Synthesis of a chiral bis(bipyridine) ligand of the Chiragen family for the self-assembly of enantiomerically pure helicates

Article abstract of DOI:10.1055/s-1998-2046

The chiral bis(bipyridine) ligand L, belonging to the 'chiragen' family, has been synthesized. The synthetic pathway involves an original preparation of acylnicotinates which is of synthetic value. The synthetic strategy described here may allow the acces

Full text of DOI:10.1055/s-1998-2046

April 1998
SYNTHESIS
431
Synthesis of a Chiral Bis(bipyridine) Ligand of the Chiragen Family for the Self-
Assembly of Enantiomerically Pure Helicates
Paul Baret,* Jacques Einhorn, Gisèle Gellon, Jean-Louis Pierre
Laboratoire de Chimie Biomimétique (LEDSS, UMR CNRS 5616), Université J. Fourier, BP 53, F-38041 Grenoble Cedex 9, France
Fax +33(4)76514836; E-mail: Paul.Baret@ujf-grenoble.fr
Received 22 July 1997; revised 17 October 1997
es by incorporation of a chiral element in the ligand L.7-10
The preparation of enantiopure well-suited ligands is
therefore required. Various strategies have been envis-
aged which introduce the chirality: (i) in the spacer be-
tween the two bidentate units,7, 11 (ii) at the ends of the
ligands.9, 10, 12
Abstract: The chiral bis(bipyridine) ligand L*, belonging to the
“chiragen” family, has been synthesized. The synthetic pathway
involves an original preparation of acylnicotinates which is of
synthetic value. The synthetic strategy described here may allow
the access to various bisbidentate ligands, well-suited to the self-
assembly of enantiomerically pure helicates.
Key words: free radical acylation, acylnicotinates, Kröhnke reac-
tion, chiral bis(bipyridine) ligand
We describe herein a ligand system in which the two iden-
tical bidentate moieties at its ends are chiral. This ligand
L* may be considered as a chiral version of the ligand L
(two bidentate bipyridine moieties linked by a spacer) pre-
viously described by us, which had led to a racemic
Metal-directed self-assembling processes, to give double
or triple helical supramolecular complexes, have attracted
considerable attention over the past ten years.1, 2 Triple-
stranded helicates resulting from the self-assembly in a
[L3M2] manner of ligands L, consisting of two bidentate
moieties linked by a spacer, and octahedral metallic M
ions, are chiral supramolecular assemblies. The triple he-
lical assembling implies homochirality of the two metallic
centers.3 In the unusual and so called achiral “meso heli-
cate” (D–L isomers), the intercrossing of the threads is
not observed.4 The resulting chirality of triple helical
complexes is due both to the D/L chirality of the metal
centers and to the P/M sense of the twisting of the strands
(the latter being induced by the former). Usually, the heli-
cates described in the literature are racemic mixtures.2 A
spontaneous resolution has been observed by Lehn and
L3FeII homochiral triple helical complex.3 The enan-
2
tiopure L* (Scheme) bears two pairs of R stereogenic cen-
ters derived from (–)-myrtenal. L* is highly inspired by
the chiragen ligand family designed and described by von
Zelewsky and co-workers.13–18
The chiral ligand L* is based on two pineno-[4¢,5¢]-fused-
2,2¢-bipyridine-5-carboxamido groups, linked through an
aliphatic C3-chain. The chiral building block comes from
commercial (–)-myrtenal 6 (Scheme). Coupling of the bi-
pyridine carboxylic acid 8 to propane-1,3-diamine was
readily achieved via the corresponding acid chloride 9. The
key intermediate ester 7 was prepared in a simple two-step
co-workers5 and resolution has been achieved by Will- procedure starting with 2-acetyl-5-alkoxycarbonylpyri-
iams and co-workers.6 Nevertheless, the preparation of
dine, by transformation into the pyridinium salt 5 followed
by a Kröhnke-type reaction19, 20, 21 with (–)-myrtenal.
enantiopure triple helicates has been achieved in few cas-
(a) H2SO4 (1 equiv), FeSO4·7 H2O (2.5 equiv), MeCHO, tBuOOH, <15°C. (b) I2 (1 equiv), pyridine, reflux, 0.5 h then r.t. overnight. (c) 6,
NH4OAc (2 equiv), formamide, 75°C, 6 h. (d) 7a, 7b: 1. KOH, EtOH; 2. H3O+; 7c: H2, Pd/C, EtOH. (e) SOCl2. (f) H2N-(CH2)3NH2, Et3N,
CH2Cl2.
Scheme

432
Papers
SYNTHESIS
A multistep preparation of 2-acetyl-5-ethoxycarbonylpy- extension of the “chiragen” family. These ligands may be
ridine (2a), involving as starting material diethyl pyridine- well-suited to the self-assembly of enantiomerically pure
2,5-dicarboxylate, has been described.22–24 We prepared helicates. Investigations on the enantioselectivity of metal
the precursors 2 by a one-step procedure, through free- helicate complexes self-assembly are currently in pro-
radical acylation.25, 26 in acidic conditions of commercial gress.
alkyl nicotinate 1. The acetyl radicals were generated
from acetaldehyde with tert-butyl hydroperoxide and
iron(II) sulfate. This direct acylation of a protonated pyri-
dine ester is, as far as we know, unprecedented and
1H NMR and 13C NMR spectra were recorded on a Bruker AC 200,
WM 250 or Varian U+ 500 NMR spectrometer, using DEPT tech-
niques and QUATD sequence for the assignment of the multiplicity
seemed to us of synthetic interest because of the simplici-
ty of the experimental conditions. The reaction of nucleo-
philic free radicals CH3CO· led to a mixture of 2-acetyl-
(2), 4-acetyl- (3), and 2,4-diacetyl- (4) nicotinates. As pre-
viously observed,25–27 the first acetyl group activates the
pyridine ring towards further acylation, even with low
conversion of the starting material. A brief study was un-
dertaken in order to improve the yield of 2-monoacetylat-
of carbon atoms; unless otherwise stated, the spectra were taken in
CDCl3/TMS.
FT-IR spectra were recorded as films on NaCl plates or as KBr pellets
(1%) on a Nicolet Impact 400 spectrometer. MS [EI (70 eV), or CI
(NH3, iBuH)] were recorded on a Nermag mass spectrometer. Optical
rotations were measured on a Perkin Elmer polarimeter 341.
Reagents were of commercial grade and were not further purified;
(–)-(1R)-myrtenal, [a]D –15 (22°C, neat), was purchased from Ald-
rich. Solvents were purified by standard methods. Mps: Büchi 530
ed derivative. First, the ratio substrate/reagent was varied (uncorrected). Chiral HPLC was performed on a Chiracel OD-H col-
from 1:1 to 1:10 and we observed (1H NMR titration on
umn with a UV-vis spectrometer (254 nm) as detector.
the crude mixture) that the maximum yield of 2 was ob-
2-Acetyl-5-benzyloxycarbonylpyridine (2c); Typical Procedure:
tained for a ratio 1:2.5. It is worthy to note that total con-
To a solution of commercial benzyl nicotinate (1c) (24.86 g, 0.116
mol), H2SO4 (11.43 g, 0.292 mol), and MeCHO (12.76 g, 0.290 mol)
version of substrate 1 is reached for a ratio 1:5; under
these conditions, the diacetyl derivative 4 becomes the
major product of the reaction. Second, the ester group was
varied (a = Et; b = i-Pr; c = Bn): more hindered benzyl es-
ter 2c gave a better yield of 2-acetyl derivative than ethyl
or isopropyl esters 2a and 2b respectively. Moreover, later
cleavage of the benzyl protecting group by hydrogenoly-
sis led to a much more convenient procedure for the isola-
tion of carboxylic acid 8. Interestingly, the separation by
column chromatography is very easy and compound 2 is
eluted first, allowing a very fast procedure. The yields are
satisfactory and the reaction can be performed on rather
large quantities. So, this way of preparation of acylnicoti-
nates seems to us of preparative value in spite of the for-
mation of a mixture.
in degassed water (50 mL), cooled at 5–10°C under argon, were si-
multaneously added dropwise a solution of FeSO4·7H2O (80.6 g,
0.29 mol) in degassed water (200 mL) and 70% t-BuOOH in water
(40 mL). The mixture was stirred for 15 min and then extracted with
CHCl3 (3 ´ 150 mL); the solution was washed with brine (100 mL).
After drying, the solvent was removed under vacuum. The product
distribution (Table 1) was determined by 1H NMR analysis of the
crude mixture. The starting material and the products of the reaction
are well-separated in TLC (silica gel 60 F254, aluminum sheets, hex-
ane/EtOAc 2:1), see Table 1. The mixture was chromatographed on a
silica gel column using 0 to 20% EtOAc/hexane, giving 2c (11.53 g,
39%).
2a (19%); 2b (30%). For spectroscopic data, see Table 2.
1-[2-(5-Benzyloxycarbonyl-2-pyridy1)-2-oxoethyl]pyridinium Io-
dide (5c); Typical Procedure:
To a solution of 2c (6.21 g, 24 mmol) in pyridine (50 mL) was added
iodine (6.22 g, 24 mmol). The mixture was refluxed under argon for
0.5 h and then stirred at r.t. overnight. The solvent was eliminated
(evaporation and azeotrope with toluene) and the black residue was
treated with water. After drying of the solid under vacuum, the prod-
uct was purified by recrystallization (95% EtOH). 5c: 10.95 g (98%).
The same procedure led to 5a (53%) and 5b (87%). For spectroscopic
data, see Table 3.
Table 1. Acetylation of 1a–c
Sub-
strate
(Rf)a
Con-
version
(%)
Product Distribution (%) (Rf)a
Isolated
Yield
2
3
4
(%)b of 2
1a (0.40) 55
1b (0.43) 70
1c (0.50) 70
35 (0.70) 32 (0.22) 33 (0.64)
43 (0.75) 30 (0.25) 27 (0.66)
56 (0.80) 22 (0.27) 22 (0.70)
19c
30d
39d
3-(5-Benzyloxycarbonyl-2-pyridyl)-7,7-dimethyl-5,6,7,8-tetrahy-
dro-6,8-methanoisoquinolines (7c); Typical Procedure:
A solution of iodo derivative 5c (7.27 g, 160 mol), (–)-myrtenal (6)
(2.53 g, 160 mol) and NH4OAc (2.6 g, 330 mol) in formamide (100
mL) was heated at 75 °C for 6 h. The resulting black mixture was con-
centrated and treated with water. The product was extracted with hex-
ane/Et2O (6 ´ 100 mL) and the organic phase washed with brine
(200 mL). After drying, the solvents were evaporated. The resulting
oil was purified by column chromatography (silica gel, 0 to 10%
EtOAc/hexane). 7c: 4.3 g (70%).
a TLC (silica gel, hexane/EtOAc 2:1):
b Column (Si 60 Geduran Merck, 0.040-0.063 mm, hexane/EtOAc 0
to 20%).
c Oil.
d Colorless solid, mp < 50°C.
Preliminary complexation studies evidenced the forma-
tion of enantiopure triple helicate complexes with iron(II)
salts. The structural and chiroptical properties of these
complexes will be described in a separate paper.28
7a (38%); 7b (43%). For spectroscopic data, see Table 4.
Enantiomeric purity of ester 7c was determined by chiral HPLC (elu-
tion: iPrOH/hexane, 15:85, 0.5 mL· min–1). The observed value of 98%
reflects the enantiomeric purity of commercial (–)-(1R)-myrtenal.
The synthetic strategy used here may be generalized,
allowing the preparation of unknown diversely 5¢-sub-
stituted “pineno”-[4,5]-fused 2,2¢-bipyridine derivatives.
These derivatives are precursors for various bis-bidentate
ligands (different spacers can be used) which constitute an
3-(5-Carboxy-2-pyridyl)-7,7-dimethyl-5,6,7,8-tetrahydro-6,8-
methanoisoquinoline (8):
From 7a or 7b:
A mixture of ester 7 (4 mmol : a = 1.29 g; b = 1.34 g), KOH (500 mg)
in EtOH (30 mL) was refluxed for 12 h. The solvent was evaporated

April 1998
SYNTHESIS
433
Table 2. Spectroscopic data for Compounds 2a–c, 3c, 4c
Producta
R
1H NMR (CDCl3/TMS)
d, J (Hz)
13C NMR (CDCl3/TMS)
d
MS (m/z)
IR n (cm–1)
2a
Et 1.44 (t, 3H, J = 7.1), 2.76 (s, 3H), 4.45 (q,
2H, J = 7.1), 8.10 (d, 1H, J = 8.1), 8.42
(dd, 1H, J = 1.7/8.1), 9.26 (d, 1H, J =
1.7)
14.2 (CH3), 25.9 (CH3), 61.8 (CH2), 120.9
(CH), 128.7 (Cq), 137.8 (CH), 150.1 (CH),
155.7 (Cq), 164.5 (Cq), 199.3 (Cq)
(EI):
194 (M+H),
165 (MH-Et),
151 (MH-Ac)
1731.0,
1702.2
2b
2c
iPr 1.41 (d, 6H, J = 6.2), 2.76 (s, 3H), 5.29 (m,
1H, J = 6.2), 8.09 (dd, 1H, J = 8. l/0.5),
8.40 (dd, 1H, J = 2.0/8.1), 9.26 (dd, 1H, J =
1.7/0.5)
21.8 (CH3), 26.0 (CH3), 69.6 (CH), 121.0
(CH), 129.1 (Cq), 137.9 (CH), 150.2 (CH),
155.7 (Cq), 164.0 (Cq), 199.4 (Cq)
(CI):
208 (M+H)
1731.4,
1708.1
Bn 2.74 (s, 3H), 5.42 (s, 2H), 7.27-7.49 (m, 5H), 25.9 (CH3), 67.4 (CH2), 121.0 (CH), 128.3
(EI):
8.08 (d, 1H, J = 7.9), 8.42 (dd, 1H, J =
2.4/7.9), 9.30 (d, 1H, J = 2.1)
(CH), 128.5 (CH), 128.55 (Cq), 128.6 (CH), 255 (M),
1728.6,
1701.5
128.7 (CH), 135.1 (Cq), 138.0 (CH), 150.3
(CH), 155.8 (Cq), 164.3 (Cq), 199.3 (Cq)
227 (M-EtH),
213 (MH-Ac),
148 (M-OBn)
3c
Bn 2.47 (s, 3H), 5.36 (s, 2H), 7.23 (dd, 1H, J =
5.0/0.5), 7.35-7.42 (m, 5H), 8.81 (d, 1H, J =
5.0), 9.18 (d, 1H, J = 0.5)
30.1 (CH3), 67.6 (CH2), 119.4 (CH), 122.1
(Cq), 128.4 (CH), 128.5 (CH), 128.7 (CH),
134.5 (Cq), 150.5 (Cq), 150.9 (CH), 153.3
(CH), 164.4 (Cq), 201.5 (Cq)
4c
Bn 2.49 (s, 3H), 2.73 (s, 3H), 5.37 (s, 2H), 7.34– 25.7 (CH3), 29.7 (CH3), 68.0 (CH2), 117.5
7.43 (m, 5H), 7.95 (s, 1H), 9.18 (s, 1H)
(CH), 128,4 (CH), 128.5 (CH), 128.6 (CH),
134.4 (Cq), 150.5 (CH), 150.9 (Cq), 155.7
(Cq), 164.1 (Cq), 198.4 (Cq), 201.5 (Cq)
a Elemental analysis of 2a–c: C ± 0.20; H ± 0.27; N + 0.42.
Table 3. Spectroscopic data for Compounds 5a–c
Product
R
1H NMR d, J (Hz)
13C NMR d, J (Hz)
(C6D6 + DMSO-d6):
5a
Et
(C6D6 + DMSO-d6):
1.10 (t, 3H, J = 7.2), 4.15 (q, 2H, J = 7.2), 6.81
(s, 2H), 7.81 (m, 2H), 8.03 (d, 1H, J = 8.2), 8.1
(m, 1H), 8.28 (dd, 1H, J = 1.7/8.2). 9.22 (m, 2H),
9.27 (d, 1H, J = 1.7)
14.2 (CH3), 61.9 (CH2), 67.4 (CH2), 122.4 (CH),
129.9 (CH), 138.7 (CH), 146,1 (CH), 146.7 (Cq), 146.8
(CH), 150.3 (CH), 153.7 (Cq), 164.2 (Cq), 191.2 (Cq)
5b
5c
iPr
Bn
(CDCl3 + DMSO-d6):
(CDCl3 + DMSO-d6):
1.43 (d, 6H, J = 6.8), 5.31 (m, 1H), 6.82 (s, 2H),
8.14–8.25 (m, 3H), 8.52 (dd, 1H, J = 1.7/7.8), 8.71
(m, 1H), 9.27–9.30 (m, 3H)
21.1 (CH3), 66.3 (CH2), 69.3 (CH), 121.3 (CH), 127.2
(CH), 129.7 (Cq), 137.7 (CH), 145.5 (CH), 145.8
(CH), 149.6 (CH), 151.9 (Cq), 162.7 (Cq), 189.4 (Cq)
(CDCl3):
(CDCl3):
5.44 (s, 2H), 6.8 (s, 2H), 7.37–7.50 (m, 5H), 8.14–8.22
(m, 3H), 8.53 (dd, 1H, J = 1.7, 7.6), 8.68 (m, 1H),
9.23 (m, 2H), 9.43 (d, 1H, J = 1.7)
66.5 (CH2), 67.0 (CH2), 121.6 (CH), 127.4 (CH),
127.8 (2 CH), 128.1 (CH), 129.3 (Cq), 134.3 (Cq),
138.1 (CH), 145.7 (CH), 147.9 (CH), 149.9 (CH),
152.2 (Cq), 163.2 (Cq), 189.4 (Cq)
under vacuum and the residue was treated with water and acidified to 1.25 g, quant.) was pure enough for the following reaction. For spec-
pH 1–2 with aq HCl. The solution was extracted with CHCl3. Drying troscopic data, see Table 5.
and elimination of the solvent gave pure acid.
7a as starting material gave 8 (0.69 g; 59%); 7b gave 8 (1.01 g;
86%).
Coupling with Propane-1,3-diamine:
To a suspension of acid chloride 9 (dihydrochloride, 1.25 g,
3.25 mmol) in CH2Cl2 (40 mL) was added dropwise, at r.t., a solution
From 7c:
of propane-1,3-diamine (118 mg, 1.6 mmol), Et3N (969 mg, 9.6
A mixture of benzyl ester 7c (1.6g, 4.1 mmol), 10% Pd/C (0.4 g) in mmol) in CH2Cl2 (20 mL). The mixture was stirred for 12 h under ar-
EtOH (100 mL) and CH2Cl2 (30 mL) was treated with H2 at r.t. The gon, then treated with aq KOH. Extraction with CHCl3, drying and
reaction was monitored by TLC (silica gel, hexane/EtOAc 3:1). The evaporation of the solvent gave the crude product as a beige powder.
solvent was evaporated and the residue was treated with Et2O giving The diamide L* was purified by column chromatography (alumina,
pure 8 as a beige powder: 1.08 g (88%).
1–2% MeOH/CH2Cl2) giving a colorless powder (858 mg, 85%); mp
For spectroscopic data, see Table 5.
152°C.
1H NMR (500 MHz, CD3CN): d = 0.63 (s, 6H), 1.19 (d, 2H, J = 9.6
Hz), 1.41 (s, 6H), 1.87 (5t, 2H, J = 6.3 Hz), 2.33–2.30 (m, 2H), 2.72
(dt, 2H, J = 9.6/5.6 Hz), 2.88 (t, 2H, J = 5.6 Hz), 3.08 (d, 4H, J = 2.6
Preparation of Ligand L*:
Acid Chloride 9:
Acid 8 (955 mg, 3.25 mmol) in SOCl2 (20 mL) was stirred under ar- Hz), 3.52 (4t, 4H, J = 6.3/6.3 Hz), 7.58 (t, 2H, J = 6.3 Hz, NH), 8.19
gon at r.t. for 1 h. SOCl2 was removed under vacuum and the residue (s, 2H), 8.22 (dd, 2H, J = 2.3/8.3 Hz), 8.24 (s, 2H), 8.42 (dd, 2H, J =
was treated with pentane. The crude product (as dihydrochloride, 8.3/0.6 Hz), 9.03 (dd, 2H, J = 0.6/2.3 Hz).

434
Papers
SYNTHESIS
Table 4. Spectroscopic and Physical Data for Compounds 7a–c
Prod- R
ucta
Yield (%) 1H NMR (CDCl3/TMS)
13C NMR (CDCl3/TMS)
d
MS (m/z)
IR n (cm–1) Physical
d, J (Hz)
Data
7a
Et
38
0.66 (s, 3H), 1.25 (d, 1H, J = 9.5),
14.28 (CH3), 21.32 (CH3), 25.93
(CH3), 31.69 (CH2), 32.86 (CH2),
39.18 (Cq), 39.96 (CH), 44.50 (CH), 293 (M-Et),
61.28 (CH2), 120.13 (CH), 121.18 279,
(CH), 125.39 (Cq), 137.77 (CH),
143.88 (Cq), 145.54 (Cq), 145.70
CH), 150.3 (CH), 153.30 (Cq),
159.87 (Cq), 165.34 (Cq)
EI:
322 (M),
1718.8
mp 96 °C
1.43 (m, 6H), 2.31–2.37 (m, 1H),
2.70 (dt, 1H, J = 9.5/5.8), 2.89 (t,
1H, J = 5.5), 3.07 (d, 2H, J = 2.6),
4.44 (q, 2H, J = 7.2), 8.24 (s,
1H), 8.27 (s, 1H), 8.38 (dd, 1H,
J = 2.0/8.2), 8.45 (d, 1H, J = 8.2),
9.25 (dd, 1H, J = 0.7/2.0)
251
7b
i-Pr 43
0.67 (s, 3H), 1.25 (d, 1H, J = 9.5),
1.41 (d, 6H, J = 6.2), 1.44 (s, 3H),
2.30–2.38 (m, 1H), 2.73 (dt, 1H,
J = 9.5/5.8), 2.89 (t, 1H, J = 5.5),
3.07 (d, 2H, J = 2.6), 5.30
21.32 (CH3), 21.88 (CH3), 25.93
(CH3), 31.69 (CH2), 32.86 (CH2),
39.18 (Cq), 39.95 (CH), 44.45 (CH), 293 (M-iPr),
68.85 (CH), 120.03 (CH), 121.14
(CH), 125.74 (Cq), 137.72 (CH),
143.82 (Cq), 145.53 (Cq), 145.70
EI:
336 (M),
1719.7
mp 115 °C
[a]D20 –73.0
(c = 2.09,
CH2Cl2)
279,
25l
(m, 1H, J = 6.2), 8.24 (s, 1H),
8.27 (s, 1H), 8.37 (dd, 1H, J = 2.0/8.7), (CH), 150.30 (CH), 153.30 (Cq),
8.47 (dd, 1H, J = 8.7/0.8),
9.24 (dd, 1H, J = 0.8/2.0)
159,73 (Cq), 164.83 (Cq)
7c
Bn
70
0.66 (s, 3H), 1.24 (d, 1H, J = 9.6),
1.43 (s, 3H), 2.30–2.37 (m, 1H), 2.72 (CH2), 32.87 (CH2), 39.18 (Cq),
(dt, 1H, J = 9.6/5.8), 2.89 (t, 1H, J
= 5.5), 3.08 (d, 2H, J = 2.7),
21.33 (CH3), 25.93 (CH3), 31.69
(CI):
385 (M+H)
341
1725.6
mp 97 °C
[a]D20 –64.4
(c = 2.04,
CH2Cl2)
39.95 (CH), 44.50 (CH), 66.95
(CH2), 120.14 (CH), 121.21 (CH),
5.42 (s, 2H), 7.35–7.50 (m, 5H), 8.23 125.07 (Cq), 128.24 (CH), 128.34
(s, 1H), 8.26 (s, 1H), 8.39 (dd, 1H,
J = 2.0/8.3), 8.46 (dd, 1H,
J = 8.3/1.0), 9.29 (dd, 1H,
J = 1.0/2.0)
(CH), 128.60 (CH), 135.55 (Cq),
137.91 (CH), 143.98 (Cq), 145.54
(Cq), 145.73 (CH), 150.45 (CH),
153.23 (Cq), 160.07 (Cq), 165.18 (Cq)
a Element Analysis of 7b and 7c · 0.25 H2O; C ± 0.25; H ± 0.07; N ± 0.15.
Table 5. Spectroscopic and Physical Data for Compounds 8 and 9
Product 1H NMR (CDCl3/TMS) d, J (H2)
13C NMR (CDCl3/TMS) d
Data
8a
0.68 (s, 3H), 1.27 (d, 1H, J = 9.6), 1.44 (s, 3H),
2.32-2.38 (m, 1H), 2.75 (dt, 1H, J = 9.6/5.5), 2.94
(t, 1 H, J = 5.5), 3.10 (d, 2 H, J = 2.6), 8.28 (s,
1H), 8.36 (s, 1H), 8.44–8.54 (m, 2H), 8.69 (brd s, 1H,
OH), 9.38 (brd s, 1H)
21.33 (CH3), 25.79 (CH3), 31.50 (CH2), 33.02 mp 226°C
(CH2), 39.12 (Cq), 39.79 (CH), 44.46 (CH),
121.02 (CH), 122.20 (CH), 126.30 (Cq),
138.72 (CH), 144.48 (CH), 144.49 (Cq),
[a]D20 –76.1
(c = 0.44, CH2Cl2)
MS (EI): m/z = 294 (M)
147.43 (Cq), 150.82 (CH), 152.52 (Cq), 158.46 279 (M-CH3), 265, 251
(Cq), 168.16 (Cq)
IR: n (cm 1) = 1710
9
0.71 (s, 3H), 1.31 (d, 1H, J = 10.2), 1.51 (s, 3H),
2.49 (brd s, 1 H), 2.85–2.96 (m, 1H), 3.16 (m, 1H),
3.34 (d, 2H, J = 2.6), 8.58 (s, 1H), 8.67 (s, 1H),
8.68–8.73 (m, 1H), 9.33 (brd d, 1H), 9.39 (d, 1H,
J = 1.7)
21.27 (CH3), 25.11 (CH3), 30.64 (CH2), 34.16
(CH2), 38.69 (Cq), 38.78 (CH), 44.38 (CH),
123.14 (CH), 125.08 (CH), 130.28 (Cq),
136.97 (CH), 140.77 (CH), 144.81 (Cq),
148.25 (Cq), 151.28 (CH), 151.36 (Cq), 158.40
(Cq), 165.89 (Cq)
a Elemental Analysis 8: calcd. for C18H18N2O2 (Found): C 73.45 (73.22), H 6.16 (6.33), N 9.52 (9.41).
13C NMR (50 MHz, CDCl3): d = 21.32 (CH3), 25.87 (CH3), 29.53
(4) Albrecht, M.; Riether, C. Chem. Ber. 1996, 129, 829.
(5) Krämer, R.; Lehn, J.-M.; De Cian, A.; Fischer, J. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 703.
(6) Charbonnière, L. J.; Bernardinelli, G.; Piguet, C.; Sargeson, A.
M.; Williams, A. F. J. Chem. Soc., Chem. Commun. 1994, 1419.
(7) Enemark, E. J.; Stack, T. D. P. Angew. Chem., Int. Ed. Engl.
1995, 34, 996.
(8) Libman, J.;Tor,Y.; Shanzer,A. J.Am. Chem. Soc. 1987, 109, 5880.
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Chem. Soc. 1996, 118, 7221.
(CH2), 31.64 (CH2), 32.86 (CH2), 36.35 (CH2), 39.12 (Cq), 39.90
(CH), 44.39 (CH), 120.30 (CH), 121.02 (CH), 128.90 (Cq), 135.66
(CH), 143.70 (Cq), 145.53 (CH), 145.54 (Cq), 147.92 (CH), 153.35
(Cq), 158.84 (Cq), 166.27 (Cq).
MS (CI, NH3, isobutane): m/z = 627 (M), 377 (MH-C17H17N2).
IR (KBr): n = 3451, 3318, 3078, 1649, 1603, 1545 cm–1.
[a]D21.5–77.4 (c = 2.0, CH2Cl2).
Anal. Calcd for C39H42N6O2·0.75 H2O (Found): C 73.16 (73.19), H
6.85 (6.88), N 13.12 (13.24).
(10) Provent, C.; Hewage, S.; Brand, G.; Bernardinelli, G.; Char-
bonnière, L. J.; Williams, A. F. Angew. Chem., Int. Ed. Engl.
1997, 36, 1287.
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1991, 74, 1843.
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1995.
(2) Williams, A. F. Chem. Eur. J. 1997, 3, 15.
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April 1998
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