Synthesis of phenazine derivatives for use as precursors to electrochemically generated bases

Article abstract of DOI:10.1039/b506295k

1,6-Disubstituted phenazine derivatives for use as precursors to electrochemically generated bases have been synthesized from readily available starting materials. Reaction of 1,6-dihydroxyphenazine with 1,10-diododecane, 1,1 1-diiodo-3,6,9-trioxaundecane

Full text of DOI:10.1039/b506295k

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A R T I C L E
Synthesis of phenazine derivatives for use as precursors to
electrochemically generated bases
A. Mateo Alonso, Roberto Horcajada, Helen J. Groombridge,†
Reshma Chudasama (ne´e Mandalia),† Majid Motevalli, James H. P. Utley* and Peter B. Wyatt*
Department of Chemistry, Queen Mary, University of London, Mile End Road, London, UK E1
4NS. E-mail: p.b.wyatt@qmul.ac.uk, j.utley@qmul.ac.uk; Fax: 44 20 78827427;
Tel: 44 20 78823267
Received 5th May 2005, Accepted 26th May 2005
First published as an Advance Article on the web 1st July 2005
1,6-Disubstituted phenazine derivatives for use as precursors to electrochemically generated bases have been
synthesized from readily available starting materials. Reaction of 1,6-dihydroxyphenazine with 1,10-diododecane,
1,11-diiodo-3,6,9-trioxaundecane or (R,R)-(−)-1,2-bis(3-iodopropoxy)cyclohexane gave planar chiral
phenazinophanes containing ether-linked bridges; molecular structures of all these compounds have been determined
by X-ray crystallography. Substituted 1,6-diaminophenazines were prepared by palladium-mediated amination of
1,6-dichlorophenazine and acylation of 1,6-diaminophenazine followed by reduction. Reaction of 1,6-bis-
(alkylamino)phenazines with sebacoyl chloride gave planar chiral phenazinophanes containing amide-linked bridges.
does not depend on which nitrogen atom acts as the base.
The compounds studied fall into two main categories: firstly,
ethers (4a) and secondly, nitrogen-containing systems (amides
and amines, 4b). In some cases the 1- and 6-positions are
Introduction
Electrochemical reduction of neutral substrates (‘probases’),
including phenazine (1) (Fig. 1), generates radical anions and
dianions which may act as bases.1,2 In a recent communication
linked together to form bridges, thus giving rise to phenazino-
we referred to some new C2-symmetric homochiral phenazine
phanes (represented by general structure 4c) that display the
derivatives, the radical-anions of which exhibited enantiose-
phenomenon of planar chirality.
lectivity in the rearrangement of the prochiral epoxide 3,4-
epoxytetrahydrothiophene-1,1-dioxide (2) to the allylic alcohol
(3).3 Here, we describe in detail the synthesis of these chiral
Results and discussion
probases and some related phenazine derivatives.
Synthesis of phenazine derivatives with oxygen substituents
The known 1,6-dimethoxyphenazine (7), prepared by the re-
action of o-anisidine (5), o-nitroanisole (6) and potassium
hydroxide in refluxing benzene,4 was the precursor to the other
phenazine ethers examined in this study (Scheme 1). Cleavage
of both methoxyl groups in 7 by refluxing boron tribromide
occurred in quantitative yield to give 1,6-dihydroxyphenazine
(8). The diol 8 reacted smoothly with unbranched primary
organic halides, potassium carbonate and DMF, leading to the
isolation of O(1),O(6)-dialkylated products as exemplified by
the di-O-decyl derivative 9. However, we were unable to obtain
useful quantities of chiral phenazine ethers through analogous
reactions in which the electrophile was the secondary halide rac-
1-phenylethyl bromide or the branched primary iodide (S)-10.
1
In the latter case a H NMR spectrum of the crude reaction
mixture was consistent with quantitative elimination of HI from
Fig. 1 Phenazine probases (1 and 4), substrate 2 and its rearrangement
product (3).
In selecting target phenazine derivatives, we were guided
by the need to produce single enantiomers that would be
configurationally stable under basic and reducing conditions. We
chose to make C2-symmetric compounds of general structure (4)
in which the 1- and 6-positions of phenazine carried identical
substituents, thus maintaining the homotopic relationship be-
tween the two nitrogen atoms of the central phenazine ring. This
should ensure that, following electrochemical reduction to form
nitrogen-centred anionic species, the magnitude and direction
of any asymmetric induction that occurs during deprotonation
† In part.
Scheme 1 Synthesis of 1,6 dioxygenated phenazines.
2 8 3 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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the iodide (S)-10 to give the methylenepyrrolidine derivative 11
(Scheme 2).
were obtained as racemates: their resolution will be considered
later in this article.
An alternative approach to enantiomerically pure planar-
chiral phenazinophanes involves the use of a chiral bis-
electrophile to form a bridge between the two phenazine
oxygen substituents. Thus the diiodide 17, prepared in two
steps from (R,R)-cyclohexane-1,2-diol (15), reacted with 1,6-
dihydroxyphenazine (8) under the usual cyclization conditions
(Scheme 5) to afford 5% yields of each of two monomeric
phenazinophane products 18a and 18b. These compounds could
be separated by flash chromatography and were shown by single
crystal X-ray diffraction to be a pair of diastereoisomers that
differed from one another in their sense of planar chirality.
Scheme 2 Elimination of HI from chiral iodide (S)-10.
We reasoned that the construction of phenazinophanes of
general structure 4c (X = O) would place the phenazine
ring in an asymmetric environment without requiring the use
of hindered alkylating agents. Such structures resemble the
chiral, but stereochemically labile, (1,5)-naphthalenophanes of
Dougherty;5 however, our use of shorter bridges in com-
bination with the larger aromatic nucleus was expected to
prevent racemization from occurring. Thus we investigated
the reactions between 1,6-dihydroxyphenazine (8) and bis-
electrophiles. 1,10-Diiododecane and potassium carbonate in
dilute DMF solution (final concentration 0.003 M) gave a
mixture of monomeric, dimeric and trimeric phenazinophanes
12a–c, which could readily be separated on the basis of their
solubility properties (Scheme 3). The analogous reaction of
1,11-diiodo-3,6,9-trioxaundecane (13) led to the isolation of the
monomeric phenazinophane 14 in 14% yield (Scheme 4). Both
the phenazinophanes 12a and 14 possess planar chirality and
Scheme 5 Preparation of cyclic ethers 18a and 18b.
Synthesis of phenazine derivatives with nitrogen substituents
We have employed two approaches for the preparation of
phenazine derivatives with nitrogen substituents at positions
1 and 6: these are (i) transition-metal catalysed amination of
1,6-dichlorophenazine (19) and (ii) dinitration of phenazine
followed by reduction and acylation.
1,6-Dichlorophenazine (19) was available in one step
from o-chloroaniline and o-chloronitrobenzene, as previ-
ously described by Pacher and Kloetzel.6 The dichloride
19 underwent Buchwald–Hartwig palladium-mediated am-
ination with the amines morpholine, 1-phenylethylamine
and 1-naphthylethylamine to give the corresponding 1,6-
diaminophenazine derivatives 20–21 (Scheme 6). The stereoiso-
meric purity of the diamines (R,R)-21a and (S,S)-21a was
confirmed by their identical NMR spectra but different reten-
tion times on chiral HPLC. Hindered amines such as cis-2,6-
dimethylpiperidine were unreactive under the conditions used.
For the second approach phenazine was nitrated according
to the literature,7 using hot concentrated nitric and sulfuric
acids (75 ◦C, 8 h). This gave a mixture of 1,6- and 1,9
dinitrophenazines, from which the desired 1,6-isomer 22 was
isolated in 30% yield by exploiting its very low solubility in
boiling glacial acetic acid. The reduction of 1,6-dinitrophenazine
(22) to give 1,6-diaminophenazine (23) has been reported to
occur in good yields using zinc in acetic acid.4 However, we
could not reproduce this last result, most probably because of
the heterogeneous nature of the reaction mixture. Our preferred
conditions for reduction involved brief catalytic hydrogenation
(2 h, 1 atm, 10% Pd/C) of a solution of 22 in trifluoroacetic
Scheme 3 Preparation of cyclic ethers 12a–c.
Scheme 4 Preparation of cyclic ether 14.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
2 8 3 3

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Scheme 6 Preparation of 1,6-diaminophenazine derivatives by catalytic
amination.
acid, giving diamine 23 in 68% yield (Scheme 7). Longer
reaction times led to over-reduction. N,Nꢀ-Diacylation, followed
by LiAlH4 or borane reduction proved to be a straightforward
way of preparing 1,6-bis(alkylamino)phenazines 25, including a
chiral example 25c derived from commercially available (R)-a-
methoxyphenylacetic acid. Further N-acylation of the amines
25 occurred without difficulty to give amides 26a and 27a–c. We
were particularly pleased by the ease with which the monomeric,
planar chiral phenazinophanes 27a–c formed when sebacoyl
chloride was used as the electrophile. Final concentrations in
these cyclizations were between 1 and 10 mM. It was notable that
the presence of the chiral N-alkyl groups in diamine 25c resulted
in the production of unequal amounts of two diastereoisomeric
phenazinophanes 27c and 27cꢀ (ca. 4 : 1 selectivity, based on the
1H NMR spectrum of the crude product and the yields following
separation of the isomers by flash chromatography). Treatment
of the tertiary aromatic amides 26a and 27 with LiAlH4 or
DIBALH led mainly to deacylation and hence reversion to
the secondary amine precursors 25, rather than providing the
intended tertiary amines. On the other hand, borane reduction
of the amides 26a and 27a was successful in forming the tertiary
amines 28a and 29a.
Resolution of phenazinophanes
We have noted above how the presence of centres of chirality
in the planar chiral phenazinophane derivatives 18a–b and 27c–
cꢀ generated pairs of diastereoisomers that could be easily be
separated by flash chromatography. These compounds could
be obtained in both enantiomerically and diastereoisomerically
pure forms, provided that a single enantiomer of the starting
material was used. The other monomeric phenazinophanes 12a,
14, 27a, 27b and 29a were formed as racemic mixtures. This
was demonstrated by separation of the enantiomers of 12a, 14,
27a and 29a by analytical HPLC using a chiral stationary phase
(ChiralPack OT).
We used the racemic phenazinophane 14 to exemplify
an approach to resolution based on the following sequence
(Scheme 8): reduction to the 5,10-dihydrophenazine 30, prepa-
ration of a pair of diastereoisomeric derivatives by reaction of a
chiral electrophile at one or both nitrogen atoms, separation of
the diastereoisomers and regeneration of the aromatic phenazine
system. The reduction step was conveniently achieved by hydro-
genation over palladium on carbon. Completion of the reaction
was indicated by the disappearance of the yellow colour from
Scheme 7 Preparation of 1,6-diaminophenazine derivatives from
1,6-dinitrophenazine.
the solution. Filtration to remove the catalyst gave a solution of
the air-sensitive dihydrophenazine 30 which was used directly in
reactions with chiral electrophilic reagents. NMR spectroscopy
indicated the formation of N-monosubstituted derivatives upon
treatment of 30 with menthyl chloroformate, camphor-10-
sulfonyl chloride and 1-methoxyphenylacetyl chloride. However,
the products formed with menthyl chloroformate and camphor-
10-sulfonyl chloride decomposed during attempted chromatog-
raphy on silica gel. Only when 1-methoxyphenylacetyl chloride
was used were we able to perform flash chromatography on
the diastereoisomeric derivatives. Following chromatography,
the lower Rf product 31a was obtained pure as judged by NMR,
whereas the higher Rf product 31b remained contaminated by ca.
10 mol% of the starting material 14. However, recrystallisation
2 8 3 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1

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Fig. 2 Molecular structure of rac-12a.
Fig. 3 Molecular structure of rac-14.
Scheme 8 Resolution of phenazinophane 14.
of 31b from heptane gave pure material and allowed the
(R,pR) configuration to be established by X-ray diffraction.
Conversion of the diastereoisomeric amides 31a and 31b into
the enantiomeric phenazinophanes (−)-(pS)-14 and (+)-(pR)-14
was achieved by refluxing in aqueous ethanolic HCl under an
atmosphere of air. Hydrolysis of 31a readily gave (−)-(pS)-14
as a single enantiomer, as indicated by chiral HPLC (Chiralpak
OT(+), MeOH). The hydrolysis of the amide 31b was found to be
significantly slower than that of its diastereoisomer 31a and the
sample of (+)-(pR)-14 as initially produced had 70% ee: partly,
at least, this low ee resulted from the difficulty in obtaining a
sample of 31b which was free from racemic 14, but it may also
indicate that some racemisation occurred under the somewhat
harsher conditions needed to hydrolyse 31b. Following three
recrystallisations from ethanol, however, (+)-(pR)-14 was also
obtained enantiomerically pure.
Fig. 4 Molecular structure of (−)-(pS)-14.
Structures of phenazinophanes
The molecular structures of the following phenazinophanes have
been established by single crystal X-ray diffraction: rac-12a,
rac-14, (−)-(pS)-14, 18a, 18b and 31b (Figs. 2–7).‡ These data
revealed that the aromatic phenazine systems were somewhat
twisted by the presence of the bridges between positions 1 and
6. A quantitative measure of this deformation was obtained by
calculating the torsion angle between the two planes generated
by least squares fitting of the positions of the carbon atoms
in the two carbocyclic rings (Table 1). The conformations of
the saturated bridges present in 12 and 14 do not maintain the
Fig. 5 Molecular structure of 18a.
C2-symmetry of these molecules in the solid state. There are
conformational differences between the structures of rac-14 and
(−)-(pS)-14, whilst 18b gives rise to two independent molecules
within the unit cell of the crystal, implying that these molecules
are somewhat flexible. Of the structures examined, compound
18b, with a cyclohexane unit in the bridge, is closest to having C2
symmetry in the solid state and also shows the greatest twisting
of the phenazine ring system, suggesting a relatively strained
structure.
‡ CCDC reference numbers 266538 and 269351. See http://dx.doi.org/
10.1039/b506295k for crystallographic data in CIF or other electronic
format.
The H and 13C NMR spectra of the monomeric aromatic
phenazinophanes were consistent with the presence of C2
1
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
2 8 3 5

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these compounds as precursors to electrogenerated bases will be
examined in the following article.12
Experimental
‘Petrol’ or ‘petroleum spirit’ refers to the fraction of bp 40–
◦
60 C. Toluene was distilled from sodium benzophenone ketyl
before use. Flash chromatography was performed on BDH silica
gel (33–70 lm). All new compounds were homogeneous as
assessed by TLC and high field NMR. Melting points were
determined using a Reichert hot stage microscope. Specific
rotations were determined on an Optical Activity Ltd AA-1000
polarimeter with a path length of 0.5 or 2 dm. IR spectra were
recorded using a Shimadzu FTIR 8300; samples were prepared
either as films by evaporation of CH2Cl2 solutions on NaCl
plates (indicated as ‘film’) or pellets formed by grinding with
KBr followed by pressing (indicated as ‘KBr’). NMR spectra
were recorded on Jeol EX270 and Bruker AM250, AMX400 or
AMX600 spectrometers. FAB mass spectra were recorded on
a ZAB-SE4F machine at the School of Pharmacy, University
of London; other mass spectra were obtained by the EPSRC
National Service in Swansea using a Finnigan MAT 900. All
HPLC experiments were performed using a Hewlett-Packard
1100 series liquid chromatography system equipped with Daicel
Chiralpak OT(+) chiral columns (0.46 cm × 5 cm guard column
and 0.46 cm × 25 cm main column) and a UV absorbance
detector.
Fig. 6 Molecular structure of 18b.
1,6-Dihydroxyphenazine (8)
Fig. 7 Molecular structure of 31b.
Boron tribromide (17 ml, 0.18 mol) was added to 1,6-
dimethoxyphenazine4 (7) (1.12 g, 4.66 mmol) under nitrogen.
The mixture was refluxed for 5 h, then cooled to room
temperature, poured onto ice (200 g) and left overnight. The
pH of the mixture was adjusted to 7 using NaOH. The yellow
precipitate was filtered off, washed with water and dried in vacuo
to give 1,6-dihydroxyphenazine (8) (0.97 g, 100%), mp 278–
Table 1 Torsion angles between the planes which best fit the positions
of the carbon atoms in the two outer rings of phenazinophanes
Number of C and O
atoms in the bridge
Phenazinophane
Torsion angle(s)/deg
rac-12a
rac-14
(−)-(pS)-14
18a
12
13
13
12
12
9
7
9
◦
279 C (lit.4 278 ◦C). dH (270 MHz, DMSO-d6) 10.5 (s, 2H,
exch D2O, OH), 7.8–7.7 (m, 4H, Ar), 7.19 (2H, dd, J 6.4 and 2.0
Hz).
10
18b
15 and 21a
a The two values reported relate to the two independent molecules within
the unit cell.
1,6-Bis(decan-1-oxy)phenazine (9)
1,6-Dihydroxyphenazine (8) (150 mg, 0.71 mmol), 1-iododecane
(0.3 ml, 1.4 mmol) and K2CO3 (0.98 g, 7.0 mmol) were stirred
together in DMF (11 ml) at 50 ◦C for 3 h. Water was added and
the solution was twice extracted with Et2O. The Et2O extracts
were washed several times with water and dried (MgSO4). The
solvent was evaporated and the residue was purified by flash
chromatography (petrol–CH2Cl2, 1 : 1) yielding 1,6-bis(decan-1-
oxy)phenazine (9) (260 mg, 75%) as a yellow solid, mp 77–79 ◦C.
(Found: C, 77.6; H, 9.6; N, 5.6. C32H48N2O2 requires C, 78.0; H,
9.8; N, 5.7%); dH (270 MHz, CDCl3) 7.89 (d, 2H, J 8.8 Hz, Ar
H-4,9), 7.63 (dd, 2H, J 8.8, 7.7 Hz, Ar H-3,8), 6.98 (d, 2H, J
7.7 Hz, Ar H-2,7), 4.23 (t, 2H, J 7.1 Hz, CH2OAr), 2.0 (quint,
2H, J 7.1 Hz, CH2CH2OAr), 1.6–1.0 (m, 14H, 7 × CH2), 0.81
(t, 2H, J 7.1 Hz, CH3); dC (68 MHz, CDCl3) 154.2, 142.9, 136.9,
129.7, 121.8, 107.5, 69.3, 31.7, 29.4, 29.3, 29.2, 28.6, 25.8, 22.5,
14.0; mmax/cm−1 (KBr) 2920, 2850, 1624, 1533, 1485, 1470, 1271,
1153, 797; m/z (FAB) 493.3800 (M + H+, C32H49N2O2 requires
493.3794).
symmetry on the NMR timescale. Some of the phenazine
derivatives, notably 31a, showed line broadening, which is
attributable to restricted rotation at amide bonds. The pairs
of protons in the bridging CH2 groups occupied diastereotopic
environments and differed from one another in their chemical
shift values. 1H NMR spectra of the phenazinophane 12a were
recorded◦in CDCl2CDCl2 at a range of temperatures between 30
and 110 C: even at the highest temperatures studied the CH2
protons did not become equivalent to each other on the NMR
timescale. The NMR spectra exhibited upfield shifts associated
with the central regions of the bridging groups, for example two
of the four central CH2 protons of 12a resonate at d + 0.1 and the
other two at d − 0.4. Similar observations have been made for
other cyclophane systems: they are attributable to ring current
effects combined with the chirality inherent in these systems.5
Conclusions
(S)-2-(Iodomethyl)-N-methanesulfonylpyrrolidine (10)
Routes have been devised to 1,6-disubstituted phenazine ethers
and amines, including C2-symmetric chiral phenazinophanes.
The planar chirality associated with bridges of 12 or 13
atoms between the 1- and 6-positions leads to distinct, isolable
stereoisomers that are accessible from inexpensive starting
materials in a few steps. The formation of amide bridges
gives good yields, whereas cyclization to form ether-bridged
phenazinophanes appears to be much less efficient. The use of
(S)-N-Methanesulfonyl-O-methanesulfonylprolinol8 (274 mg,
1.07 mmol) and NaI (260 mg, 1.70 mmol) were refluxed in
acetone (10 ml) for 6 d. The solvent was evaporated and the solid
residue was partitioned between Et2O and H2O. The organic
layer was washed with saturated aqueous sodium metabisulfite,
then with brine, and dried (MgSO4). The solvent was evaporated
to yield the iodide 10 (262 mg, 85%), [a]2D7 −61.2 (c 0.93, CH2Cl2),
2 8 3 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1

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mp 96–98 ◦C; dH (270 MHz, CDCl3) 3.9–3.7 (m, 1H, H-1); 3.6–
3.3 (m, 3H, CH2N + CHI); 3.24 (t, 1H, J 9.4 Hz, CHI); 2.86 (s,
3H, CH3); 2.2–1.7 (m, 4H, CCH2CH2C); dC (68 MHz, CDCl3):
60.5, 49.9, 36.0, 32.4, 24.0, 11.6; mmax/cm−1 (film) 3022, 2935,
1425, 1321, 1145; m/z (FAB) 289.9705 (M + H+, C6H13INO2S
requires 289.9712).
3 h. The solvent was evaporated and the residue was distributed
between Et2O and saturated aqueous sodium metabisulfite. The
ether phase was washed with water, dried (MgSO4) and the sol-
vent was evaporated to leave 1,11-diiodo-3,6,9-trioxaundecane
(13) (332 mg, 84%) as a pale yellow oil, dH (270 MHz, CDCl3) d
3.70 (t, 4H, J 6.9 Hz, ICH2CH2O), 3.61 (s, 8H, OCH2CH2O) and
3.20 (t, 4H, J 6.9 Hz, ICH2CH2O); dC (68 MHz, CDCl3) 71.75,
70.47, 70.02; mmax/cm−1 (film) 2866, 1458, 1413, 1350, 1263, 1169,
1105, 1034, 995, 976; m/z (FAB) 414.9248 (M + H+, C8H17I2O3
requires 414.9267).
rac-2,13-Dioxa-1(1,6)-phenazinacyclotridecaphane (rac-12a)
1,6-Dihydroxyphenazine (8) (0.80 g, 3.8 mmol) and K2CO3
(5.25 g, 38 mmol) in DMF (625 ml) were heated at 80 ◦C
under nitrogen. A solution of 1,10-diiododecane (1.57 g, 3.8
mmol) in DMF (625 ml) was then added over a period of
30 h using a dropping funnel. Once the addition was complete,
the mixture was stirred at 80 ◦C for further 3 h. DMF was
removed by evaporation under vacuum. The residue was
dissolved in CHCl3, washed with brine and dried (MgSO4).
Evaporation of the solvent and flash chromatography (CHCl3)
gave a mixture containing the cyclic monomer 12a, dimer
12b and trimer 12c. The monomer rac-12a was soluble in
cold petrol, whereas the dimer 12b was only soluble in the
hot solvent, and the trimer 12c was completely insoluble. The
mixture was added to petrol, which was boiled for 5 min. The
insoluble material was filtered off and on the basis of mass
spectrometry and NMR was considered to comprise mainly
2,5,8,11,14-Pentaoxa-1(1,6)-(phenazina)cyclotetradecaphane
(14)
A mixture of 1,6-dihydroxyphenazine (8) (1.00 g, 4.7 mmol)
and K2CO3 (6.55 g, 47 mmol) in DMF (700 ml) was heated to
80 ◦C under N2. A solution of 1,11-diiodo-3,6,9-trioxaundecane
(1.95 g, 4.7 mmol) in DMF (700 ml) was added over 27 h by
HPLC pump. The mixture was stirred at 80 ◦C for an additional
3 h after the addition was complete. DMF was removed by
evaporation under reduced pressure. The residue was dissolved
in dichloromethane and washed with water and brine. The or-
ganic phase was dried (MgSO4) and the solvent was evaporated.
The residue was purified by flash chromatography (CHCl3) and
recrystallization from EtOH to yield rac-2,5,8,11,14-pentaoxa-
1(1,6)-(phenazina)cyclotetradecaphane (14) (240 mg, 14%) as
orange crystals, mp 184–185 ◦C (Found: C, 64.7; H, 6.1; N,
7.4. C20H22N2O5 requires C, 64.85; H, 6.0; N 7.6%). mmax/cm−1
(film) 3067, 2924, 2862, 1624, 1525, 1483, 1254, 1138, 1119;
dH (270 MHz, CDCl3, assignment by COSY) 8.06 (dd, 2H, J
8.8, 1.0 Hz, Ar H-4,9), 7.73 (dd, 2H, J 8.8, 7.4 Hz, Ar H-3,8),
7.39 (dd, 2H, J 7.4 and 1 Hz, Ar H-2,7), 4.90 (ddd, 2H, J
12.9, 3.7, 1.5 Hz, ArOCH), 4.48 (ddd, 2H, J 12.9, 8.7, 1.2 Hz,
ArOCH), 4.03 (ddd, 2H, J 11.1, 8.7, 1.5 Hz, ArOCH2CH),
3.69 (ddd, 2H, J 11.1, 3.7, 1.2 Hz, ArOCH2CH), 3.00–2.88
(m, 4H, ArOCH2CH2OCH2), 2.63 (dt, 2H, J 10.6, 4.2 Hz,
ArOCH2CH2OCH2CH), 2.37 (ddd, 2H, J 10.9, 6.4, 4.7 Hz,
ArOCH2CH2OCH2CH); dC (101 MHz, CDCl3, assignment by
HSQC) 156.3, 143.3, 139.2, 129.9 (Ar C-3,8), 124.2 (Ar C-
4,9), 117.2 (Ar C-2,7), 74.2 (ArOC), 72.1 (ArOCH2C), 69.7
(ArOCH2CH2OC), 69.2 (ArOCH2CH2OCH2C); m/z (FAB)
371.1613 (M + H+, C20H23N2O5 requires 371.1607); HP◦LC
tR/min [Chiralpak OT(+), MeOH, 0.1 ml min−1; k 271 nm; 0 C]
63.1 (50%), 66.8 (50%).
the
trimer
2,12,14,25,27,38-hexoxa-1(1,6),13(1,6),26(1,6)-
(triphenazina)cyclononatriacontaphane (12c) (264 mg, 20%) as
◦
a yellow solid, mp 157–163 C; dH (270 MHz, CDCl3) 7.95 (d,
6H, J 9.0 Hz, Ar), 7.67 (t, 6H, J 9.0 Hz, Ar), 7.03 (d, 6H, J
9.0 Hz, Ar), 4.29 (t, 12H, J 6.5 Hz, OCH2), 2.06 (quint, 12H, J
6.5 Hz, OCH2CH2), 1.8–1.2 (m, 36H, 18 × CH2); dC (68 MHz,
CDCl3) 155.0, 143.0, 137.0, 129.9, 122.0, 107.8, 69.5, 29.5, 28.8,
26.1; m/z (FAB) 1051.6048 (M + H+, C66H79N6O6 requires
1051.6060).
The petrol extract was cooled down to room tempera-
ture and half of the solvent evaporated at room temper-
ature overnight. Then the dimer 1(1,6),13(1,6)-diphenazina-
2,12,14,24-(tetroxa)cyclohexadocosaphane (12b) (33 mg, 2%)
precipitated as a yellow solid, mp 205–210 ◦C; dH (270 MHz,
CDCl3) 7.82 (dd, 4H, J 8.9 and 1 Hz, Ar), 7.57 (dd, 4H, J 8.9
and 7.4 Hz, Ar), 6.88 (d, 4H, J 7.4 and 1 Hz, Ar), 4.18 (t, 8H, J
6.4 Hz, OCH2), 1.87 (quint, 8H, J 6.4 Hz, OCH2CH2), 1.5–1.2
(m, 24H, 12 × CH2) m/z (FAB) 701.4091 (M + H+, C44H53N4O4
requires 701.4067).
The mother liquor was evaporated and the residue
was recrystallised from EtOH to yield 2,13-dioxa-1(1,6)-
(phenazina)cyclotridecaphane (rac-12a) (227 mg, 17%) as or-
ange crystals, mp 162–164 ◦C. (Found C 75.1; H 7.6; N 8.0.
C22H26N2O2 requires C 75.4; H 7.5; N 8.0%); dH (400 MHz,
CDCl2CDCl2, assignment by COSY) 8.07 (dd, 2H, J 8.9 and
0.9 Hz, Ar H-4,9) 7.77 (dd, 2H, J 8.9 and 7.8 Hz, Ar H-
3,8), 7.38 (dd, 2H, J 7.8 and 0.9 Hz, Ar H-2,7), 4.9–4.7
(m, 2H, ArOCH), 4.5–4.4 (m, 2H, ArOCH), 1.5–1.4 (m, 4H,
ArOCH2CH2), 1.0–0.8 (m, 2H, OCH2CH2CH), 0.6–0.5 (m,
4H, OCH2CH2CHCH), 0.50–0.35 (m, 2H, OCH2CH2CH2CH),
0.15–0.02 (m, 2H, OCH2CH2CH2CH2CH), −0.3–−0.5 (m, 2H,
OCH2CH2CH2CH2CH); dC (101 MHz, CDCl2CDCl2, assign-
ment by HSQC) 154.9, 142.7, 138.2, 130.3 (Ar C-3,8), 123.7
(Ar C-4,9), 117.5 (Ar C-2,7), 72.8 (CH2O), 28.2 (OCH2CH2),
28.1 (OCH2CH2CH2CH2), 27.9 (OCH2CH2CH2CH2CH2), 25.0
(OCH2CH2CH2); mmax/cm−1 (film) 2924, 2852, 1732, 1622, 1526,
1481, 1464, 1346, 1252, 1132, 1115, 816; m/z (FAB) 351.2055
(M + H+, C22H27N2O2 requires 351.2077); HPLC tR/min [Chiral-
pak OT(+); hexane–propan-2-ol, 99 : 1; 0.7 ml min−1; k 276 nm;
30 ◦C] 18.5 (50%), 20.9 (50%).
(R,R)-(−)-1,2-Bis(allyloxy)cyclohexane (16)
The ether 16 was prepared according to the literature10 except
that the starting material (R,R)-(−)-cyclohexane-1,2-diol (15)
had been obtained by catalytic desymmetrisation of cyclohexane
oxide by Jacobsen’s procedure,11 then hydrolysis of the resulting
benzoate ester. (R,R)-(−)-1,2-Bis(allyloxy)cyclohexane (16) was
obtained as a pale yellow oil (87% yield from 15), [a]2D5 −46 (c
=
1.25, CH2Cl2). dH (270 MHz, CDCl3) 6.00–5.85 (m, 2H, CH),
=
5.27 (dq, 2H, J 17.1, 1.7 Hz, CH), 5.12 (dd, 2H, J 10.1, 1.5 Hz,
CH), 4.12 (dt, 4H, J 5.7, 1.5 Hz, CH2O), 3.22 (t, 2H, 4.0 Hz,
=
OCH), 2.00–1.15 (m, 8H, [CH2]4).
(R,R)-(−)-1,2-Bis-(3-iodopropoxy)cyclohexane (17)
(R,R)-(−)-1,2-Bis(allyloxy)cyclohexane (16) (1.00 g, 5.09 mmol)
was stirred in THF (50 ml) at 0 ◦C under nitrogen. 0.5 M 9-
BBN in THF (41 ml, 20.4 mmol) was added slowly and the
solution was stirred at 0 ◦C for 1 h and then at room temperature
for 5 h. Anhydrous methanol (33 ml) was added. Then a
solution of sodium acetate (4.11 g, 50.1 mmol) in methanol
(50 ml) was added followed by a solution of sodium iodide
(7.51 g, 50.1 mmol) in water (50 ml). Subsequently a solution
of chloramine T trihydrate (14.11 g, 50.1 mmol) in methanol
(50 ml) was added. The mixture was stirred overnight at room
temperature, then it was extracted with petroleum ether, which
1,11-Diiodo-3,6,9-trioxaundecane (13)
Our procedure is similar to that of Marquis et al.9 Tetra(ethylene
glycol) di-p-tosylate (0.50 g, 0.96 mmol) and sodium iodide
(0.23 g, 1.54 mmol) were refluxed together in acetone (5 ml) for
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
2 8 3 7

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was washed with a saturated aqueous sodium metabisulfite.
The organic phase was washed with water, dried (MgSO4) and
the solvent was evaporated. The crude mixture was purified
by flash chromatography (petroleum ether–ethyl acetate, 50 :
2) to yield (R,R)-(−)-1,2-bis-(3-iodopropoxy)cyclohexane (17)
(859 mg, 38%) as a colourless liquid, [a]2D4 −27 (c 1, CH2Cl2).
dH (270 MHz, CDCl3) 3.7–3.5 (m, 4H, OCH2), 3.30 (t, 4H, J
6.7 Hz, ICH2), 3.2–3.0 (m, 2H, OCH cyclohexane), 2.2–1.8 (m,
4H, OCH2CH2CH2I), 1.7–1.5 (m, 4H, 2 × CH2), 1.3–1.0 (m, 4H,
2 × CH2); m/z (FAB) 452.9775 (M + H+, C12H23I2O2 requires
452.9788).
in dry toluene (1 ml). Morpholine (96 ll, 1.1 mmol) was added
and the mixture was heated at 80 ◦C for 24 h, then cooled and
filtered through Celite. Evaporation of the solvent gave a red
residue, which after flash chromatography (CH2Cl2–EtOAc, 9 :
1) gave 1,6-bis(morpholino)phenazine (20) (162 mg, 93%) as an
orange solid, mp 276–277 ◦C. dH (270 MHz, CDCl3) 7.85 (d,
2H, J 8.6 Hz, Ar), 7.69 (dd, 2H, J 8.6, 7.4 Hz, Ar), 7.11 (d,
2H, J 7.4 Hz, Ar), 4.10 (t, 8H, J 4.4 Hz, CH2O), 3.53 (t, 8H,
J 4.4 Hz, CH2N); dC (68 MHz, CDCl3) 148.8 (Ar), 142.6 (Ar),
138.2 (Ar), 130.3 (Ar), 123.9 (Ar), 115.1 (Ar), 67.3 (CH2), 52.7
(CH2); mmax/cm−1 (KBr) 2943, 2851, 1612, 1528, 1481, 1119; m/z
(EI) 350.17399 (M+, C20H22O2N4 requires 350.17488).
(R,R,pS)-(+)-/(R,R,pR)-(−)-7(1,2)-Cyclohexana-1(1,6)-
phenazina-2,6,8,12-tetraoxacyclododecaphanes (18a and 18b)
1,6-Bis(1-phenylethylamino)phenazine (21a)
1,6-Dihydroxyphenazine (1.03 g, 4.89 mmol) and potassium
carbonate (6.75 g, 48.9 mmol) in DMF (700 ml) were de-
gassed by bubbling nitrogen for 90 min and then heated
to 80 ◦C under nitrogen. A solution of (R,R)-(−)-1,2-bis(3-
iodopropoxy)cyclohexane (17) (2.21 g, 4.89 mmol) in DMF
(700 ml) was added over 27 h by HPLC pump. The solution was
then stirred at 80 ◦C for an additional 3 h. DMF was removed
by rotary evaporation. The residue was extracted with CHCl3
and filtered. The filtrate was washed with brine, dried (MgSO4)
and the solvent evaporated. The crude residue was purified by
flash chromatography (CHCl3–petrol–Et2O, 7 : 2 : 1) yielding
first (R,R,pS)-(+)- and then (R,R,pR)-(−)-7(1,2)-cyclohexana-
1(1,6)phenazina-2,6,8,12-tetraoxacyclododecaphanes (18a and
18b).
1,6-Bis(1-phenylethylamino)phenazine (21a) was prepared by
analogy with 1,6-bis(morpholino)phenazine (20), by using
(R,R)- or (S,S)-1-phenylethylamine in place of morpholine.
Flash chromatography (petrol–CH2Cl2, 7 : 3) gave enan-
tiomerically pure (R,R)- or (S,S)-1,6-bis(1-phenylethylamino)-
phenazine (99% yield for (R,R)-21a; 86% yield for (S,S)-21a)
as a red solid, mp 155–157 ◦C. dH (270 MHz, CDCl3) 7.48–
7.24 (m, 14H, Ar–H); 6.79 (d, 2H, J 6 Hz, NH); 6.35 (dd, 2H,
J 6.4, 2.2 Hz); 4.72 (quintet, 2H, J 6 Hz, CHMe); 1.74 (d,
6H, J 6.8 Hz, Me); dC (68 MHz, CDCl3) 144.9, 143.5, 141.7,
135.4, 131.4, 128.9, 127.2, 126.1, 115.4, 104.3, 53.6 (CMe), 25.2
(Me); mmax/cm−1 (KBr): 3404, 3061, 2966, 1618, 1541, 1491, 1354;
m/z (FAB) 419.2236 (M + H+, C28H27N4 requires 419.2236);
kmax (MeOH) 250 (e 7200), 296 (56300) and 522 (4400); HPLC,
tR/min [Daicel Chiralpak OT (+), propan-2-ol, 0.5 ml min−1]
13.4 (R,R)-enantiomer, 15.3 (S,S)-enantiomer.
The (R,R,pS)-(+)-diastereosomer 18a was recrystallized from
MeOH to yield orange crystals (106 mg, 5%). Rf 0.42 (CHCl3–
petrol–Et2O 7 : 2 : 1), mp 143–145 ◦C, [a]D26 +486 (c 1, CHCl3).
(Found: C, 70.1%; H, 7.0%; N, 7.0%. C24H28N2O4 requires C,
70.6%; H, 6.9%; N, 6.9%).dH (600 MHz, CDCl3, assignment
by COSY) 8.06 (dd, 2H, J 8.8, 1.2 Hz, Ar H-4,9), 7.71 (dd,
2H, J 8.8, 7.4 Hz, Ar H-3,8), 7.48 (dd, 2H, J 7.4, 1.2 Hz,
Ar H-2,7), 5.46 (ddd, 2H, J 12.5, 10.2, 1.8 Hz, ArOCH), 4.39
(ddd, 2H, J 12.5, 5.2, 2.9 Hz, ArOCH), 3.12 (ddd, 2H, J 9.5,
5.8, 3.7 Hz, CyOCH), 2.13 (td, 2H, J 10.8, 6.8, CyOCH),
1.98–1.91 (m, 2H, ArOCH2CHHCH2OCy), 1.84–1.77 (m, 2H,
ArOCH2CHHCH2OCy), 1.2–0.9 (m, 10H, Cy); dC (151 MHz,
CDCl3, assignment by HSQC and DEPT, quaternary carbons
not reported due to unfavourable signal/noise) 130.2 (Ar C-
3,8), 124.6 (Ar C-4,9), 119.5 (Ar C-2,7), 75.4 (Cy C-1,2),
69.0 (ArOCH2), 63.9 (CyOCH2), 31.9 (ArOCH2C), 23.6, 19.3;
mmax/cm−1 (film) 2933, 1623, 1527, 1481, 1254, 1163, 1128; m/z
(FAB) 409.2129 (M + H+, C24H29N2O4 requires 409.2127).
The (R,R,pR)-(−)-diastereosomer 18b was recrystallized from
EtOH to yield orange crystals (102 mg, 5%). Rf 0.28 (CHCl3–
petrol–Et2O, 7 : 2 : 1), mp 157–159 ◦C, [a]D26 −452 (c 1, CHCl3).
(Found: C, 70.5%; H, 7.0%; N, 7.1%. C24H28N2O4 requires C,
70.6%; H, 6.9%; N, 6.9%). dH (600 MHz, CDCl3, assignment
by COSY) 8.06 (dd, 2H, J 8.8 Hz and 1.1 Hz, Ar H-4,9),
7.78 (dd, 2H, J 8.8 and 7.4 Hz, Ar H-3,8), 7.37 (dd, 2H, J
7.4 and 1.1 Hz, Ar H-2,7), 4.79 (ddd, J 11.5, 6.7, 3.4 Hz,
2H, ArOCH), 4.28 (ddd, 2H, J 11.5, 8.4, 2.8 Hz ArOCH),
3.10–3.04 (m, 2H, CyOCH), 2.63–2.58 (m, 2H, CyOCH),
2.02–1.95 (m, 2H, ArOCH2CHHCH2OCy), 1.67–1.59 (m, 2H,
ArOCH2CHHCH2OCy), 1.2–0.7 (m, 10H, Cy); dC (151 MHz,
CDCl3, assignment by HSQC and DEPT, quaternary carbons
not reported due to unfavourable signal/noise) 130.5 (Ar C-
3,8), 123.9 (Ar C-4,9), 117.9 (Ar C-2,7), 75.1 (Cy C-1,2),
72.1 (ArOCH2), 64.7 (CyOCH2), 30.5 (ArOCH2C), 24.8, 19.6;
mmax/cm−1 (film) 2933, 1621, 1525, 1481, 1263, 1112, 1069; m/z
(FAB) 409.21251 (M + H+, C24H29N2O4 requires 409.21272).
1,6-Bis(1-naphthylethylamino)phenazine (21b)
1,6-Bis(1-naphthylethylamino)phenazine (21b) was prepared
by analogy with 1,6-bis(morpholino)phenazine (22), by us-
ing (R,R)- or (S,S)-1-naphthylethylamine in place of mor-
pholine. Flash chromatography (petroleum spirit–CH2Cl2, 7 :
3), followed by recrystallization from MeOH gave 1,6-bis(1-
naphthylethylamino)phenazine (21b) (60% yield for (R,R)-21b;
◦
53% yield for (S,S)-21b) as a red solid, mp 199–200 C (from
MeOH). dH (270 MHz, CDCl3) 8.25 (d, 2H, J 8 Hz), 7.94 (t,
2H, J 8 Hz), 7.76 (d, 2H, J 8 Hz), 7.51–7.69 (m, 5H), 7.33–7.49
(m, 7H), 6.93 (d, 2H, J 6 Hz, NH), 6.21 (d, 2H, J 7 Hz), 5.48–
5.57 (m, 2H, CH), 1.89 (d, 6H, J 6.6 Hz, CH3); dC (68 MHz,
CDCl3): 143.3, 141.7, 139.5, 135.4, 134.3, 131.5, 131.0, 129.4,
127.8, 126.4, 126.1, 125.7, 122.7, 122.4, 115.4, 104.4, 49.7 (CMe),
23.8 (Me); mmax/cm−1 (KBr) 3394, 3049, 2962, 1618, 1541, 1490,
1353; m/z (EI) 518.2460 (M+, C36H30N4 requires 518.2470).
1,6-Diaminophenazine (23)
A mixture of 1,6-dinitrophenazine (22) (1 g, 3.7 mmol), triflu-
oroacetic acid (5 ml) and 10% palladium on charcoal (250 mg)
stirred under a balloon of hydrogen gas for 2 h. The solution
was then basified with concentrated aqueous ammonia. The red
suspension was extracted into chloroform, dried (MgSO4) and
evaporated to gi◦ve 23 as a lustrous red solid (528 mg, 68%), mp
242 ◦C (lit.4 245 C). dH (270 MHz, CDCl3) 7.51 (t, 2H, J 7.7 Hz,
Ar H-3,8), 7.32 (d, 2H, J 7.7 Hz, Ar), 6.86 (d, 2H, J 7.7 Hz, Ar),
6.29 (s, 4H, NH2).
1,6-Bis(acetamido)phenazine (24a)
1,6-Diaminophenazine (23) (325 mg, 1.54 mmol) was dissolved
in a mixture of acetic acid (20 ml) and acetic anhydride (5 ml).
The mixture was allowed to stir for 4 h at room temperature.
Water (10 ml) was added, and the resultant yellow precipitate
was filtered off and dried to give 1,6-bis(acetamido)phenazine
(24a) (352 mg) as a yellow solid. Evaporation of the filtrate, then
flash chromatography (CH2Cl2–EtOAc, 85 : 15) gave 20 mg more
of the title compound (24a) (combined yield 372 mg, 82%), mp
1,6-Bis(morpholino)phenazine (20)
1,6-Dichlorophenazine (19) (125 mg, 0.5 mmol), Pd2(dba)3
(10.7 mg, 0.012 mmol), (R)-(−)-BINAP (17.2 mg, 0.028 mmol),
and tBuONa (139 mg, 1.45 mmol) were dissolved under nitrogen
2 8 3 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1

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◦
224 C (sublimes). dH (270 MHz, CDCl3,) 9.8 (br s, 2H, NH),
3418, 2924, 1618, 1553, 1495, 1391, 1354, 799, 741; m/z (FAB)
8.87 (d, 2H, J 8.8 Hz, Ar), 8.0–7.8 (m, 4H, Ar), 2.46 (s, 6H,
CH3CO); mmax/cm−1 (KBr) 3348, 1670, 1535, 1516, 1402, 1288,
1118, 806; m/z (FAB) 295.1192 (M + H+, C16H15N4O2 requires
295.1195).
238.1214 (M+, C14H14N4 requires 238.1218).
(R,R)-1,6-Bis[(2-methoxy-2-phenyl)ethylamino)]phenazine (25c)
A 1 M solution of borane in THF (5 ml, 5 mmol) was added at
room temperature under nitrogen to (R,R)-1,6-bis(a-methoxy-
phenylacetamido)phenazine (24c) (143 mg, 0.282 mmol);
the mixture was then refluxed for 1 h. The unreacted borane
was then destroyed by addition of methanol (20 ml), followed
by reflux for 30 min. After evaporation of the solvent and
purification by flash chromatography (CH2Cl2) (R,R)-1,6-bis[(2-
methoxy-2-phenyl)ethylamino)]phenazine (25c) (109 mg, 81%)
was obtained as a red solid, mp 153–155 ◦C. dH (270 MHz,
CDCl3) 7.69 (dd, 2H, J 8.7, 7.4 Hz, Ar), 7.6–7.4 (m, 12H, Ar
and Ph), 6.89 (br t, 2H, J 6 Hz, NH), 6.72 (d, 2H, J 7.4 Hz, Ar),
4.71 (dd, 2H, J 7.5, 5.0 Hz, CH), 3.8–3.6 (m, 4H, CH2), 3.47 (s,
6H, OCH3); dC (68 MHz, CDCl3,) 144.6 (Ar), 141.8 (Ar), 140.1
(Ar), 135.6 (Ar), 131.3 (Ar), 128.9 (Ar), 128.4 (Ar), 127.0 (Ar),
115.7 (Ar), 102.9 (Ar), 82.3 (CH), 57.3 (CH3O), 50.5 (CH2N);
mmax/cm−1 (KBr) 3412, 2924, 2853, 1618, 1541, 1458, 1111; m/z
(FAB) 479.2462 (M + H+, C30H31N4O2 requires 479.2447).
1,6-Bis(methoxycarbamido)phenazine (24b)
A mixture of 1,6-diaminophenazine (23) (223 mg, 1.02 mmol),
dry dichloromethane (50 ml) and dry pyridine (157 ll,
1.94 mmol) was treated with methyl chloroformate (156 ll,
2.02 mmol). The mixture was stirred at room temperature for
1 h, and then the golden yellow precipitate was filtered off to give
1,6-bis(methoxycarbamido)phenazine (24b) (254 mg, 76%), mp
◦
210–220 C (sublimes). dH (270 MHz, CDCl3,) 9.23 (br s, 2H,
NH), 8.49 (d, 2H, J 8.4 Hz, Ar), 7.8–7.9 (4H, m, Ar), 3.92
(6H, s, OCH3); mmax/cm−1 (KBr) 3368, 1747, 1545, 1518, 1429,
1406, 1306, 1227, 1038, 800; m/z (FAB) 327.1096 (M + H+,
C16H15N4O4 requires 327.1093).
(R,R)-1,6-Bis(a-methoxyphenylacetamido)phenazine (24c)
1,6-Diaminophenazine (23) (200 mg, 0.95 mmol) was dissolved
in dry dichloromethane (5 ml) and pyridine (162 ll, 2.00 mmol)
was added to the solution. (R)-a-methoxyphenylacetyl chloride
(332 mg, 1.80 mmol), dissolved in dried dichloromethane (2 ml),
was then added. After 24 h, the solvent was removed and
unreacted 1,6-diaminophenazine was removed by stirring for
30 min with acetic acid (25 ml) and acetic anhydride (10 ml).
Water (10 ml) was then added to the system to destroy excess
acetic anhydride and after evaporation of the acetic acid,
(R,R)-1,6-bis(a-methoxyphenylacetamido)phenazine (24c) was
isolated by flash chromatography (CH2Cl2) and obtained as a
bright yellow solid (267 mg, 59% from the acid chloride), mp
203–205 ◦C. dH (270 MHz, CDCl3) 11.09 (s, 2H, NH), 8.85 (d,
2H, J 7, Ar), 8.03 (d, 2H, J 7 Hz, Ar), 7.85 (t, 2H, J 7 Hz,
Ar), 7.3–7.7 (m, 10H, Ph), 4.94 (s, 2H, CH), 3.64 (s, 6H, OCH3);
mmax/cm−1 (KBr) 3329, 1686, 1541, 1508, 1406, 1097; m/z (FAB)
507.2036 (M + H+, C30H27N4O4 requires 507.2032).
1,6-Bis(N-ethylacetamido)phenazine (26a)
A mixture of 1,6-bis(ethylamino)phenazine (25a) (179 mg, 0.67
mmol), acetic acid (10 ml) and acetic anhydride (2 ml) was re-
fluxed for 24 h, then water (10 ml) was added. After evaporation
of the solvent and flash chromatography (EtOAc–petrol, 3 : 1),
1,6-bis(N-ethylacetamido)phenazine (26a) (149 mg, 63%) was
obtained as a yellow solid, mp 199 ◦C (decomp); dH (270 MHz,
CDCl3) 8.33 (d, 2H, J 8.8 Hz, Ar), 7.92 (dd, 2H, J 8.7, 7.2 Hz,
Ar), 7.78 (d, 2H, J 7.2 Hz, Ar), 4.4–4.2 (br m, 2H, NCH2), 3.9–
3.6 (br m, 2H, NCH2), 1.9–1.7 (br m, 6H, CH3), 1.4–1.1 (br m,
6H, CH3); dC (68 MHz, CDCl3) 171.1 (CO), 144.2 (Ar), 140.7
(Ar), 140.4 (Ar), 131.0 (Ar), 130.8 (Ar), 130.5 (Ar), 44.4 (Ac),
23.0 (CH2), 13.6 (CH3); mmax/cm−1 (KBr) 2928, 1659, 1624, 1531,
1485, 1393, 1288, 1130, 1061; m/z (FAB) 351.1814 (M + H+,
C20H23N4O2 requires 351.1821).
2,13-Diethyl-2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane-
3,12-dione (27a)
1,6-Bis(ethylamino)phenazine (25a)
Sebacoyl chloride (202 ll, 0.95 mmol) in dry dichloromethane
(80 ml) was added dropwise at room temperature over 24 h to a
stirred mixture of 1,6-bis(ethylamino)phenazine (25a) (253 mg,
0.95 mmol), dry dichloromethane (80 ml) and pyridine (144 ll,
1.78 mmol). Evaporation of the solvent and flash chromatogra-
phy (CH2Cl2–EtOAc, 4 : 1) gave 2,13-diethyl-2,13-diaza-1(1,6)-
(phenazina)cyclotridecaphane-3,12-dione (27a) (293 mg, 71%)
as a yellow solid, mp 159 ◦C. dH (270 MHz, CDCl3) 8.30 (d, 2H, J
9 Hz), 7.92 (dd, 2H, J 9, 7 Hz), 7.77 (d, 2H, J 7 Hz), 4.37 (dq, 2H,
J 14, 7 Hz, NCHHCH3), 3.91 (dq, 2H, J 14, 7 Hz, NCHHCH3),
1.8–0.6(m, 22 H, 8 × CH2 + 2 × CH3); dC (68 MHz, CDCl3) 174.2
(CO), 143.7 (Ar), 141.0 (Ar), 140.2 (Ar), 130.5 (Ar), 130.44 (Ar),
130.37 (Ar), 43.8 (CH2), 33.6 (CH2), 27.8 (CH2), 26.4 (CH2),
24.8 (CH2), 13.6 (CH3); mmax/cm−1 (KBr) 2931, 1670, 1647, 1625,
1527, 1327, 1308, 1265, 1076, 884; m/z (FAB) 433.2592 (M +
H+, C26H33N4O2 requires 433.2604; HPLC, tr/min (methanol,
column OT(+), detector 255 nm, flow 0.5 ml min−1) 14.2 (50%),
16.0 (50%).
1,6-Bis(acetamido)phenazine 24a (210 mg, 0.71 mmol) was
refluxed with LiAlH4 (107 mg, 2.82 mmol) in dry THF (20 ml)
until the colour of the mixture changed from red to green (2 h).
Aqueous 5% NaOH (5 ml) was added and the mixture
R
was filtered through Celiteꢀ. The filtrate was washed with
distilled water and the THF was evaporated to give 1,6-
bis(ethylamino)phenazine (25a) (179 mg, 95%) as a red solid,
mp 152 ◦C (sublimes); dH (270 MHz, CDCl3) 7.58 (t, 2H, J
8.5 Hz, Ar–H), 7.38 (d, 2H, J 8.5 Hz, Ar–H), 6.60 (d, 2H, J
8.5 Hz, Ar–H), 6.27 (br s, 2H, N–H), 3.34–4.49 (m, 4H, CH2),
1.54 (t, 6H, J 7.3 Hz, CH3), dC (68 MHz, CDCl3,) 145.8 (Ar),
142.1 (Ar), 136.6 (Ar), 131.8 (Ar), 113.6 (Ar), 102.4 (Ar), 38.8
(CH2), 14.5 (CH3); mmax/cm−1 (KBr) 3384, 2964, 1618, 1543,
1485, 1396, 1342, 1294, 1188, 794; m/z (FAB) 266.1543 (M+,
C16H18N4 requires 266.1531).
1,6-Bis(methylamino)phenazine (25b)
1,6-Bis(methoxycarbamido)phenazine (24b) (95 mg, 0.291
mmol) was refluxed with LiAlH4 (65.9 mg, 1.74 mmol) in dry
THF (20 ml) under nitrogen. After 3 h the mixture, which had
become green, was cooled to 0 ◦C and treated with 5% aqueous
2,13-Dimethyl-2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane-
3,12-dione (27b)
Sebacoyl chloride (55 ll, 0.257 mmol) in dry dichloromethane
(100 ml) was added dropwise at room temperature over 24 h
to a stirred mixture of 1,6-bis(methylamino)phenazine (25b)
(61.2 mg, 0.257 mmol), dichloromethane (100 ml) and pyridine
(42 ll, 0.52 mmol). Evaporation of the solvent and flash
chromatography (CH2Cl2–EtOAc, 1 : 1) gave 2,13-dimethyl-
2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane-3,12-dione (27b)
R
NaOH (5 ml). The mixture was filtered through Celiteꢀ, then
the filtrate was washed with water and the THF evaporated to
give 1,6-bis(methylamino)phenazine (25b) (65 mg, 94%) as a red
solid, mp 169 ◦C. dH (270 MHz, CDCl3) 7.62 (2H, t, J 7.5 Hz,
Ar), 7.39 (2H, d, J 7.5 Hz, Ar), 6.53 (2H, d, J 7.5 Hz, Ar), 6.3–
6.4 (2H, m, NH), 3.51 (6H, d, J 5.2 Hz, Me); mmax/cm−1 (KBr)
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
2 8 3 9

View Article Online
(78 mg, 75%) as a yellow solid, mp 222–223 ◦C. dH (270 MHz,
CDCl3) 8.30 (d, 2H, J 9 Hz), 7.92 (dd, 2H, J 9, 8 Hz), 7.82
(d, 2H, J 8 Hz), 3.62 (s, 6H, Me), 1.9–0.5 (m, 16 H, 8 ×
CH2); dC (68 MHz, CDCl3) 174.9 (CO), 143.8 (Ar), 142.1 (Ar),
140.8 (Ar), 130.8 (Ar), 130.6 (Ar), 129.7 (Ar), 37.6, 33.1, 27.9,
26.7, 25.0; mmax/cm−1 (KBr) 2928, 1661, 1641, 1529, 1483, 1448,
1412, 1379; m/z (FAB) 405.2272 (M + H+, C24H29N4O2 requires
405.2291).
(d, 2H, J 8.5 Hz, Ar H-4,9), 7.63 (dd, 2H, J 8.5, 7.5 Hz,
Ar H-3,8), 7.01 (d, 2H, J 7.6 Hz, Ar H-2,7), 4.92–4.84 (m,
2H, NCHHCH2), 3.57 (dq, 2H, J 14, 7 Hz, NCHHCH3),
3.31 (m, 4H, NCHHCH2 and NCHHCH3), 1.43 (t, 6H, J
7.0 Hz, CH3), 1.37–1.12 (m, 4H, NCH2CH2), 0.99–0.76 (m, 4H,
NCH2CH2CH2), 0.58–0.48 (m, 2H, NCH2CH2CH2CH), 0.48–
0.39 (m, 2H, NCH2CH2CH2CH2CH), 0.27–0.16 (m, 2H,
NCH2CH2CH2CH), −0.24–(−0.35) (m, 2H, NCH2CH2CH2-
CH2CH); dC (101 MHz, CDCl3, assignments supported by
1
DEPT and H–13C correlation) 147.2 (Ar quaternary), 141.4
(R,R)-2,13-Bis[(2-methoxy-2-phenyl)ethyl]-2,13-diaza-1(1,6)-
(phenazina)cyclotridecaphane-3,12-diones (27c and 27cꢀ)
(Ar quaternary), 137.3 (Ar quaternary), 129.7 (Ar CH), 121.2
(Ar CH), 115.9 (Ar CH), 51.0 (CH2CH2N), 45.3 (CH3CH2N),
28.6 (NCH2CH2CH2CH2C), 26.8 (NCH2CH2CH2C), 25.3
(NCH2CH2CH2), 23.3 (NCH2CH2), 12.8 (CH3CH2); mmax/cm−1
(KBr) 2924, 2851, 1528, 1477, 1458, 1321, 1267, 1101, 800,
739; m/z (FAB) 404.2925 (M+, C26H36N4 requires 404.2940);
HPLC, tR/min [Daicel Chiralpak OT (+), hexane–propan-2-ol
(9 : 1), 1.0 ml min−1, detector 297 nm, T = 12 ◦C] 5.9
and 6.5.
A solution of sebacoyl chloride (54 ll, 0.253 mmol) in
dichloromethane (15 ml) was added dropwise at room tem-
perature over 12 h to a stirred mixture of (R,R)-1,6-bis[(2-
methoxy-2-phenyl)ethylamino)]phenazine (25c) (120 mg, 0.251
mmol), dichloromethane (10 ml), and pyridine (40 ll, 0.508
mmol). Evaporation of the solvent and separation by flash
chromatography (40% ethyl acetate in petroleum ether) gave first
27c (69 mg, 43%) and then 27cꢀ (18 mg, 11%), both as yellow
solids.
(R,pS)-(−)-/(R,pR)-(+)-2,5,8,11,14-Pentaoxa-1(1,6)-[5-(a-
methoxyphenylacetyl)-5,10-dihydrophenazina]-
cyclotetradecaphanes (31a and 31b)
The major product 27c had the following properties. mp 74–
◦
76 C, [a]2D7 +127 (c 0.5, CH2Cl2). dH (270 MHz, CDCl3) 8.19
(dd, 2H, J 8.8, 1.2 Hz, Ar), 8.04 (dd, 2H, J 7.0, 1.2 Hz, Ar),
7.91 (dd, 2H, J 8.8, 7.0 Hz, Ar H-3,8), 7.45–7.25 (m, 10H, m,
Ph), 4.93 (dd, 2H, J 9.8, 2.4 Hz, OCH), 4.73 (dd, 2H, J 14.0,
2.4 Hz, NCH2), 3.52 (dd, 2H, J 14.3, 9.8 Hz, NCH2), 3.35 (s, 6H,
OCH3), 1.9–1.7 (m, 4H, chain), 1.5–1.3 (m, 2H, chain), 1.2–1.0
(m, 2H, chain), 0.85–0.55 (m, 4H, chain), 0.1–0.0 (m, 2H, chain),
−0.6–(−0.8) (m, 2H, chain), dC (68 MHz, CDCl3) 175.3 (CO),
143.7 (Ar), 141.9 (Ar), 140.0 (Ar), 131.2 (Ar), 130.9 (Ar), 130.4
(Ar), 128.7 (Ar), 128.0 (Ar), 126.9 (Ar), 112.5 (Ar), 82.9 (CH),
57.7, 57.3, 33.4, 27.9, 27.1, 24.9; mmax/cm−1 (KBr) 2924, 1660,
1529, 1107, 750; m/z (FAB) 667.3245 (M + Na+, C40H44N4O4Na
requires 667.3260).
rac-2,5,8,11,14-Pentaoxa-1(1,6)-(phenazina)cyclotetradecaphane
(14) (124 mg, 0.336 mmol) and 10% Pd/C (240 mg) were stirred
in dry, oxygen-free CH2Cl2 (2 ml) under a hydrogen balloon
at room temperature until the yellow solution had become
colourless (30 min). Then the mixture was filtered through
celite under nitrogen and the celite was rinsed with CH2Cl2
(4 ml). The solvent was evaporated under vacuum and CH2Cl2
(1 ml) was added to the residue under nitrogen. (R)-a-Metho-
xyphenylacetyl chloride (155 mg, 0.84 mmol) and anhydrous
pyridine (68 ll, 0.84 mmol) were added and the mixture was
heated overnight at 40 ◦C. The solvent was evaporated and
the crude mixture was purified by flash chromatography on
silica which had previously been washed with 10% Et3N in
hexane. Elution with CHCl3–Et2O (9 : 1) gave (R,pS)-(−)-
2,5,8,11,14-pentaoxa-1(1,6)-[5-(a-methoxyphenylacetyl)-5,10-
dihydrophenazina]cyclotetradecaphane (31a) (42 mg, 24%)
and (R,pR)-(+)-2,5,8,11,14-pentaoxa-1(1,6)-[5-(a-methoxyphe-
nylacetyl)-5,10-dihydrophenazina]cyclotetradecaphane (31b)
The minor product, 27cꢀ had dH (270 MHz, CDCl3) 8.22 (dd,
2H, J 9, 1 Hz, Ar), 7.75 (dd, 2H, J 9,7 Hz, Ar), 7.33–7.45 (10H,
m, Ph), 6.11 (dd, 2H, J 7, 1 Hz, Ar), 4.80 (dd, 2H, J 8.5, 6 Hz,
PhCH), 4.57 (dd, 2H, J 14, 8 Hz, NCH2), 3.94 (dd, 2H, J 14,
5 Hz, CH2), 3.04 (s, 6H, OMe), 1.9–1.7 (m, 4H), 1.5–0.5 (m,
10H), 0.1–(−0.1) (m, 2H), −0.6–(−0.8) (m, 2H).
1
1,6-Bis(diethylamino)phenazine (28a)
(51 mg; contaminated with 10 mol% of 14 as judged by H
NMR) as pale yellow solids. Recrystallisation from heptane
gave spectroscopically pure 31b (14 mg, 8%).
Borane solution (1 M in THF; 5 ml, 5 mmol) was added
under nitrogen to 1,6-bis(N-ethylacetamido)phenazine (26a)
(149 mg, 0.425 mmol). The mixture was refluxed for 2 h, then
methanol (10 ml) was added and the mixture was refluxed
for a further 5 min. Evaporation of the solvent followed
by flash chromatography (CH2Cl2–EtOAc, 9 : 1) gave 1,6-
bis(diethylamino)phenazine (28a) (113 mg, 82%) as a red solid,
mp 55–56 ◦C. dH (270 MHz, CDCl3) 7.76 (dd, 2H, J 8.7, 1.2 Hz,
Ar), 7.61 (dd, 2H, J 8.7, 7.7 Hz, Ar), 7.01 (dd, 2H, J 7.7, 1.2 Hz,
Ar), 3.67 (q, 8H, J 7.1 Hz, CH2), 1.25 (t, 12H, J 7.1 Hz, CH3);
dC (68 MHz, CDCl3) 147.2 (Ar), 142.5 (Ar), 138.8 (Ar), 129.7
(Ar), 121.6 (Ar), 115.3 (Ar), 47.2 (CH2), 12.4 (CH3); mmax/cm−1
(KBr) 2970, 2928, 1607, 1530, 1484, 1265, 1209, 1094, 801; m/z
(FAB) 323.2250 (M + H+, C20H27N4 requires 323.2236).
The (R,pS)-(−)-diastereoisomer 31a had the following prop-
◦
erties. Rf 0.04 (CHCl3–Et2O, 9 : 1), mp >230 C, [a]2D0 −114 (c
1, CH2Cl2); dH (400 MHz, CDCl3) 7.5–6.2 (m, 12H, Ar + NH),
5.29 (br s, 1H, MeOCH), 4.5–4.2 (m, 4H, ArOCH2), 3.7–2.5
(m, 15H); dC (101 MHz, CDCl3, assignment by DEPT) 171.1
=
(br, C O), 153.6 (Ar C quat), 146.7 (Ar C quat), 146.2 (Ar C
quat), 144.1 (Ar C quat), 143.4 (Ar C quat), 136.2 (Ar C quat),
131.8 (Ar C quat), 128.4 (Ar CH), 128.0 (Ar), 127.9 (Ar), 127.7
(Ar), 127.4 (Ar), 127.1 (Ar CH), 120.0 (Ar CH), 119.3 (Ar CH),
114.6 (Ar CH), 112.3 (Ar CH), 108.5 (Ar CH), 80.3 (OCH),
72.7 (CH2), 72.65 (CH2), 71.8 (CH2), 71.2 (CH2), 70.8 (CH2),
70.7 (CH2), 70.1 (CH2), 57.1 (CH3); mmax/cm−1 (film) 3400 (br,
+
=
N–H), 1679 (C O); m/z (ESI) 521.2287 (M + H , C29H33N2O7
requires 521.2282).
2,13-Diethyl-2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane
(29a)
The (R,pR)-(+)-diastereoisomer 31b had the fo◦llowing prop-
erties. Rf 0.14 (CHCl3–Et2O, 9 : 1), mp 182–184 C (heptane),
[a]2D6 +42 (c 0.25, CH2Cl2). dH (400 MHz, CDCl3) 7.39 (m, 1H,
Ar), 7.2–7.0 (m, 4H, Ar), 6.9–6.7 (m, 5H, Ar), 6.31 (m, 2H, Ar
and NH), 5.28 (s, 1H, MeOCH), 4.5–4.2 (m, 4H, ArOCH2), 3.8–
3.5 (m, 4H, ArOCH2CH2), 3.47 (s, 3H, CH3O), 3.2–2.5 (m, 8H,
ArOCH2CH2OCH2CH2O); dC (101 MHz, CDCl3, assignment
Borane solution (1 M in THF; 10 ml, 10 mmol) was added to
2,13-diethyl-2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane-
3,12-dione (27a) (184 mg, 0.425 mmol) under nitrogen. The
mixture was refluxed for 5 h, then methanol (20 ml) was added
and the mixture was refluxed for a further 15 min. Evaporation
of the solvent followed by flash chromatography (CHCl3) gave
2,13-diethyl-2,13-diaza-1(1,6)-(phenazina)cyclotridecaphane
(29a) (103 mg, 60%) as a red solid, mp 123–125 ◦C, dH
(400 MHz, CDCl3, assignments supported by COSY) 7.82
=
by DEPT) 171.1 (C O), 153.6 (Ar C quat), 146.2 (Ar C quat),
144.1 (Ar C quat), 136.2 (Ar C quat), 131.9 (Ar C quat), 128.1
(Ar), 127.9 (Ar), 127.8 (Ar), 127.5 (Ar), 127.3 (Ar), 120.0 (Ar
CH), 119.6 (Ar CH), 117.7 (Ar CH), 114.4 (Ar CH), 112.6 (Ar
2 8 4 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1

View Article Online
CH), 108.7 (Ar CH), 81.5 (OCH), 72.6 (CH2), 71.8 (CH2), 71.6
(CH2), 71.5 (CH2), 71.1 (CH2), 70.7 (CH2), 70.14 (CH2), 70.08
final R indices [I > 2 r(I)] R1 = 0.0660, wR2 = 0.1564 and for
all data R1 = 0.1357, wR2 = 0.1887. CCDC reference number
269351.
(CH2), 57.1 (CH3); mmax/cm−1 (film) 3435 (br, N–H), 1679 (C O);
=
m/z (ESI) 521.2287 (M + H+, C29H33N2O7 requires 521.2282).
Crystal data for rac-14.‡ C20H22N2O5, M = 370.40, Mono-
˚
clinic, a = 14.5548(2), b = 7.2083 (1), c = 17.2662(4) A, a =
◦
3
˚
(pS)-(−)-2,5,8,11,14-Pentaoxa-1(1,6)-
(phenazina)cyclotetradecaphane (pS-14)
90.00, b = 103.938(1), c = 90.00 , V = 1758.15(5) A , space
group P21/c, Z = 4, Dc = 1.399 Mg m−3, l = 0.101 mm−1,
reflections measured 23675, reflections unique 4011 with Rint =
0.0573, T = 120(2) K, final R indices [I > 2 r(I)] R1 = 0.0432,
wR2 = 0.1058 and for all data R1 = 0.0670, wR2 = 0.1167.
CCDC reference number 266538.
(R,pS)-(−)-2,5,8,11,14-Pentaoxa-1(1,6)-[5-(a-methoxyphenylace-
tyl)-5,10-dihydrophenazina]cyclotetradecaphane 31a (91 mg,
0.245 mmol) was refluxed in a mixture of EtOH (5 ml) and
0.1 M hydrochloric acid (10 ml) for 3 d. Water was added and
the solution was extracted twice with dichloromethane. The
organic phase was washed with saturated aqueous NaHCO3
and with brine. Then it was dried (MgSO4) and the solvent was
evaporated at reduced pressure. The crude mixture was purified
by flash chromatography (chloroform) then recrystallisation
from EtOH to yield the title compound (pS)-14 (20 mg, 31%) as
yellow crystals, mp 170–174 ◦C, [a]D28 −325 (c 0.4, CH2Cl2). The
1H NMR spectrum of (pR)-14 was identical to that of rac-14
described above. HPLC tR/min [Chiralpak OT(+), MeOH,
0.1 ml min−1, k 271 nm, 0 ◦C] 63.1.
Acknowledgements
We thank Queen Mary, University of London (studentship for
RH), the EPSRC (AMA project studentship and MS mea-
surements at the National Mass Spectrometry Service Centre,
Swansea), the EPSRC National Crystallography Service for data
collection and the Nuffield Foundation (HG, Undergraduate
Research Bursary) for support.
References
(pR)-(+)-2,5,8,11,14-Pentaoxa-1(1,6)-
(phenazina)cyclotetradecaphane (pR)-14
1 J. H. P. Utley and M. F. Nielsen, in Organic Electrochemistry—
Electrogenerated Bases, ed H. Lund and O. Hammerich, Marcel
Dekker Inc., New York, 2001, ch. 30.
2 A.-P. Bettencourt, A. M. Freitas, M. I. Montenegro, M. F. Nielsen
and J. H. P. Utley, J. Chem. Soc., Perkin Trans. 2, 1998, 515–522.
3 A. Mateo-Alonso, R. Horcajada, H. J. Groombridge, R. Mandalia,
M. Motevalli, J. H. P. Utley and P. B. Wyatt, Chem. Commun., 2004,
412–413.
4 E. Breitmaier and U. Hollstein, J. Org. Chem., 1976, 41, 2104–
2108.
5 M. H. Chang, B. B. Masek and D. A. Dougherty, J. Am. Chem. Soc.,
1985, 107, 1124–1133.
(R,pR)-(+)-2,5,8,11,14-Pentaoxa-1(1,6)-[5-(a-methoxyphenylace-
tyl)-5,10-dihydrophenazina]cyclotetradecaphane 31b (128 mg,
0.345 mmol) was refluxed in a mixture of EtOH (5 ml) and
0.3 M hydrochloric acid (10 ml) for 7 d. Product isolation as
for (pS)-14 above, but with three recrystallisations from ethanol
yielded (pR)-14 (31 mg, 34%) as yellow crystals, mp 170–173 ◦C,
1
[a]2D8 +346 (c 0.4, CH2Cl2). The H NMR spectrum of (pR)-14
(400 MHz, CDCl3) was identical to that of rac-14 described
above; HPLC tR/min [Chiralpak OT(+), MeOH, 0.1 ml min−1,
k 271 nm, 0 ◦C] 66.8.
6 I. J. Pacher and M. C. Kloetzel, J. Am. Chem. Soc., 1951, 73, 4958–
4961.
7 P. Huszthy, E. Samu, B. Vermes, G. Mezey-Vandor, M. No´gra´di, J. S.
Bradshaw and R. M. Izatt, Tetrahedron, 1999, 58, 1491–1504.
8 G. F. Cooper, Synthesis, 1991, 859–860.
9 D. Marquis, J.-P. Desvergne and H. Bouas-Laurent, J. Org. Chem.,
1995, 60, 7984–7996.
10 R. C. Hayward, C. H. Overton and G. H. Whitham, J. Chem. Soc.,
Perkin Trans. 1, 1976, 2413–2415.
11 E. N. Jacobsen, F. Kakiuchi, R. G. Konsler, J. F. Larrow and M.
Tokunaga, Tetrahedron Lett., 1997, 38, 773–776.
12 A. Mateo-Alonso, R. Horcajada, M. Motevalli, J. H. P. Utley and
P. B. Wyatt, Org. Biomol. Chem., 2005, 3, DOI: 10.1039/b506309d.
Crystallography
Crystal data for (−)-(pS)-14, 18a, 18b and 31b were reported in
our preliminary communication.3
Crystal data for rac-12a.‡ C22H26N2O2, M = 350.45, Mono-
˚
clinic, a = 21.854(12), b = 10.992(5), c = 7.770(10) A, a = 90.00,
◦
3
˚
b = 90.01(7), c = 90.00 , V = 1867(3) A , space group P21/a, Z
= 4, Dc = 1.247 Mg m−3, l = 0.080 mm−1, reflections measured
3265, reflections unique 3298 with Rint = 0.0227, T = 160(2) K,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 8 3 2 – 2 8 4 1
2 8 4 1