A simple protocol for the synthesis of chiral bidentate imidodiphosphoric tetramide ligands: Application in the metal-free asymmetric allylation of aldehydes

Article abstract of DOI:10.1016/S0040-4039(01)01047-4

The reaction of a series of chiral phosphorus triamides with BuLi and subsequent addition of a phosphoroxychloride diamide afforded the corresponding imidodiphosphoric tetramides in high yield. The use of enantiomerically pure diamides allowed access to bidentate imidodiphosphoric tetramides without loss of optical purity. These bidentate ligands have been used successfully to catalyze the addition of allyltrichlorosilane to aldehydes in an enantioselective fashion up to 60% ee.

Full text of DOI:10.1016/S0040-4039(01)01047-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5417–5419
A simple protocol for the synthesis of chiral bidentate
imidodiphosphoric tetramide ligands: application in the metal-free
asymmetric allylation of aldehydes
Jasmin Hellwig, Thomas Belser and J u¨ rgen F. K. M u¨ ller*
Institute of Inorganic Chemistry, University of Basel, Spitalstraße 51, CH-4056 Basel, Switzerland
Received 15 June 2001
Abstract—The reaction of a series of chiral phosphorus triamides with BuLi and subsequent addition of a phosphoroxychloride
diamide afforded the corresponding imidodiphosphoric tetramides in high yield. The use of enantiomerically pure diamides
allowed access to bidentate imidodiphosphoric tetramides without loss of optical purity. These bidentate ligands have been used
successfully to catalyze the addition of allyltrichlorosilane to aldehydes in an enantioselective fashion up to 60% ee. © 2001
Elsevier Science Ltd. All rights reserved.
Phosphoric triamides have found widespread use in
organic chemistry. The strong donor properties and
triethylamine proceeds smoothly and gives the phos-
phoric triamides 2a–g in high yields (see Table 1). In
1
4,5
Lewis basicity make them excellent ligands for small
and hard metal ions and thus modulate the reactivity of
metal centers. Recently, chiral representatives of phos-
phoric triamides have been considered as strong Lewis
bases in asymmetric catalysis in the absence of
metals. To obtain a rigid chiral environment around
a coordinated Lewis acid, chiral bidentate phosphoric
triamide-derived ligands may be employed. However,
such ligands are hitherto still unknown. In our contri-
bution we would like to present an efficient synthetic
approach to that novel class of chiral ligands. It turned
out, that these ligands act as highly enantioselective
chiral catalysts for the asymmetric allylation of alde-
hydes in the reaction with trichloroallylsilane.
a subsequent step, deprotonation of the amides is
achieved with n-BuLi followed by addition of a second
equivalent of 1a–g leading to the final imidophosphoric
6
tetramides 3a–g in high yields. Chiral primary amines
as bridging units allowed the synthesis of
diastereomeric imido phosphorus tetramides 3d,e in
excellent yields. As a suitable test reaction for asymmet-
ric, Lewis-base-promoted catalysis we have chosen the
allylation of aldehydes with trichlorosilane (Table 2).
The initial observation that Lewis bases are able to
accelerate this type of CꢀC bond-forming reaction,
originally reported by Sakurai, stimulated in 1994 Den-
mark and later Iseki to introduce chiral phosphoric
2
,3
7
–13
triamides as Lewis-base catalysts for this reaction.
The reaction of the chiral bicyclic phosphoric diamides
We reasoned that a bidentate ligand would be better in
stabilizing the putative hexa-coordinate siliconate spe-
1a–g with primary amines in toluene and in presence of
R1
N
R1
N
R1
R1
N
O
O
P
N
O
2
O
R NH
n-BuLi
2
P
P
P
NEt , toluene
1a-g, toluene
Cl
3
N
NH
R2
N
N
N
N
R1
R2
R1
R1
R1
1a-g
2a-g
3a-g
Keywords: allylation; catalysis; imidophosphortetramides.
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01047-4

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J. Hellwig et al. / Tetrahedron Letters 42 (2001) 5417–5419
OH
Table 1. Synthesis of bidentate imidophosphoric tetra-
SiCl3 10 Mol-% 3a-g
mides 3a–g
Catalyst
3a
PhCHO +
Ph
-
78°C, CH Cl2
2
R1
R2
Ph
Yield (%)
4
R1
R1
Me
Me
Me
Me
Me
83
87
76
68
64
79
85
3b
3c
3d
3e
p-CF -C H
p-MeO-C H
(R)-PhEt
(S)-PhEt
Ph
O
O
P
3 6 4
N
N
6
4
P
N
N
N
R1
R2
R1
3f
CH Ph
(CH ) Bu
2
t
3
g
Ph
2
2
3a-g
Table 2. Allylation of benzaldehyde in presence of 3a–g
cies compared to a monodentate ligand thus inducing
higher enantioselectivities.
R3
ee (%)a
Catalyst
Yield (%)
†
3
a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
63
65
88
15
31
67
65
24
27
18
19
60
49
32
Firstly, catalyst 3a led to a high yield but only a low ee
of 24% in the product alcohol 4. The introduction of
electron-withdrawing substituents in the para-position
of the aromatic bridging unit in 3b reduced the catalytic
activity and only moderate yields were accessible (25%)
accompanied by a ee of 27%. Electron-donating sub-
stituents in this position had a tremendous effect on the
rate and the yield of the reaction, almost after 45 min
the reaction was complete and high yields of 4 were
generated. Again the enantioselectivity had not
changed. The introduction of chiral-bridging amines in
3b
3c
3d
3
3
3
e
f
g
a
Determined by HPLC (OD-H Daicel).
the diastereomeric catalysts 3d,e gave raise to a high ee
with 3e (60% ee, 31% yield, matched case) and to a low
ee with 3d (19% ee, 15% yield, mismatched case), but in
general moderate yields. The replacement of the N-
methyl groups in the five-membered heterocycle by
more bulky benzyl groups in 3f led to a good ee of 49%
and high yield (67%), in contrast to the introduction of
†
Typical procedure: To a solution of 260 mg (0.62 mmol) (S,S)-2g in
2
0 ml toluene, 0.25 ml (0.68 mmol) of n-BuLi (2.8 M in n-hexane)
was added at −78°C. After 1 h a solution of 224 mg (0.62 mmol) 1g
in 1 ml toluene was added dropwise to the reaction mixture. The
reaction mixture was refluxed for 12 h. The solvent was removed in
vacuo and the resulting brown oil was purified by columm chro-
t
2
(CH ) Bu groups, which led only to 32% ee (65%
yield).
2
.
matography (hexane/ethyl acetate=1:1), which afforded 3g as a
colorless solid (390 mg, 85%). Experimental data for 3g: R =0.7
f
In summary we have shown the bidentate imidophos-
phoric triamides are easily accessible in a few steps.
These compounds act as enantioselective catalysts in
the allylation of benzaldehydes with allyltrichlorosilane.
Further studies focus on the use of Lewis-base catalysts
1
(
hexane/ethyl acetate=1:1). H NMR (500 MHz, CDCl ): l 0.82 (s,
3
3
3
6H), 1.15–2.01 (m, 24H), 2.58–2.69 (bm, 2H), 2.71–3.15 (m, 8H),
1
3
.51–3.64 (m, 2H), 6.62 (m, 2H), 6.69 (m, 1H), 7.05 (m, 2H).
C
NMR (125 MHz, CDCl ): l 23.95, 24.34, 24.81, 28.16, 28.56, 28.94,
3
2
3
6
9.21, 29.33, 29.39, 29.67, 29.75, 29.92, 30.08, 30.16, 38.32, 38.69,
9.20, 39.42, 39.91, 40.72, 41.82, 42.21, 43.15, 60.74, 61.43, 61.94,
2.03, 62.14, 62.23, 126.67, 128.09, 131.32, 140.14. P NMR (202
14
in metal-free epoxide openings.
3
1
MHz, CDCl , OP(OPh) as external standard l −18): l 18.37,
3
3
+
2
(
1.30. MS (EI, 70 eV) m/z (%)=746 [M] (15), 671 (23), 420 (58). IR
References
KBr): 2934, 2863, 2812, 1212, 1004 cm− . Typical allylation proce-
1
dure: To a solution of 200 mg (1.88 mmol) benzaldehyde and 150
1
2
. Dykstra, R. R. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; John Wiley & Sons: New
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mg (0.19 mmol) 3g in 5 ml dry CH Cl , 0.27 ml (1.88 mmol) of
2
2
trichloroallylsilane was added at −78°C. After 4 h, 2 ml methanol
were added dropwise to the reaction mixture, the stirring was
continued for 30 min at −78°C and the solution was then treated
with saturated NaHCO solution followed by extraction with ethyl
3
acetate. The organic layer was dried over Na SO4 and the solvent
3. For a review, see: Buono, G.; Chiodi, O.; Wills, M.
2
was removed in vacuo. The resulting yellow oil was purified by
columm chromatography (hexane/ethyl acetate=10:1), which
Synlett 1999, 377.
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4
5
6
afforded 4a as a colorless oil (32% ee, 180 mg, 65%). Experimental
1
data for 4a: R =0.1 (hexane/ethyl acetate=10:1). H NMR (500
f
MHz, CDCl ): l 2.07 (bs, 1H), 2.4–2.45 (m, 2H), 4.63–4.65 (m, 1H),
3
5
.04–5.10 (m, 2H), 5.68–5.75 (m, 1H), 7.16–7.28 (m, 5H). 13C NMR
(
125 MHz, CDCl ): l 43.77, 73.24, 118.35, 125.76, 127.49, 128.36,
3
+
1
34.41, 143.81. MS (FAB) m/z (%)=148 [M] (26), 123 (47), 109
38). Anal. calcd for C10H12O: C, 81.04; H, 8.16. Found: C, 80.63;
H, 8.50.
(
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