Chiral (salen)Co(III)(N-benzyl-l-serine)-derived phosphites: monodentate P-ligands for enantioselective catalytic applications

Article abstract of DOI:10.1016/j.tetasy.2009.04.001

Reaction of the (S,S)-salen-cobalt(III)-N-benzyl-l-serine complex 2 with four diol-derived chlorophosphites afforded phosphites 3a-3d in moderate yields (37-72%). Structural studies of these monodentate phosphite ligands and of their Rh-complexes were per

Full text of DOI:10.1016/j.tetasy.2009.04.001

Tetrahedron: Asymmetry 20 (2009) 1185–1190
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral (salen)Co(III)(N-benzyl-L-serine)-derived phosphites: monodentate
P-ligands for enantioselective catalytic applications
Stefano Carboni , Luca Pignataro a,b, Cesare Gennari b,*, Umberto Piarulli
a
a,*
a
Dipartimento di Scienze Chimiche e Ambientali, Università degli Studi dell’Insubria, Via Valleggio 11, Como I-22100, Italy
Dipartimento di Chimica Organica e Industriale, Centro Interdipartimentale C.I.S.I., Università degli Studi di Milano, Via Venezian 21, Milano I-20133, Italy
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of the (S,S)-salen-cobalt(III)-N-benzyl-L-serine complex 2 with four diol-derived chlorophosph-
Received 3 March 2009
Accepted 1 April 2009
Available online 6 May 2009
ites afforded phosphites 3a–3d in moderate yields (37–72%). Structural studies of these monodentate
1
31
phosphite ligands and of their Rh-complexes were performed in solution by H and P NMR spectros-
copy. The ligands were screened in several enantioselective catalytic applications, showing good activity
and moderate enantioselectivity in the palladium-catalyzed desymmetrization of meso-cyclopenten-2-
ene-1,4-diol biscarbamate.
Ó 2009 Elsevier Ltd. All rights reserved.
1
. Introduction
Chiral (salen)cobalt(II) and cobalt(III) complexes have found
N-benzylamino acid is nicely accommodated in the binding pocket
of the chiral cobalt complex.
Prompted by these achievements, we decided to take advantage
of the (salen)cobalt(III)-N-Bn-AA coordination properties and to
develop a salen-cobalt(III)-N-benzyl-serine complex as a chiral
platform for the preparation of new families of monodentate P-li-
gands (Fig. 1).
1
wide application in several asymmetric transformations. We have
recently reported a novel approach to the resolution of racemic
N-benzyl
the lipophilic chiral (salen)cobalt(III) complex (R,R)-N,N -bis(3,5-
di-tert-butylsalicylidene)-1,2-cyclo-hexanediaminocobalt(III) ace-
tate, in excellent yield and enantioselectivity.2 As a result of the
a
-amino acids (N-Bn-AA) by liquid–liquid extraction, using
0
O
H
resolution by extraction, one enantiomer of the N-benzyl a-amino
O
Co
O
H
H
O
acid predominates in the aqueous phase, while the other enantio-
mer is driven into the organic phase by complexation to the cobalt
center. The complexed amino acid can then be released by a reduc-
tive (Co ?Co ) counter extraction into an aqueous phase. The ori-
ginal chiral cobalt(III) complex can be regenerated and reused with
essentially no loss of reactivity and selectivity. Spectroscopic and
molecular modeling investigations have revealed that, in the
O
H
N
P
N
N
O
O
III
II
t-Bu
t-Bu
t-Bu
t-Bu
(N-Bn-AA)Co(salen) complex the (R,R)-salen ligand is in a cis-b-
Figure 1. Monodentate (salen)cobalt(III)(N-Bn-Ser) phosphites.
folded arrangement around the octahedral cobalt ion, with the
Herein we report the synthesis of several phosphites obtained
by reaction of the (S,S)-salen-cobalt(III)-N-benzyl-L-serine complex
with diol-derived chlorophosphites and their application to Pd-cat-
alyzed allylic substitution reactions.
remaining two cis coordination sites being occupied by the N-ben-
2
b
zylamino acid. The amino acid coordination takes place in such a
way that a meridional arrangement of the three oxygen and three
nitrogen atoms is obtained (meridional N
3 3
O structure). Using the
(R,R)-salen ligand, the favored diastereomeric complex contains
the (R)-enantiomer of the N-benzylamino acid, while the absolute
configuration of the additional stereogenic elements (the octahe-
dral cobalt and the tetrasubstituted nitrogen of the N-benzylamino
2. Results and discussion
2.1. Synthesis of the ligands
acid) was assigned as
D and (S), respectively. As a consequence, the
The chiral (salen)cobalt(III) acetate complex 1 was prepared
3
following well-established procedures, starting from commercially
available (S,S)-N,N -bis(3,5-di-tert-butylsalicylidene)-1,2-cyclo-hexan-
*
Corresponding authors. Tel.: +39 02 5031 4091; fax: +39 02 5031 4072 (C.G.);
0
tel.: +39 031 238 6444; fax: +39 031 238 6449 (U.P.).
E-mail addresses: cesare.gennari@unimi.it (C. Gennari), umberto.piarulli@unin
subria.it (U. Piarulli).
ediaminocobalt(II). (S,S)-Salen-cobalt(III)-N-benzyl-L-serine com-
plex 2 was then easily synthesized (Scheme 1), applying our
0
957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.04.001

1
186
S. Carboni et al. / Tetrahedron: Asymmetry 20 (2009) 1185–1190
low temperature and the reaction mixtures were then warmed to
room temperature and stirred for 20 min. After purification by
flash chromatography, phosphites 3a–3d were obtained in moder-
ate yields (37–72%, Scheme 2).
N
O
N
O
Bn
Co
NH
COOH
We found that longer reaction times were not beneficial to the
yields and, on the contrary, caused decomposition of the product.
In the synthesis of 3a, a decomposition product was isolated and
tentatively characterized as a cobalt(III) complex containing the
chiral salen moiety, a biphenyl phosphorous acid diester ligand,
and no trace of the N-benzylamino acid. The structure of the ligand
t-Bu
t-Bu
HO
t-Bu
t-Bu
OAc
1
3
1
was supported by the P NMR spectrum where a singlet at d
5
3
7.5 ppm was detected. Chiral phosphorous acid diesters, which
exist in a tautomeric equilibrium between a (RO) P–OH and a
RO) (H)P@O form, have recently been reported to perform as ac-
2
(
2
N
O
N
tive and enantioselective ligands in the Ir-catalyzed hydrogenation
Co
DCM/H O
5
2
of imines. From a mechanistic point of view, it can be assumed
t-Bu
O
t-Bu
that, once formed, the phosphite activates the OH group of the ser-
ine toward an elimination reaction, which is promoted by the base
rt, 24h
9
6%
t-Bu
Bn NH
t-Bu
O
(
TEA) present in the reaction medium. The biphenyl phosphorous
acid diester which is thus formed, apparently acts as a better ligand
toward cobalt and displaces the amino acid derivative.
2
An analogous synthetic pathway was attempted using N-ben-
O
zyl-
stereogenic center. The chiral (S,S)-salen-cobalt(III)-N-benzyl-
threonine complex was prepared and isolated, after flash chroma-
L-threonine instead of serine to study the effect of an additional
OH
L-
Scheme 1. Synthesis of the (S,S)-salen-cobalt(III)-N-benzyl-L-serine complex 2.
2
b
tography, in good yield (83%). Unfortunately, all attempts to
proceed further with the formation of the phosphite met with no
success and only the decomposition complex described above
could be isolated.
reported biphasic extraction procedure,2a,b starting from (S,S)-1
and using 2 equiv of N-benzyl- -serine.
The biphasic procedure, where the water-soluble N-benzyl-
L
L
-
serine is extracted into the dichloromethane phase, following
complexation to the cobalt center, was preferred to reaction in
2
.2. Structural and complexation studies
pure dichloromethane, where N-benzyl-L-serine is sparingly solu-
A NMR investigation of the ligands was then undertaken. The
ble and the complexation becomes extremely slow. The reaction
was performed on a multigram scale and complex 2 was ob-
tained in excellent yield (96%) after chromatographic purification
over silica gel, thus confirming the excellent stability of these
complexes.
The corresponding phosphite ligands 3a–3d were then synthe-
sized by reaction of complex 2 with four (tropos and atropos) diol-
derived chlorophosphites.4 The chlorophosphites were added at
3
experiments were conducted in CDCl , which was degassed and
passed over a short pad of neutral alumina. H NMR NOESY studies,
performed on ligand 3a, showed a number of common contacts to
1
the parent (salen)cobalt(III)-N-benzyl-L-serine, thus revealing a
similar configuration of the octahedral cobalt ion and arrangement
2b
31
of the substituents. The P NMR spectra of the phosphites dis-
played a singlet at similar chemical shifts in all cases: 3a, d
1
44.6 ppm; 3b, d 150.7 ppm; 3c, d 146.6 ppm; 3d, d 144.2 ppm.
N
O
N
O
Co
O
P
O
dry THF, TEA
2
t-Bu
t-Bu
Cl
from -78°C to rt
2
0 min
t-Bu
t-Bu
Bn NH
O
O
3
O
O P
O
O
O
O
O
O
O
O
O
O
O
a (50%)
b (72%)
c (Sa) (37%)
d (Ra) (45%)
-serine-derived phosphites 3a–d.
Scheme 2. Synthesis of the (S,S)-salen-cobalt(III)-N-Bn-
L

S. Carboni et al. / Tetrahedron: Asymmetry 20 (2009) 1185–1190
1187
a
b
155
150
145
140
ppm
155
150
145
140
ppm
Figure 2. 31P NMR spectra of the rhodium complexes resulting from the combination of ligand 3a with Rh(acac)(C
H )
4
in (a) 1:1 ratio and (b) 2.1:1 ratio.
2
2
The complexation of ligand 3a with [Rh(acac)(C
then studied (Fig. 2). Upon addition of 1.0 equiv of 3a with
respect to the rhodium source, doublet at 148.6 ppm
P–Rh = 312.2 Hz) and a doublet at d 138.0 ppm (JP–Rh = 302.2 Hz)
2
H
4
)
2
] was
Ts
NH HN
Ts
O
O
HO
OH
TsNCO
5°C, 1h
a
d
5
(J
O
O
were observed (in 3:1 ratio). When the ratio 3a/Rh was increased
to 2.1:1, the spectrum displayed only the doublet at d 148.6 ppm,
plus a small singlet at d 144.6 ppm corresponding to excess li-
gand. Therefore, it can be concluded that the doublet at d
4
5
Ts
N
Ts
N
Pd (dba) (5.0 mol%)
1
38.0 ppm corresponds to the substitution of one ethylene mole-
2
3
3
H
H
a-3d (20 mol%)
cule, while the doublet at d 148.6 ppm contains two ligands coor-
dinated to the rhodium atom. It is interesting to note that two
ligands are accommodated around the rhodium atom, notwith-
standing their steric hindrance.
O
O
THF, TEA (1 equiv)
30 min
O
O
H
H
-
2 2
CO ; - TsNH
6
(S,R)
6 (R,S)
2
.3. Catalytic applications
Scheme 3. Pd-catalyzed desymmetrization of meso-cyclopenten-2-ene-1,4-diol
biscarbamate.
The ligands were then screened for several enantioselective cat-
alytic applications. Unfortunately, in the rhodium-catalyzed enan-
tioselective hydrogenation of functionalized olefins and in the
rhodium-catalyzed asymmetric conjugate addition of arylboronic
acids to enones, reduction of cobalt(III) to cobalt(II) was observed,
with consequent loss of the (salen)Co(N-Bn-Ser) phosphite ligand
integrity. On the contrary, when the Pd-catalyzed allylic substitu-
tion of rac-1,3-diphenyl-3-acetoxyprop-1-ene with dimethyl mal-
Table 1
Screening of ligands 3a–3d in the Pd-catalyzed desymmetrization of meso-cyclopen-
ten-2-ene-1,4-diol biscarbamate 5
Entry
Ligand
T (°C)
TEA
Conv. (%)a
6 (S,R):(R,S)b
1
2
3
4
5
6
7
8
9
None
3a
3a
25
25
25
0
25
0
25
25
25
25
No
No
—
96
100
85
90
90
100
99
100
93
—
6
50:50
15:85
18:82
48:52
28:72
90:10
80:20
35:65
32:68
onate was tested, the ligands proved to be perfectly stable and
gave excellent conversions, albeit with low enantiomeric excess
Yes
Yes
Yes
Yes
No
Yes
No
Yes
3a
(
3
up to 35% ee using ligand 3a). Quite surprisingly, the use of bulkier
,3 ,5,5 -tetramethyl-2,2 -biphenol derivative 3b gave the opposite
3b
3b
3c
3c
3d
3d
0
0
0
enantiomer, while the use of axially chiral BINOL derivatives 3c
and 3d led to racemic products.
Ligands 3a–3d were then screened in the Pd-catalyzed desym-
10
metrization of meso-cyclopenten-2-ene-1,4-diol biscarbamate 5
a
Determined by 1H NMR analysis of the crude reaction mixture.
er values and absolute configurations were determined by HPLC using a Chi-
7
(Scheme 3). This intramolecular allylic substitution reaction was
b
developed by Trost and co-workers and has proven to be a very
powerful method in several synthetic approaches to biologically
relevant targets. The ligands used in the original examples are
ralcel OD-H column (see Ref. 9).
8
chiral bidentate phosphines and give the product with excellent
enantioselectivity (ee up to 99%) while, to our knowledge, no
monodentate phosphite ligands have ever been reported for this
reaction.
The reaction was performed using 10 mol % of palladium (5% of
2 3
the dimer Pd dba ) and 20 mol % of ligands 3a–3d. In several cases,
Reaction conversions were always good, in many cases quanti-
tative, with all four ligands 3a–3d. Addition of TEA to the reaction
with ligand 3a was fundamental to achieve higher levels of enanti-
oselectivity while, in the case of ligand 3c, TEA had a negative ef-
fect. Remarkably, the use of complex 3a, containing a tropos
biphenol moiety (entries 3 and 4), afforded enantiomeric ratios
9
0
a stoichiometric amount of triethylamine (TEA), which has been
comparable (yet opposite) to 3c, containing an atropos (S )-1,1 -
a
9
reported to increase the enantioselectivity of the reaction, was
binaphthyl moiety (entries 7 and 8). All these observations confirm
that the chiral and well-organized structure of the salen-cobal-
added to the mixture. The results are summarized in Table 1.

1
188
S. Carboni et al. / Tetrahedron: Asymmetry 20 (2009) 1185–1190
t(III)-N-benzyl-
reochemical outcome of the reaction.
L
-serine complex is relevant in determining the ste-
t = triplet, q = quartet, m = multiplet, br = broad signal, dd = dou-
1
3
blet of doublet. C NMR spectra were recorded on a 400 MHz
spectrometer operating at 100.56 MHz, with complete proton
decoupling. Carbon chemical shifts are reported in ppm (d) rela-
tive to TMS with the respective solvent resonance as internal
3
. Conclusion
3
1
standard (CDCl
3
, 77.0 ppm). P NMR spectra were recorded on
In this work, we have investigated the use of an octahedral (S,S)-
a 400 MHz spectrometer operating at 162 MHz, with complete
(
salen)cobalt(III)-N-benzyl-L-serine complex for the formation of
3
1
proton decoupling.
ppm (d) relative to external 85% H
downfield). Infrared spectra were recorded on a standard FT/IR
P NMR chemical shifts are reported in
monodentate phosphites, to be used as chiral ligands in enantiose-
lective catalytic applications. The ligands were obtained in moder-
ate yields by reaction of (S,S)-(salen)cobalt(III)-N-benzyl-L-serine
3
PO at 0 ppm (positive value
4
ꢁ1
spectrometer; bands are reported in cm . Optical rotation val-
ues were measured on an automatic polarimeter with a 1 dm
cell at the sodium D line (k = 589 nm). HPLC analyses were per-
formed with a chiral stationary phase column Chiralcel OD-H
with diol-derived chlorophosphites. These phosphites showed
remarkable air and moisture stability. 1H NMR NOESY studies re-
vealed that formation of the phosphite does not alter the original
structure of the (salen)cobalt(III)-N-Bn-
ligands were then screened for several asymmetric catalytic appli-
cations, showing good activity and moderate enantioselectivity in
the palladium-catalyzed desymmetrization of meso-cyclopenten-
b
L
-serine complex.2 These
(
eluent hexane/isopropanol 90:10, flow 0.6 mL/min, t
R
= 35 min
(
first enantiomer) 44 min (second enantiomer), k = 254 nm. High
resolution mass spectra (HRMS) were performed on Fourier
Transform Ion Cyclotron Resonance (FT-ICR), Mass Spectrometer
APEX II, and Xmass software (Bruker Daltonics)-4.7 T Magnet
2
-ene-1,4-diol biscarbamate.
Coordination complexes have recently been used for the prepa-
(
Magnex). Commercially available reagents were used as
ration of supramolecular bidentate P-ligands.10 In this approach,
two monodentate P-ligands self-assemble around a transition me-
tal (Rh, Pd) by virtue of an additional coordinative bonding of
nitrogen to zinc. In particular, Reek and co-workers developed a
0
received.
(S,S)-N,N -Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclo-
3
14
hexanediaminocobalt(III) acetate 1, N-benzyl-
L
-serine,
and
diol-derived monochlorophosphites were synthesized as reported
4
in the literature.
‘
SUPRAPhos’ library, where the supramolecular bidentate P-ligands
1
1
are formed by a porphyrinatozinc(II)ꢀ ꢀ ꢀpyridyl interaction. The
members of this library include porphyrin phosphites and phos-
phoramidites, pyridyl phosphites, phosphoramidites and phos-
4
.2. Synthesis of (S,S) salen-Co(III)-N-Bn-L-serine complex 2
To a solution of the cobalt complex (S,S)-(salen)Co(III)(OAc) 1
1.65 g, 2.38 mmol) in dichloromethane (300 mL) at rt in a 1 L
round-bottomed flask, solution of N-Bn- -serine (464 mg,
.0 equiv, 2.38 mmol) in H O (100 mL) was added. The biphasic
phanes. Using
a different approach, Takacs and co-workers
(
reported the use of enantiomeric chiral bisoxazolines to direct
the self-assembly upon addition of zinc(II), with preferential for-
mation of the heterodimeric zinc(II)-complexes.12 The bifunctional
chiral bisoxazolines were substituted with a series of phenyl-
methyl or biphenylmethyl tethers terminating in a TADDOL-de-
rived phosphite. The advantage of these supramolecular
approaches is the expectation that degrees of freedom in the
respective transition metal coordination complex are reduced,
resulting in the simulation of a preorganized bidentate system
with predictable geometric properties, as in conventional biden-
tate ligands.
a
L
1
2
mixture was stirred vigorously overnight at rt, and then trans-
ferred to a separating funnel. The organic phase was removed
and the aqueous phase washed twice with dicholoromethane
(
H
40 mL). The combined organic phases were washed once with
O (40 mL), dried over Na SO4, and the solvent removed under re-
duced pressure. The crude was purified by flash chromatography
dicholoromethane/methanol 95:5) to afford the product as a
green powder (1.82 g, yield 96%). Mp decomposition at 160 °C.
2
2
(
22
½
a
ꢂ
¼ ꢁ1671:1 (c 0.027, CHCl
3
); IR (Nujol)
mmax 3346, 3215,
D
Studies aimed at the introduction of an additional phosphorus
functionality in the salen moiety of the salen-cobalt(III)-N-ben-
zyl-serine-derived phosphite ligands are currently underway to
realize a new class of supramolecular bidentate ligands.
2
7
7
1
730, 1638, 1644, 1615, 1524, 1377, 1256, 1168, 1015, 930,
ꢁ
1 1
81 cm
3
. H NMR (CDCl ) d 7.92 (s, 1H), 7.44 (d, 1H, J = 2.4 Hz),
.39 (s, 1H), 7.30 (d, 1H, J = 2.4 Hz), 7.26–7.19 (m, 4H),7.13 (d,
H, J = 2.3), 6.62 (d, 2H, J = 7.0 Hz), 5.35 (m, 1H) 4.63(m, 2H), 4.02
(
d, 1H, J = 13.6 Hz), 3.43–3.25 (m, 3H), 2.94 (m, 1H), 2.80 (m, 1H),
2.29 (m, 1H), 2.18 (m, 1H), 1.73–1.61 (m, 3H), 1.54 (s, 9H), 1.38
4
4
. Experimental
1
3
(
s, 19 H), 1.18 (s, 9H), 1.0–0.94 (m, 2H) ppm. C NMR (CDCl
163.7, 163.3, 162.6, 160.1, 144.3, 141.1, 137.3, 136.9, 134.4,
29.8, 129.2, 128.9, 128.2, 125.7, 122.6, 117.4, 75.2, 70.8, 62.7,
55.4, 35.8, 34.0, 33.8, 31.5, 31.4, 31.0, 29.7, 29.6, 25.1, 22.6 ppm.
3
) d
.1. General methods
1
All reactions were carried out in flame-dried glassware with
+
magnetic stirring under a nitrogen atmosphere, unless otherwise
stated. Commercially available dry solvents (over molecular
sieves in bottles with crown cap) were stored under nitrogen
and used without further distillation. TEA was distilled over
HRMS (ESI+) m/z calcd for [C46
[M+Na] ; found: 820.40507.
3
H64CoNaN O
5
] : 820.40702
+
4.3. General procedure for the synthesis of the (S,S)-salen-
Co(III)-N-Bn- -serine complex phosphites 3a–3d
CaH
2
under nitrogen. Reactions were monitored by analytical
L
thin-layer chromatography (TLC) using Silica Gel 60 F254 pre-
coated glass plates (0,25 mm thickness). Visualization was
accomplished by irradiation with a UV lamp and/or staining with
a permanganate alkaline solution. Flash chromatography was
The (S,S)-salen-Co(III)-N-Bn-
mmol) was dissolved in THF (1.0 mL) in a Schlenk under a nitrogen
atmosphere. Freshly distilled TEA (42 L, 0.3 mmol, 2 equiv) was
L-serine complex 2 (120 mg, 0.15
l
performed using Silica Gel 60 Å, particle size 40–64
l
m, follow-
added to the green solution at rt and the whole mixture was cooled
to ꢁ78 °C. A solution of the diol-derived monochlorophosphite
(0.18 mmol, 1.2 equiv) in THF (1.0 mL) was added dropwise and
the reaction mixture was allowed to warm to rt. After 20 min the sol-
vent was removed under reduced pressure and the crude was
quickly purified by flash chromatography to afford the product as a
green fine powder.
ing the procedure by Still and co-workers.13 1H NMR spectra
were recorded on a spectrometer operating at 400.13 MHz. Pro-
ton chemical shifts are reported in ppm (d) with the solvent ref-
erence relative to tetramethylsilane (TMS) employed as the
3
internal standard (CDCl 7.28 ppm). The following abbreviations
are used to describe spin multiplicity: s = singlet, d = doublet,

S. Carboni et al. / Tetrahedron: Asymmetry 20 (2009) 1185–1190
1189
4
.3.1. (S,S)-Salen-Co(III)-N-Bn-
Hexane/AcOEt 3:2 R
= 0.50) (76 mg, yield 50%). ½
c 0.094, CHCl ). IR (Nujol) max 3231, 2705, 1672, 1643, 1615,
529, 1377, 1321, 1250, 1207, 1168, 1096, 1015, 897, 739 cm . H
) d 7.84 (s, 1H), 7.44–7.43 (m, 4H), 7.36–7.12 (m, 12H),
.65 (d, 2H, J = 7.3 Hz), 5.16 (m, 1H), 4.66 (dd, 1H, J = 13.6 Hz,
J = 3.8 Hz), 4.12 (dd, 1H, J = 5.9 Hz, J = 3.8 Hz), 4.02 (m, 2H), 3.46
L
-serine-biphenyl-phosphite 3a
23.6 ppm. 31P NMR (CDCl
3
) d 146.6 ppm. HRMS (ESI+) m/z calcd for
23
+
+
(
f
a
ꢂ
¼ ꢁ681:8
[C66
3
H75CoNaN O
7
P] : 1134.45668 [M+Na] ; found: 1134.45474.
D
(
1
3
m
ꢁ1 1
a
4.3.4. (S,S)-Salen-Co(III)-N-Bn-L-serine-(R )-binaphthyl-phos-
phite 3d
NMR (CDCl
6
3
2
D
3
(Hexane/AcOEt 2:1 R
(c 0.055, CHCl ); IR (Nujol)
1377, 1314, 1256, 1168, 1095, 1023, 945; 823, 744 cm . H NMR
(CDCl ) d 8.06–7.59 (m, 3H), 7.80 (s, 1H), 7.59 (d, 1H, J = 8.7 Hz),
f
= 0.40) (75 mg, yield 45%). ½
a
ꢂ
¼ ꢁ1227:3
3
m
max 3221, 2725, 1670, 1652, 1634, 1521,
ꢁ1 1
(
m, 1H), 2.98 (m, 1H), 2.82 (m, 1H), 2.71 (m, 1H), 1.96–1.55 (m,
1
3
4
H), 1.55 (s, 10H), 1.42 (s, 9H), 1.36 (s, 10H), 1.17 (s, 10H) ppm.
) d 179.8, 164.9, 163.5, 163.4, 160.7, 150.1, 149.3,
44.9, 141.2, 137.7, 137.0, 135.2, 131.8, 130.4, 130.3, 130.1, 129.8,
29.7, 129.6, 129.4, 129.1, 128.8, 126.0, 125.7, 125.6, 122.8, 122.5,
22.4, 120.9, 118.1, 117.9, 75.9, 70.6, 65.5, 65.3, 64.89, 64.8, 55.9,
6.2, 34.5, 34.2, 32.0, 31.9, 31.1, 30.3, 29.9, 29.3, 25.0, 24.3 ppm.
C
3
NMR (CDCl
3
7.51–7.45 (m, 2H), 7.42–7.27 (m, 7H), 7.20 (d, 1H, J = 2.4 Hz), 7.09–
6.96 (m, 5H), 6.59–6.57 (m, 3H), 4.85 (m, 1H), 4.59 (m, 1H), 4.17–
4.09 (m, 2H), 3.91 (m, 1H), 3.42 (m, 1H), 2.88–2.75 (m, 2H), 2.61
(m, 1H), 1.99–1.85 (m, 3H), 1.56–1.41 (m, 19H), 1.36–1.34 (m,
1
1
1
3
1
3
3
10H), 1.28–1.25 (m, 1H), 1.22–1.12 (m, 11H) ppm. C NMR (CDCl )
3
1
P NMR (CDCl
3
) d 164.6 ppm. HRMS (ESI+) m/z calcd for [C58
H
71Co-
d 179.2, 164.4, 162.9, 161.2, 159.6, 148.3, 147.0, 144.4, 140.8, 137.1,
136.4, 134.8, 132.7, 132.3, 131.6, 130.8, 130.6, 129.9, 129.8, 129.3,
129.1, 129.0, 128.8, 128.4, 128.3, 126.9, 126.8, 126.4, 126.3, 126.0,
125.6, 125.2, 125.1, 124.5, 123.9, 123.5, 122.6, 75.5, 70.4, 66.3,
66.1, 65.1, 55.5, 35.7, 34.1, 33.7, 31.7, 31.4, 30.6, 29.8, 29.4, 29.0,
+
+
NaN
tion by-product: H NMR (CDCl
.51 (d, 1H, J = 2.4 Hz), 7.44 (d, 1H, J = 2.4 Hz), 7.32 (dd, 1H,
J = 7.4 Hz, J = 1.3 Hz), 7.26 (d, 1H, J = 7.2 Hz), 7.21 (d, 1H, J = 2.4 Hz),
3 7
O P] : 1034.42538 [M+Na] ; found: 1034.42271. Decomposi-
1
3
) d 8.30 (br s, 1H), 8.01 (br s, 1H),
7
3
1
7.17 (d, 1H, J = 2.4 Hz), 7.13–7.04 (m, 2H), 6.99–6.95 (m, 1H), 6.68–
6.64 (m, 1H), 6.14 (d, 1H, J = 7.7 Hz), 5.47 (d, 1H, J = 8.2 Hz), 4.25–
4.18 (m, 1H), 3.73–3-67 (m, 1H), 2.91 (d, 1H, J = 10.5 Hz), 2.78 (d,
1H, J = 9.7 Hz), 2.09–2.05 (m, 2H), 1.96–1.87 (m, 1H), 1.78–1.68 (m,
1H), 1.63–1.49 (m, 2H), 1.48 (s, 9H), 1.43 (s, 9H), 1.40 (s, 9H), 1.22
3
24.5, 23.7 ppm. P NMR (CDCl ) d 144.2 ppm. HRMS(ESI+) m/z calcd
+
+
3 7
for [C66H75CoNaN O P] : 1134.45668 [M+Na] ; found: 1134.45423.
4.4. General procedure for the Pd-catalyzed desymmetrization
of meso-cyclopenten-2-ene-1,4-diol biscarbamate
9
3
1
(
s, 9H) ppm. P NMR (CDCl
3
) d 37.5 ppm.
To a solution of the meso-cyclopenten-2-ene-1,4-diol (10 mg,
0.099 mmol) in 0.5 mL of THF, tosyl isocyanate (35 lL, 0.232 mmol,
0
0
4
.3.2. (S,S)-Salen-Co(III)-N-Bn-
phite 3b
Hexane/AcOEt
L
-serine-3,3 ,5,5 -biphenyl-phos-
2.35 equiv) was added. The mixture was stirred at rt for 15 min to
give a colorless solution and then heated to 55 °C for 1 h. The reac-
tion was cooled back to rt, and triethylamine (14.0 lL, 0.099 mmol,
(
3:1
R
f
= 0.40)
); IR (Nujol)
680, 1645, 1618, 1535, 1380, 1320, 1257, 1212, 1168, 1093, 1015,
(115 mg,
yield
72%).
2
3
½
a
1
ꢂ
¼ ꢁ1050:8 (c 0.077, CHCl
3
m
max 3251, 3232, 2726,
D
1.0 equiv) was added. The resulting white slurry was brought to
the chosen temperature conditions and a solution of tris(dib-
enzylidine acetone)dipalladium(0) chloroform complex (5.1 mg,
ꢁ1
1
8
60, 739 cm
.
3
H NMR (CDCl ) d 7.81 (s, 1H), 7.42 (d, 1H,
J = 2.5 Hz), 7.38–7.28 (m, 4H), 7.27 (d, 1H, J = 2.4 Hz), 7.18 (s, 1H),
7
2
1
2
3
1
1
1
1
3
1
.12–7.11 (m, 2H), 7.06 (s, 1H), 7.00 (d, 1H, J = 2.3 Hz), 6.75 (m,
H), 6.51 (s, 1H), 5.04 (m, 1H), 4.68 (m, 1H), 4.34 (m, 1H), 4.15 (dd,
H, J = 14.3 Hz, J = 7.13 Hz), 4.01–3.92 (m, 2H), 3.52 (m, 1H), 2.89–
.78 (m, 2H), 2.62–2.58 (m, 1H), 2.46 (s, 3H), 2.37 (s, 6H), 2.30 (s,
H), 1.83–1.70 (m, 3H), 1.57 (s, 9H), 1.50 (s, 9H), 1.36 (s, 10H),
4.94 lmol) and ligand (20.25 lmol) in 0.5 mL of THF was added
(the solution of the Pd-source and the ligand was prepared under
nitrogen and stirred for 40 min at rt, 10 min at 55 °C and finally
cooled back to rt). The reaction solution was stirred for 30 min.
The solvent was removed in vacuo and purified by flash
chromatography on a short pad of silica gel (10 cm, hexane/AcOEt
80:20) gave the desired products as a slightly brown solid. Conver-
sions were determined by NMR analysis of the crude reaction mix-
ture. Enantiomeric excesses were determined by chiral HPLC
(column Chiralcel OD-H, n-hexane/2-propanol 90:10, flow 0.6 ml/
min).
.23–1.17 (m, 11H) ppm. 13C NMR (CDCl
3
) d 179.3, 164.8, 163.5,
47.4, 145.0, 144.8, 141.2, 137.6, 135.6, 135.1, 134.8, 133.9, 132.1,
31.9, 131.3, 131.2, 130.7, 130.4, 130.2, 129.6, 129.5, 129.0, 128.4,
27.7, 126.0, 122.8, 118.2, 75.9, 71.0, 66.3, 66.1, 65.9, 60.8, 55.9,
6.1, 34.6, 34.1, 32.2, 31.9, 31.3, 30.3, 29.9, 29.5, 25.0, 23.9, 21.3,
7.4, 16.9, 14.6 ppm. 31P NMR (CDCl
) d 150.7 ppm. HRMS (ESI+)
3
+
+
m/z calcd for [C62
H
79CoNaN
3
O
7
P] : 1090.48798 [M+Na] ; found:
1
090.48576.
Acknowledgments
4
.3.3. (S,S)-Salen-Co(III)-N-Bn-L-serine-(S )-binaphthyl-phos-
a
We thank the European Commission [EST-project ‘Foldamers’
MEST-CT-2004-515968 and RTN Network (R)Evolutionary Cataly-
sis MRTN-CT-2006-035866] for financial support. The Università
degli Studi dell’Insubria is gratefully acknowledged for a post-doc-
toral fellowship (assegno di ricerca) to L.P. C.G. thanks Merck Re-
search Laboratories for the Merck’s Academic Development
Program Award.
phite 3c
2
D
2
(
Hexane/AcOEt 2:1 R
f
= 0.40) (62 mg, yield 37%). ½
a
ꢂ
¼ ꢁ775:2
(c 0.078, CHCl
3
); IR (Nujol) max 3159, 2722, 1660, 1634, 1615,
m
ꢁ
1 1
1
526, 1365, 1321, 1255, 1230, 1168, 945, 828, 730 cm . H NMR
(
CDCl
3
) d 8.06 (d, 1H, J = 8.8 Hz), 7.97 (d, 1H, J = 8.3 Hz), 7.87 (d, 1H,
J = 8.5 Hz), 7.82 (d, 1H, J = 8.8 Hz), 7.77 (m, 1H), 7.62 (d, 1H,
J = 8.7 Hz), 7.50–7.33 (m, 9H), 7.31–7.26 (m, 3H), 7.13 (d, 1H,
J = 8.7 Hz), 7.08–7.06 (m, 2H), 6.73 (m, 2H), 5.32 (m, 1H), 4.67 (m,
1
2
1
References
H), 4.16–4.04 (m, 3H), 3.59 (m, 1H), 3.46 (m, 1H), 2.80 (m, 1H),
.73–2.68 (m, 2H), 1.77–1.63 (m, 3H), 1.54 (s, 9H), 1.42 (s, 9H),
1.
Larrow, J. R.; Jacobsen, E. N. Top. Organomet. Chem. 2004, 6, 123–152. and
1
3
.41–1.35 (m, 2H), 1.33 (s, 9H), 1.19–1.12 (m, 10H) ppm. C NMR
) d 179.2, 164.4, 163.1, 162.9, 160.7, 152.0, 147.7, 146.8,
references therein.
(
CDCl
3
2. (a) Reeve, T. B.; Cros, J.-P.; Gennari, C.; Piarulli, U.; de Vries, J. G. Angew. Chem.,
Int. Ed. 2006, 45, 2449–2453; (b) Dzygiel, P.; Reeve, T. B.; Piarulli, U.; Krupicka,
M.; Tvaroska, I.; Gennari, C. Eur. J. Org. Chem. 2008, 1253–1264; For the
1
1
1
1
3
44.5, 140.8, 137.3, 136.9, 134.8, 132.9, 132.1, 131.7, 131.0, 130.7,
30.5, 130.4, 130.2, 129.9, 129.8, 129.3, 128.6, 128.5, 128.4, 127.2,
27.0, 126.6, 126.5, 126.2, 125.7, 125.4, 124.9, 122.1, 122.0, 121.6,
19.3, 118.0, 117.7, 75.5, 69.7, 64.6, 64.5, 63.6, 63.5, 55.4, 35.8,
4.1, 33.7, 31.6, 31.4, 30.4, 30.1, 29.8, 29.5, 29.1, 28.5, 24.4,
3
extension of this method to the resolution of racemic N-benzyl b -amino acids,
see: (c) Dzygiel, P.; Monti, C.; Piarulli, U.; Gennari, C. Org. Biomol. Chem. 2007, 5,
3464–3471.
3.
Nielsen, P. C. L.; Stevenson, P. C.; Blackmond, D. G.; Jacobsen, E. N. J. Am. Chem.
Soc. 2004, 126, 1360–1362.

1
190
S. Carboni et al. / Tetrahedron: Asymmetry 20 (2009) 1185–1190
4
.
For the synthesis of the diol derived chlorophosphites see: Franciò, G.; Arena, C.
G.; Faraone, F.; Graiff, C.; Lanfranchi, M.; Tiripicchio, A. Eur. J. Inorg. Chem. 1999,
219–1227.
Reetz, M. T.; Bondarev, O. Angew. Chem., Int. Ed. 2007, 46, 4523–4526. and
references therein.
Diéguez, M.; Pàmies, O.; Claver, C. J. Org. Chem. 2005, 70, 3363–3368.
Ruffo, F.; Del Litto, R.; De Roma, A.; D’Errico, A.; Magnolia, S. Tetrahedron:
Asymmetry 2006, 17, 2265–2269.
9. Trost, B. M.; Patterson, D. E. J. Org. Chem. 1998, 63, 1338–1341.
10. (a) Reetz, M. T. Angew. Chem., Int. Ed. 2008, 47, 2556–2588. and references
therein; (b) Sandee, A. J.; Reek, J. N. H. Dalton Trans. 2006, 3385–3391; (c) Breit,
B. Angew. Chem., Int. Ed. 2005, 44, 6816–6825.
11. Goudriaan, P. E.; Jang, X.-B.; Kuil, M.; Lemmens, R.; Van Leeuwen, P. W. N. M.;
Reek, J. N. H. Eur. J. Org. Chem. 2008, 6079–6092. and references therein.
12. Moteki, S. A.; Takacs, J. M. Angew. Chem., Int. Ed. 2008, 47, 894–897. and
references therein.
1
5
.
6
7
.
.
8
.
(a) Graening, T.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2003, 42, 2580–2584; (b)
Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921–2943.
13. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925.
14. Quitt, P.; Hellerbach, J.; Vogler, K. Helv. Chim. Acta 1963, 46, 327–333.