Chelating phosphines with C2 and C3 symmetry

Article abstract of DOI:10.1070/MC2004v014n06ABEH002026

Amide formation between ring opened aziridines and 2-(diphenylphosphino) benzoic acid provides an easy access to chelating di- and triphosphines with C₂ and C₃ symmetry.

Full text of DOI:10.1070/MC2004v014n06ABEH002026

,
2004, 14(6), 276–277
Chelating phosphines with C and C symmetry
2
3
Emilie Brulé, Yuxin Pei, Fredrik Lake, Fredrik Rahm and Christina Moberg*
Department of Chemistry, Royal Institute of Technology, SE 100 44 Stockholm, Sweden. Fax: +46 8 791 2333; e-mail: kimo@kth.se
DOI: 10.1070/MC2004v014n06ABEH002026
Amide formation between ring opened aziridines and 2-(diphenylphosphino)benzoic acid provides an easy access to chelating di-
and triphosphines with C and C symmetry.
2
3
The tetrahedral carbon atom attached to four different groups is
the most common reason for chirality in organic compounds.
Asymmetric metal catalysis is a powerful method by which a
large variety of chiral compounds can be prepared in enantio-
merically pure forms. In the design of metal catalysts, the steric
and electronic properties of the chiral ligands responsible for
chirality transfer are crucial for the success of the catalytic
system. The symmetry of the chiral ligands and their metal
complexes is an additional factor that occasionally should be
considered for efficient chiral recognition and transformation.
B
(a)
(b)
L
L
L
L
A
B
A
B
L
Figure 1 (a) In a square planar complex with a C -symmetric ligand, A
2
and B are homotopic, and (b) A, B and C are homotopic in an octahedral
complex with a C -symmetric tridentate ligand.
3
Rotational axes, C , are the only symmetry elements com-
sole symmetry elements, have been extensively employed in
asymmetric synthesis, whereas examples of the use of those
n
1
patible with chirality. The presence of C elements of symmetry
n
in the ligands responsible for chiral transfer in metal-catalysed
reactions may be beneficial since symmetry can reduce the
number of possible intermediates/transition states, thus increasing
the probability of a successful result. Compounds belonging to
point groups C or D , having twofold rotational axes as their
belonging to groups with threefold rotational symmetry axes,
2
C and D , are more scarce. By definition, C symmetry is
3
3
2
characterised by the fact that an identical situation is obtained
upon the rotation of C -symmetric species 180° about the rota-
2
tion axis. In an event involving chiral recognition, this implies
2
2
2
76 Mendeleev Commun. 2004

,
2004, 14(6), 276–277
tuents. However, whereas 2 has true inherent threefold sym-
metry and is expected to give C -symmetric metal complexes, 1
3
has only time-averaged symmetry; in the latter compound, there
O
O
NH
N
HN
is no single stable conformation with C symmetry. In contrast
2
Bu
to the situation in 2, metal complexes of 1 where the central
nitrogen atom takes part in coordination to the metal are devoid
of symmetry due to the tetrahedral nitrogen. The rotational
symmetry of the ligand is advantageous, however, in that com-
plex formation is restricted to form one single complex.
PPh2
Ph2P
1
O
With the present method for the synthesis of phosphine
ligands, a wide variety of derivatives are easily accessible. We
have recently demonstrated that, in addition to ammonia and
aliphatic primary amines, diamines and primary amines con-
taining a variety of functional groups and primary amines with
central, axial and planar chirality can be employed in the
N
H
O
N
HN
Ph2P
PPh2
NH
PPh2
3
reaction with differently substituted aziridines. Therefore, the
O
electronic and steric properties of the ligands can be easily
varied while maintaining their symmetry. By analogy to the
Trost diphosphine ligand prepared by amidation of (R*,R*)-
2
1
,2-diaminocyclohexane,6 1 and 2 are expected to exhibit
that two complexes, which are identical in the C case, would
interesting catalytic properties.
2
be diastereomeric in the C1 case. Thus, in a square-planar
complex (Figure 1) containing a bidentate C -symmetric ligand,
We are grateful to Delphine Marches and Richard Holzwarth
for synthetic work. The project was supported by EU (grant
no. HPRN-CT-2001-00187).
2
the two vacant coordination sites are homotopic. With threefold
symmetry each rotation of 120° yields an identical situation,
resulting in three homotopic coordination sites in an octahedral
complex with a tridentate ligand having a threefold rotational
axis (Figure 1). For this reason, the preparation of chiral ligands
with rotational symmetry is an important issue.
References
1
2
J. K. Whitesell, Chem. Rev., 1989, 89, 1581.
C. Moberg, Angew. Chem., Int. Ed. Engl., 1998, 37, 248.
We present here the syntheses of C -symmetric diphosphine
2
3 F. Lake and C. Moberg, Eur. J. Org. Chem., 2002, 3179.
4 M. Cernerud, A. Skrinning, I. Bérgère and C. Moberg, Tetrahedron:
Asymmetry, 1997, 8, 3437.
1
and C -symmetric triphosphine 2 starting from dipodal and
3
tripodal amines. The required amines were prepared by a
previously developed modular approach, whereby a chiral
N-activated aziridine, in turn obtained from easily available
enantiopure amino alcohols, reacted with a primary amine or
5 K. Ishihara, Y. Karumi, S. Kondo and H. Yamamoto, J. Org. Chem.,
1
998, 63, 5692.
(a) B. M. Trost, D. L. Van Vranken and C. Bingel, J. Am. Chem. Soc.,
992, 114, 9327; (b) B. M. Trost, J. Org. Chem., 2004, 69, 5813.
6
1
ammonia to give chelating bis(tosylamides) and tris(tosyl-
amides), respectively (Scheme 1).3 After deprotection, the
Received: 7th September 2004; Com. 04/2351
desired C - and C -symmetric amines are obtained.
†
2
3
Ligand 1: compound 5 (1 mmol, 43 mg), 2-(diphenylphosphino)-
For the preparation of ligand 1, (S)-N-tosyl-2-isopropyl-
benzoic acid (2.1 mmol, 643 mg), DCC (2.2 mmol, 454 mg), and DMAP
(0.11 mmol, 13.4 mg) in CH Cl (6.4 ml) were stirred at room tempe-
rature for 14 h. The reaction mixture was filtered through celite, the filter
cake was washed with CH2Cl2, and the solvent was removed in vacuo.
Purification by flash chromatography [hexane/EtOAc (3:1) to which
i
aziridine (3, R = Pr ) was reacted with butylamine to give
2
2
i
dipodal tosylamide 4 (R = Pr , R' = Bu) with time averaged C2
symmetry in 85% yield, using a procedure analogous to that
4
used for the corresponding triflates. Deprotection of the amino
0
.5% Et N and 0.5% MeOH were added] afforded compound 1 as a
groups using aqueous HBr and phenol gave 5 (with two primary
amino groups) in 83–92% yield. The analogous ring opening
with ammonia has been shown to proceed in high yield using
3
white foam-like solid. Yield 64%; R 0.23 (30% ethyl acetate in hexane);
f
1
[
a]24 = +30.6 (c 1.37, CHCl ); mp 166.2–166.8 °C. H NMR (CDCl3,
3
4
00 MHz) d: 7.43 (dd, 2H, J 7.6 and 4.0 Hz), 7.19–7.35 (m, 20H), 7.16
dt, 2H, J 7.6 and 1.0 Hz), 7.00 (dt, 2H, J 7.6 and 1.0 Hz), 6.91 (dd, 2H,
J 7.8 and 4.0 Hz), 6.24 (d, 2H, J 8.3 Hz), 4.04–4.15 (m, 2H), 2.40–2.53
i
microwave irradiation to yield 6 (R = Pr ). Deprotection, forming
(
7
, was performed by the same procedure as that used for 4.
In order to finally obtain phosphine ligands 1 and 2, amines 5
(
(
m, 1H), 2.23–2.40 (m, 1H), 2.47 (dd, 2H, J 12.6 and 9.1 Hz), 2.29
dd, 2H, J 12.7 and 5.9 Hz), 1.81–1.94 (m, 2H), 1.18–1.40 (m, 4H),
and 7 were reacted with 2-(diphenylphosphino)benzoic acid.
In the reaction with 5, amide coupling was performed using
N,N'-dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)-
0.72–0.81 (t, 3H), 0.85 (d, 6H, J 7.05 Hz), 0.73 (d, 6H, J 7.05 Hz).
1
3
C NMR (CDCl , 500 MHz) d: 169.5, 142.5 (d, J 26.5 Hz), 138.2 (d,
3
pyridine (DMAP), providing the C -symmetric ligand in 64%
J 12.1 Hz), 137.9 (d, J 11.3 Hz), 135.8 (d, J 21.2 Hz), 134.7, 134.4,
134.25, 134.20, 134.0, 130.2, 129.1, 128.9 (several signals), 128.41,
2
†
yield. Use of the same procedure for the preparation of C -
3
3
1
1
28.38, 55.5, 54.0, 52.2, 29.9, 28.9, 21.1, 19.5, 17.6, 14.7. P NMR
symmetric 2 gave an impure compound, which proved difficult
to purify. However, by changing to 1-[3-(dimethylamino)propyl]-
(CDCl , 500 MHz) d: –9.51. Found (%): C, 75.94; H, 7.29; N, 5.09.
3
Calc. for C H N O P (%): C, 76.17; H, 7.25; N, 5.12.
5
2
59
5
2 2
3
-ethylcarbodiimide hydrochloride (EDC) and N-hydroxy-
‡
Ligand 2: a solution of 7 (1 mmol, 0.27 g) and 2-(diphenylphosphino)-
5
benzotriazole (HOBt), the desired product was obtained in
3
benzoic acid (3.1 mmol, 950 mg) in CH Cl (20 ml) was added dropwise
to a solution of EDC (4.5 mmol, 860 mg) and HOBt (4.5 mmol, 600 mg)
in CH Cl (20 ml) at 0 °C. Ethyldiisopropylamine (5 mmol, 0.68 ml) was
‡
2
2
0% yield.
The symmetry of the ligands is evident from their NMR
2
2
1
13
31
spectra. The two ligands exhibited one set of H, C and
P
added dropwise to the resulting mixture. After being stirred at 0 °C for
signals for the phosphorus-containing substituents on the central
nitrogen atoms, clearly demonstrating the identity of the substi-
4
h, the reaction mixture was allowed to stir overnight at room tempera-
ture. The mixture was then extracted with water, 1 M HCl, 1 M NaOH,
and NaHCO (sat aq.). The organic layer was dried over MgSO , and the
3
4
solvent was evaporated. The crude product obtained as a yellow oil was
R
R
purified by flash chromatography (hexane/ethyl acetate, 7:3) to give 2
R' NH2
R' N
R' N
1
Ts
N
NHTs 2
NH2
NH2
as a white solid (30%). Rf = 0.25 (hexane/ethyl acetate, 7:3). H NMR
2
3
(
CDCl , 400 MHz) d: 7.32 (dd, 3H, J 6.8 and 3.8 Hz), 7.22–7.03 (m,
4
5
3
NH3
33H), 6.86 (dt, 3H, J 7.5 Hz, J 1.0 Hz), 6.79 (dd, 3H, J 8.0 and 4.8 Hz),
6
.10 (d, 3H, J 9.4 Hz), 4.05 (m, 3H), 2.55–2.61 (m, 3H), 2.19–2.24 (m,
H), 1.69–1.76 (m, 3H), 0.75 (d, 9H, J 6.8 Hz), 0.64 (d, 9H, J 6.8 Hz).
R
R
R
3
3
N
N
1
3
C NMR (CDCl , 400 MHz) d: 169.3, 141.9 (d, J 25.5 Hz), 138.2 (d,
NHTs 3
3
J 10.1 Hz), 138.1 (d, J 8.8 Hz), 136.5 (d, J 21.1 Hz), 134.7, 134.6, 134.4,
6
7
1
5
34.2, 134.0, 130.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.2, 128.1, 56.2,
Scheme 1
31
2.0, 30.0, 20.2, 17.3. P NMR (CDCl , 500 MHz) d: –8.77.
3
Mendeleev Commun. 2004 277