H,
J ) 3, 12 Hz), 2.26 (dt, 2H, J ) 2, 11 Hz), 1.77 (dt, 2H, J ) 4,
11 Hz), 1.43 (dt, 2H, J ) 3, 11 Hz), 1.40-0.91 (m, 4H), 0.61
(br s, 3H); 1H NMR (CDCl3, 300 MHz) δ 8.20 (m, 2H), 7.56 (m,
2H), 7.26 (s, 2H), 4.80 (d, 2H, J ) 14 Hz), 3.61 (d, 2H, J ) 14
Hz), 2.75 (ddd, 2H, J ) 1, 5, 12 Hz), 2.34 (dt, 2H, J ) 1, 11
Hz), 1.79 (dt, 2H, J ) 4, 11 Hz), 1.71 (br s, 3H), 1.45-1.16 (m,
6H); 13C NMR (CDCl3, 75 MHz) δ 135.9, 132.3, 126.5, 125.9,
125.1, 51.3, 45.0, 42.3, 29.5; HRMS (FAB+) calcd for C18H26N3
(M + H)+ 284.2126, found 284.2109.
2,5,8-Tr ia za [9](1,4)n a p h th a len ecyclop h a n e (6f). Com-
pound 5f (114 mg, 0.15 mmol, 1 equiv) and CsF (456 mg, 3.0
mmol, 20 equiv) in 3 mL of DMF afforded 6f after purification
(34.4 mg, 0.13 mmol, 86%).
2,6,10-Tr iaza[11](9,10)an th r acen ecycloph an e (6g). Com-
pound 5g (200 mg, 0.24 mmol, 1 equiv) and CsF (763 mg, 4.8
mmol, 20 equiv) in 5 mL of DMF afforded 6g (69.5 mg, 0.21
mmol, 87%) after purification.22
2,5,8-Tr ia za [9](9,10)a n th r a cen ecyclop h a n e (6h ). Com-
pound 5h (104 mg, 0.13 mmol, 1 equiv) and CsF (395 mg, 2.6
mmol, 20 equiv) in 3 mL of DMF afforded 6h (38.5 mg, 0.14
mmol, 90%) after purification.
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for support of this research (Grant
No. 31790-GB4). G.A.D. and L.S.S. thank Macalester
College for a summer stipend from the Violet Olson
Beltmann Fund. M.F.L. thanks the Howard Hughes
Medical Institute for a summer stipend (Grant No.
71196-5044020).
1,5,9-Tr ia za cyclod od eca n e (6a ). Compound 5a (30 mg,
0.05 mmol, 1 equiv) and CsF (75 mg, 0.50 mmol, 10 equiv) in
0.5 mL of DMF afforded 6a 20 after purification (6.2 mg, 0.04
mmol, 81%).
1-Oxa -4,8,12-tr ia za cyclotetr a d eca n e (6b). Compound 5b
(100 mg, 0.14 mmol, 1 equiv) and CsF (425 mg, 2.8 mmol, 20
equiv) in 3 mL of DMF afforded 6b21 after purification (21 mg,
0.09 mmol, 71%).
1,4,7-Tr ia za cyclon on a n e (6c). Compound 5c (100 mg,
0.16 mmol, 1 equiv) and CsF (486 mg, 3.2 mmol, 20 equiv) in
3 mL of DMF afforded 6c20 (14 mg, 0.11 mmol, 68%).
3,7,11,17-Tetr a a za bicyclo[11.3.1]h ep ta d eca -1(17),13,15-
tr ien e (6d ). Compound 5d (70 mg, 0.10 mmol, 1 equiv) and
CsF (305 mg, 2.0 mmol, 20 equiv) in 2 mL of DMF afforded
6d 21 after purification (25 mg, 0.08 mmol, 83%).
Su p p or tin g In for m a tion Ava ila ble: Product character-
1
ization data for 3b, 5b-h , and 6f-h ; H NMR and 13C NMR
spectra for compounds 6e-h . This information is available free
of charge via the Internet at http://pubs.acs.org.
J O001639O
2,6,10-Tr iaza[11](1,4)n aph th alen ecycloph an e (6e). Com-
pound 5e (116.4 mg, 0.15 mmol, 1 equiv) and CsF (455 mg,
(22) This compound was also prepared by a one-pot procedure. After
3a (1 equiv), 9.10-di(bromomethyl)anthracene (1 equiv), and Cs2CO3
(5 equiv) were stirred in DMF at room temperature for 48 h, CsF (20
equiv) was added and the reaction mixture was heated at 95 °C for 24
h. DMF was removed in vacuo, and the product was isolated after
(20) Breillmann, M.; Kaderli, S.; Meyer, C. J .; Zuberbuhler, A. D.
Helv. Chim. Acta 1987, 70, 680.
(21) Lukyanenko, N. G.; Basok, S. S.; Filonova, L. K. J . Chem. Soc.,
Perkin Trans. 1 1988, 3141.
filtration through
comparable to the two-step procedure.
a column of neutral alumina. The yield was