Synthesis and structural studies of 5,12-dioxocyclams capped by 4-substituted pyridines across the amine nitrogens

Article abstract of DOI:10.1021/jo0301393

A series of 4-substituted pyridine-capped 5,12-dioxocyclams was synthesized and fully characterized. The 4-substituent varied from electron-withdrawing groups (NO₂, NO, CN) to electron-donating groups (NHCbz, NH₂). The most versatile substituent was the 4-bromo group, which could be replaced by a variety of groups using Stille, Sonogashira, or Buchwald-Hartig palladium-catalyzed chemistry. Copper complexes of a majority of these capped dioxocyclams were synthesized and characterized as well.

Full text of DOI:10.1021/jo0301393

Syn th esis a n d Str u ctu r a l Stu d ies of 5,12-Dioxocycla m s Ca p p ed by
4-Su bstitu ted P yr id in es Acr oss th e Am in e Nitr ogen s
Michal Achmatowicz, Louis S. Hegedus,* and Scott David
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
hegedus@lamar.colostate.edu
Received April 21, 2003
A series of 4-substituted pyridine-capped 5,12-dioxocyclams was synthesized and fully characterized.
The 4-substituent varied from electron-withdrawing groups (NO2, NO, CN) to electron-donating
groups (NHCbz, NH2). The most versatile substituent was the 4-bromo group, which could be
replaced by a variety of groups using Stille, Sonogashira, or Buchwald-Hartig palladium-catalyzed
chemistry. Copper complexes of a majority of these capped dioxocyclams were synthesized and
characterized as well.
In tr od u ction
than covalent bondssare of current interest in the
context of self-assembly of supramolecular structures.6
When the bridging ligands can transmit electronic in-
formation, these coordination oligomers can have inter-
esting electronic, magnetic, and optical properties.7 Di-
oxocyclams capped with pyridines bearing ligating groups
in the 4-position should be able to coordinate to two
different metals in a manner similar to that observed
with their pyrazine-capped analogues.5 Synthetic and
complexation studies of this new class of capped dioxo-
cyclams are detailed below.
Recent research in these laboratories has centered on
the synthesis of functionalized 5,12-dioxocyclams as
macrocyclic ligands for transition metals.1,2 Dioxocyclams
are intermediate between macrocyclic peptides and mac-
rocyclic polyamines, having two amide and two secondary
amine linkages as part of the ring periphery. The amines
are nucleophilic and reactive toward a range of electro-
philes. The use of bis-electrophiles can result in either
linking or capping these macrocycles.3 The synthesis of
pyridine-capped4 and pyrazine-capped5 dioxocyclams has
recently been reported from these laboratories. These
macrocycles provide a rigid, 5-coordinate ligand site for
copper and have unusual structural features. The pyra-
zine-capped system5 is capable of coordinating metals
both inside the macrocyclic cavity and outside the cavity
through the remote pyrazine nitrogen, allowing formation
of polymetallic coordination oligomers. Coordination
oligomerssarrays connected by metal-ligand bonds rather
Resu lts a n d Discu ssion
Syn th esis of Ca p p in g Agen ts. The synthesis of
4-nitro-8 and 4-cyano-2,6-bis(bromomethyl)pyridine began
with oxidation of 2,6-lutidine to the N-oxide with either
m-CPBA8 or H2O2 (Scheme 1). Nitration followed by
9
reduction of the N-oxide gave 4-nitro-2,6-lutidine, which
was overbrominated with NBS and then reduced back
to the desired 4-nitro-2,6-bis(bromomethyl)pyridine 1
with diethyl phosphite.10 This two-step procedure gave
substantially better yields (44% vs 11%) than direct,
stoichiometric benzylic bromination. O-Methylation of
lutidine N-oxide followed by treatment with aqueous
potassium cyanide11 gave 4-cyano-2,6-lutidine in low
(1) For reviews on dioxocyclams, see: (a) Kimura, E. Pure Appl.
Chem. 1989, 61, 823-828. (b) Kimura, E. New developments in
macrocyclic polyamine chemistry. In Crown Ethers and Analogous
Compounds; Hiraoka, M., Ed.; Elsevier: New York, 1992; Studies in
Organic Chemistry, Vol. 45, pp 381-478. (c) Krakowiak, K. E.;
Bradshaw, J . S. Ind. Eng. Chem. Res. 2000, 39, 3499-3507.
(2) (a) Puntener, K.; Hellman, M. D.; Kuester, E.; Hegedus, L. S. J .
Org. Chem. 2000, 65, 8301-8306. (b) Kuester, E.; Hegedus, L. S.
Organometallics 1999, 18, 5318-5321. (c) Hsiao, Y.; Hegedus, L. S. J .
Org. Chem. 1997, 62, 3586-3591. (d) Dumas, S.; Lastra, E.; Hegedus,
L. S. J . Am. Chem. Soc. 1995, 117, 3368-3379. (e) Hegedus, L. S.;
Moser, W. H. J . Org. Chem. 1994, 59, 7779-7784. (f) Betschart, C.;
Hegedus, L. S. J . Am. Chem. Soc. 1992, 114, 5010-5017.
(3) (a) Kurosaki, H.; Yoshida, H.; Fujimoto, A.; Goto, M.; Shionoya,
M.; Kimura, E.; Espinosa, E.; Barbe, J .-M.; Guilard, R. J . Chem. Soc.,
Dalton Trans. 2001, 898-901. (b) Kurosaki, H.; Bucher, C.; Espinosa,
E.; Barbe, J .-M.; Guilard, R. Inorg. Chim. Acta 2001, 322, 145-149.
(c) Denat, F.; Brandes, S.; Guilard, R. Synlett 2000, 561-574. (d)
Brande`s, S.; Denat, F.; Lacour, S. Rabiet, F.; Barbette, F.; Pullumbi,
P.; Guilard, R. Eur. J . Org. Chem. 1998, 2349, 9-2360. (e) Denat, F.;
Lacour, S.; Brande`s, S.; Guilard, R. Tetrahedron Lett. 1997, 38, 4417-
4420.
(6) For recent reviews, see: (a) Navarro, J . A. R.; Lippert, B. Coord.
Chem. Rev. 2001, 222, 219-250. (b) Swiegers, G. F.; Malefetse, T. J .
Chem. Rev. 2000, 100, 3483-3538. (c) Leininger, S.; Olenyuk, B.;
Stang, P. J . Chem. Rev. 2000, 100, 853-908. (d) Fujita, M.;Chem. Soc.
Rev. 1998, 27, 417-425.
(7) (a) Baxter, P. N. W. J . Org. Chem. 2000, 65, 1257-1272. (b)
Ziessel, R.; Hissler, M.; El-ghayoury, A.; Harriman, A. Coord. Chem.
Rev. 1998, 178-180, 1251-1298. (c) Hanack, M.; Kamenzin, S.;
Kamenzin, C.; Subramanian, L. R. Synth. Met. 2000, 110, 93-103. (d)
Geiss, A.; Vahrenkamp, H. Inorg. Chem. 2000, 39, 4029-4036.
(8) Teixidor, F.; Angle`s, P.; Vin˜as, C.; Kiveka¨s, R.; Sillanpa¨a¨, R.
Inorg. Chem. 2001, 40, 4010-4015.
(9) Boekelheide, V.; Linn, W. J . J . Am. Chem. Soc. 1954, 76, 1286-
1291.
(10) Liu, P.; Chen, Y.; Deng, J .; Tu, Y. Synthesis 2001, 2078-2080.
(11) Feely, W. E.; Beavers, E. M. J . Am. Chem. Soc. 1959, 81, 4004-
4007.
(4) Wynn, T.; Hegedus, L. S. J . Am. Chem. Soc. 2000, 122, 5034-
5042.
(5) Hegedus, L. S.; Sundermann, M. J .; Dorhout, P. K. Inorg. Chem.
2003, 42, 4346-4354.
10.1021/jo0301393 CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/22/2003
J . Org. Chem. 2003, 68, 7661-7666
7661

Achmatowicz et al.
SCHEME 1. Syn th esis of 4-Su bstitu ted
Bis(br om om eth yl)p yr id in es 1 a n d 2a
SCHEME 2. Syn th esis of
4-Br om obis(tosyloxym eth yl)p yr id in e 3a
a
Reagents and conditions: (i) NaOEt, EtOH, 55 °C, then aq
HCl; (ii) 25% aq NH3, 0 f 25 °C; (iii) PBr5, CHCl3, reflux, then
MeOH; (iv) NaBH4, abs EtOH, 0 f 25 °C, then TsCl, CH2Cl2, 40%
aq KOH, 0 f 25 °C.
SCHEME 3. Syn th esis of 4-Su bstitu ted
P yr id in e-Ca p p ed Dioxocycla m s 6a -ca
a
Reagents and conditions: (i) 30% H2O2, glacial AcOH, 80 °C;
(ii) HNO3/H2SO4, 130 °C, then PCl3, CHCl3, 80 °C; (iii) 6.4 equiv
i
of NBS, hν, PhH, reflux, then HP(O)(OEt)2, Pr2NEt, THF, 0 °C;
(iv) (MeO)2SO2, 80-100 °C, then KCN, H2O, 25 °C.
(16% vs 40% reported11) yield. The same overbromination
followed by diethyl phosphite reduction gave the desired
4-cyano-2,6-bis(bromethyl)pyridine 2 in 44% yield.
Because the yields of benzylic bromination were always
low and highly dependent on substrate structure, a more
versatile capping agent that would avoid the problematic
bromination step as well as provide the opportunity for
efficient introduction of a range of functionality in the
4-position was sought. Because of the rich organometallic
chemistry available for functionalizing heteroaromatic
halides,12 4-bromo-2,6-bis(tosyloxymethyl)pyridine 3 was
chosen. Treatment of chelidamic acid (commercially
available or easily synthesized from diethyl oxalate,
acetone, and ammonia) with PBr5 followed by methanol
produced dimethyl 4-bromo-2,6-pyridinedicarboxylate.
Reduction followed by tosylation13 gave 3 in good yield
(Scheme 2).
a
Reagents and conditions: (i) hν, CH2Cl2, 60 psi CO, 35 °C; (ii)
H2, 10% Pd/C, Et3N, MeOH; (iii) cat. (()-CSA, CH2Cl2, then rxt.
CH2Cl2/hexanes, cat. (()-CSA; (iv) NaCNBH3, CH2Cl2/MeOH, 0
f 25 °C.
With these materials in hand, capping studies were
initiated.
capped dioxocyclams 6a -c in good yield (Scheme 3).
Bromomethyl capping agents 1 and 2 capped efficiently
at concentrations as high as 0.1 M, while the tosyloxym-
ethyl agent 3 required higher dilution (0.0066 M) to
prevent the bridging of two cyclam groups in competition
with capping (at 0.1 M, 3 gave 52% of the bridged bis-
cyclam and 41% of the desired capped cyclam).
4-Bromopyridyl-capped cyclam 6c was a versatile
intermediate amenable to further elaboration (Scheme
4). It underwent clean Stille coupling14 with heteroaryl-
and vinylstannanes to give 6d and 6e, Sonogashira
coupling15 to give 6f and 6g, and palladium-catalyzed
amination16 to give 6h . Compounds 6d and 6f have the
desired additional coordinating group external to the
Ca p p in g Stu d ies. The desired centrosymmetric di-
oxocyclam 5 was synthesized as described previously2e,f
by photolysis of the requisite chromium carbene complex
with protected dimethyl imidazoline, followed by depro-
tection and acid-catalyzed dimerization, producing bis-
imine 4 as a 1:1 mixture of centro- and C2-symmetric
diastereoisomers. These equilibrate under acid catalysis,
and the centrosymmetric diastereoisomer preferentially
crystallizes, allowing conversion of the 1:1 mixture
completely to the centrosymmetric diastereoisomer 4
after three recrystallizations. Reduction followed by
treatment with capping agents 1-3 in the presence of
sodium carbonate (1) or Hu¨nig’s base (2 and 3) led to
(12) Li, J . J .; Gribble, G. W. Palladium in Heterocyclic Chemistry;
Pergamon: Amsterdam, 2000.
(13) Tahri, A.; Cielen, E.; Van Aken, K. J .; Hoornaert, G. J .; De
Schryver, F. C.; Boens, N.; J . Chem. Soc., Perkin Trans. 2 1999, 8,
1739-1748.
(14) Farina, V.; Krishnamurthy, V.; Scott, W. J . The Stille Reaction.
Org. React. 1997, 50, 1-652.
(15) Campbell, I. B. Sonogashira Cu-Pd-catalysed alkyne coupling
reaction. In Organocopper reagents: a practical approach; Taylor, R.
J . K., Ed.; Oxford University Press: Oxford, 1994; pp 217-235.
7662 J . Org. Chem., Vol. 68, No. 20, 2003

Synthesis and Structural Studies of 5,12-Dioxocyclams
SCHEME 4. F u n ction a liza tion of
SCHEME 5. In tr od u ction of Cop p er (II) in to 6a , 6b,
6d , a n d 6fa
4-Br om op yr in e-Ca p p ed Dioxocycla m 6ca
a
Reagents and conditions: (i) ZSnBu3, Pd2(dba)3‚CHCl3, Ph3P,
THF, 60-70 °C; (ii) BocNH2, PhONa, Pd2(dba)3‚CHCl3, tBu3P,
PhCH3, 100 °C; (iii) HCtCCH3, CuI, (Ph3P)2PdCl2, Et3N, MeCN,
80 °C; (iv) HCtCTMS, CuI, (Ph3P)2PdBr2, Et3N, MeCN, 80 °C,
then KF, MeOH, reflux.
macrocycle, while 6e, 6g, and 6h have functionality
suitable for further coupling to generate bis-cyclam
structures. (Capped cyclams 6a (Z ) NO2), 6b (Z ) CN),
and 6d (Z ) 4-Py) have been characterized by X-ray
crystallography. See the Supporting Information for
details.)
Com p lexa tion Stu d ies. Introduction of copper into
these macrocycles was attempted using previously de-
veloped conditions (Cu(BF4)2, K2CO3, MeOH, reflux).4,5
These proved effective for 7d (Z ) NHBoc), but less so
for 6b (Z ) CN). For the 4-nitro compound 7a , a good
yield of copper complex was obtained, but it proved to be
the 4-nitroso complex 7a ′ rather than the expected 4-nitro
compound 7a . It is not clear what the reducing agent was,
but methanol is the most likely candidate. 4-Nitrosopy-
ridine itself is unstable,17 although the N-oxide is known.18
Apparently, coordination to copper stabilized this moiety.
The desired 4-nitro complex 7a was obtained by running
the reaction in dichloromethane rather than methanol,
conditions which also proved to be slightly more efficient
for the synthesis of 7b as well (Scheme 5).
Str u ctu r a l a n d Sp ectr oscop ic Stu d ies. The X-ray
crystal structures of complexes 7a ′ (Z ) NO), 7d (Z )
4-Py), and 8 (Z ) NH2) were obtained (see the Supporting
Information for full details), and key structural features
were compared to those of the parent, pyridine-capped
cyclam copper complex4 (Z ) H) (Table 1). The nature of
the 4-substituent had little effect on coordination sphere
about copper. The copper-amine bond lengths (N2, N4),
copper-amide nitrogen bond lengths (N1, N3), and cop-
per-pyridine nitrogen bond lengths (N5), as well as the
nitrogen-copper-nitrogen bond angles, were similar
among the complexes, despite substantial differences in
the electron-donating or -accepting properties of the
4-substituent. This is likely due to the relative inflex-
ibility of capped cyclams, allowing little variation in
structure.
a
Reagents and conditions: (i) Cu(BF4)2, K2CO3, wet CH2Cl2,
60 °C; (ii) Cu(BF4)2, K2CO3, MeOH, 60 °C; (iii) 10% HCl/MeOH,
then aq NaHCO3, CH2Cl2.
group became increasingly electron-withdrawing (8, Z )
NH2, λmax(ꢀ) 701 nm (90); 7f, Z ) NHBoc, λmax(ꢀ) 691 nm
(300); 7a ′, Z ) NO, λmax(ꢀ) 685 nm (90); 7d , Z ) 4-Py,
λ
max(ꢀ) 684 nm (100); 7b, Z ) CN, λmax(ꢀ) 670 nm (110);
7a , Z ) NO2, λmax(ꢀ) 658 nm (140)). The ESR spectra were
all very similar, with GISO values ranging from 2.1318
(Z ) 4-Py, 7d ) to 2.1378 (Z ) 4-NH2, 8) with no apparent
correlation to the 4-substituent.
In summary, a series of dioxocyclams capped with
4-substituted pyridines was synthesized and character-
ized. The 4-bromopyridyl compound 6c was a versatile
precursor to a range of other 4-substituted pyridyl
compounds via organopalladium chemistry. Copper(II)
complexes of these macrocyclic ligand systems were
prepared, and characterized. Studies designed to syn-
thesize oligomers by coordination to other metal com-
plexes through the pyridine 4-substituent are under way.
Exp er im en ta l Section
Syn t h esis of 2,6-Bis(b r om om et h yl)-4-n it r op yr id in e19
(1). A mixture of NBS (125 g, 0.702 mol) and 4-nitro-2,6-
lutidine20 (17 g, 0.11 mol) in benzene (1.0 L) was stirred
vigorously at reflux for 3 days with irradiation with visible
light. The dark brown mixture was concentrated under
reduced pressure. The residue was taken up in diethyl ether
and passed through a Celite pad, and the solvent was removed
under vacuum to give crude 2,6-bis(tribromomethyl)-4-nitro-
pyridine as a clear dark brown oil (77 g). A portion of the crude
material (8.76 g, 11% of the total amount) was dissolved in
dry THF (65 mL) and placed in an ice bath under an argon
atmosphere. Diisopropylethylamine (6.57 mL, 51.0 mmol) was
The infrared spectra of all of the complexes showed the
expected shift in the position of the amide carbonyl band
from 1650 to 1660 cm-1 for the free ligand to 1570-1590
cm-1 for the complexes. The visible spectra showed an
increasing blue shift as the 4-substituent on the pyridine
(16) Hartwig, J . F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K.
H.; Alcazar-Roman, L. M. J . Org. Chem. 1999, 64, 5575-5580.
(17) Marty, M.; Clyde-Watson, Z.; Twyman, L. J .; Nakash, M.;
Sanders, J . K. M. Chem. Commun. 1998, 2265-2266.
(18) Gowenlock, B. G.; Cameron, M.; Boyd, A. S. F. J . Chem. Res.
Synth. 1995, 358-359.
(19) Teixidor, F.; Angles, P.; Vinas, C.; Kivekas, R.; Sillanpaa, R.
Inorg. Chem. 2001, 40, 4010-4015.
(20) Ochiai, E. J . Org. Chem. 1953, 18, 4-551.
J . Org. Chem, Vol. 68, No. 20, 2003 7663

Achmatowicz et al.
TABLE 1. Com p a r ison of Selected Bon d Len gth s (Å) a n d Bon d An gles (°) for P yr id in e-Ca p p ed Cop p er Dioxocycla m
Com p lexes 7a ′, 7d a n d 8a
bond lengths (Å)
bond angles (deg)
complex
N1-Cu
N2-Cu
N3-Cu
N4-Cu
N5-Cu
N1-Cu-N3
N3-Cu-N5
N1-Cu-N5
Z ) H (ref 4)
1.936 (3)
1.954 (3)
1.938 (10)
1.951 (9)
1.916 (7)
1.923 (7)
1.901 (7)
2.102 (3)
2.118 (3)
2.117 (9)
2.119 (7)
2.147 (7)
2.128 (7)
2.147 (7)
1.948 (3)
1.957 (3)
1.960 (12)
1.932 (9)
1.921 (8)
1.907 (7)
1.919 (7)
2.100 (3)
2.138 (3)
2.106 (9)
2.099 (7)
2.145 (7)
2.167 (7)
2.192 (7)
2.125 (3)
2.121 (3)
2.087 (10)
2.076 (7)
2.143 (7)
2.106 (7)
2.105 (8)
157.9 (1)
142.8 (1)
153.9 (4)
152.8 (3)
150.9 (3)
150.1 (3)
150.1 (3)
105.0 (1)
106.8 (1)
104.6 (5)
103.7 (3)
103.5 (3)
103.6 (3)
103.7 (3)
96.9 (1)
110.3 (1)
101.5 (5)
103.4 (3)
105.6 (3)
106.2 (3)
106.2 (3)
7a ′ (Z ) NO)
7d (Z ) 4-Py)
8 (Z ) NH2)
a
Complexes having two sets of entries had two slightly different molecules in the unit cell. Data for both are recorded.
added. Diethyl phosphite (8.88 mL, 51.0 mmol) was added
dropwise, and the reaction progress was monitored by TLC
(hexanes/EtOAc 9:1, 1: Rf 0.2). Within 5 min of the end of the
addition, the multiple products were converted into a single
product. The reaction mixture was poured into ice-cold water.
The product was extracted with Et2O, dried (Na2SO4), and
concentrated in vacuo. Flash chromatography on silica (hex-
anes/EtOAc 75:25) afforded pure 1 (1.75 g) as a yellowish oil:
yield 44%.
stirred at 0 °C for 45 min and then washed into separatory
funnel using CH2Cl2 (80 mL) and water (80 mL). The layers
were separated, and the aqueous layer was extracted with CH2-
Cl2 (2 × 80 mL). The combined organic solutions were washed
with brine, dried over Na2SO4, and concentrated under vacuum.
Recrystallization by addition of hexanes to a saturated dichlo-
romethane solution of the crude product afforded pure bis-
tosylate 3 (3.42 g) as colorless flakes: yield 81%; mp 111-112
°C (lit.13 110-111 °C); 1H NMR (CDCl3, 300 MHz) δ 7.78 (d, J
) 8.4 Hz, 4H), 7.42 (s, 2H), 7.33 (d, J ) 8.4 Hz, 4H), 5.01 (s,
4H), 2.44 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 154.7, 145.2,
134.4, 132.4, 129.9, 127.9, 124.3, 70.4, 21.7. FT-IR (film) 1597,
1574, 1367, 1190, 1176, 1096, 1032 cm-1; LRMS (FAB+, m/z)
525 (M + H+), 527 (M + H+).
Syn t h esis of 4-Nit r op yr id in e-Ca p p ed Dioxocycla m
(6a ). A mixture of the dibromide 1 (35 mg, 0.11 mmol), meso-
dioxocyclam 5 (30 mg, 80 µmol), and Na2CO3 (43 mg, 0.41
mmol) was flushed with argon. Acetonitrile (3 mL) was added,
and the resulting mixture was stirred at 85 °C for 3 days. The
reaction mixture was cooled to room temperature and passed
through a pad of Celite using MeCN as eluent. The combined
solutions were concentrated under reduced pressure. Flash
chromatography on silica (CH2Cl2/MeOH 95:5) afforded pure
capped dioxocyclam 6a (33 mg) as a cream colored solid. X-ray
quality crystals were obtained by recrystallization from CH2-
Cl2/hexanes (liquid diffusion): yield 80%; 1H NMR (CDCl3, 300
MHz) δ 8.74 (s, 1H), 7.69 (s, 1H), 7.65 (s, 2H), 4.38-4.05 (m,
4H), 3.41 (s, 3H), 3.21 (d, 1H, J ) 14 Hz), 2.90-2.85 (m, 5H),
2.57 (d, 1H, J ) 14 Hz), 2.48 (s, 3H), 2.29 (d, 1H, J ) 15 Hz),
1.45 (s, 3H), 1.42 (s, 3H), 1.33 (s, 6H), 1.32 (s, 3H), 1.19 (s,
3H); 13C NMR (CDCl3, 75 MHz) δ 173.2, 172.6, 166.8, 162.1,
155.2, 112.1, 111.8, 82.6, 79.4, 74.6, 72.8, 69.6, 67.4, 65.7, 64.8,
55.9, 54.7, 51.9, 50.4, 26.3, 25.6, 23.5, 23.4, 20.0, 19.2; FT-IR
(film) 1660, 1537, 1355 cm-1; HRMS (FAB+, m/z) calcd for
C25H41N6O6 (M + H+) 521.3088, found 521.3096. The molecular
structure was determined by single-crystal X-ray diffraction.
Syn t h esis of 2,6-Bis(b r om om et h yl)-4-cya n op yr id in e
(2). A mixture of NBS (2.14 g, 12 mmol) and 4-cyano-2,6-
lutidine11 (0.40 g, 3.0 mmol) in CCl4 (20 mL) placed in a tightly
sealed reaction vessel was stirred vigorously at 70 °C for 2 h
with irradiation with visible light. The resulting light brown
slurry was cooled to room temperature, and insoluble material
was removed by filtration through a Celite pad. The clear light
brown filtrate was concentrated in vacuo, and the resulting
clear yellow oil was redissolved in dry THF (60 mL). The
solution, under an argon atmosphere, was placed in an ice
bath. Diisopropylethylamine (2.1 mL, 12 mmol) was added
followed by dropwise addition of diethyl phosphite (1.54 mL,
12 mmol). The cooling bath was removed, and the reaction
progress was monitored by TLC. After ca. 5 h at room
temperature, the multiple products were converted into a
single product (by TLC). Water (50 mL) was added, and most
of the THF was removed under reduced pressure. The result-
ing slurry was diluted with saturated NaHCO3 (aq) (50 mL)
and extracted with CH2Cl2 (2 × 50 mL). The combined organic
extracts were washed with brine, dried over Na2SO4, and
concentrated in vacuo. Flash chromatography (30 g silica;
hexanes/EtOAc 85:15) afforded pure 2 (385 mg) as a yellowish
1
crystalline solid: yield 44%; mp 95-96 °C; H NMR (CDCl3,
300 MHz) δ 7.61 (s, 2H), 4.54 (s, 4H); 13C NMR (CDCl3, 75
MHz) δ 158.2, 124.2, 122.4, 115.7, 32.0; FT-IR (film) 3073,
2973, 1596, 1557, 1434, 1411, 1247, 1212 cm-1; HRMS (FAB+,
m/z) calcd for C8H7N2Br281 (M + H+) 292.8935, found 292.8936.
Syn t h esis of 4-Br om o-2,6-b is(t osyloxym et h yl)p yr i-
d in e13 (3). To the dimethyl 4-bromo-2,6-pyridinedicarboxy-
late21 (2.20 g, 8.00 mmol) solution in absolute EtOH (20 mL)
was added NaBH4 (0.56 g, 15 mmol) portionwise at -5 °C.
Upon addition, the previously colorless solution turned orange
and then gradually decolorized as the reaction progressed.
Several minutes after the last portion of NaBH4 was added,
the cooling was removed which resulted in spontaneous
warming slightly above room temperature (exothermic reac-
tion). At the point at which the reaction mixture was only
slightly colored, it was brought to reflux for 5 min. Solvent
was removed under reduced pressure, and then traces of EtOH
were removed under high vacuum to give a colorless powder
(6.47 g). The crude material was taken up in a precooled (0
°C) mixture of CH2Cl2 (40 mL) and KOH (18 g) in water (22
mL). Tosyl chloride (5.8 g, 30 mmol) was added, and the
resulting heterogeneous mixture was shaken vigorously until
all the solids dispersed. The resulting colorless emulsion was
Syn t h esis of 4-Cya n op yr id in e-Ca p p ed Dioxocycla m
(6b). A mixture of the dibromide 2 (240 mg, 0.83 mmol), meso-
dioxocyclam 5 (308 mg, 0.83 mmol), and diisopropylethylamine
(1.5 mL, 8.5 mmol) in MeCN (12 mL) was stirred at reflux for
ca. 3 h until the dibromide could not be detected by TLC
(hexanes/EtOAc 8:2, Rf 0.45). The solvent was removed under
reduced pressure. The solid residue was dissolved in CH2Cl2
(50 mL) and washed with saturated NaHCO3 (10 mL). The
aqueous layer was extracted with CH2Cl2 (15 mL). The
combined organic solutions were dried over Na2SO4 and
concentrated under vacuum. Flash chromatography on silica
(35 g, CH2Cl2/MeOH 97:3 f 95:5) afforded pure capped
dioxocyclam 6b (0.27 g) as a yellowish foam. X-ray quality
crystals were obtained by recrystallization from CH2Cl2/
1
Et2O: yield 65%; mp 290-291 °C dec; H NMR (CDCl3, 300
MHz) δ 8.76 (s, 1H), 7.62 (s, 1H), 7.20 (s, 1H), 7.17 (s, 1H),
4.24-3.96 (m, 4H), 3.40 (s, 3H), 3.18 (d, J ) 13.5 Hz, 1H),
3.03-2.86 (m, 5H), 2.55 (d, J ) 14.1 Hz, 1H), 2.50 (s, 3H),
2.26 (d, J ) 14.1 Hz, 1H), 1.43 (s, 3H), 1.40 (s, 3H), 1.32 (s,
3H), 1.30 (s, 3H), 1.18 (s, 3H), 1.12 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 172.8, 172.1, 164.6, 160.0, 121.1, 120.9, 120.2, 116.4,
(21) Lamture, J . B.; Zhou, Z. H.; Kumar, A. S.; Wensel, T. G. Inorg.
Chem. 1995, 34, 864-869.
7664 J . Org. Chem., Vol. 68, No. 20, 2003

Synthesis and Structural Studies of 5,12-Dioxocyclams
82.4, 79.2, 74.4, 72.5, 69.0, 67.2, 65.1, 64.5, 55.7, 54.5, 51.7,
50.2, 26.1, 25.5, 23.3 (2C), 19.0; FT-IR (film) 3259, 2959, 2928,
2827, 1660, 1560, 1516, 1453, 1132, 1101 cm-1; LRMS (FAB+,
m/z) 501 (M + H+). The molecular structure was determined
by single-crystal X-ray diffraction.
was tightly sealed, and the reaction mixture was stirred at 60
°C overnight. The solvent was removed under reduced pressure
and the residue purified by flash chromatography (CH2Cl2/
MeOH 95:5) to afford pure capped dioxocyclam 6e (62 mg) as
a yellowish oil: yield 83%; 1H NMR (CDCl3, 300 MHz) δ 9.06
(s, 1H), 8.03 (s, 1H), 6.92 (s, 1H), 6.87 (s, 1H), 6.63 (dd, J 1
)
Syn th esis of 4-Br om op yr id in e-Ca p p ed Dioxocycla m
(6c). A mixture of the ditosylate 3 (1.34 g, 2.55 mmol), meso-
dioxocyclam 5 (950 mg, 2.55 mmol), and diisopropylethylamine
(4.6 mL, 26 mmol) in MeCN (0.47 L) was stirred at reflux for
2 days until the ditosylate could not be detected by TLC. The
solvent was removed under reduced pressure. The solid residue
was dissolved in CH2Cl2 (0.15 L) and washed with saturated
NaHCO3 (30 mL). The aqueous layer was then extracted with
CH2Cl2 (50 mL). The combined organic solutions were dried
over Na2SO4 and concentrated under vacuum. Flash chroma-
tography on silica (40 g, CH2Cl2/MeOH 97:3) afforded pure
capped dioxocyclam 6c (1.13 g) as an off-white foam. X-ray
quality crystals were obtained by recrystallization from hot
MeCN: yield 80%; mp 225 °C dec; 1H NMR (CDCl3, 300 MHz)
δ 8.88 (s, 1H), 7.78 (s, 1H), 7.10 (s, 1H), 7.06 (s, 1H), 4.10-
3.80 (m, 4H), 3.35 (s, 3H), 3.11 (d, J ) 13.5 Hz, 1H), 2.96-
2.78 (m, 5H), 2.56-2.46 (m, 4H), 2.25 (d, J ) 14.4 Hz, 1H),
1.38 (s, 3H), 1.36 (s, 3H), 1.29 (s, 3H), 1.25 (s, 3H), 1.14 (s,
3H), 1.07 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 172.8, 172.2,
164.1, 159.6, 133.3, 122.1, 121.8, 82.2, 79.2, 74.2, 72.3, 68.7,
67.1, 64.9, 64.4, 55.6, 54.4, 51.6, 50.0, 26.0, 25.4, 23.2 (2C),
19.0; FT-IR (film) 3248, 2959, 2930, 2826, 1660, 1569, 1518,
1453, 1132, 1103 cm-1. Anal. Calcd for C25H40N5O4Br: C,
54.15; H, 7.22; N, 12.64. Found: C, 54.24; H, 7.36; N, 12.45.
Syn th esis of 4-(4-P yr id yl)p yr id in e-Ca p p ed Dioxocy-
cla m (6d ). A solution of the bromide 6c (500 mg, 0.902 mmol)
and tributyl(4-pyridyl)tin22 (0.45 g, 1.2 mmol) in MeCN (11
mL) placed in a pressure tube was degassed by repeating
freeze-pump-thaw sequence four times. Pd2(dba)3‚CHCl3 (47
mg, 45 µmol) was added followed by triphenylphosphine (95
mg, 0.36 mmol), and the resulting clear yellow solution was
stirred at 80 °C under argon for 2 days. The reaction mixture
was passed through a Celite pad to produce a clear orange
solution which was subsequently concentrated in vacuo. The
residue was taken up in Et2O (0.10 L) and 1 M HCl aq (0.10
L). Layers were separated, and the aqueous layer was washed
with one more Et2O portion (0.10 L) to remove all the organotin
material. All organic solutions were discarded. The aqueous
layer was made basic using concentrated KOH (aq) and
extracted with CH2Cl2 (3 × 80 mL). The combined extracts
were dried over Na2SO4 and concentrated under reduced
pressure. Recrystallization from hot MeCN afforded pure
capped dioxocyclam 6d (400 mg) as colorless needles: yield
80%; mp 270 °C dec; 1H NMR (CDCl3, 300 MHz) δ 9.06 (s,
1H), 8.74 (s, 1H), 8.72 (s, 1H), 7.96 (s, 1H), 7.53 (s, 1H), 7.51
(s, 1H), 7.18 (s, 1H), 7.15 (s, 1H), 4.28-3.98 (m, 4H), 3.41 (s,
3H), 3.21 (d, J ) 13.8 Hz, 1H), 3.02-2.86 (m, 5H), 2.60 (d, J
) 14.4 Hz, 1H), 2.51 (s, 3H), 2.35 (d, J ) 14.1 Hz, 1H), 1.46 (s,
3H), 1.43 (s, 3H), 1.37 (s, 3H), 1.32 (s, 3H), 1.19 (s, 3H), 1.13
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 173.0, 172.4, 163.9, 159.3,
150.5, 146.8, 145.5, 121.3, 116.8, 116.5, 82.4, 79.4, 74.4, 72.5,
69.2, 67.2, 65.5, 64.5, 55.8, 54.6, 51.7, 50.1, 26.1, 25.5, 23.4,
23.3, 19.1; FT-IR (film) 3239, 2960, 2930, 2825, 1658, 1593,
1543, 1518, 1454, 1132, 1102 cm-1; HRMS (FAB+, m/z) calcd
for C30H45N6O4 (M + H+) 553.3502, found 553.3486. The
molecular structure was determined by single-crystal X-ray
diffraction.
10.8 Hz, J 2 ) 17.7 Hz, 1H), 5.94 (d, J ) 17.7 Hz, 1H), 5.46 (d,
J ) 10.8 Hz, 1H), 4.18-3.87 (m, 4H), 3.39 (s, 3H), 3.17 (d, J )
13.5 Hz, 1H), 2.98-2.80 (m, 5H), 2.55 (d, J ) 14.4 Hz, 1H),
2.50 (s, 3H), 2.32 (d, J ) 14.1 Hz, 1H), 1.43 (s, 3H), 1.40 (s,
3H), 1.32 (s, 3H), 1.28 (s, 3H), 1.17 (s, 3H), 1.11 (s, 3H); 13C
NMR (CDCl3, 75 MHz) δ 173.3, 172.6, 163.2, 158.6, 146.0,
134.8, 118.7, 116.1, 115.8, 82.4, 79.4, 74.3, 72.4, 69.0, 67.1, 65.4,
64.5, 55.7, 54.6, 51.7, 50.0, 26.0, 25.4, 23.4, 23.2, 19.0; FT-IR
(film) 3233, 2956, 2927, 2827, 1659, 1605, 1558, 1519, 1453,
1133, 1103 cm-1; HRMS (FAB+, m/z) calcd for C27H44N5O4 (M
+ H+) 502.3393, found 502.3394.
Syn th esis of 4-(NHBoc)p yr id in e-Ca p p ed Dioxocycla m
(6f). The bromide 6c (50 mg, 90 µmol), tert-butyl carbamate
(42 mg, 0.36 mmol), freshly prepared sodium phenoxide (42
mg, 0.36 mmol), and Pd2(dba)3‚CHCl3 (4.9 mg, 4.7 µmol) were
combined in a screw-cap pressure tube under argon. The
mixture was suspended in dry, oxygen-free toluene (2.5 mL).
t
To the resulting dark-red slurry was added 0.05 M Bu3P in
toluene (0.36 mL, 18 µmol) and the pressure tube was tightly
sealed. The reaction mixture was then stirred at 100 °C
overnight (16 h). The dark-orange reaction mixture was cooled
to room temperature, diluted with CH2Cl2, and washed with
5% aq NaHCO3. The aqueous layer was then back-extracted
twice with CH2Cl2. The combined organic solutions were dried
(Na2SO4) and concentrated under reduced pressure. Flash
chromatography on silica (CH2Cl2/MeOH 95:5 f 50:50) af-
forded capped dioxocyclam 6f (34 mg) as a colorless solid: yield
64%; mp 165 °C dec; 1H NMR (CDCl3, 300 MHz) δ 9.08 (s,
1H), 8.27 (s, 1H), 7.14 (s, 1H), 7.08 (s, 1H), 6.86 (s, 1H), 4.14-
3.84 (m, 4H), 3.38 (s, 3H), 3.17 (d, J ) 13.5 Hz, 1H), 2.98-
2.80 (m, 5H), 2.59 (s, 3H), 2.50 (d, J ) 9.6 Hz, 1H), 2.32 (d, J
) 14.4 Hz, 1H), 1.51 (s, 9H), 1.44 (s, 3H), 1.40 (s, 3H), 1.29 (s,
3H), 1.28 (s, 3H), 1.19 (s, 3H), 1.12 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 173.2, 172.6, 163.3, 159.2, 152.0, 146.7, 107.2, 107.1,
82.4, 81.7, 79.5, 74.1, 72.6, 68.8, 66.9, 65.7, 64.6, 55.7, 54.7,
51.7, 50.2, 28.3, 26.1, 25.5, 23.4 (2C), 19.1; FT-IR (film) 3227,
2973, 2931, 2827, 1733, 1653, 1594, 1521, 1456, 1368, 1266,
1233, 1156, 1133, 1104 cm-1; HRMS (FAB+, m/z) calcd for
C
30H51N6O6 (M + H+) 591.3870, found 591.3878.
Syn th esis of 4-(1-P r op yn yl)p yr id in e-Ca p p ed Dioxo-
cycla m (6g). The bromide 6c (55 mg, 0.10 mmol) was placed
in an argon-flushed pressure tube. After being dissolved in a
mixture of dry MeCN (2.0 mL) and dry Et3N (1.0 mL), the
solution was degassed by three freeze-pump-thaw sequences.
(Ph3P)2PdCl2 (7 mg, 10 µmol) and CuI (9.8 mg, 50 µmol) were
added under argon. The pressure tube was fitted with a
pressure head,and connected to a propyne tank. The pressure
tube was then placed in a liquid nitrogen bath, and propyne
(0.7 g, 17 mmol) was condensed into the reaction vessel. The
pressure tube was then tightly sealed and placed in a 80 °C
bath with stirring (ca. 50 psi of internal pressure developed)
for 20 h. The reaction mixture was then passed through Celite
and concentrated under reduced pressure. Purification by flash
chromatography (hexanes/EtOAc 2:8) afforded pure product
6g as a yellowish wax (50 mg). X-ray quality crystals were
obtained by recrystallization from CH2Cl2/MeCN by slow
Syn t h esis of 4-Vin ylp yr id in e-Ca p p ed Dioxocycla m
(6e). To a solution of the bromide 6c (84 mg, 0.15 mmol) in
dry, oxygen-free THF (3.0 mL) was added triphenylphosphine
(19 mg, 74 µmol) followed by Pd2(dba)3‚CHCl3 (8.4 mg, 8.0
µmol) under argon. The resulting red solution was stirred for
10 min upon which the solution turned yellow-orange. Tribu-
tyl(vinyl)tin (66 µL, 0.23 mmol) was added, the reaction vessel
1
evaporation: yield 98%; mp 236-8 °C; H NMR (CDCl3, 300
MHz) δ 8.98 (s, 1H), 7.94 (s, 1H), 6.89 (s, 1H), 6.86 (s, 1H),
4.12-3.82 (m, 4H), 3.38 (s, 3H), 3.16 (d, J ) 13.8 Hz, 1H),
2.98-2.80 (m, 5H), 2.56 (s, 3H), 2.53 (d, J ) 13.8 Hz, 1H),
2.29 (d, J ) 14.1 Hz, 1H), 2.04 (s, 3H), 1.42 (s, 3H), 1.39 (s,
3H), 1.31 (s, 3H), 1.28 (s, 3H), 1.17 (s, 3H), 1.10 (s, 3H); 13C
NMR (CDCl3, 75 MHz) δ 173.3, 172.7, 162.8, 158.3, 133.4,
121.3, 120.9, 91.1, 82.5, 79.6, 74.5, 72.6, 69.1, 67.4, 65.4, 64.7,
55.9, 54.8, 51.9, 50.4, 26.3, 25.7, 23.6, 23.5, 19.3, 4.8; FT-IR
(film) 3279, 3207, 2957, 2933, 2827, 2245, 1655, 1601, 1549,
(22) Guillier, F.; Nivoliers, F.; Godard, A.; Marsais, F.; Queguiner,
G.; Siddiqui, M. A.; Snieckus, V. J . Org. Chem. 1995, 60, 292-296.
J . Org. Chem, Vol. 68, No. 20, 2003 7665

Achmatowicz et al.
1519, 1456, 1368, 1263, 1182, 1135, 1104, 1089, 1062 cm-1
;
Cop p er com p lex (7a ): yield 69%; FT-IR (film) 1576, 1542,
1355 cm-1; UV-vis (MeOH) λmax(ꢀ) 658 (1.4 × 102); ESR (CH2-
Cl2/PhH 3:1) 2.1343; HRMS (FAB+, m/z) calcd for C25H39N6O6-
Cu (M + H+) 582.2227, found 582.2231.
HRMS (FAB+, m/z) calcd for C28H44N5O4 (M + H+) 514.3393,
found 514.3395.
Syn th esis of 4-(Eth yn yl)p yr id in e-Ca p p ed Dioxocy-
cla m (6h ). The bromide 6c (220 mg, 0.397 mmol) and
(trimethylsilyl)acetylene (0.28 mL, 2.0 mmol) were combined
in an argon-flushed pressure tube. After being dissolved in a
mixture of dry MeCN (4.0 mL) and dry Et3N (4.0 mL), the
solution was degassed by three freeze-pump-thaw sequences.
(Ph3P)2PdBr2 (32 mg, 40 µmol) and CuI (52 mg, 0.27 mmol)
were added under argon, and the pressure tube was tightly
sealed and placed in a 80 °C bath with stirring for 22 h. The
resulting dark-brown reaction mixture was passed through a
Celite pad and concentrated in vacuo. The residue was taken
up in CH2Cl2 and washed with saturated NaHCO3 (aq). The
aqueous layer was extracted with CH2Cl2. The combined
organic solutions were dried (Na2SO4) and concentrated under
reduced pressure. Purification by flash chromatography (CH 2-
Cl2/MeOH 93:7) afforded TMS-protected product as a brownish
foam (220 mg): yield 96%; 1H NMR (CDCl3, 300 MHz) δ 8.91
(s, 1H), 7.91 (s, 1H), 6.95 (s, 1H), 6.91 (s, 1H), 4.12-3.82 (m,
4H), 3.36 (s, 3H), 3.13 (d, J ) 13.8 Hz, 1H), 2.94-2.78 (m,
5H), 2.52 (s, 3H), 2.49 (d, J ) 13.8 Hz, 1H), 2.26 (d, J ) 13.8
Hz, 1H), 1.40 (s, 3H), 1.37 (s, 3H), 1.27 (s, 3H), 1.25 (s, 3H),
1.14 (s, 3H), 1.08 (s, 3H), 0.21 (s, 9H); 13C NMR (CDCl3, 75
MHz) δ 173.0, 172.4, 162.6, 158.1, 132.0, 121.1, 120.7, 102.0,
99.3, 82.2, 79.3, 74.1, 72.4, 68.7, 67.0, 65.1, 64.4, 55.6, 54.5,
51.6, 50.1, 26.0, 25.4, 23.2, 19.0, -0.3. The TMS-acetylene
derivative was dissolved in MeOH (10 mL) and treated with
KF (44 mg, 0.76 mmol). The resulting brown solution was
heated to reflux and then allowed to stand at room tempera-
ture for 4 h. The solvent was removed under reduced pressure.
The residue was taken up in CH2Cl2, passed through a Celite
pad, and then concentrated in vacuo. Purification by flash
chromatography (CH2Cl2/MeOH 93:7) afforded pure terminal
alkyne 6h (159 mg) as a yellowish oil. X-ray quality crystals
were obtained by recrystallization from hot MeCN: yield 80%;
mp 210 °C dec; 1H NMR (CDCl3, 300 MHz) δ 8.94 (s, 1H), 7.87
(s, 1H), 7.01 (s, 1H), 6.98 (s, 1H), 4.17-3.85 (m, 4H), 3.40 (s,
3H), 3.25 (s, 1H), 3.18 (d, J ) 13.5 Hz, 1H), 2.99-2.81 (m,
5H), 2.59-2.49 (m, 4H), 2.29 (d, J ) 14.4 Hz, 1H), 1.43 (s,
3H), 1.40 (s, 3H), 1.32 (s, 3H), 1.29 (s, 3H), 1.17 (s, 3H), 1.11
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 172.9, 172.3, 162.8, 158.3,
131.1, 121.4, 121.0, 82.2, 81.4, 81.0, 79.3, 74.2, 72.3, 68.8, 67.1,
65.1, 64.4, 55.6, 54.5, 51.6, 50.0, 26.0, 25.4, 23.2, 19.0; FT-IR
(film) 3242, 2960, 2931, 2827, 2104, 1659, 1599, 1556, 1518,
1453, 1367, 1325, 1132, 1102, 1058 cm-1; HRMS (FAB+, m/z)
calcd for C27H42N5O4 (M + H+) 500.3237, found 500.3238.
Gen er a l P r oced u r e for th e P r ep a r a tion of Cop p er (II)
Com p lexes. A ligand 6 (50 µmol), Cu(BF4)2‚6H2O (85 mg, 0.25
mmol), and K2CO3 (0.14 g, 1.0 mmol) were combined in a
screw-cap pressure tube. The mixture was suspended in a
solvent (MeOH or wet CH2Cl2, 5 mL), and the reaction vessel
was tightly sealed and placed in 80-100 °C bath with stirring
for 1-5 days. The resulting colored slurry was passed through
a Celite pad and concentrated in vacuo. For reactions with
MeOH as a solvent, the solid residue was triturated with CH2-
Cl2, and passed through a Celite pad again to produce a clear
green solution. Purification by flash chromatography on silica
(CH2Cl2/MeOH, copper(II) complexes 7 reversibly change color
from green to purple in contact with silica), and/or by recrys-
tallization.
Cop p er Com p lex (7a ′). X-ray quality crystals by recrys-
tallization from CH2Cl2/hexanes (slow evaporation): yield 69%;
FT-IR (film) 1583, 1358 cm-1; UV-vis (MeOH) λmax(ꢀ) 685 (0.9
× 102); ESR (CH2Cl2/PhH 3:1) 2.1341. The molecular structure
was determined by single-crystal X-ray diffraction.
Cop p er Com p lex (7b). X-ray quality crystals by recrys-
tallization from CH2Cl2/hexanes (vapor diffusion): yield 60%;
mp 200 °C dec; FT-IR (film) 3416, 2918, 1574, 1450, 1365,
1184, 1132, 1074 cm-1; UV-vis (MeOH) λmax(ꢀ) 670 (1.1 × 102);
ESR (CH2Cl2/PhH 3:1) 2.1351; LRMS (FAB+, m/z) 562 (M +
H+).
Cop p er Com p lex (7d ). X-ray quality crystals by recrys-
tallization from CH2Cl2/hexanes/EtOAc (slow evaporation):
yield 55%; mp 158-160 °C; FT-IR (film) 3238, 2956, 2926,
2855, 1590, 1452, 1368, 1132, 1071 cm-1; UV-vis (MeOH) λmax
-
(ꢀ) 684 (1.0 × 102); ESR (CH2Cl2/PhH 3:1) 2.1318; LRMS
(FAB+, m/z) 614 (M+ H+). The molecular structure was
determined by single-crystal X-ray diffraction.
Cop p er Com p lex (7f). Purification by flash chromatogra-
phy (CH2Cl2/MeOH 95:5 f 50:50 f 0:100) afforded pure
complex 7f as a green wax: yield 65%; FT-IR (film) 3224, 2925,
1582, 1461, 1451, 1427, 1366, 1260, 1241, 1156, 1084, 1018
cm-1; UV-vis (MeOH) λmax(ꢀ) 691 (3 × 102); LRMS (FAB+, m/z)
652 (M + H+).
Cop p er Com p lex (8). The copper complex 7f (7.2 mg, 11
µmol) was dissolved in 10% HCl/MeOH (1 mL) with concomi-
nant gas evolution to produce a dark violet solution. The
solvent was removed under reduced pressure. The residue was
dissolved in saturated NaHCO3 (aq) (10 mL). The resulting
clear violet solution was concentrated under reduced pressure.
The solid residue was dried under vacuum until the color
changed from light violet to light green and was then tritu-
rated with CH2Cl2 to produce a green solution. Recrystalliza-
tion from CH2Cl2/hexanes afforded pure complex 8 (6.0 mg)
as green crystals: yield quantitative; mp 300 °C dec; FT-IR
(film) 3308, 2881, 1581, 1447, 1365, 1135, 1090 cm-1; UV-vis
(MeOH) λmax(ꢀ) 701 (0.9 × 102); ESR (CH2Cl2/PhH 3:1) 2.1378;
HRMS (FAB+, m/z) calcd for C25H41N6O4Cu (M + H+) 552.2485,
found 552.2477. The molecular structure was determined by
single-crystal X-ray diffraction.
Ack n ow led gm en t. Support for this research under
Grant No. CHE-9908661 from the National Science
Foundation is gratefully acknowledged. Mass spectra
were obtained on instruments supported by National
Institutes of Health shared instrumentation grant GM
49631.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 2 and 6a ,b,d -h . ORTEP diagrams,
crystal data and structure refinement parameters, atomic
coordinates, bond lengths and bond angles, torsion angles,
anisotropic displacement coefficients, and H-atom coordinates
for compounds 6a ,b,d , 7a ′,d , and 8. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O0301393
7666 J . Org. Chem., Vol. 68, No. 20, 2003