Asymmetric activation of the tropos biphenyldiamidophosphite moiety: Synthesis and complexation to rhodium of a deoxycholic acid derived diamidophosphite

Article abstract of DOI:10.1016/j.jorganchem.2016.01.031

A tropos deoxcholic acid derived diamidophosphite was synthesised starting from deoxycholic acid and N,N′-dimethyl-2,2′-diamino-1,1′biphenyl and its stereodinamic characteristics were assessed by VT-NMR spectroscopy. The capability of the diamidophosphite

Full text of DOI:10.1016/j.jorganchem.2016.01.031

Journal of Organometallic Chemistry 806 (2016) 88e94
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Asymmetric activation of the tropos biphenyldiamidophosphite
moiety: Synthesis and complexation to rhodium of a deoxycholic acid
derived diamidophosphite
*
Grazia Iannucci, Anna Iuliano
Dipartimento di Chimica e Chimica Industriale, Universit aꢀ di Pisa, Via Moruzzi 13, 56124 Pisa, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 November 2015
Received in revised form
A tropos deoxcholic acid derived diamidophosphite was synthesised starting from deoxycholic acid and
0
0
0
N,N -dimethyl-2,2 -diamino-1,1 biphenyl and its stereodinamic characteristics were assessed by VT-NMR
spectroscopy. The capability of the diamidophosphite to act as Rh-ligand was investigated in the for-
mation of ionic as well as covalent Rh-complexes. The stereodinamic properties of these complexes were
studied by VT-NMR spectroscopy.
21 January 2016
Accepted 25 January 2016
Available online 28 January 2016
©
2016 Elsevier B.V. All rights reserved.
Keywords:
Tropos ligands
Monophosphorus ligands
Rh-complexes
Chiral ligands
Diamidophosphites
1
. Introduction
and can increase further after metal complexation [3]. By using a
natural compound as configurationally stable subunit for the
asymmetric activation of a biphenyl moiety, a chiral auxiliary
possessing independent stereogenic elements can be obtained,
without any step of enantiomeric resolution [4].
We have used this approach in the synthesis of bile acid derived
tropos biphenylphosphites which have been successfully used as
chiral ligands in different Rh-catalyzed asymmetric reactions [5].
Encouraged by these results, we decided to approach in the same
way the achievement of monophosphorus ligands, possessing
different electronic and steric features.
Rh complexes of optically active monophosphorus ligands have
received a great deal of attention as catalytic precursors in enan-
tioselective hydrogenations [1] as well as in asymmetric CeC bond
forming reactions [2]. The success of this approach lies in the easy
achievement of the monodentate ligands with respect the biden-
tate ones, together with the good capability of asymmetric induc-
tion of their Rh-complexes. The easy preparation of
enantiomerically pure monophosphorus ligands makes possible to
check new and different structures aimed at reaching better results
in asymmetric catalysis. Among the features making appealing a
monophosphorus ligand, the presence of a chiral flexible moiety
represents an interesting structural motif, which, by means of
asymmetric activation, permits to obtain chiral tropos ligands [3].
The asymmetric activation is realized by covalently linking the
flexible moiety to a chiral framework possessing fixed stereogenic
elements: in this way a new chiral compound that adopt a prefer-
ential diastereomeric conformation is obtained. The conforma-
tional preference will depend on the capability of the
configurationally stable moiety to transfer the chiral information
To this aim we turned our attention toward the synthesis of bile
acid derived biphenyldiamidophosphites, where the phosphorus is
linked to one oxygen and two nitrogen atoms, which can be ob-
0
tained starting from N,N -dimethylbiphenyl diamine and a bile acid
derivative possessing only one reactive hydroxyl group. Here we
present the synthesis of the biphenyldiamidophosphite 1 (Fig.1)
derived from deoxycholic acid and its stereochemical character-
ization by variable temperature NMR spectroscopy. The results
concerning the formation of some Rh-complexes of 1 are also
presented, together with their dynamic stereochemical
characterization.
*
Corresponding author.
E-mail address: anna.iuliano@unipi.it (A. Iuliano).
http://dx.doi.org/10.1016/j.jorganchem.2016.01.031
022-328X/© 2016 Elsevier B.V. All rights reserved.
0

G. Iannucci, A. Iuliano / Journal of Organometallic Chemistry 806 (2016) 88e94
89
spectroscopy measurements were used. The 31P NMR spectrum
recorded at 298 K in toluene-d as a solvent shows a sharp signal at
68.2 ppm that, on lowering the temperature, undergoes a pro-
8
1
gressive broadening and splits in two broad signals at 233 K (Fig. 3).
The splitting is maximum at 223 K where two sharp and very
well distinguishable signals are found at 164.6 and 169.0 ppm. This
behaviour suggests that 1 exists as a mixture of diastereoisomers
fast interconverting at 298 K; the equilibrium between the two
diastereomeric species slows down at lower temperatures and the
signals of the M and P forms are well separated at 223 K. The value
of the integrated areas of the signals at this temperature gives a
diasteromeric ratio of 53:47. These results point out the tropos
nature of the diamidophosphite 1, which exists in solution as a
mixture of fast interconverting M-P diastereoisomers, whose the
activation energy for the interconversion process has been evalu-
ated, on the basis of the variable temperature NMR parameters [8],
as 10.3 kcal/mol.
Fig. 1. Structure of the biphenyldiamidophosphite 1.
2
. Results and discussion
2.1. Synthesis and characterisation of diamidophosphite 1
2
.2. Characterisation of the Rh-complexes of 1
0
0
0
The N,N -dimethyl-2,2 -diamino-1,1 -biphenyl 5 was prepared
0
0
starting from the commercial 2,2 -dinitro-1,1 -biphenyl 2 according
to Scheme 1. The catalytic hydrogenation [6] of 2 gave the diamine
in 70% yield, which was reacted with ethyl chloroformate [7]
leading to the dicarbamoyl derivative 4 in 75% yield after recrys-
tallization of the crude. Reduction of 4 by LiAlH
diamine 5 as chemically pure product in 75% yield.
To check the capability of diamidophosphite 1 to act as ligand,
its cationic and neutral Rh-complexes, which can be used as cata-
lytic precursors in different asymmetric reactions [1,2], were
analyzed by P NMR spectroscopy.
3
31
4
[7] afforded
The cationic Rh-complex was prepared by stirring a solution of 1
and Rh(cod) BF , at P:Rh ¼ 2 M ratio, in deuterated dichloro-
2
4
31
The synthesis of diamidophosphite 1 was approached at first
with the same procedure used for the synthesis of the analogous
biphenylphosphite [5a], by preparing the chlorodiamidophosphite
of 5, then by reacting it with the appropriate deoxycholic acid de-
rivative. Unfortunately in this way low conversion of the substrate
was observed and a product in low yield and low chemical purity
was isolated. Therefore we changed strategy and the synthesis was
performed as summarised in Scheme 2.
The deoxycholic acid derivative 6, prepared as previously
described [5a], was reacted with an excess of phosphorus tri-
chloride until complete conversion of the substrate was detected by
TLC. The resulting chlorophosphite 7 was not isolated but directly
used for the next step, by reacting it with diamine 5 in the presence
of triethylamine at the reflux of toluene, until complete conversion
of the diamine was detected by TLC. The pure product was obtained
in 50% yield after filtration on a pad of neutral alumina under ni-
trogen atmosphere. The chemical identity of diamidophosphite 1
was assessed by NMR spectroscopy ( H, C, P) and NMR-COSY
see supplementary data) and its dynamic stereochemical proper-
ties by variable temperature P NMR spectroscopy.
In fact the presence of the flexible chiral biphenyl moiety can
give rise to the formation of two diastereoisomers of 1, which will
be in slow or fast equilibrium between themselves, depending on
the activation energy to the interconversion of the M and P forms
methane as a solvent for 30 min. The P NMR spectrum (Fig. 4)
recorded at 298 K on the solution, shows the presence of a doublet
signal at 135.9 ppm (J ¼ 211 Hz) and, very close to this, at lower
chemical shifts, a broad low signal, whereas the signal allied to the
free ligand at 168.3 ppm is absent.
The lack of the signal of the free ligand and the presence of a
doublet signal with a typical PeRh coupling constant suggests the
complete coordination of 1 to Rh, which gives rise to the formation
of a disubstituted complex. Given the tropos nature of the ligand,
this complex can be constituted, in principle, by three species
(Scheme 3), which can be in equilibrium among themselves: 8M
and 8P will give rise in the spectrum to a couple of doublets,
distinguishable at room temperature if the equilibrium is slow, or at
lower temperature if the equilibrium is fast; whereas 8MP, where
the two P atoms are unequivalents, will produce two double dou-
blets at room temperature or at lower temperatures, depending on
the kinetic of the equilibrium.
1
13
31
The nature of the complex and its composition in terms of
31
(
diastereomeric species can be analyzed by VT P NMR spectros-
copy. Lowering of the temperature until 223 K (decoalescence
temperature for the signals of the free ligand) guarantees that also
the decoalescence point of the signals of the complexes has been
reached: in fact, it is known that the activation energy to the M-P
interconversion rises after coordination to a metallic centre [3a].
The variable temperature P NMR profile (Fig. 5) shows no
significant changes as far as the doublet signal is concerned, which
does not undergo broadening, splitting or even shift in the range
31
31
(
Fig. 2).
To check the dynamic stereochemical nature (labile or stable) of
and to assess its diastereomeric composition, VT P NMR
31
1
O
Cl OEt
)
Pyridine, 0°C
COOEt
1
1
) LiAlH , 0°C
H2
4
NO2
NO2
NH2
NH2
NH
NH
NH
Pd / C
NH
2) THF reflux, 4h
2) toluene, 2h, rt
COOEt
2
3
4
5
0
0
0
Scheme 1. Synthesis of N,N -dimethyl-2,2 -diamino-1,1 -biphenyl diamine (5).

90
G. Iannucci, A. Iuliano / Journal of Organometallic Chemistry 806 (2016) 88e94
Scheme 2. Synthesis of diammidophosphite 1 starting from deoxycholic acid derivative 6.
N
N
N
P
O
O
N
P
O
O
OCH3
OCH3
O
O
H C
3
O
H C
3
O
Fig. 2. Interconversion between the diastereomeric M and P forms of diammidophosphite 1.
2
98e223 K. By contrast, the less intense broad signal gives several
a solution of 1 and [Rh(C
2
H
4
)
2
acac] in toluene-d
8
at P:Rh ¼ 2 M
31
small signals, already resolved at 253 K and partially superimposed
to the more intense doublet.
ratio for 30 min. The P NMR spectrum, recorded on the solution at
298 K (Fig. 6), shows the presence of two doublet signals, at
151.4 ppm (J ¼ 260 Hz) and at 149.9 ppm (J ¼ 256 Hz), together with
the signal at 168.3 due to the resonance of the free ligand.
The observed trend suggests that the doublet signal is attrib-
utable to one of the diastereomeric forms 8M or 8P, in which the P
atoms are magnetically equivalent, taking into consideration that it
does not undergo changes with the temperature. In addition, since
only one doublet is visible, there is likely a very large prevalence of
one diastereoisomer, the other one being under the detection limit
of the NMR technique. This was confirmed by Circular Dichroism
31
The P NMR spectrum, recorded after 24 h, showed the same
signals at the same frequencies, suggesting that the ligand does not
coordinate totally to the metallic centre, even prolonging the re-
action time.
Taking into account the complexation behaviour of the parent
phosphite [4c], we hypothesized that the lack of complete coordi-
nation of 1 could be attributable to the bulkiness of the ligand,
which prevents the formation of a disubstituted complex. To
(
CD) measurements: as a matter of fact the CD spectrum of the
complex (see supplementary data) is much more intense with
respect to the CD spectrum of the free ligand (see supplementary
data), suggesting a very high prevalence of one the two diaste-
reomeric forms in the complex [5b]. The less intense broad signal,
which undergoes resolution on lowering the temperature, can be
attributable to the presence of a small percentage of a complex,
originated from a different coordination mode of the ligand (may
be involving also the nitrogen atom). This complex must be flexible
and the diastereomeric species are in fast equilibrium at room
temperature and are distinguishable only at lower temperatures:
however, the structure of this minor species cannot be inferred on
the basis of these data.
confirm this hypothesis a solution of 1 and [Rh(C
2 4 2
H ) acac] in
toluene at P:Rh ¼ 1 M ratio was stirred for 30 min and analyzed by
31
31
P NMR. Much to our delight, the P NMR spectrum (Fig. 6)
showed the same two doublets, at 151.4 ppm (J ¼ 260 Hz) and at
149.9 ppm (J ¼ 256 Hz), but no signal of the free ligand was
detectable.
On the basis of these results we can reasonably assume the
formation of a monosubstituted complex in both cases, the bulki-
ness of 1 preventing the coordination of two ligands to the Rh
centre also at P:Rh ¼ 2 M ratio. The presence of a couple of doublets
suggests that two diastereoisomers of the complex are formed, due
The mononuclear covalent Rh-complex was prepared by stirring

G. Iannucci, A. Iuliano / Journal of Organometallic Chemistry 806 (2016) 88e94
91
Fig. 5. 31P NMR spectra (80 MHz, CD
2
Cl
98 K, (b) 273 K, (c) 253 K, (d) 233 K, (e) 223 K.
:1 ¼ 1:2 at: (a)
2
2 2 4
) of the mixture Rh(cod) BF
Fig. 3. 31P NMR spectra (80 MHz, toluene-d
43 K, (e) 233 K, (f) 223 K.
) of 1 at: (a) 298 K, (b) 273 K, (c) 253 K, (d)
8
2
Fig. 6. 31P NMR spectra (80 MHz, toluene-d
Rh(C acac]: 1 ¼ 1:2.
acac]: 1 ¼ 1:1; (b) [Rh(C
8
) at 298 K of the mixture: (a)
[
2 4
H )
2
2 4 2
H )
both samples confirm this hypothesis. In fact, on lowering the
temperature until 233 K the signals remain unchanged (Fig. 7),
whereas on rising the temperature, the two doublets coalesce at
Fig. 4. 31P NMR spectrum (80 MHz, CD
Rh(cod) BF
:1 ¼ 1:2.
at 298
K
of the mixture
2
Cl
2
)
2
4
BF4
Rh
+
L
(
2 eq)
(1 eq)
8
+
+
LM
BF
4
LP
LP
BF4
LP
BF4
Rh
Rh
Rh
LM
LM
8M
8P
8MP
Scheme 3. Equilibrium among the three species 8M, 8P and 8MP.
to the different M or P screw sense assumed by the biphenyl moiety
of the coordinated diamidophosphite. The VT P NMR analysis on
313 K, and at 343 K a well defined doublet appears at 150.1 ppm
(J ¼ 258.4 Hz).
31

92
G. Iannucci, A. Iuliano / Journal of Organometallic Chemistry 806 (2016) 88e94
cases all the ligand is coordinated to the metallic centre.
A doublet signal at 144.2 (J ¼ 178.0 Hz) is present in both
spectra; in addition, the spectrum of the sample at P:Rh ¼ 1 M ratio
shows also a less intense doublet signal at 142.5 ppm (J ¼ 259 Hz). A
31
different situation is found in the P NMR spectrum of the sample
at P:Rh ¼ 1 M ratio recorded after 16 h (Fig. 8c), where the doublet
at 144.2 is absent and only the doublet at 142.5 is clearly visible.
31
Since in the P NMR spectrum of the sample at P:Rh ¼ 2 M ratio the
signal of the free ligand is absent it is conceivable to deduce that a
disubstituted complex is formed. The same complex is also present
in the sample at P:Rh ¼ 1 M ratio, considering that there is the same
signal in the spectrum recorded after 30 min. The less intense
signal, which become the only one present in the spectrum recor-
ded after 16 h, can be attributed to a monosubstituted complex,
already present in small amount in the just prepared sample, which
is the only species after 16 h. This trend reflects the behaviour
observed for the complexation of the parent phosphite [4c]: the
formation of a disubstituted complex is preferred for kinetic rea-
sons, but a monosubstituted complex is thermodynamically
favourite because of the bulkiness of the ligand. Therefore on the
basis of the P:Rh molar ratio and the reaction time it is possible to
obtain dinuclear Rh-complexes having different composition.
Both mono and disubstituted complexes can be present as dia-
stereomeric mixtures, due to the M-P interconversion and, since at
room temperature for both species only one signal is visible, these
can be detectable only at lower temperatures. In particular the
disubstituted complex can exist as mixtures of three diastereomeric
species: two in which the biphenyl groups of the two ligands co-
ordinated at the same metallic centre assume the same screw sense
(MM and PP) and the other one where the two ligands have
Fig. 7. 31P NMR spectra (80 MHz, toluene-d
¼ 1:1 at: (a) 343 K, (b) 313 K, (c) 298 K, (d) 273 K, (e) 233 K.
8
2 4 2
) of the mixture [Rh(C H ) acac]:
1
31
biphenyl groups with opposite screw sense (MP). The VT P NMR
profile of the disubstituted complex (see supplementary data)
shows no changes until 223 K: the doublet signal neither splits nor
shifts, suggesting that only one diasereoisomeric complex in which
the biphenyl groups of all the ligands assume the same screw sense
is formed after coordination.
2 4 2
Therefore, the coordination of 1 to [Rh(C H ) acac] gives two
diastereomeric complexes in slow equilibrium at room tempera-
ture and fast interconverting at 343 K, where the two species give
only one doublet signal. The integrated areas of the two signals at
33 K gives a diastereomeric ratio of 60:40.
A covalent dinuclear Rh-complex of 1 can be obtained by
The same trend is observed in the case of the monosubstituted
2
31
complex: no changes are observed in the P NMR spectra recorded
at lower temperatures (see supplementary data), suggesting that
also in this case a highly prevalent diastereoisomer is formed.
reacting the ligand with [Rh(C
formation of both mono and disubstituted complexes is possible in
principle, [Rh(C Cl] was reacted with different amounts of 1 in
toluene-d and the resulting solutions were analyzed by P NMR
2 4 2 2
H ) Cl] . Since, also in this case the
2
4
H )
2
2
31
3. Conclusions
8
31
spectroscopy. The P NMR spectra of both samples at P:Rh ¼ 1 and
at P:Rh ¼ 2 M ratio recorded at 298 K after 30 min (Fig. 8) show no
presence of the signal of the free ligand, suggesting that in both
The diamidophosphite 1 is able to work as Rh-ligand both for
the preparation of ionic and covalent complexes. The reaction with
Rh(cod)
eoselectivity, whereas the reaction with [Rh(C
monosubstituted complex constituted by
2
BF
4
afforded a ionic complex with very high diaster-
acac] gave a
mixture of di-
2 4 2
H )
a
astereoisomers in slow equilibrium at room temperature and fast
interconverting at 343 K. The reaction with the dinuclear covalent
complex [Rh(C H ) Cl] afforded different complexes depending on
2 4 2 2
the P:Rh molar ratio and the reaction time: both monosubstituted
and disubstituted complexes with very high diastereoselectivity
have been obtained under suitable reaction conditions. On the basis
of these results the ionic and the dinuclear covalent complexes can
be used as catalytic precursors in asymmetric Rh-catalyzed re-
actions, such as asymmetric hydrogenations and enantioselective
CeC bond formations: these results will be discussed in due course.
4. Experimental section
4.1. General methods and materials
Fig. 8. 31P NMR spectra (80 MHz, toluene-d
room temperature, (b) P: Rh ¼ 1 M ratio at room temperature after 30 min, (c) P:
Rh ¼ 1 M ratio after 16 h.
) of the samples: (a) P: Rh ¼ 2 M ratio at
8
TLC analyses were performed on Merck 60 F254 plates (0.2 mm)
and chromatography purifications were carried out with

G. Iannucci, A. Iuliano / Journal of Organometallic Chemistry 806 (2016) 88e94
93
MachereyeNagel silica gel (230e400 mesh) or with Sigma Aldrich
neutral alumina (Brockmann I). All the reactions involving sensitive
compounds were carried out under dry N , in flame-dried glass-
2
ware. Toluene was refluxed over sodium-benzophenone and
distilled before the use. THF was refluxed over potassium-
benzophenone and distilled before the use. Dichlorometane, trie-
(3 ꢂ 50 ml). The filtrate and washings were combined and dried
over anhydrous Na SO . The solvent was removed at reduce pres-
sure obtaining the diamine 5 (5.3 g, 75%) as a white solid.
2
4
1
H NMR (CDCl
3
, 200 MHz,
J ¼ 8.1 Hz, J ¼ 0.7 Hz, 2H), 6.79 (td, J ¼ 7.4 Hz, J ¼ 1.2 Hz, 2H),
7.11e7.31 (m, 4H).
d): 2.22 (s, 6H), 3.56 (br, 2H), 6.55 (dd,
3
4
3
4
13
thylamine and pyridine were refluxed over CaH
before the use. The hexane was refluxed over Na/K and distilled
before the use. PCl and 1,5-cyclooctadiene were distilled before
2
and distilled
C NMR (CDCl
147.2.
3
, 50 MHz, d): 30.2, 109.8, 117.1, 124.3, 129.3, 131.1,
3
the use. Unless otherwise specified, the other compounds were
commercially available and used as received. Bile acid derivative 6
4.5. Diamidophosphite 1
was obtained as described previously [5a].
To a solution of bile acid derivative 6 (0.5 g, 1.11 mmol) in dry
1
H NMR spectra were recorded in CDCl
Cl on a 200 MHz NMR spectrometer; the following ab-
breviations are used: singlet (s), doublet (d), double doublet (dd),
3
, benezene-d
6
, toluene-
dichlorometane (6 ml), under N , was added PCl (0.29 ml,
2
3
d
8
or CD
2
2
3.34 mmol). The reaction mixture was subsequently stirred at room
temperature for 24 h. After removing the solvent at reduced pres-
sure, the crude product was dissolved in dry toluene (2.5 ml) and a
solution of 5 (197 mg, 0.93 mmol) and triethylamine (0.47 ml,
3.34 mmol) in dry toluene (3 ml) was added dropwise under N2.
The reaction mixture was subsequently refluxed for 16 h, then the
suspension was cooled to room temperature and dry hexane was
13
triple doublet (td), triplet (t), multiplet (m), broad (br). C NMR
spectra were recorded in CDCl or benezene-d at 50 MHz. The
temperature was controlled to ±0,1 C. H and C NMR chemical
3
6
13
ꢀ
1
31
shifts (ppm) are referred to TMS as external standard. P NMR
spectra were recorded in benzene-d , toluene-d or CD Cl at
0 MHz; chemical shifts (ppm) are referred to H PO as external
standard.
6
8
2
2
8
3
4
added (5 ml). The reaction mixture was filtered under N and the
2
solvent removed under reduced pressure. The crude product was
Circular dichroic (CD) spectra were obtained using a 0.01 or
dissolved in dry dichlorometane and was purified by filtration
0
.05 cm path length cell and spectropolarimetric grade acetonitrile
under N on a pad of neutral alumina (3 g, Brockmann I), obtaining
2
ꢀ
and CH
2
Cl
2
solvents, at 25 C. Sample concentrations for CD ana-
pure diamidophosphite 1 (0.316 g, 50%) as a white solid.
ꢁ
4
ꢁ3
1
lyses were in the range from 10 to 10 M.
6 3
H NMR (benzene-d , 600 MHz, d): 0.54 (s, 18-CH , 3H), 0.74 (s,
1
3 3
9-CH , 3H), 0.96 (d, 21-CH , 3H), 1.03e1.92 (m, 24H), 1.65 (s, OC(O)
0
0
3
4
.2. 2,2 -diamino-1,1 -biphenyl, 3
CH , 3H), 2.09e2.29 (m, 2H), 2.76 (d, J ¼ 12.0 Hz, -NCH3, 3H), 2.83
3
3
(
d, J ¼ 11.6 Hz, -NCH3, 3H), 3.33 (s, -OCH3, 3H), 4.25 (m,12-CH,1H),
0
0
3
4
2
,2 -dinitro-1,1 -biphenyl 2 (16,7 g, 68 mmol) and 10% Pd/C
2,8 g) were combined with 45 ml of AcOEt in a hydrogen vessel.
The vessel was pressurized to 6 atm H for 72 h. The slurry was
filtered through a plug of celite. Rotary evaporation followed by
drying on a vacuum line gave pure product as a light yellow/orange
solid (8.81 g, 70%).
4.77 (m, 3-CH, 1H), 6.99 (dd, J ¼ 7.32 Hz, J ¼ 1.25 Hz, 2H),
3 4
(
7.08e7.16 (m, 4H), 7.22 (dd, J ¼ 7.60 Hz, J ¼ 1.45 Hz, 1H), 7.26 (dd,
3
4
2
J ¼ 7.60 Hz, J ¼ 1.45 Hz, 1H).
13
6
C NMR (50 MHz, benzene-d ) d ppm: 12.8, 18.1, 18.2, 21.1, 23.2,
24.3, 26.7, 27.0, 27.1, 27.4, 27.5; 28.1, 31.3, 31.4, 32.6, 33.9, 34.6, 35.4,
36.1, 36.3, 37.3 (d, J ¼ 5.2 Hz), 38.0 (d, J ¼ 6.3 Hz), 42.1, 46.4, 47.5,
47.6, 48.2, 51.0, 74.0, 77.5 (d, J ¼ 11.7 Hz), 123.6 (d, J ¼ 16.0 Hz), 124.5
1
3
H NMR (CDCl
3
, 200 MHz,
d): 2.12 (br, 4H), 6.83 (dd, J ¼ 8.0 Hz,
4
3
3
4
J ¼ 1.1 Hz, 2H), 6,87 (td, J ¼ 7.4 Hz, J ¼ 1.2 Hz, 2H), 7.15 (dd,
(d, J ¼ 15.8 Hz), 130.3, 130.5, 137.9, 169.6, 173.7.
4
3
4
13
31
J ¼ 7.5 Hz, J ¼ 1.5 Hz, 2H), 7.23 (dd, J ¼ 7.8 Hz, J ¼ 1.5 Hz, 2H).
C
P NMR (80 MHz, benzene-d )
d
ppm: 168.2.
6
NMR (CDCl
3
, 50 MHz,
d
): 115.8, 119.1, 124.9, 129.1, 131.4, 144.4.
Acknowledgements
0
0
4
.3. Diethyl-1,1 - biphenyl-2,2 -diyldicarbamate, 4
This work was supported by University of Pisa (PRA_2016_46).
We thank Dott. Francesco Zinna for the registration of the CD
spectra.
To a solution of diamine 3 (8.17 g, 44 mmol) in toluene (225 ml)
ꢀ
and pyridine (32.6 ml) under N
2
, cooled to 0 C, was added a so-
lution of ethyl chloroformate (10.8 ml, 113 mmol) in toluene
25 ml). The reaction mixture was warmed to room temperature
(
Appendix A. Supplementary data
and stirred overnight. The reaction was subsequently quenched by
addition of 2 N KOH (300 ml), the organic layer was separated and
washed with 10% HCl (3 ꢂ 30 ml) and the aqueous layer was
extracted with toluene (3 ꢂ 80 ml). The organic layers were com-
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.01.031.
bined and dried over anhydrous Na
2
SO
4
. After removing the solvent
Cl /hexane, pure 4 was ob-
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