Synthesis and x-ray crystallography of chiral tropocoronands

Article abstract of DOI:10.1081/SCC-100000574

The synthesis of several chiral tropocoronands (6 and 7) has been accomplished. These compounds have been shown to complex with various metals. Tropocoronands that have been synthesized include H₂(TC-3,cyhex) through H₂(TC-6,cyhex) (6) and H₂ (TC-3,diphen) through H₂(TC-6,diphen) (7). The route is short and the tropocoronands are easily purified by chromatography or recrystallization. Two other groups have been incorporated into tropocoronands, H₂(TC-3,binap) (9) and H₂(TC-6,pent) (10).

Full text of DOI:10.1081/SCC-100000574

This article was downloaded by: [University of California, San Francisco]
On: 28 November 2014, At: 04:47
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
SYNTHESIS AND X-RAY CRYSTALLOGRAPHY OF CHIRAL
TROPOCORONANDS
Philip J. Chenier a , Jason A. Halfen a , Tami L. Raguse a , Autumn E. Rich a , Kathryn E.
Splan a , Kazuki Yoshioka a & Thomas R. Hoye b
a Department of Chemistry , University of Wisconsin—Eau Claire , Eau Claire, Wisconsin,
54702-4004, U.S.A.
b Department of Chemistry , University of Minnesota Minneapolis , Minnesota,
55455-0431
Published online: 16 Aug 2006.
To cite this article: Philip J. Chenier , Jason A. Halfen , Tami L. Raguse , Autumn E. Rich , Kathryn E. Splan , Kazuki
Yoshioka & Thomas R. Hoye (2001) SYNTHESIS AND X-RAY CRYSTALLOGRAPHY OF CHIRAL TROPOCORONANDS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:4, 487-503, DOI:
10.1081/SCC-100000574
To link to this article: http://dx.doi.org/10.1081/SCC-100000574
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 31(4), 487–503 (2001)
SYNTHESIS AND X-RAY
CRYSTALLOGRAPHY OF CHIRAL
TROPOCORONANDS
Philip J. Chenier,1,∗ Jason A. Halfen,1 Tami L. Raguse,1
Autumn E. Rich,1 Kathryn E. Splan,1
Kazuki Yoshioka,1 and Thomas R. Hoye2,∗
1Department of Chemistry, University of Wisconsin—Eau
Claire, Eau Claire, Wisconsin 54702-4004
2Department of Chemistry, University of Minnesota
Minneapolis, Minnesota 55455-0431
ABSTRACT
The synthesis of several chiral tropocoronands (6 and 7) has
been accomplished. These compounds have been shown to complex
with various metals. Tropocoronands that have been synthesized
include H2(TC-3,cyhex) through H2(TC-6,cyhex) (6) and H2(TC-
3,diphen) through H2(TC-6,diphen) (7). The route is short and the
tropocoronands are easily purified by chromatography or recrystal-
lization. Two other groups have been incorporated into tropocoro-
nands, H2(TC-3,binap) (9) and H2(TC-6,pent) (10).
INTRODUCTION
A very active area of organic synthetic research in the last few years has
been asymmetric or enantioselective catalysis. A number of recent monographs
∗Corresponding author.
487
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

ORDER
REPRINTS
488
CHENIER ET AL.
O
O
O
O
H2N(CH2)nNH2
TsCl
Et3N, EtOH, ∆
n = 2-6
OH
OTs
NH(CH2)nNH
tropolone
3a, n = 3
3b, n = 4
3c, n = 5
3d, n = 6
2
(CH3)2SO4
toluene, ∆
CH3
O
CH3
N(CH2)mNH
O
H2N(CH2)mNH2
EtOH,25°C
NH(CH2)nN
tropocoronands
1
N(CH2)nN
4a, n = 3
4b, n = 4
n = 5
n = 6
4c,
4d,
Scheme 1.
and reviews on this subject have been published (1–7). The generation of chiral
molecules as single enantiomers has been the subject of intense interest for many
years, but only recently have great strides been made using chiral ligands in cat-
alysts to promote asymmetry in reactions. Tropocoronands (1) represent a new
class of molecules with potential to be modified with a chiral moiety and applied
to enantioselective reactions.
Tropocoronands (Scheme 1) are macrocycles containing two cyclohepta-
triene rings and four nitrogens linked by two chains. They were first synthe-
sized by Nakanishi, Lippard, and Nozoe (8,9). Symmetrical tropocoronands where
m = n = 2–6 have been made in a four-step synthesis from tropolone. Either
2-tosyloxytropone (2) (10–13) or 2-chlorotropone can be made from tropolone
and then reacted with the appropriate diamine to give diaminodiketones 3. These
diketones then give dialkoxydiimines 4 by treatment with dimethyl sulfate in
refluxing toluene, or with triethyloxonium tetrafluoroborate in refluxing chlo-
roform/hexamethylphosphoramide. The resulting dialkoxides can then undergo
amine displacement and ring closure at 25◦C to the tropocoronands 1. Reported
yields in the cyclization are generally 20–40%, but only 2% when m = n = 2.
However, Nozoe has demonstrated yields of 55–65% for m = n = 3 using methyl
fluorosulfate in methylene chloride as the alkylating agent (14).
Recently, unsymmetrical tropocoronands have been synthesized where the
numberofcarbonsofthesimplestraight-chainlinkagesisdifferent(m=n)(15,16).
These compounds, H2(TC-3,4) (1, where m = 3, n = 4) and H2(TC-4,5) (1, m =
4, n = 5), were the only unsymmetrical tropocoronands reported until our work.

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
489
Lippard has studied tropocoronands as ligands for copper(I) and (II),
rhodium(I), nickel(II), cobalt(III), and other metals (15,16). The structures of these
complexes have been characterized in detail. Ethanol solutions of salts of Fe(II)
through Zn(II) have been found to form intense colors with methylene chloride
solutions of tropocoronands where the linker chains contain 3–6 carbons, suggest-
ing that the complexation of these substances with transition metal ions is very
general. These ligands and their complexes have contained only simple achiral
linker chains. Incorporation of a chiral moiety into the tropocoronand macrocy-
cle and subsequent study of metal complexes derived from such chiral ligands
have not been reported, except for our preliminary communication (17). The only
uses of a related ligand in asymmetric catalysis are those described by Brunner
(18) and Lippard (19,20). Tropolone derivative 5 was shown to induce asymmetry
CH3
Ar
NH
N
Ar
CH3
5
during the course of ketone hydrosilylation and 1,4-addition of cuprates to enones,
respectively.
Many potential applications of chiral tropocoronand ligands to catalytic,
enantioselective reactions can be envisioned. They are similar in structure to the
versatile salen catalysts developed by Jacobsen, and certain porphyrins, both of
which are used extensively in enantioselective processes (1–7).
RESULTS AND DISCUSSION
We now report the details of the synthesis of a number of tropocoronands that
have chiral diamines incorporated into their macrocycle. These are unsymmetrical
where one linker chain is chiral and the other is derived from simple straight chain
α,ω-diamines with 3, 4, 5, or 6 carbons. Series 6a–d is derived from trans-1,2-
diaminocyclohexane and series 7a–d from (R*,R*)-1,2-diphenylethylenediamine,
both commercially available as either enantiomer. Using the synthesis as outlined
in Scheme 1, but substituting trans-1,2-diaminocyclohexane in the final step, we
have made H2(TC-3,cyhex) (6a), H2(TC-4,cyhex) (6b), H2(TC-5,cyhex) (6c), and
H2(TC-6,cyhex) (6d). In analogous fashion, we have used chiral (R*,R*)-1,2-
diphenylethylenediamine to synthesize H2(TC-3,diphen) (7a) through H2(TC-6,
diphen) (7d). The syntheses proceeded well, although yields in the cyclization step

ORDER
REPRINTS
490
CHENIER ET AL.
were low, as is typical for the syntheses of the simple achiral analogs such as 1.
The diaminodiketones 3 are easily prepared in large quantities and are stable.
Ph
N
PH
N
NH
NH
NH(CH2)nN
NH(CH2)nN
6a, n = 3
6b, n = 4
6c, n = 5
6d, n = 6
7a, n = 3
7b, n = 4
7c, n = 5
7d, n = 6
H2(TC-n,cyhex)
H2(TC-n,diphen)
The dimethoxydiimines 4 were prepared and used in the cyclization step in the
same day. All of the tropocoronands 6 and 7 are high melting, yellow to orange,
crystalline compounds that can be isolated and purified easily by chromatography
or recrystallization. Spectroscopic properties are in accord with their structure.
Isolated yields of recrystallized material range from 10–39% in the cyclization.
An alternative synthesis, that of placing the chiral group in the sequence first
to form a diaminoketone such as 8, followed by cyclization with a straight chain
O
O
NH
NH
8
diamine in the last step, was not successful. The diaminoketone can be made, but
it is difficult to purify and separate from tropolone tosylate, so the alternative order
of diamine incorporation was not investigated further.
We also attempted the synthesis of smaller ring sizes, particularly H2(TC-
2,cyhex) (6, n = 2), but were unsuccessful in the cyclization step of the dimethoxy-
diimine 4 (n = 2). This is not surprising in view of the difficulty Nozoe had
synthesizing smaller members of the achiral tropocoronands.
In addition to the 6 and 7 series of tropocoronands, H2(TC-3,binap) (9)
and H2(TC-6,pent) (10), containing a binaphthyl and 2,4-pentdiyl chiral subunit,
respectively, have also been prepared. 1,1ꢂ-Binaphthyl-2,2ꢂ-diamine is not suffi-
ciently reactive with the dialkoxydiimine 4a so a modification of the usual proce-
dure was required to synthesize 9. Treatment of 1,1ꢂ-binaphthyl-2,2ꢂ-diamine with
two equivalents of n-butyllithium in tetrahydrofuran gave the dilithium salt. The

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
491
H3C
CH3
NH
N
NH
N
NH(CH2)3N
NH(CH2)6N
10
9
dialkoxydiimine 4a was dissolved in tetrahydrofuran and added to the dilithium
salt. The solution was then refluxed to complete the reaction. Both R and S
enantiomers of the binaphthyldiamine were used. Very small yields of the tropo-
coronands were realized, but they can be isolated by chromatography.
( )-H2(TC-6,pent) and one optically active sample of 10 has also been
prepared starting from dialkoxydiimine 4d and 2,4-diaminopentane (21). A 9%
yield of 10 was realized.
Solid state structures have been determined for three tropocoronands—( )-
6a, R-7b, and ( ) -10. The x-ray crystal structure of ( ) -6a (Fig. 1), which
crystallizes in the centrosymmetric space group P21/c, reveals a structure that
is entirely consistent with the proposed molecular formula. In crystals of optically
pure R-7b (Fig. 2) the tropocoronand crystallizes in the chiral space group P21
and co-crystallizes with a single acetone solvate. Structural analysis of 10 indi-
cates that, while bulk sample is racemic, the tropocoronand spontaneously resolves
upon crystallization, such that the molecule crystallizes in the chiral space group
P212121. The absolute configuration of 10 in the sample analyzed cannot be deter-
mined, however, due to the lack of an appropriate heavy atom in the compound to
C(9)
C(10)
C(8)
C(6)
C(5)
C(12)
N(3)
C(11)
C(13)
N(2)
C(7)
C(4)
C(14)
C(1)
N(1)
C(3)
C(17)
N(4)
C(2)
C(15)
C(16)
C(23)
C(18)
C(22)
C(19)
C(21)
C(20)
Figure1. Thermalellipsoidrepresentation(35%probabilityellipsoids)ofthex-raycrystal
structure of 6a.

ORDER
REPRINTS
492
CHENIER ET AL.
C(29)
C(30)
C(31)
C(28)
C(26)
C(25)
C(24)
C(27)
C(21)
C(20) C(19)
N(1) N(4)
C(16)
C(17)
C(32)
C(1)
C(2)
C(3)
C(23)
C(15)
C(22)
C(4)
C(18)
C(14)
C(7)
C(12)
C(5)
N(2)
N(3)
C(13)
C(6)
C(8)
C(11)
C(9)
C(10)
Figure2. Thermalellipsoidrepresentation(35%probabilityellipsoids)ofthex-raycrystal
structure of R-7b.
provide for anomalous dispersion of the x-ray beam. In contrast to the structures
of 6a and 7b, the structure of 10 (Fig. 3) reveals a highly distorted macrocycle,
the conformation of which may result from unfavorable intramolecular interac-
tion between the tropylidene rings and the nearby methyl groups of the chiral
spacer.
C(22)
C(25)
C(24)
C(21)
C(2)
C(3)
C(23)
N(4)
C(19)
C(1)
C(18)
C(17)
C(4)
N(1)
C(20)
C(7)
N(3)
N(2)
C(5)
C(14)
C(15)
C(6)
C(16)
C(8)
C(9)
C(13)
C(11)
C(12)
C(10)
N(2)
N(4)
N(1)
N(3)
Figure 3. Top and side views of the x-ray crystal structure of 10. Thermal ellipsoids are
drawn at the 35% probability level, and only one conformation of the disordered hexyl
linker is shown.

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
493
C(9)
C(6)
C(5)
N(2)
C(10)
C(7)
C(8)
C(4)
C(11)
C(13)
C(1)
C(12)
N(1)
C(3)
C(2)
a
N(2B)
N(1B)
N(1C)
N(2C)
O
c
b
Figure4. Thermalellipsoidrepresentation(35%probabilityellipsoids)ofthex-raycrystal
structure of 11, and view of the observed solid-state hydrogen bonding pattern.
Some interesting side products (of a type previously not reported) arise in
the cyclization step to form these chiral tropocoronands. In the cyclization for
both series 6 and 7, a second major product of the reaction was either 11 or 12.
For instance, 11 was isolated from the synthesis of 6a, 6b, and 6d. Proton NMR
N
N
Ph
Ph
NH
NH
11
12
and high-resolution mass spectral data are in accord with the structure of 11, but
the structure was in doubt because of the carbon NMR spectrum, which shows only
four resonances. The x-ray crystal structure of 11 (Fig. 4) confirms the proposed
molecular structure. The compound crystallizes in the chiral space group C2, and
lies on a non-crystallographic two-fold symmetry axis that passes through C4 and
bisects the C2-C7, C8-C13, and C10-C11 bonds, which renders the two nitrogen
atoms equivalent. As a result, the single N-bound hydrogen atom is statistically
disordered over both nitrogen atoms, and provides for the formation of hydrogen-
bonded chains of molecules that run parallel to the crystallographic c axis. These
❛
chains are characterized by relatively short N···N distances of 3.014(6) A and

ORDER
REPRINTS
494
CHENIER ET AL.
NH2 NH2
CH3
CH3
CH3O
O
NH2
O
NH
OCH3
N(CH2)nN
NH(CH2)nN
4
13
NH
NH
OCH3
CH3O
+
NH
NH(CH2)nN
N
H2N(CH2)nN
14
11
Scheme 2.
❛
3.104(6) A. Similarly, 12 has fewer carbon resonances than expected, but other
data prove its structure. These side products are no doubt caused by the ability of
both nitrogens of the chiral diamine to undergo nucleophilic attack on the same
tropylidene ring, eliminating the straight-chain amine, perhaps through interme-
diates such as 13 and 14 (Scheme 2). However, both products 11 and 12 can be
separated easily from the tropocoronands and do not cause problems synthetically
other than lowered yields of desired macrocycles.
In summary, we have developed a synthesis of chiral tropocoronands. Sev-
eral have been examined by x-ray crystallographic studies and are found to have
significantly different geometries surrounding the central array of four nitrogen
atoms.
EXPERIMENTAL
Melting and boiling points are uncorrected. NMR data are given in ppm
(referenced to TMS = 0 ppm). 1H and 13C NMR spectra were taken at various field
strengths as noted. Elemental analyses were performed by M-H-W Laboratories,
Phoenix, AZ and Midwest Microlab, Indianapolis, IN. 2-Tosyloxytropone (2) (11)
and diaminodiketones 3 (9) (prepared from 2) were made by literature methods.
( )-H2(TC-4,cyhex) (6b)
Following the general procedure of Nozoe and Nakanishi (9), crude diamin-
odiketone 3b (14.2 g, 47.9 mmol) was mixed with toluene (240 mL) at reflux and

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
495
dimethyl sulfate (13.3 g, 105.6 mmol) was added over 1 min. The mixture was
refluxed for 1–2 h. A dark insoluble oil was formed, which solidified on cooling.
The mixture was extracted with water (3 × 480 mL), in which the solid dissolved.
The combined aqueous layers were washed with chloroform (2 × 480 mL) and
then made alkaline with 5% sodium carbonate (1.2 L) to a pH of 9–10. The aqueous
phase was extracted with chloroform (3 × 360 mL). The combined chloroform
extracts were dried with anhydrous potassium carbonate, filtered, and concen-
trated to give crude dimethoxydiimine 4b as a dark oil. The oil was dissolved in
absolute ethanol (1 L) in a separatory funnel. In a second funnel, ( )-trans-1,2-
diaminocyclohexane (6.58 g, 57.6 mmol) was also dissolved in absolute ethanol
(1 L). The two solutions were added at the same rate over 3 h to a flask contain-
ing absolute ethanol (200 mL) with magnetic stirring. The solution was stirred
overnight. Rotary evaporation of the ethanol yielded crude material. This was dis-
solved in chloroform (500 mL) and filtered through a 4-cm long column of basic
alumina. The alumina was rinsed with chloroform (750 mL) and the combined elu-
ent was rotary evaporated to give crude 6b as an orange solid (13.66 g, 36.5 mmol,
76%). The crude tropocoronand was recrystallized from acetone to give purer
product (3.82 g, 10.2 mmol, 21%), useful for further studies. Two additional re-
1
crystallizations from acetone gave pure 6b: mp 231◦–233◦C; H NMR (CDCl3,
400 MHz) δ 7.80 (br s, 2H), 6.75 (m, 4H), 6.30 (d, J = 11.0 Hz, 2H), 6.12 (m,
4H), 3.46 (m, 2H), 3.34 (ddd, J = 13.5, 2.5, and 2.5 Hz, 2H), 3.07 (t, J = 12.4 Hz,
2H), 2.50 (br d, J = 13.2 Hz, 2H), 1.90 (m, 4H), 1.60 (m, 2H), 1.47 (m, 2H), and
1.30 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 155.0, 154.9, 133.3, 132.7, 117.5,
110.4, 110.2, 61.5, 46.3, 30.2, 26.5, 25.2; IR (KBr) 3436, 3248, 2929, 2857, 1587,
1546, 1513, 1463, 1381, 1271, 1212, 727 cm−1. HRMS (EI) calcd for C24H30N4
374.2470, found 374.2471. Anal. calcd for C24H30N4: C, 76.97; H, 8.07. Found:
C, 77.13; H, 7.75.
(−)-[R-(R*,R*)]-H2(TC-4,cyhex) (6b)
Followingasimilarprocedurecrudediaminodiketone 3b(4.44g, 15.0mmol)
and (R-trans)-1,2-diaminocyclohexane (1.83 g, 16.0 mmol) gave [R-(R*,R*)]-6b
of good purity, mp 235–240◦C (1.73 g, 4.63 mmol, 31%). The 1H and 13C NMR
spectra of this compound were identical to racemic 6b. [α]RDT = −76.7◦ (c = 0.3
in CHCl3).
( )-H2(TC-3,cyhex) (6a)
Followingthesameprocedureasdetailedfor6b, diaminodiketone3a(1.98 g,
7.00 mmol), toluene (35 mL), dimethyl sulfate (1.90 g, 15.1 mmol), ( )- trans-
1,2-diaminocyclohexane (0.874 g, 7.66 mmol), and absolute ethanol (600 mL)

ORDER
REPRINTS
496
CHENIER ET AL.
were used and gave, after one recrystallization from acetone, ( )-6a (0.42 g, 1.17
mmol, 17%). Three additional recrystallizations from acetone gave pure 6a as or-
ange crystals: mp 218◦–221◦C; 1H NMR (CDCl3, 400 MHz) δ 8.45 (br s, 2H), 6.75
(m, 4H), 6.37 (d, J = 11.0 Hz, 2H), 6.21 (d, J = 10.6 Hz, 2H), 6.13 (t, J = 9.2 Hz,
2H), 3.50 (m, 4H), 3.35 (m, 2H), 2.46 (d, J = 13.2 Hz, 2H), 1.92 (m, 4H), 1.59
(m, 2H), and 1.42 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 156.5, 155.3, 133.6,
132.9, 118.2, 111.1, 110.9, 62.9, 48.0, 31.3, 29.6, 25.3; IR (KBr) 3446, 3229, 2937,
2862, 1594, 1538, 1513, 1463, 1376, 1283, 1215, 742, 698, 661 cm−1. HRMS (EI)
calcdforC23H28N4 360.2314, found360.2313. Anal. calcdforC23H28N4:C, 76.63;
H, 7.83. Found: C, 76.47; H, 7.66.
(−)-[R-(R*,R*)]-H2(TC-3,cyhex) (6a)
By the same procedure, diaminoketone 3a (3.40 g, 12.0 mmol) and (R-trans)-
1,2-diaminocyclohexane (1.50 g, 13.2 mmol) gave [R-(R*,R*)]-6a of good purity,
mp 200◦–202◦C (0.67 g, 1.90 mmol, 16%). The 1H and 13C NMR spectra of this
compound were identical to racemic 6a. [α]RDT = −66.7◦ (c = 0.3 in CHCl3). The
structure was confirmed by x-ray crystallography.
( )-H2(TC-5,cyhex) (6c)
Followingthesameprocedureasdetailedfor6b, diaminodiketone3c(3.09 g,
10.0 mmol), toluene (50 mL), dimethyl sulfate (2.87 g, 22.8 mmol), ( )-trans-
1,2-diaminocyclohexane (1.34 g, 11.7 mmol), and absolute ethanol (850 mL) were
used and gave, after one recrystallization from acetone, ( )-6c (0.40 g, 1.03 mmol,
10%). Three additional recrystallizations from acetone gave pure 6c: mp 186◦–
188◦C; 1H NMR (CDCl3, 400 MHz) δ 7.0–8.0 (br, 2H), 6.75 (m, 4H), 6.43 (d, J =
11.0 Hz, 2H), 6.23 (d, J = 10.6 Hz, 2H), 6.14 (t, J = 9.2 Hz, 2H), 3.63 (m, 2H),
3.42 (m, 2H), 3.31 (m, 2H), 2.37 (br d, J = 13.9 Hz, 2H), 1.2–1.9 (m, 12 H); 13
C
NMR (CDCl3, 100 MHz) δ 154.2, 153.3, 132.9, 132.4, 117.7, 111.8, 109.4, 61.5,
44.5, 30.2, 27.4, 25.2, 22.8; IR (KBr) 3440, 3259, 2937, 2860, 1608, 1531, 1461,
1351, 1270, 1206, 1096, 848, 724, 636 cm−1. HRMS (EI) calcd for C25H32N4
388.2627, found 388.2605. An analytical sample could not be obtained because
of occluded solvent.
( )-H2(TC-6,cyhex) (6d)
The same procedure was followed using diaminodiketone 3d (0.150 g,
0.463 mmol), toluene (4 mL), dimethyl sulfate (0.125 g, 0.991 mmol), ( )-trans-
1,2-diaminocyclohexane (0.0623 g, 0.546 mmol), and absolute ethanol (125 mL)

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
497
to obtain, after one recrystallization from hexane-acetone, ( )-6d (0.0214 g,
0.0532 mmol, 12%). Two additional recrystallization from hexane-acetone gave
1
pure 6d as yellow needles, mp 221◦–222◦C; H NMR (CDCl3, 400 MHz) δ
7.3–7.9 (br, 2H), 6.73 (m, 4H), 6.50 (d, J = 11.3 Hz, 2H), 6.16 (d, J =
10.6 Hz, 2H), 6.11 (t, J = 9.15 Hz, 2H), 3.67 (m, 2H), 3.50 (dt, J = 14.7 and
4.6, 2H), 3.29 (m, 2H), 2.28 (br d, J = 13.9 Hz, 2H), 1.0–1.9 (m, 14H); 13C NMR
(CDCl3, 75 MHz) δ 154.1, 152.2, 132.9, 132.1, 117.3, 113.3, 107.5, 61.7, 43.4,
29.8, 26.9, 26.4, 25.3; IR (KBr) 3438, 3248, 2931, 2854, 1588, 1539, 1511,
1462, 1384, 1349, 1272, 1209, 752, 709 cm−1. HRMS (FAB) calcd for C26H35N4
[M+1]+ 403.2862, found 403.2830. Anal. calcd for C26H34N4: C, 77.57; H, 8.51.
Found: C, 77.25; H, 8.79.
[S-(R*,R*)]-H2(TC-6,cyhex) (6d)
By the same procedure diaminodiketone 3d (0.450 g, 1.39 mmol) and (S-
trans)-1,2-diaminocyclohexane (0.187 g, 1.64 mmol) gave [S-(R∗,R∗)]-6d of good
purity after one recrystallization from hexane-acetone, mp 244◦–248◦C (0.0850 g,
0.211 mmol, 15%). The 1H and 13C NMR spectra of this compound were identical
to racemic 6d.
[S-(R*,R*)]-H2(TC-3,diphen) (7a)
The same procedure was followed with diaminoketone 3a (1.22 g,
4.30 mmol), toluene (20 mL), dimethyl sulfate (1.17 g, 9.28 mmol), [S-(R∗,R∗)]-
1,2-diphenylethylenediamine (1.00 g, 4.71 mmol), and absolute ethanol (370 mL)
to obtain, after chromatography on silica gel and elution with hexane:ethyl acetate
mixtures containing 3% triethylamine, [S-(R∗,R∗)]-7a (0.55 g, 1.2 mmol, 28%).
Recrystallization four times from hexaneethyl acetate gave pure 7a as a yellow
1
solid, mp 151◦–154◦C; H NMR (CDCl3, 400 MHz) δ 10.12 (br s, 2H), 7.19
(m, 10H), 6.76 (t, J = 10 Hz, 2H), 6.49 (t, J = 10 Hz, 2H), 6.34 (d, J = 11.0 Hz,
2H), 6.02 (m, 4H), 4.72, (s, 2H), 3.69 (m, 4H), and 2.21 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 154.7, 153.4, 143.0, 133.5, 133.4, 128.4, 127.1, 127.0, 117.8,
112.6, 110.6, 66.8, 47.7 and 33.0; IR (KBr) 3435, 3268, 3195, 3058, 3024, 2913,
2854, 1590, 1544, 1507, 1462, 1385, 1259, 1124, 1020, 882, 700, and 640 cm−1
.
HRMS (EI) calcd for C31H30N4 458.2470, found 458.2471. Anal. calcd for
C31H30N4: N, 12.22. Found: N, 12.06.
[R-(R*,R*)]-H2(TC-3,diphen) (7a)
A procedure identical to [S-(R∗,R∗)]-7a but with [R-(R∗,R∗)]-1,2-
diphenyle-thylenediamine gave, after chromatography, [R-(R∗,R∗)]-7a (0.45 g,

ORDER
REPRINTS
498
CHENIER ET AL.
0.98 mmol, 23%). The 1H and 13C spectra for this compound were identical to the
spectra for the S enantiomer.
[R-(R*,R*)-H2(TC-4,diphen) (7b)
The same procedure was followed with diaminodiketone 3b (0.592 g, 2.00
mmol), toluene (20 mL), dimethyl sulfate (0.53 g, 4.20 mmol), [R-(R∗,R∗)]-1,2-
diphenylethylenediamine (0.506 g, 2.38 mmol), and absolute ethanol (400 mL) to
obtain, after chromatography on silica gel and elution with hexane-ethyl acetate
mixtures containing 3% triethylamine, [R-(R∗,R∗)]-7b (0.171 g, 0.362 mmol,
18%). Recrystallization from hexane-acetone gave a yellow powder, mp 105◦–
110◦C; 1H NMR (CDCl3, 400 MHz) δ 9.31 (br s, 2H), 7.1–7.5 (m, 10H), 6.73 (t,
J = 10.1 Hz, 2H), 6.51 (t, J = 10.1 Hz, 2H), 6.32 (d, J = 11.0 Hz, 2H), 6.03 (t, J =
9.3 Hz, 2H), 5.97 (d, J = 11.0 Hz, 2H), 4.90 (s, 2H), 3.44 (d, J = 13.9 Hz, 2H), 3.23
(t, J = 12.8 Hz, 2H), 2.22 (m, 2H), and 2.03 9m, 2H); 13C NMR (CDCl3, 100 MHz)
δ 154.3, 153.0, 142.8, 133.4, 133.2, 128.7, 128.4, 127.0, 126.8, 117.5, 111.6, 110.8,
65.9, 46.4, 27.8; IR (KBr) 3442, 3222, 3063, 3022, 2925, 2853, 1583, 1542,
1506, 1460, 1388, 1276, 1112, 748, 707 cm−1. HRMS (EI) calcd for C32H32N4
472.2627, found 472.2613. The structure was confirmed by x-ray crystallo-
graphy.
[R-(R*,R*)]-H2(TC-5,diphen) (7c)
The same procedure was followed with diaminodiketone 3c (4.74 g, 15.3
mmol), toluene (75 mL), dimethyl sulfate (4.00 g, 31.7 mmol), [R-(R∗,R∗)]-1,2-
diphenylethylenediamine (3.78 g, 17.8 mmol), and absolute ethanol (1.2 L) to
obtain, after chromatography on silica gel and elution with hexane-ethyl acetate
mixtures containing 3% triethylamine, [R-(R*,R*)]-7c (0.79 g, 1.93 mmol, 13%).
Recrystallization four times from hexane-acetone gave a yellow solid, mp 154◦–
156◦C; 1H NMR (CDCl3), 400 MHz) δ 8.95 (br s, 2H), 7.37 (d, J = 7.3 Hz, 4H),
7.22 (t, J = 7.7 Hz, 4H), 7.14 (t, J = 7.2 Hz, 2H), 6.67 (t, J = 10.1 Hz, 2H), 6.43
(t, J = 10.3 Hz, 2H), 6.31 (d, J = 11.3 Hz, 2H), 5.97 (t, J = 9.2 Hz, 2H), 5.91
(d, J = 11.0 Hz, 2H), 5.05 (s, 2H), 3.46 (m, 4H), 1.8–2.1 (m, 6H); 13C NMR
(CDCl3, 100 MHz) δ 153.2, 142.6, 133.1, 132.8, 128.3, 127.0, 126.9, 117.6,
111.0, 110.7, 65.7, 44.0, 27.6, 22.8; IR (KBr) 3453, 3235, 3067, 3024, 2931,
2856, 1588, 1519, 1389, 1277, 1215, 749, 698, 630 cm−1. HRMS (EI) calcd for
C33H34N4 486.2783, found 486.2785. Anal calcd for C33H34N4: N, 11.51. found:
N, 11.28.

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
499
[S-(R*,R*)]-H2(TC-6,diphen) (7d)
The same procedure was followed with diaminodiketone 3d (0.450 g,
1.39 mmol), toluene (10 mL), dimethyl sulfate (0.381 g, 3.02 mmol), [S-(R∗,R∗)]-
1,2-diphenylethylenediamine (0.348 g, 1.64 mmol), and absolute ethanol (375 mL)
to obtain [S-(R∗,R∗)]-7d (0.276 g, 0.552 mmol, 39%). Recrystallization from
hexane-acetone gave a yellow solid, mp 178◦–181◦C; 1H NMR (CDCl3, 400 MHz)
δ 8.81 (br s, 2H), 7.1–7.4 (m, 10H), 6.67 (t, J = 10.2 Hz, 2H), 6.46 (t, J =
10.2 Hz, 2H), 6.31 (d, J = 11.0 Hz, 2H), 5.99 (t, J = 9.2 Hz, 2H), 5.93 (d, J =
11.0 Hz, 2H), 4.90 (s, 2H), 3.48 (m, 4H), 1.5–2.0 (m, 8H); 13C NMR (CDCl3,
100 MHz) δ 153.4, 153.1, 142.0, 133.1, 132.9, 128.2, 127.2, 126.9, 117.5, 111.6,
110.2, 66.7, 44.5, 28.6, 26.5; IR (KBr) 3436, 3023, 2928, 2854, 1590, 1539, 1513,
1500, 1464, 1386, 1274, 1265, 748, 700 cm−1. HRMS (FAB) calcd for C34H37N4
[M+1]+ 501.3018, found 501.3033. Anal. calcd for C34H36N4: N, 11.19. found:
N, 10.89.
[S]-H2(TC-3,binap) (9)
The usual procedure was followed to produce crude dimethoxydiimine 4a
fromdimethylsulfate(0.44g, 3.48mmol), diaminodiketone3a(0.45g, 1.61mmol),
and toluene (10 mL). At the same time, S-1,1ꢂ-binaphthyl-2,2ꢂ-diamine (0.50 g,
1.76 mmol) in tetrahydrofuran (THF, 100 mL) was added to a three-neck flask
equipped with a condenser and an addition funnel, and held under nitrogen. n-
Butyllithium (2.31 mL/1.6M in hexanes, 3.70 mmol) was added over 15 min with
stirring to form the dilithium salt. The dimethoxydiimine 4a dissolved in THF
(100 mL) was added to the solution over 2 h and the resulting mixture was re-
fluxed for 1 h. It was then cooled and stirred overnight.
Water was added and the mixture was rotary evaporated. Chloroform was
added (50 mL) and the solution was washed with water (5 × 50 mL), dried over
anhydrous potassium carbonate, filtered, and run through a 4-cm long column
of basic alumina. The alumina was rinsed with chloroform (150 mL) and the
combined eluent was rotary evaporated. Chromatography on silica gel, elution with
hexane-ethyl acetate mixtures containing 3% triethylamine, and recrystallization
from methyl isobutyl ketone-hexane or acetone gave the pure product as an orange
solid (6.6 mg, 0.012 mmol, 1%): mp 290◦–294◦C dec; 1H NMR (CDCl3, 400 MHz)
δ 9.29 (br s, 2H), 7.76 (d, J = 8.4 Hz, 4H), 7.25 (m, 4H), 7.12 (m, 4H), 6.73
(t, J = 11 Hz, 2H), 6.56 (d, J = 11.0 Hz, 2H), 6.37 (t, J = 11 Hz, 2H), 6.28 (d, J =
11.0 Hz, 2H), 6.08 (t, J = 9 Hz, 2H) 3.60 (m, 4H), and 2.14 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 153.5, 152.3, 143.6, 134.9, 133.3, 132.9, 130.4, 128.7, 127.7,
126.6, 125.8, 124.3, 123.7, 123.1, 119.8, 117.6, 110.7, 46.1, and 29.0; IR (KBr)

ORDER
REPRINTS
500
CHENIER ET AL.
3446, 3207, 3053, 2922, 2851, 1589, 1539, 1509, 1462, 1320, 1246, 1095, 1037,
940, 820, 751, and 709 cm−1. HRMS (EI) calcd for C37H30N4 530.2470, found
530.2472.
[R]-H2(TC-3,binap) (9)
A procedure similar to the one used in the synthesis of [S]-H2(TC-3,binap)
(9) was followed to produce the R enantomer. Diaminodiketone 3a (1.13 g,
4.03 mmol) was made into dimethoxydiimine 4a, which was reacted with the
dilithium salt of R-1,1ꢂ-binaphthyl-2,2ꢂ-diamine (1.25 g, 4.40 mmol) to produce
[R]-H2(TC-3,binap) (9, 4.5 mg, 0.0085 mmol, 0.2%) after purification by column
1
chromatography and recrystallization from acetone. The H and 13C spectra for
this compound were identical to the spectra of the S enantomer.
( )-H2(TC-6,pent) (10)
Dimethoxydiimine 4d was made by the usual procedure from dimethyl sul-
fate (7.69 g, 61.0 mmol), diaminodiketone 3d (8.98 g, 27.7 mmol), and toluene
(180 mL) and dissolved in absolute ethanol (1 L). ( )-2,4-Diaminopentane hy-
drochloride (3.40 g, 19.4 mmol) was prepared by the literature method (21) and
was stirred with 50% KOH (13.5 mL) in a nitrogen atmosphere. Solid KOH was
added and the liquid was decanted. The top organic layer was separated and dried
with solid KOH and pipetted into absolute ethanol (1 L).
These two solutions were mixed in the usual procedure and the product
was purified by chromatography on silica gel, elution with hexane-ethyl acetate
mixtures containing 3% triethylamine, and recrystallization from acetone to give
( )-H2(TC-6,pent) (10) as a yellow solid (0.41 g, 1.05 mmol, 5%): mp 113◦–
1
115◦C; H NMR (CDCl3, 400 MHz) δ 7.0–8.5 (br, 2H), 6.73 (m, 4H), 6.31 (d,
J = 11.0 Hz, 2H), 6.27 (d, J = 11.4 Hz, 2H), 6.09 (t, J = 9.3 Hz, 2H), 4.04
(sextet, J = 5.9 Hz, 2H), 3.35 (m, 5H), 2.13 (t, J = 5.1 Hz, 2H), 1.52–1.90
(m, 8H), 1.16 (d, J = 6.6 Hz, 6H); 13C NMR (CDCl3, 100 MHz) δ 153.2, 152.0,
132.8, 132.6, 117.0, 110.3, 109.4, 47.8, 46.3, 42.6, 28.8, 27.8, 19.8; IR (KBr) 3447,
3229, 2918, 2844, 1581, 1507, 1277, 705 cm−1. HRMS (EI) calcd for C25H34N4
390.2783, found 390.2780. Anal. calcd for C25H34N4: N, 14.34. Found: N, 14.78.
The structure was confirmed by x-ray crystallography.
(+)-H2(TC-6,pent) (10)
( )-2,4-Diaminopentane hydrochloride was resolved by the method of
Bosnich (21) and (+)-2,4-diaminopentane hydrochloride was obtained, [α]DRT
=
+5.9◦ (c = 1 in 1M HCl). (+)-10 was obtained by a procedure identical to that

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
501
for ( )-10 on the same scale. After chromatography, a 5% yield was obtained.
Spectral properties were identical to those of ( )-10.
Diaminodiketone 8
2-Tosyloxytropone (10–12) (2, 2.76 g, 10.0 mmol), triethylamine (1.16 g,
11.5 mmol), and ( )-trans-1,2-diaminocyclohexane (0.64 g, 5.60 mmol) were
refluxed for 5 h in absolute ethanol (30 mL). Workup according to the usual method
(9) for other diaminodiketones (3) and chromatography and recrystallization from
chloroform gave a yellow solid (0.153 g, 0.475 mmol, 8%): mp 299◦– 301◦C; 1H
NMR (CDCl3, 400 MHz) δ 7.3 (br s, 2H), 7.16 (dd, J = 9.5 and 11.3 Hz, 4H),
7.01 (d, J = 11.0 Hz, 2H), 6.68 (d, J = 10.3 Hz, 2H), 6.61 (dd, J = 8.8 and 9.9 Hz,
2H), 3.72 (m, 2H), 2.16 (m, 2H), 1.89 (m, 2H, 1.4–1.7 (m, 4H); 13C NMR (CDCl3,
100 MHz) δ 176.4, 154.8, 137.1, 136.1, 128.7, 122.7, 109.1, 55.8, 31.5, 24.1; IR
(KBr) 3441, 3247, 3049, 2932, 2857, 1596, 1552, 1514, 1501, 1476, 1397, 1256,
1219, 754, 720, 706 cm−1; HRMS (EI) calcd for C20H22N2O2 322.1681, found
322.1679. Anal. calcd for C20H22N2O2: N, 8.69. found: N, 9.01.
Side Product 11
A second product of the cyclizations to tropocoronands 6a, 6b, and 6d was
isolated and purified by chromatography and recrystallization. In one experiment,
when ( )-6b was purified by recrystallization from acetone for a 21% yield, a
second crop of crystals after concentration of the solution yielded side product
1
11 at 6% based on starting diaminodiketone 3b: mp 203◦–220◦C dec; H NMR
(CDCl3, 400 MHz) δ 6.49 (t, J = 10.4 Hz, 2H), 6.24 (d, J = 10.6 Hz, 2H), 6.08
(t, J = 9.3 Hz, 1H), 4.77 (br s, 1H), 2.69 (m, 2H), 2.18 (m, 2H), 1.79 (m, 2H),
1.1–1.5 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 131.3, 121.4, 32.5, 24.8; HRMS
(EI) calcd for C13H16N2 200.1313, found 200.1305. The structure was confirmed
by x-ray crystallography.
Side Product 12
A second product of the cyclizations to tropocoronands 7 was isolated and
purified. In one experiment, when 7d was isolated by chromatography on silica
gel with hexane ethyl acetate mixtures containing 3% triethylamine in 12% yield,
later fractions yielded side product 12 at 11% based on starting diaminodiketone
3d. Three recrystallizations from acetone gave a pure sample: mp 199◦–201◦C;
1H NMR (CDCl3, 400 MHz) δ 7.2 (m, 8H), 6.9 (m, 4H), 6.60 (t, J = 9.7 Hz, 2H),
6.5 (br, 1H), 6.23 (t, J = 9.7 Hz, 1H), 4.1 (br, 2H); 13C NMR (CDCl3, 100 MHz)

ORDER
REPRINTS
502
CHENIER ET AL.
δ 140.3, 131.3, 128.2, 127.8, 127.4, 122.6, 64 (br); IR (KBr) 3465, 3185, 3036,
2893, 2775, 1589, 1520, 1460, 1314, 760, 698, 599 cm−1; HRMS (EI) calcd for
C21H18N2 298.1470, found 298.1471. Anal. calcd for C21H18N2: N, 9.39. Found:
N, 8.96.
X-Ray Crystallographic Data
Complete experimental details, as well as full tables of atomic positional
and anisotropic displacement parameters, and tables of derived bond lengths and
angles, can be provided upon request in Crystallographic Information File (CIF)
format. In general, crystals of ( )-6a, R-7b, and ( )-10 were analyzed using a
Siemens SMART diffractometer at 173K, while 11 was analyzed using an Enraf
NoniusCAD4diffractometerat298K. Thestructuresweresolvedandrefinedusing
the SHELXTL V-5.1 crystallographic software package (Bruker AXS, Madison,
WI). For 10, there is disorder of the hexyl linker chain, which was located in two
orientations of occupancies 0.71 and 0.29. Bond length and anisotropic displace-
ment parameter restraints were applied to the carbon atoms in these disordered
groups. Final R1 values for these compounds were 0.0529 ( 6a), 0.0477 (R-7b),
0.0790 ( 10), and 0.0575 (11). Details of the x-ray analysis in Crystallographic
Information File (CIF) can be provided by writing to the author (PJC).
ACKNOWLEDGMENTS
This research was supported in part by the donors of the Petroleum Research
Fund, and administered by the American Chemical Society; Research Corporation;
the University of Wisconsin–Eau Claire; and the National Institutes of Health.
REFERENCES
1. Seyden-Penne, J. Chiral Auxiliaries and Ligands in Asymmetric Synthesis;
John Wiley and Sons: New York, 1995.
2. Noyori, R. Asymmetric Catalysis in Organic Synthesis, John Wiley and Sons:
New York, 1994.
3. Catalytic Asymmetric Syntheses; Ojima, I., Ed.; VCH Publishers: New York,
1993.
4. Nogradi, M. Stereoselective Syntheses: A Practical Approach, 2nd ed.; VCH
Publishers: New York, 1995.
5. Togni, A.; Venanzi, L.M. Angew. Chem. Int. Ed. Engl. 1994, 33, 497.
6. Mukaiyama, T. Aldrichchimica Acta 1996, 29, 59.

ORDER
REPRINTS
CHIRAL TROPOCORONANDS
503
7. Regan, A.C. J. Chem. Soc., Perkin Trans. I 1998, 1151.
8. Imajo, S.; Nakanishi, K.; Roberts, M.; Lippard, S.J.; Nozoe, T. J. Am. Chem.
Soc. 1983, 105, 2071.
9. Zask, A.; Gonnella, N.; Nakanishi, K.; Turner, C.J.; Imajo, S.; Nozoe, T.
Inorg. Chem. 1986, 25, 3400.
10. Doering, W.v.; Knox, C.H. J. Am. Chem. Soc. 1952, 74, 5683.
11. Doering, W.v.; Hiskey, C.F. J. Am. Chem. Soc. 1952, 74, 5688.
12. Sato, T. Nippan Kagabu Zasshi 1959, 80, 1058.
13. Nozoe, T.; Someya, T. Bull. Chem. Soc. Jpn. 1978, 51, 3316.
14. Shindo, K.; Wakabayashi, H.; Zhang, L.-C.; Ishikawa, S.; Nozoe, T. Hetero-
cycles 1994, 39, 639.
15. Jaynes, B.S.; Doerrer, L.H.; Liu, S.; Lippard, S.J. Inorg. Chem. 1995, 34,
5735.
16. Jaynes, B.S.; Ren, T.; Masschelwin, A.; Lippard, S.J. J. Am. Chem. Soc.
1993, 115, 5589.
17. Chenier, P.J.; Judd, A.S.; Raguse, T.L.; Hoye, T.R. Tetrahedron Lett. 1997,
38, 7341.
18. Brunner, H.; Knott, A.; Benn, R.; Rufinska, A. J. Organomet. Chem. 1985,
295, 211.
19. Villacorta, G.M.; Rao, C.P.; Lippard, S.J. J. Am. Chem. Soc. 1988, 110, 3175.
20. Ahn, K.; Klassen, R.B.; Lippard, S.J. Organometallics 1990, 9, 3178.
21. Bosnich, B.; Harrowfield, J.M. J. Am. Chem. Soc. 1972, 94, 3425.
Received in the USA May 27, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100000574