Synthesis of highly functionalized macrocycles by the peripheral functionalization of macrocyclic diimines

Article abstract of DOI:10.1021/jo0614689

The easily available macrocyclic diimines 4-7 can be stereoselectively transformed to macrocyclic bis-β-amino acids 13-17, macrocyclic bisazetidines 18-20, and macrocyclic bisamides 21 and 22 by means of the corresponding bis-β-lactam scaffolds 8-12. Thes

Full text of DOI:10.1021/jo0614689

Synthesis of Highly Functionalized Macrocycles by the Peripheral
Functionalization of Macrocyclic Diimines
Miguel A. Sierra,* Daniel Pellico, Mar Go´mez-Gallego,* Mar´ıa Jose´ Manchen˜o, and
Rosario Torres†
Departamento de Qu´ımica Orga´nica and Laboratorio de Difraccio´n de Rayos X, Facultad de Qu´ımica,
UniVersidad Complutense, 28040 Madrid, Spain
sierraor@quim.ucm.es; margg@quim.ucm.es
ReceiVed July 14, 2006
The easily available macrocyclic diimines 4-7 can be stereoselectively transformed to macrocyclic bis-
â-amino acids 13-17, macrocyclic bisazetidines 18-20, and macrocyclic bisamides 21 and 22 by means
of the corresponding bis-â-lactam scaffolds 8-12. These key intermediates are available through standard
Staudinger reaction and obtained as the cis-cis diastereomers, exclusively. An interesting relation between
the proximity of the reactive CdN bonds and the selectivity in the formation of the bis-â-lactams 8-12
is observed. Thus, diimine 4 leads to low selectivities, producing a 1:1 mixture of cis-syn-cis and cis-
anti-cis diastereomers, while diimines 5-7 having the diimine sites more separated lead almost exclusively
to the cis-anti-cis diastereomers. The stereochemistry of all the products was unambiguously assigned
by X-ray diffraction analysis of compounds cis-syn-cis 8 and cis-anti-cis 12-Co2CO6 complex.
Introduction
pounds in the functionalization of macrocycles is surprising.
Romo3 and Wasserman4 have elegantly employed the 2-azeti-
dinone ring as a macrolactamization agent. Hegedus reported
the synthesis of cyclams and biscyclams5 starting from aza-
carbapenams and bisazacarbapenams, respectively. Otherwise,
the building of one or more â-lactam rings in a preformed
macrocyclic imine or polyimine to further manipulate the four-
Despite the plethora of synthesis of compounds having the
â-lactam ring1 and the number of transformations in which the
2-azetidinone ring is involved,2 the scarce use of these com-
† To whom inquires regarding the X-ray determination of the structures of
compound 8 and compound 12-Co2(CO)6 should be addressed.
(1) See: (a) Go´mez-Gallego, M.; Manchen˜o, M. J.; Sierra, M. A.
Tetrahedron 2000, 56, 5743. Selected reviews in the synthesis and biology
of â-lactams: (b) Du¨rckheimer, W.; Blumbach, J.; Lattrell, R.; Scheun-
emann, K. H. Angew. Chem., Int. Ed. Engl. 1985, 24, 180. (c) The Organic
Chemistry of â-Lactams; Georg, G. I., Ed.; VCH: New York, 1992.
(2) In fact, the term â-lactam synthon approach was coined for these
methodologies. See: (a) Hatanaka, N.; Abe, R.; Ojima, I. Chem. Lett. 1982,
445. Reviews: (b) Ojima, I. AdV. Asymmetry Synth.1995, 1, 95-146. (c)
Manhas, M. S.; Wagle, D. R.; Chiang, J.; Bose, A. K. Heterocycles 1988,
27, 1755-1802. (d) Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide, M.
Pure Appl. Chem. 2000, 72, 1763.
(3) Romo, D.; Rzasa, R. M.; Shea, H. A.; Park, K.; Langenhan, J. M.;
Sun, L.; Akhiezer, A.; Liu, J. O. J. Am. Chem. Soc. 1998, 120, 12237.
(4) Wasserman, H. H.; Matsuyama, H.; Robinson, R. P. Tetrahedron
2002, 58, 7177 and references therein.
(5) (a) Achmatowicz, M.; Hegedus, L. S.; David, S. J. Org. Chem. 2003,
68, 7661. (b) Hegedus, L. S.; Sundermann, M. J.; Dorhout, P. K. Inorg.
Chem. 2003, 42, 4346. (c) Wynn, T.; Hegedus, L. S. J. Am. Chem. Soc.
2000, 122, 5034. (d) Gil, J. M.; David, S.; Reiff, A. L.; Hegedus, L. S.
Inorg. Chem. 2005, 44, 585 and references therein.
10.1021/jo0614689 CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/07/2006
J. Org. Chem. 2006, 71, 8787-8793
8787

Sierra et al.
SCHEME 1
membered ring and to produce differently functionalized mac-
rocycles is unknown.6
Macrocyclic polyimines have been prepared in the context
of metal chelating cavities,7 and they are very attractive scaffolds
to construct macrocyclic bisazetidinones that can be further
elaborated to macrocyclic polyamino acids, macrocyclic amides,
and macrocyclic azetidines within the diversity oriented syn-
thesis (DOS) concept.8 Reported in this paper is the implemen-
tation of this idea.
Results and Discussion
Dialdehydes 1-39 were condensed with 1,3-diaminopropane
and 1,4-diamino-2-butyne in nearly quantitative yields in boiling
MeOH or EtOH to form the macrocyclic imines 4-7 used in
this work (Scheme 1). The reaction conditions have been tuned
up to avoid the formation of dimers or oligomers as byprod-
ucts.10 Diimine 4 was reacted with phenoxyacetyl chloride in
dry CH2Cl2 at -78 °C in the presence of Et3N. After heating
to room temperature and quenching with MeOH/H2O, a 1:1
mixture of two bis-â-lactam derivatives (78% yield) was
obtained. The mixture was separated by column chromatography
to yield compounds 8 and 9, isolated in 23 and 27% yields,
respectively (Scheme 2). Both compounds have a cis-cis
stereochemistry in the â-lactam ring as deduced from the
coupling constants of H3-H4 and H3′-H4′ protons (J3,4 ) 4.5
and 4.4 Hz for compounds 8 and 9, respectively).11 Therefore,
the reaction yielded both the cis-syn-cis 8 and the cis-anti-cis 9
isomers. No trace amounts of any of the remaining isomers
having one or both rings in a trans-stereochemistry were
detected. A single crystal of cis-syn-cis 8 was submitted to X-ray
diffraction analysis thus unambiguously establishing this relative
stereochemistry.
Having unambiguously characterized compound 8 as the cis-
syn-cis isomer, the cis-anti-cis stereochemistry was assigned to
compound 9. Reactions of imines 5-7 and phenoxyacetyl
chloride under the conditions discussed above yielded products
10, 11, and 12 in 78, 45, and 74%, respectively. Compounds
SCHEME 2
(6) The formation of some macrocyclic bis-â-lactams in very low yields
has been reported for the preparation of 4,7-fused â-lactam synthesis. See:
Brooks, G.; Hunt, E. J. Chem. Soc., Perkin Trans. 1 1983, 115.
(7) (a) Armstrong, L. G.; Lindoy, L. F. Inorg. Chem. 1975, 14, 1322.
(b) Armstrong, L. G.; Grimsley, P. G.; Lindoy, L. F.; Lip, H. C.; Norris,
V. A.; Smith, R. J. Inorg. Chem. 1978, 17, 2350. (c) Lindoy, L. F.; Lip, H.
C.; Power, L. F.; Rea, J. H. Inorg. Chem. 1976, 15, 1724. (d) Anderegg,
G.; Ekstrom, A.; Lindoy, L. F.; Smith, R. J. J. Am. Chem. Soc. 1980, 102,
2670. (e) Baldwin, D.; Duckworth, P. A.; Erickson, G. R.; Lindoy, L. F.;
McPartlin, M.; Mockler, G. M.; Moody, W. E.; Tasker, P. A. Aust. J. Chem.
1987, 40, 1861. (f) Adam, K. R.; Leong, A. J.; Lindoy, L. F.; Lip, H. C.;
Skelton, B.; White, A. H. J. Am. Chem. Soc. 1983, 105, 4645. (g) Miyokawa,
K.; Hirashima, H.; Masuda, I. Tetrahedron 1985, 41, 1891. (h) Leoni, P.;
Grilli, E.; Pasquali, M.; Tomassini, M. J. Chem. Soc., Dalton Trans. 1985,
2561. (i) Martell, A. E.; Hancock, R. D. Chem. ReV. 1989, 89, 1875.
(8) Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed. 2004, 43, 46.
(9) Simion, C.; Simion, A.; Mitoma, Y.; Nagashima, S.; Kawaji, T.;
Hasimoto, I.; Tashiro, M. Heterocycles 2000, 53, 2459.
(10) The formation of dimers and oligomers as undesired byproducts in
the synthesis of macrocyclic diimines depends not only on the reaction
conditions employed but also on the size and conformational flexibility of
the molecules involved. See for example: Simion, A.; Simion, C.; Kanda,
T.; Nagashima, S.; Mitoma, T.; Yamada, T.; Mimura, K.; Tashiro, M. J.
Chem. Soc., Perkin Trans. 1 2001, 2071 and ref 7a.
(11) The most usual method for the determination of the relative
stereochemistry of 2-azetidinones is 1H NMR. The J3,4 cis value is ca. 4.5-6
Hz, while J3,4 trans is ca. 2-2.5 Hz. See for example: (a) Manhas, M. S.;
Ghosh, M.; Bose, A. K. J. Org. Chem. 1990, 55, 575. (b) Sharma, A. K.;
Mazumdar, S. N.; Mahajan, M. P. J. Org. Chem. 1996, 61, 5506. (c) Alca´zar,
R.; Ram´ırez, P.; Vicente, R.; Manchen˜o, M. J.; Sierra, M. A.; Go´mez-
Gallego, M. Heterocycles 2001, 55, 511.
10-12 were isolated as single diastereomers. Traces (<10%)
of the other cis-cis diastereomers were observed in the crude
reaction mixture, but they could not be isolated. All compounds
10-12 have the signal corresponding to the â-lactam H4
shielded (4.88, 4.88, and 5.38 ppm, respectively) compared to
that of the minor isomers (5.34, 5.36, and 5.58 ppm, respec-
tively12). This shielding was also observed in compound 9 (δH4
) 5.17) compared to compound 8 (δH4 ) 5.41) from which the
(12) Data measured in 1H NMR spectra of the mixtures enriched in these
minor isomers.
8788 J. Org. Chem., Vol. 71, No. 23, 2006

Peripheral Functionalization of Macrocyclic Diimines
SCHEME 4
relative stereochemistry was unambiguously ascertained by
X-ray analysis. Therefore, the cis-anti-cis stereochemistry was
assigned to products 10-12 (Scheme 3).13 Definitive confirma-
tion of the stereochemical assignment for these compounds was
achieved by preparing the Co2(CO)6 complex derived from 12.
Compound 12‚Co2(CO)6 produced crystals suitable for X-ray
diffraction analysis that unambiguously confirmed the cis-anti-
cis stereochemistry of this product and, by analogy, the validity
of the stereochemical assignment made for compounds 9-11.
SCHEME 3
The stereochemistry observed in the double Staudinger
reaction leading to compounds 8-12 deserves some comments.
It is known that cyclic imines prefer to form the trans-â-lactams
due to the fixed Z-configuration of the imine CdN bond
imposed by the cyclic structure.14 This is not the case for
macrocyclic imines 4-7 that have E-configuration15 and follow
the usual pattern observed for open-chain imines16 giving only
the cis-â-lactams. More intriguing is the observed selectivity
during the formation of the bis-â-lactam system. Except for
diimine 4, which forms the equimolecular amount of cis-syn-
cis and cis-anti-cis isomers, imines 5-7 have a clear bias for
the formation of cis-anti-cis isomers. These facts suggest a direct
influence of one of the emerging four-membered rings on the
torquoselectivity17 of the second ring closure but only when
both centers are not too close to each other as in compound 4,
in which the tether between the O-Ar groups is a CH2-CH2
chain (compare the stereochemistry of the reaction products
derived from compounds 4 and 5 or 7). The formation of 1:1
syn/anti diastereomeric mixtures has been also reported in the
synthesis of acyclic cis-bis-â-lactams linked by an ethylene
bridge.18 The origin of the selectivity in the formation of
â-lactams and the influence of several factors (structural,
electronic, reaction conditions) is still a subject of debate.14b
The diastereoselectivity reported in this paper may be due to a
better stabilization of the intermediate zwitterions and could be
topologically demanding. While this effect has been observed
previously in peripheral functionalization,19 it has not been
rationalized. A theoretical model to reflect this effect is being
developed in our laboratories and will be reported in due time.
With an efficient and stereoselective entry to macrocyclic bis-
â-lactams ascertained, the use of these compounds as scaffolds
to obtain functionalized macrocycles was explored next. The
hydrolysis of compounds 8-12 to the novel macrocyclic bis-
â-amino acids 13-17 was carried out by boiling compounds
8-12 in 10 N HCl. The amino acids were obtained as
hydrochlorides in good to excellent yields with retention of the
stereochemistry of the starting bis-â-lactam. The use of Evans’
conditions (LiOH, H2O2 at 0 °C)20 in compounds 8-10 also
formed bisamino acids 13-15 in good yields (Scheme 4).
(13) Preliminary MM studies carried out with compounds 8 and 9 show
that the rigidity imposed in the macrocycle by the embedding of two
â-lactam ring places the aromatic ring of one four-membered ring close to
the other in the cis-anti-cis isomer. This effect is not seen in the cis-syn-cis
isomer.
(14) Jiao, L.; Liang, Y.; Xu, J. J. Am. Chem. Soc. 2006, 128, 6060 and
references therein.
(15) The E-configuration of the cyclic diimines derived from dialdehydes
1-3 has been reported. See: References 7h and 10.
(16) (a) Dumas, S.; Hegedus, L. S. J. Org. Chem. 1994, 59, 4967. (b)
Hegedus, L. S.; Montgomery, J.; Narukawa, Y.; Sanustad, D. C. J. Am.
Chem. Soc. 1991, 113, 5784.
(17) Cossio, F. P.; Arrieta, A.; Lecea, B.; Ugaldby, J. M. J. Am. Chem.
Soc. 1994, 116, 2085 and references therein.
(18) Karupaiyan, K.; Puranik, V. G.; Deshmukh, A. R. A. S.; Bhawal,
B. M. Tetrahedron 2000, 56, 8555.
(19) (a) Still, W. C.; Romero, A. G. J. Am. Chem. Soc. 1986, 108, 2105.
(b) Schreiber, S. L.; Sammakia, T.; Hulin, B.; Schulte, G. J. Am. Chem.
Soc. 1986, 108, 2106.
J. Org. Chem, Vol. 71, No. 23, 2006 8789

Sierra et al.
SCHEME 5
In conclusion, easily available macrocyclic imines can be
stereoselectively transformed to macrocyclic bis-â-amino acids,
macrocyclic bisazetidines, and macrocyclic bisamides by means
of the corresponding bis-â-lactam scaffolds. These key inter-
mediates are available through standard Staudinger reaction.
Efforts to extend this approach to the peripheral functionalization
of bigger macrocycles and to use the obtained products as
chelating agents are being currently pursued in our laboratories.
Experimental Section
General procedures have been previously reported.23 Dialdehydes
1 and 2 were obtained following the reported procedure.9 Diimines
4-7 were prepared following a modification of the literature
procedure.7a,10
Synthesis of Dialdehyde 3: K2CO3 (30 g, 0.2 mol) was
suspended in butanone (75 mL) in a two-neck round flask equipped
with a reflux condenser and magnetic stirring bar. A solution of
2-hydroxynaphthalene-1-carbaldehyde (4 g, 0.023 mol) in butanone
(40 mL) was added dropwise, and the solution became dark green.
The mixture was purged with argon and stirred under reflux for
1.30 h. Then, NaI (80 mg, 05. mol) and a solution of 1,3-
dibromopropane (2.42 g, 0.012 mol) in butanone (20 mL) was
added. The mixture was stirred under reflux under argon for 48 h.
After reaching room temperature, the crude reaction mixture was
filtered through Celite, then 100 mL of distilled water was added
to the organic layer that was subsequently extracted with dichlo-
romethane (3 × 100 mL). The organic extracts were dried over
MgSO4, filtered, and evaporated to dryness at reduced pressure.
The resulting solid was recrystallized in EtOH to yield 1.38 g (30%)
SCHEME 6
1
of a pale brown solid: mp 193-196 °C; H NMR (300 MHz,
CDCl3) δ 10.95 (s, 2H), 9.24 (d, J ) 8.7 Hz, 2H), 8.06 (d, J ) 9.2
Hz, 2H), 7.77 (d, J ) 8.0 Hz, 2H), 7.65-7.59 (m, 2H), 7.45-7.42
(m, 2H), 7.29 (d, J ) 9.2 Hz, 2H), 4.50 (t, J ) 5.9 Hz, 4H), 2.50
(q, J ) 5.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 191.5, 163.0,
137.7, 131.5, 129.9, 128.6, 128.2, 124.9, 124.8, 116.8, 113.2, 65.6,
29.5; IR (KBr) νmax 3442, 2935, 2887, 1670,1591, 1512, 1245, 1151,
1058 cm-1. Anal. Calcd for C25H20O4: C, 78.11; H, 5.24. Found:
C, 78.32; H, 5.41.
General Procedure for the Synthesis of â-Lactams (8-12):
A solution of phenoxyacetyl chloride in dry CH2Cl2 was purged
with argon and cooled at -78 °C. Then, a solution of triethylamine
in dry CH2Cl2 was added dropwise. The mixture was stirred for 30
min, and a solution of the corresponding diimine in dry CH2Cl2
was added dropwise by means of a syringe pump for 2 h. The
reaction mixture was stirred at room temperature for the periods
specified in each case, quenched with MeOH and water, and
extracted with CH2Cl2. The organic layer was washed with 0.5 M
HCl (to remove the excess of triethylamine) and brine, and then
dried with MgSO4. The desiccant was removed by filtration and
the solvent evaporated at reduced pressure. The crude solid was
suspended in Et2O, filtered, and dried.
The amide CdO group of compounds 8, 9, and 12 was
reduced to form the corresponding bisazetidines 18-2021 in the
presence of AlCl2H in very high yields.22 Compounds 18-20
were obtained as single stereoisomers and retain the stereo-
chemistry of the starting 2-azetidinones (Scheme 5). It should
be noted that cis-syn-cis bis-â-lactam 8 and its derivatives 13
and 18 are meso-forms, while the cis-anti-cis bis-â-lactams
9-12 and their derivatives 14-20 are racemic mixtures. This
may be of interest if an enantioselective route to these
compounds will be developed.
To finally demonstrate the versatility of macrocyclic bis-â-
lactams 8-12 to produce functionalized macrocycles, com-
pounds 8-10 were submitted to reaction with Li/NH3. Under
these conditions, macrocycles 21 and 22 were produced in high
yields. It is worthy to note that together with the fragmentation
of the N1-C4 bond breakage the phenoxy group is also
reductively removed.
Synthesis of â-Lactams 8 and 9: Following the general
procedure, phenoxyacetyl chloride (1.77 g, 10.4 mmol) in dry CH2-
Cl2 (20 mL), triethylamine (2.11 g, 20.8 mmol) in dry CH2Cl2 (10
mL), and diimine 4 (1.07 g, 3.5 mmol) in dry CH2Cl2 (10 mL)
were reacted for 16 h. The reaction yielded 1.58 g (78%) of a 1:1
mixture of isomers 8 and 9. The isomers were separated by flash
chromatography in hexane/AcOEt 7:3 affording 465 mg (23%) of
8 and 550 mg (27%) of 9. The structure of 8 was confirmed by
X-ray diffraction. â-Lactam 8: white crystals; mp 215-217 °C
(20) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett. 1987,
28, 6141.
(21) Polyamines having the azetidine ring embedded in a macrocyclic
structure are interesting ligands for metal ions since the four-membered
ring imposes strong conformational restrictions from which some unusual
characteristics may emerge. See: Harrowfield, J.; Kim, J. Y.; Kim, Y.;
Lee, Y. H.; Thue´ry, P. Polyhedron 2005, 24, 1569 and the pertinent
references therein.
1
(CH2Cl2/MeOH); H NMR (300 MHz, CDCl3) δ 7.40 (dd, J1 )
(23) Ram´ırez-Lo´pez, P.; Go´mez-Gallego, M.; Manchen˜o, M. J.; Sierra,
M. A.; Bilurbina, M.; Ricart, S. J. Org. Chem. 2003, 68, 3538.
Simion, C.; Simion, A.; Mitoma, Y.; Nagashima, S.; Kawaji, T.; Hasimoto,
I.; Tashiro, M. Heterocycles 2000, 53, 2459.
(22) Ojima, I.; Zhao, M.; Yamato, T.; Nakahashi, K.; Yamashita, M.;
Abe, R. J. Org. Chem. 1991, 56, 5263.
8790 J. Org. Chem., Vol. 71, No. 23, 2006

Peripheral Functionalization of Macrocyclic Diimines
7.6 Hz, J2 ) 1.6 Hz, 2H), 7.27-7.11 (m, 6H), 6.96-6.75 (m, 10H),
5.57 (d, J ) 4.5 Hz, 2H), 5.41 (d, J ) 4.5 Hz, 2H), 4.55-4.41 (m,
4H), 3.48-3.30 (m, 2H), 3.10-2.96 (m, 2H), 1.70-1.47 (m, 2H);
13C NMR (50 MHz, CDCl3) δ 166.1, 157.0, 156.3, 130.5, 129.7,
129.2, 121.9, 121.4, 120.8, 115.4, 111.5, 81.2, 65.6, 54.6, 38.1,
24.4; IR (KBr) νmax 3446, 1757, 1598, 1492, 1409, 1290, 1236,
1060, cm-1. ESI-MS: 577.0 [M + H]+. Anal. Calcd for
C35H32N2O6: C, 72.90; H, 5.59. Found: C, 73.21; H, 5.74.
â-Lactam 9: white crystals; mp 217-220 °C (CH2Cl2/MeOH); 1H
NMR (300 MHz, CDCl3) δ 7.36 (dd, J1 ) 7.7 Hz, J2 ) 1.4 Hz,
2H), 7.26 (dt, J1 ) 7.8 Hz, J2 ) 1.5 Hz, 2H), 7.09 (t, J ) 7.7 Hz,
4H), 7.00 (t, J ) 7.4 Hz, 2H), 6.90-6.81 (m, 4H), 6.67 (d, J ) 8.1
Hz, 4H), 5.36 (d, J ) 4.4 Hz, 2H), 5.16 (d, J ) 4.4 Hz, 2H), 4.48-
4.38 (m, 4H), 3.70-3.61 (m, 2H), 2.86-2.76 (m, 2H), 1.77-1.71
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 165.9, 157.3, 156.7, 129.7,
129.1, 128.9, 121.8, 121.0, 120.7, 115.3, 112.1, 81.4, 67.7, 53.87,
36.6, 23.2; IR (KBr) νmax 3447, 1756 1598, 1494, 1409, 1292, 1235,
1053 cm-1. ESI-MS: 577.0 [M + H]+. Anal. Calcd for
C35H32N2O6: C, 72.90; H, 5.59. Found: C, 72.54; H, 5.71.
Synthesis of â-Lactam 10: Following the general procedure,
phenoxyacetyl chloride (2.25 g, 13.2 mmol) in CH2Cl2 (20 mL),
triethylamine (2.67 g, 26.4 mmol) in CH2Cl2 (10 mL), and diimine
5 (1.42 mg, 4.4 mmol) in CH2Cl2 (10 mL) were reacted for 15 h.
The crude reaction yielded 2.04 g (78%) of â-lactam 10 as white
1091, 1064 cm-1. Anal. Calcd for C36H30N2O6: C, 73.71; H, 5.15.
Found: C, 73.94; H, 5.33.
Synthesis of 12‚Co2(CO)6 Complex: In a flame-dried round-
bottom flask equipped with a magnetic stirring bar and in an argon
atmosphere, a solution of â-lactam 12 (100 mg, 0.17 mmol) in dry
and degassed CH2Cl2 (10 mL) was stirred with Co(CO)6 (87 mg,
0.26 mmol) for 3 h. The crude product was filtered through Celite,
and the solvent was evaporated at reduced pressure. The reaction
yields 140 mg (94%) of a purple solid. The cobalt complex was
recrystallized in MeOH/CH2Cl2 (1:1) to produce suitable crystals
that were analyzed by NMR and X-ray: 1H NMR (200 MHz,
CDCl3) δ 7.37 (d, J ) 7.3 Hz, 2H), 7.31-7.23 (m, 2H), 7.12 (t, J
) 7.8 Hz, 4H), 6.98 (t, J ) 7.3 Hz, 2H), 6.88 (t, J ) 7.3 Hz, 2H),
6.83-6.71 (m, 6H), 5.56 (d, J ) 4.3 Hz, 2H), 5.43 (d, J ) 4.3 Hz,
2H), 5.23 (d, J2 ) 16.3 Hz, 2H), 4.45 (s, 4H), 3.98 (d, J2 ) 16.3
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 198.8, 166.3, 156.9, 156.7,
130.4, 130.1, 129.0, 121.9, 120.9, 120.3, 115.5, 110.9, 90.0, 82.2,
65.7, 58.1, 43.0.
General Procedure for the Synthesis of â-Amino acids 13-
17: In a round-bottom flask equipped with a magnetic stirring bar
and a reflux condenser, a suspension of the corresponding â-lactam
in 10 M HCl was refluxed for 24-48 h. The crude product was
extracted with CH2Cl2, and the aqueous layer was dried and the
solvent removed at reduced pressure. The solid obtained was washed
with CH2Cl2. The amino acids were obtained as hydrochlorides.
Synthesis of â-Amino acid 13: A suspension of â-lactam 8 (400
mg, 0.68 mmol) in 10 M HCl (25 mL) was refluxed for 24 h.
â-Amino acid 13 (350 mg, 86%) was obtained as a pale pink
solid: 1H NMR (300 MHz, DMSO-d6, 65 °C) δ 7.79 (d, J ) 7.5
Hz, 2H), 7.42-7.28 (m, 2H), 7.27-7.14 (m, 4H), 7.11-6.89 (m,
10H), 5.33 (d, J ) 8.2 Hz, 2H), 5.10 (d, J ) 8.2 Hz, 2H), 4.56-
4.49 (m, 2H), 4.39-4.29 (m, 2H), 2.94-2.82 (m, 2H), 2.64-2.52
(m, 2H), 2.20-2.09 (m, 2H); 13C NMR (75 MHz, CD3OD) δ 170.7,
158.2, 157.8, 133.6, 130,9, 124.1, 123.1, 118.4, 117.2, 116.9, 113.5,
78.5, 67.4, 55.0, 43.0, 22.4; IR (KBr) νmax 3411, 2939, 1735, 1589,
1496, 1224, 1180, 1053 cm-1. ESI-MS: 613.7 [M + H]+. Anal.
Calcd for C35H38N2O8Cl2: C, 61.32; H, 5.59; Cl, 10.34; N, 4.09.
Found: C, 61.18; H, 5.42.
Synthesis of â-Amino acid 14: A suspension of â-lactam 9 (100
mg, 0.17 mmol) in 10 M HCl (15 mL) was refluxed for 24 h.
â-Amino acid 14 (95 mg, 90%) was obtained as a pale pink solid:
1H NMR (500 MHz, DMSO-d6, 65 °C) δ 7.73 (d, J ) 7.1 Hz,
2H), 7.37 (t, J ) 7.8 Hz, 2H), 7.22 (t, J ) 7.8 Hz, 4H), 7.10 (d, J
) 8.3 Hz, 2H), 7.02-6.89 (m, 8H), 5.35 (d, J ) 8.7 Hz, 2H), 5.01
(d, J ) 8.7 Hz, 2H), 4.38 (s, 4H), 3.06-2.97 (m, 2H), 2.92-2.86
(m, 2H), 2.18-2.12 (m, 2H); 13C NMR (125 MHz, DMSO-d6, 65
°C) δ 168.0, 156.2, 156.1, 131.0, 129.8, 128.9, 121.8, 120.5, 118.1,
115.7, 111.7, 77.2, 66.4, 53.7, 42.5, 20.5; IR (KBr) νmax 3412, 2941,
1734, 1586, 1495, 1224, 1177, 1054 cm-1. Anal. Calcd for
C35H38N2O8Cl2: C, 61.32; H, 5.59; Cl, 10.34; N, 4.09. Found: C,
61.60; H, 5.37.
Synthesis of â-Amino acid 15: A suspension of â-lactam 10
(250 mg, 0.42 mmol) in 10 M HCl (25 mL) was refluxed for 72 h.
â-Amino acid 15 (220 mg, 85%) was obtained as a pale pink
solid: 1H NMR (300 MHz, DMSO-d6) δ 7.75 (d, J ) 7.8 Hz, 2H),
7.38-7.26 (m, 2H), 7.22 (t, J ) 7.9 Hz, 4H), 7.12 (d, J ) 8.2 Hz,
2H), 7.06-6.88 (m, 4H), 6.84 (d, J ) 8.2 Hz, 4H), 5.08 (d, J )
8.1 Hz, 2H), 5.01 (d, J ) 8.1 Hz, 2H), 4.36-4.28 (m, 2H), 4.08-
3.99 (m, 2H), 2.87-2.78 (m, 2H), 2.69-2.58 (m, 2H), 2.19-2.10
(m, 2H), 1.94-1.82 (m, 2H); 13C NMR (75 MHz, CD3OD) δ 170.4,
158.9, 158.0, 133.5, 130.8, 130.2, 124.0, 123.4, 119.4, 117.1, 116.0,
78.9, 68.8, 54.7, 43.2, 30.2, 20.3; IR (KBr) νmax 3421, 2939, 1733,
1589, 1494, 1226, 1180, 1055 cm-1. Anal. Calcd for C35H38N2O8-
Cl2: C, 61.80; H, 5.76; Cl, 10.13; N, 4.00. Found: C, 61.58; H,
5.77.
1
crystals: mp 225-228 °C (CH2Cl2/MeOH 3:1); H NMR (300
MHz, CDCl3) δ 7.30 (dd, J1 ) 7.5 Hz, J2 ) 1.6 Hz, 2H), 7.21 (dt,
J1 ) 7.8 Hz, J2 ) 1.6 Hz, 2H), 7.08 (t, J ) 7.5 Hz, 4H), 6.99 (t,
J ) 7.5 Hz, 2H), 6.88-6.74 (m, 4H), 6.60 (d, J ) 8.0 Hz, 4H),
5.42 (d, J ) 4.3 Hz, 2H), 4.88 (d, J ) 4.3 Hz), 4.30-4.25 (m,
2H), 4.03-3.99 (m, 2H), 3.80-3.66 (m, 2H), 2.82-2.73 (m, 2H),
2.41-2.31 (m, 2H), 1.84-1.74 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 165.7, 156.9, 156.5, 129.8, 128.7, 128.5, 121.7, 121.0,
120.4, 115.3, 111.8, 81.4, 66.6, 53.6, 35.8, 28.7, 22.9; IR (KBr)
ν
max 3486, 2925, 1751, 1598, 1589, 1490, 1404, 1290, 1232, 1087
cm-1. ESI-MS: 591.1 [M + H]+. Anal. Calcd for C36H34N2O6:
C, 73.20; H, 5.80. Found: C, 73.42; H, 5.66.
Synthesis of â-Lactam 11: Following the general procedure,
phenoxyacetyl chloride (725 mg, 4.26 mmol) in CH2Cl2 (15 mL),
triethylamine (860 mg, 8.5 mmol) in CH2Cl2 (10 mL), and diimine
7 (600 mg, 1.42 mmol) in CH2Cl2 (5 mL) were reacted for 20 h.
The crude reaction mixture was purified by flash chromatography
in hexane/AcOEt (1:1) to yield 450 mg (45%) of â-lactam 11 as
1
white crystals: mp 135-138 °C (CH2Cl2/MeOH 3:1); H NMR
(300 MHz, CDCl3) δ 8.16 (d, J ) 8.3 Hz, 2H), 7.79 (d, J ) 9.0
Hz, 2H), 7.73 (d, J ) 7.6 Hz, 2H), 7.48 (t, J ) 7.1 Hz, 2H), 7.36
(t, J ) 7.1 Hz, 2H), 7.28 (d, J ) 9.0 Hz, 2H), 7.03 (t, J ) 7.6 Hz,
4H), 6.80 (t, J ) 7.1 Hz, 2H), 6.60 (d, J ) 8.2 Hz, 4H), 6.11 (d,
J ) 4.6 Hz, 2H), 5.28 (d, J ) 4.6 Hz, 2H), 4.59-4.48 (m, 2H),
4.46-4.35 (m, 2H), 3.59-3.48 (m, 2H), 2.66-2.53 (m, 4H), 1.81-
1.72 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 165.7, 156.8, 156.1,
133.5, 131.9, 129.8, 129.6, 128.8, 128.6, 127.2, 124.7, 124.0, 121.6,
115.0, 114.2, 113.5, 82.8, 67.1, 54.6, 37.6, 29.6, 23.7; IR (KBr)
ν
max 3431, 1755, 1669, 1596, 1494, 1240, 1058, 1037 cm-1. Anal.
Calcd for C44H38N2O6: C, 76.50; H, 5.54. Found: C, 76.72; H,
5.66.
Synthesis of â-Lactam 12: Following the general procedure,
phenoxyacetyl chloride (1.79 g, 10.5 mmol) in CH2Cl2 (15 mL),
triethylamine (2.13 g, 21.1 mmol) in CH2Cl2, and diimine 6 (1.12
g, 3.52 mmol) in CH2Cl2 (15 mL) were reacted for 18 h. The crude
solid product was dispersed in 100 mL of diethyl ether, filtered,
and dried under vacuum to afford 1.53 g (74%) of pure â-lactam
1
12 as white crystals: mp 266-268 °C (CH2Cl2/MeOH 3:1); H
NMR (300 MHz, CDCl) δ 7.37-7.26 (m, 4H), 7.14-7.00 (m, 6H),
6.91-6.79 (m, 4H), 6.71 (d, J ) 7.9 Hz, 4H), 5.65 (d, J ) 4.6 Hz,
2H), 5.39 (d, J ) 4.6 Hz, 2H), 4.64 (d, J ) 17.1 Hz, 2H), 4.38 (d,
J ) 7.3 Hz, 2H), 4.24 (d, J ) 7.3 Hz, 2H), 3.56 (d, J ) 17.1 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 165.4, 156.73, 156.70, 129.6,
128.8, 128.0, 121.8, 120.8, 120.7, 115.4, 110.6, 82.3, 77.1, 66.4,
53.7, 29.4; IR (KBr) νmax 1770, 1596, 1492, 1400, 1292, 1230,
Synthesis of â-Amino acid 16: A suspension of â-lactam 11
(80 mg, 0.11 mmol) in 6 M HCl (15 mL) was refluxed for 24 h.
â-Amino acid 16 (38 mg, 42%) was obtained as a pale brown
solid: 1H NMR (300 MHz, CD3OD) δ 8.17 (d, J ) 8.9 Hz, 2H),
J. Org. Chem, Vol. 71, No. 23, 2006 8791

Sierra et al.
7.62 (d, J ) 7.8 Hz, 2H), 7.53 (t, J ) 7.2 Hz, 2H), 7.40-7.30 (m,
10H), 7.07 (t, J ) 7.2 Hz, 2H), 6.88 (d, J ) 8.2 Hz, 4H), 5.25 (d,
J ) 9.2 Hz, 2H), 5.12 (d, J ) 9.2 Hz, 2H), 4.91-4.84 (m, 2H),
4.62-4.51 (m, 2H), 3.00-2.88 (m, 4H), 2.70-2.57 (m, 2H), 1.86-
1.76 (m, 2H); 13C NMR (50 Hz, CD3OD) δ 168.4, 159.2, 157.6,
134.6, 132.9, 131.0, 130.6, 130.1, 128.8, 124.7, 123.2, 122.4, 116.7,
116.4, 116.2, 80.6, 71.6, 64.5, 58.9, 30.9, 30.4; IR (KBr) νmax 3425,
2933, 1735, 1587, 1495, 1231, 1118, 1057 cm-1. Anal. Calcd for
C44H44N2O8Cl2: C, 66.08; H, 5.55; Cl, 8.87; N, 3.50. Found: C,
66.35; H, 5.28.
Synthesis of â-Amino acid 17: A suspension of â-lactam 12
(100 mg, 0.17 mmol) in 6 M HCl (15 mL) was refluxed for 24 h.
â-Amino acid 17 (81 mg, 81%) was obtained as a pale pink solid:
1H NMR (300 MHz, DMSO-d6, 65 °C) δ 8.20-7.69 (m, 8H), 7.34
(t, J ) 7.2 Hz, 2H), 7.18 (t, J ) 8.0 Hz, 4H), 7.06-6.85 (m, 10H),
5.30 (d, J ) 7.8 Hz, 2H), 5.09 (d, J ) 7.8 Hz, 2H), 4.32 (d, J )
8.1 Hz, 2H), 4.19 (d, J ) 8.1 Hz, 2H), 3.93 (d, J ) 16.0 Hz, 2H),
3.51 (d, J ) 16.0 Hz, 2H); 13C NMR (75 MHz, DMSO-d6, 65 °C)
δ 168.2, 156.4, 156.3, 130.5, 128.9, 128.7, 121.7, 120.4, 115.5,
111.7, 78.7, 77.7, 66.4, 53.8, 34.5; IR (KBr) νmax 3421, 2927, 1728,
1589, 1496, 1220, 1122, 1064 cm-1. Anal. Calcd for C36H36N2O8-
Cl2: C, 62.16; H, 5.22; Cl, 10.19; N, 4.03. Found: C, 62.34; H,
4.96.
General Procedure for the Hydrolysis with LiOH/H2O2: In a
round-bottom flask equipped with a magnetic stirring bar, a solution
(or suspension) of the corresponding â-lactam in THF/H2O (3:1)
was cooled to 0 °C with an ice bath prior to the addition of H2O2
(30%). Then, LiOH‚H2O was added to the mixture at 0 °C. The
system was left to reach room temperature, and the reaction was
stirred until complete disappearance of the starting â-lactam
(followed by TLC in CHCl3/MeOH (1:1)). The reaction was
quenched with a 1.5 M solution of Na2SO3. The crude mixture was
extracted with CH2Cl2, and the aqueous layer was evaporated at
reduced pressure. The solid obtained was purified by flash
chromatography in CHCl3/MeOH.
Reaction of â-Lactam 8 with LiOH/H2O2: Following the
general procedure, from â-lactam 8 (250 mg, 0.44 mmol), 30%
H2O2 (534 mg, 5.2 mmol), and LiOH‚H2O (80 mg, 1.6 mmol).
After 6 h at room temperature, the reaction was quenched, extracted,
and the residue purified by flash chromatography (CHCl3/MeOH,
2:1) to yield 200 mg (74%) of â-amino acid 13 as a white powder.
Reaction of â-Lactam 9 with LiOH/H2O2: Following the
general procedure, from â-lactam 9 (250 mg, 0.44 mmol), 30%
H2O2 (534 mg, 5.2 mmol), and LiOH‚H2O (80 mg, 1.6 mmol).
After 6 h at room temperature, the reaction was quenched, ex-
tracted, and the residue purified by flash chromatography (CHCl3/
MeOH, 2:1) to yield â-amino acid 14 (200 mg, 74%) as white
powder.
stirring, the reaction was quenched and extracted to afford 45 mg
(95%) of azetidine 18 as brown oil: 1H NMR (200 MHz, CDCl3)
δ 7.96 (dd, J ) 7.4, 1.6 Hz, 2H), 7.19 (dt, J ) 8.0, 1.6 Hz, 2H),
7.09 (t, J ) 7.6 Hz, 4H), 7.00-6.87 (m, 4H), 6.77 (t, J ) 7.6 Hz,
2H), 6.53 (dd, J1 ) 8.1 Hz, J2 ) 0.9 Hz, 4H), 4.71 (dt, J1 ) 6.4
Hz, J2 ) 2.0 Hz, 2H), 4.59 (d, J ) 8.0 Hz, 2H), 4.45-4.36 (m,
4H), 3.66 (d, J ) 9.4 Hz, 2H), 3.14 (dd, J1 ) 9.4 Hz, J2 ) 6.4 Hz,
2H), 2.66-2.54 (m, 2H), 2.43-2.33 (m, 2H), 1-14-1.01 (m, 2H);
13C NMR (50 MHz, CDCl3) δ 157.4, 155.7, 133.3, 128.8, 128.1,
126.3, 120.4, 120.2, 114.8, 110.7, 70.4, 67.0, 62.0, 58.8, 56.4, 29.6;
IR (KBr) νmax 3031, 2922, 1598, 1587, 1487, 1452, 1222, 1109,
1055, 1026 cm-1. Anal. Calcd for C35H36N2O4: C, 76.62; H, 6.61.
Found: C, 76.75; H, 6.79.
Synthesis of Azetidine 19: Following the general procedure,
from 16 mg (0.43 mmol) of LiAlH4, 56 mg (0.43 mmol) of AlCl3,
and 40 mg (0.069 mmol) of â-lactam 9. After 20 min of vigorous
stirring, the reaction was quenched and extracted to afford 32 mg
(95%) of azetidine 19 as brown oil: 1H NMR (300 MHz, CDCl3)
δ 7.78 (dd, J ) 7.6, 1.6 Hz, 2H), 7.23-7.07 (m, 6H), 7.00-6.77
(m, 6H), 6.67 (d, J ) 8.1 Hz, 2H), 5.44 (d, J ) 6.1 Hz, 2H), 5.12
(dt, J1 ) 6.1 Hz, J2 ) 3.0 Hz, 2H), 4.48-4.40 (m, 4H), 3.75-3.64
(m, 4H), 2.79-2.58 (m, 4H), 1.26-1.18 (m, 2H); 13C NMR (75
MHz, CDCl3) δ 157.3, 154.4, 132.1, 128.9, 128.1, 120.5, 120.3,
120.1, 114.8, 110.4, 70.6, 64.4, 62.4, 59.0, 53.2, 29.6; IR (KBr)
ν
max 3032, 2922, 1598, 1586, 1485, 1452, 1223, 1110, 1054, 1026
cm-1. Anal. Calcd for C35H36N2O4: C, 76.62; H, 6.61. Found: C,
76.80; H, 6.34.
Synthesis of Azetidine 20: Following the general procedure
from 40 mg (1.02 mmol) of LiAlH4, 136 mg (1.02 mmol) of AlCl3,
and 100 mg (0.17 mmol) of â-lactam 12. After 20 min of vigorous
stirring, the reaction was quenched and extracted to afford 260 mg
(93%) of azetidine 20 as brown oil: 1H NMR (200 MHz, CDCl3)
δ 7.81 (d, J ) 6.8 Hz, 2H), 7.31-7.22 (m, 2H), 7.11-7.04 (m,
6H), 6.81-6.76 (m, 4H), 6.61 (d, J ) 7.9 Hz, 4H), 5.44 (d, J )
5.6 Hz, 2H), 4.91 (t, J ) 5.4 Hz, 2H), 4.34-4.22 (m, 4H), 3.79-
3.71 (m, 2H), 3.61 (d, J ) 5.4 Hz, 4H), 3.36 (d, J ) 8.4 Hz, 2H);
13C NMR (50 MHz, CDCl3) δ 157.4, 156.0, 129.2, 128.8, 128.2,
125.1, 120.7, 120.5, 115.2, 109.7, 79.5, 71.8, 66.0, 62.2, 53.4, 41.7;
IR (KBr) νmax 3028, 2929, 1598, 1589, 1487, 1452, 1257, 1230,
1099, 1072 cm-1. Anal. Calcd for C36H34N2O4: C, 71.40; H, 6.13.
Found: C, 71.48; H, 6.17.
General Procedure for the Reactions with Li/NH3: In a three-
neck round-bottom flask equipped with an NH3 condenser and
magnetic stirring bar at -78 °C, Na was introduced, and a NH3
(gas) was injected in the system until 10-20 mL of liquid NH3
condensed over the Na (the solution turns dark blue). Then, a
solution of the â-lactam in dry THF/tBuOH was added dropwise
via syringe. The mixture was stirred for 5-10 min and quenched
with solid NH4Cl until complete disappearance of the blue color.
The crude mixture was kept at room temperature until the NH3
was evaporated. Then, water was added, and the solution was
extracted with CH2Cl2. The organic layer was washed with water
and brine, dried over MgSO4, filtered, and the solvent evaporated
at reduced pressure. The crude products were purified by flash
chromatography in hexane/AcOEt (6:4).
Reaction of â-Lactam 10 with LiOH/H2O2: Following the
general procedure, from a suspension of â-lactam 10 (250 mg, 0.42
mmol), 30% H2O2 (534 mg, 5.2 mmol), and LiOH‚H2O (80 mg,
1.6 mmol). After 6 h at room temperature, the reaction was
quenched, extracted, and the residue purified by flash chromatog-
raphy (CHCl3/MeOH, 2:1) to yield â-amino acid 15 (200 mg, 75%)
as a white powder.
General Procedure for the Synthesis of Azetidines (18-20):
To a suspension of LiAlH4 in dry THF in a flame-dried round-
bottom flask equipped with a magnetic stirring bar under argon
and at 0 °C was transferred a solution AlCl3 in dry THF via cannula.
The mixture was stirred for 30 min at room temperature to form
the alane. Then, the suspension was cannulated over a solution of
the â-lactam in dry THF at 0 °C. The reaction was stirred for 20
min at room temperature, then quenched with ice and extracted
with diethyl ether (3 × 10 mL). The organic layer was washed
with brine and dried with MgSO4. The solvent was evaporated under
reduced pressure to yield pure azetidines.
Reaction of â-Lactam 8 with Li/NH3: About 20 mL of NH3
was condensed over 10 mg of Na (1.2 mmol). A solution of
â-lactam 8 (65 mg, 0.12 mmol) in dry THF (5 mL) with a few
drops of tBuOH was added dropwise to the solution. After 10 min
stirring, the reaction was quenched, extracted, and the crude product
purified by flash chromatography to yield 40 mg (83%) of
macrocycle 21 as pale brown oil: 1H NMR (200 MHz, CDCl3) δ
7.20-7.14 (m, 4H), 6.90 (t, J ) 6.2 Hz, 4H), 5.84 (br s, 2H), 4.38
(s, 4H), 3.22 (dd, J ) 6, 11.3 Hz, 4H), 2.96 (t, J ) 7.5 Hz, 4H),
2.44 (t, J ) 7.5 Hz, 4H), 1.60-1.52 (m, 2H); 13C NMR (50 MHz,
CDCl3) δ 172.9, 156.2, 130.1, 129.3, 127.5, 121.0, 111.3, 66.6,
38.4, 36.6, 29.6, 26.5; IR (KBr) νmax 3300, 2923, 1751,1647, 1598,
1550, 1490, 1238, 1132, 1058 cm-1. Anal. Calcd for C23H28N2O4:
C, 69.67; H, 7.12; N, 7.07. Found: C, 69.95; H, 7.28.
Synthesis of Azetidine 18: Following the general procedure
from 20.2 mg (0.53 mmol) of LiAlH4, 70 mg (0.53 mmol) of AlCl3,
and 50 mg (0.086 mmol) of â-lactam 8. After 20 min of vigorous
8792 J. Org. Chem., Vol. 71, No. 23, 2006

Peripheral Functionalization of Macrocyclic Diimines
Reaction of â-Lactam 10 with Li/NH3: About 50 mL of NH3
was condensed over 20 mg of Na (2.4 mmol). â-Lactam 10 (100
mg, 0.17 mmol) was added over the NH3 solution with a few drops
for C24H30N2O4: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.08; H,
7.64.
Acknowledgment. Financial support by the Spanish Min-
isterio de Educacio´n y Ciencia (Grant CTQ2004-06250-01-
BQU) is gratefully acknowledged. D.P. thanks the Spanish
Ministerio de Defensa for financial support.
t
of BuOH. After 10 min stirring, the reaction was quenched,
extracted, and the crude purified by flash chromatography to yield
70 mg (88%) of macrocycle 22 as a pale yellow oil: 1H NMR
(300 MHz, CDCl3) δ 7.18-7.14 (m, 4H), 6.89 (d, J ) 7.8 Hz,
2H), 6.79 (dt, J1 ) 7.5 Hz, J2 ) 1.2 Hz, 2H), 4.27 (t, J ) 5.7 Hz,
4H), 4.06 (br s, 2H), 2.98-2.92 (m, 4H), 2.90-2.83 (m, 4H), 2.37
(q, J ) 6.0 Hz, 2H) 2.07-2.02 (m, 4H), 1.35-1.30 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 171.5, 156.3, 131.4, 128.7, 127.8, 120.1,
110.6, 62.6, 38.2, 36.8, 29.6, 28.1, 26.1; IR (KBr) νmax 3298, 2925,
1753, 1650, 1596, 1548, 1490, 1236, 1128, 1055 cm-1. Anal. Calcd
Supporting Information Available: Full experimental and
characterization data for imines 4-7, data for the X-ray charac-
terization of compounds 8 and 12‚Co2(CO)6, and copies of 1H and
13C NMR spectra of compounds 4-22. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO0614689
J. Org. Chem, Vol. 71, No. 23, 2006 8793