New phosphine-imine ligands derived from D-gluco- and D-galactosamine in Pd-catalysed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tetlet.2015.06.031

New phosphine-imine chiral ligands which were easily prepared from D-gluco- and D-galactosamine furnished a high level of enantiomeric excess (up to 99%) in the Pd(0)-catalysed asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propenyl acetate with malonates.

Full text of DOI:10.1016/j.tetlet.2015.06.031

Tetrahedron Letters xxx (2015) xxx–xxx
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Tetrahedron Letters
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New phosphine–imine ligands derived from D-gluco- and
D-galactosamine in Pd-catalysed asymmetric allylic alkylation
⇑
Izabela Szulc, Robert Kołodziuk, Bogusław Kryczka, Anna Zawisza
´
´
Department of Organic and Applied Chemistry, University of Łódz, Tamka 12, 91-403 Łódz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
New phosphine–imine chiral ligands which were easily prepared from D-gluco- and D-galactosamine
Received 8 April 2015
Revised 8 May 2015
Accepted 11 June 2015
Available online xxxx
furnished a high level of enantiomeric excess (up to 99%) in the Pd(0)-catalysed asymmetric allylic
alkylation of racemic 1,3-diphenyl-2-propenyl acetate with malonates.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
D-Glucosamine
D-Galactosamine
Iminophosphine
Homogeneous catalysis
Asymmetric alkylation
Palladium
The preparation of new and efficient enantiopure ligands for
asymmetric catalysis is a continued research focus for many
groups. Impressive results have been obtained in a wide range of
catalytic asymmetric reactions using carbohydrate derived
ligands.1 Derivatives of the most accessible NH2-containing sugar,
The ligands 5 and 6 were easily prepared in two steps according
to Scheme 1.
Glucosamine hydrochloride 1 and galactosamine hydrochloride
2
were first treated with trimethylsilylchloride (TMSCl) and
hexamethyl disilazane (HMDS) in pyridine5 to yield per-O-silyl
D
-glucosamine, have been evaluated as chiral ligands in the asym-
protected a
-derivatives 35b and 46 as colourless oil. Under these
metric allylic substitution reaction which is a fundamental trans-
formation in organic synthesis and one of the most powerful
tools for the formation of carbon–carbon and carbon–heteroatom
conditions the amino functional group remained unprotected.5b
Condensation of 2-(diphenylphosphino)-benzaldehyde onto
D
-glucopyranose 3 and D-galactopyranose 4 derivatives in toluene
bonds. In particular,
D
-glucosamine based phosphorus–oxazoline2
furnished the corresponding phosphine–imine derivatives 57 and
and phosphine–amide3 ligands have produced excellent results.
Several phosphine–imine ligands with a pyranoside backbone have
also been developed for the Pd-catalysed allylic substitution of
1,3-diphenyl-2-propenyl acetate (Fig. 1).4,3c,d
68 in 77% and 67% yield, respectively.
Initially, we investigated the palladium-catalysed allylic
substitution of 1,3-diphenyl-2-propenyl acetate 7 with dimethyl-
malonate as a model system using the chiral
D-glucosamine
Previous studies have indicated that having the imine–
phosphine residue at C2 provides better enantioselectivities than
when the residue is located at the C1 position of the pyranoside
backbone. Additionally replacement of the C2 by an amine group
has also provided good results.3c
derived phosphine–imine ligand 5 (Table 1, entries 1–9).
Using NaH as base and THF as the solvent; the yield was only
50% after 24 h, with a low enantioselectivity (34% ee) in favour of
the (R)-enantiomer (Table 1, entry 1). The use of a mixture of
N,O-bis(trimethylsilyl)acetamide (BSA) and KOAc as base afforded
(S)-8 in higher yields and enantioselectivity (Table 1, entries
2–9). These results indicated that enantioselectivity depends on
the reaction conditions. We found it difficult to explain this ‘chiral
switching’ when the bases were changed, which was discovered by
Li,9 Beller10 and Wang.1f Additionally, we examined the influence
of solvent (THF or CH2Cl2), Pd/ligand ratio and substrate/
nucleophile ratio on the outcome of the asymmetric allylic
alkylation. The best results were obtained with a Pd/ligand ratio
Herein, we report the simple and efficient synthesis of novel
phosphine–imine chiral ligands from commercially available
D
-gluco and D-galactosamine hydrochloride and their application
in the Pd-catalysed allylic alkylation reaction with various
nucleophiles.
⇑
Corresponding author. Tel.: +48 42 6355802; fax: +48 42 6655162.
E-mail address: azawisza@chemia.uni.lodz.pl (A. Zawisza).
http://dx.doi.org/10.1016/j.tetlet.2015.06.031
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Szulc, I.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.06.031

2
I. Szulc et al. / Tetrahedron Letters xxx (2015) xxx–xxx
OAc
O
OR
OR
O
O
AcO
AcO
-gluco
R = Me; 56% (S)
OR
RO
RO
X
RO
RO OAc
-galacto
X
PPh2
PPh2
N
N
N
PPh2
OAc
D
D
-gluco
D
X = CH2, R = Ac; 20% (S)
X = O, R = H; 0.4% (R)
X = O, R = Ac; 0.6% (S)
R = H; 1.3% (R)
R = Ac; 2.7% (S)
R = t-Bu; 87% (S)
R = Bn; 82% (S)
OAc
O
OBn
O
MeO
R =
; 86% (S)
OBn
O
AcO
OR
AcO
PPh2
N
OBn
AcO HN
PPh2
AcO OAc
D
-gluco
D
-gluco
20% (S)
71% (S)
Figure 1. Phosphine–imine ligands and enantioselectivities obtained in the Pd(0)-catalysed asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propenyl acetate with
dimethyl malonate.
OH
OTMS
O
OTMS
O
O
TMSCl, HMDS
Py, rt
Ph2P CHO
toluene, 60 °C
HO
OH
TMSO
OTMS
TMSO
TMSO
-gluco (77%)
OTMS
PPh2
HO NH2⋅HCl
TMSO NH2
N
1.
2.
D
D
-gluco
-galacto
3.
4.
D
D
5.
6.
D
-gluco (82%)
-galacto (82%)
D-galacto (67%)
Scheme 1. Synthesis of ligands 5 and 6.
Table 1
Optimisation of reaction conditions for ligand 5a
[Pd(η3-C3H5)Cl]2
chiral ligand 55
OAc
Nu
Ph
+
Nu-H
Ph
Ph
Ph
base
7
8
Entry
Nu–H
Nu–H (equiv)
Pd/L ratio
Base
NaH
KOAc, BSA
KOAc, BSA
KOAc, BSA
KOAc, BSA
KOAc, BSA
KOAc, BSA
KOAc, BSA
KOAc, BSA
Solvent
Temp (°C)
Yieldb (%)
eec (%)
config.d
1
2
3
4
5
6
7
8
9
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Me)2
3
3
3
2
2
2
2
2
2
1:2
1:2
1:2
1:1
1:1
1:2
1:2
1:2
1:2
THF
THF
CH2Cl2
THF
CH2Cl2
THF
CH2Cl2
CH2Cl2
CH2Cl2
25
25
25
25
25
25
25
0
50
98
96
97
98
97
97
96
97
34 (R)
49 (S)
40 (S)
55 (S)
70 (S)
55 (S)
73 (S)
81 (S)
80 (S)
ꢀ20
a
b
c
Reaction conditions: [7]:[NaH]:[Pd] = 1:3:0.05; [7]:[KOAc]:[BSA]:[Pd] = 1:0.05:2 or 3:0.05.
Isolated product.
Determined by HPLC analysis (column Chiralcel OJ-H 0.46 ꢁ 25 cm).
d
Determined by comparison with an authentic sample.1e
of 1:2 and substrate/nucleophile ratio of 1:2 in CH2Cl2. In this case,
an enantioselectivity of 73% with a yield of 97% was observed after
a reaction time of 24 h at 25 °C (Table 1, entry 7). Lowering the
temperature to 0 °C and ꢀ20 °C improved the selectivity of the
reaction, giving an ee of 81% and 80%, respectively (Table 1,
entries 8 and 9).
The phosphine–imine ligands
D
-gluco 5 and
D
-galacto 6 were
also applied to allylic alkylation and allylic amination reactions
using nucleophiles such as: diethyl malonate, dimethyl methyl-
malonate, benzylamine and isopropylamine (Table 2, entries
3–11). The reaction with ligand 5 and diethyl malonate at 25 °C
required longer reaction times and was characterised by low yields
(30%) and an ee of 71%. Increasing the temperature to 36 °C
afforded the product in an improved yield of 96% after 24 h but
did not improve the selectivity of the reaction (Table 2, entries 3
and 4). Ligand 6 was more reactive with the same nucleophile
and gave 8 with an improved yield and enantioselectivity; 83%
ee at 25 °C and 99% ee at 0 °C in favour of the (R)-enantiomer
(Table 2, entries 5 and 6). A similar correlation was observed for
the reactions with dimethyl methylmalonate (Table 2, entries
7–9) however, in this reaction, both ligands 5 and 6 gave the
Ligand 6 derived from
D-galactosamine was more reactive
under the same conditions and gave compound 8 with higher
enantioselectivity; 85% ee at 25 °C and 99% ee at 0 °C (Table 2,
entries 1 and 2). It should be noted that the configuration of the
substituent at the C4 position of the carbohydrate moiety of the
D-galacto ligand 6 also had an influence on the configuration of
the alkylation product 8. The (R) configuration of the obtained pro-
duct was opposite to that observed for the reaction using ligand 5
(Table 2, entries 1 and 2).
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I. Szulc et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
Table 2
Acknowledgments
Asymmetric allylic alkylation of racemic 1,3-diphenylprop-2-enyl acetate 7 using
various nucleophilesa
This work was part-financed by the European Union within the
European Regional Development Fund (POIG.01.01.02-14-102/09).
Entry Ligand Nu–H
Temp
(°C)
Time
(h)
Yieldb
(%)
eec (%)
(config.)d
1
2
3
4
5
6
7
8
6
6
5
5
6
6
5
6
6
5
6
CH2(CO2Me)2
CH2(CO2Me)2
CH2(CO2Et)2
CH2(CO2Et)2
CH2(CO2Et)2
CH2(CO2Et)2
MeCH(CO2Me)2 25
MeCH(CO2Me)2 25
MeCH(CO2Me)2
BnNH2
25
0
25
36
25
0
24
24
78
24
24
24
24
48
48
96
96
98
96
30
96
98
97
33
95
84
65
0
85 (R)
99 (R)
71 (S)
67 (S)
83 (R)
99 (R)
74 (R)
75 (R)
96 (R)
35 (R)
—
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.06.
031.
References and notes
9
10
11
0
36
36
1. (a) Diéguez, M.; Pàmies, O.; Claver, C. Chem. Rev. 2004, 104, 3189–3215; (b)
Diéguez, M.; Pàmies, O.; Ruiz, A.; Diaz, Y.; Castillon, S.; Claver, C. Coord. Chem.
Rev. 2004, 248, 2165–2192; (c) Diéguez, M.; Claver, C.; Pàmies, O. Eur. J. Org.
Chem. 2007, 4621–4634; (d) Woodward, S.; Diéguez, M.; Pàmies, O. Coord.
Chem. Rev. 2010, 254, 2007–2030; (e) Coll, M.; Pàmies, O.; Diéguez, M. Org. Lett.
2014, 16, 1892–1895; (f) Xing, A.; Pang, Z.; Li, H.; Wang, L. Tetrahedron 2014,
70, 8822–8828; (g) Boysen, M. M. K. Carbohydrates—Tools for Stereoselective
Synthesis; Wiley-VCH, 2013.
i-PrNH2
a
b
c
Reaction conditions: [7]:[Nu–H]:[KOAc]:[BSA]:[Pd]:[L] = 1:2:0.05:2:0.05:0.1.
Isolated product.
Determined by HPLC analysis (column Chiralcel OJ-H and Chiralcel OD-H
0.46 ꢁ 25 cm).
Determined by comparison with an authentic sample.1e
d
2. (a) Gläser, B.; Kunz, H. Synlett 1998, 53–55; (b) Yonehara, K.; Hashizume, T.;
Mori, K.; Ohe, K.; Uemura, S. Chem. Commun. 1999, 415–416; (c) Yonehara, K.;
Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 9374–9380;
(d) Mata, Y.; Diéguez, M.; Pàmies, O.; Claver, C. Adv. Synth. Catal. 2005, 347,
1943–1947; (e) Mata, Y.; Pàmies, O.; Diéguez, M. Adv. Synth. Catal. 2009, 351,
3217–3234; (f) Hashizume, T.; Yonehara, K.; Ohe, K.; Uemura, S. J. Org. Chem.
2000, 65, 5197–5201.
3. (a) Tollabi, M.; Framery, E.; Goux-Henry, C.; Sinou, D. Tetrahedron: Asymmetry
2003, 14, 3329–3333; (b) Glegoła, K.; Framery, E.; Goux-Henry, C.;
Pietrusiewicz, K. M.; Sinou, D. Tetrahedron 2007, 63, 7133–7141; (c) Glegoła,
K.; Johannesen, S. A.; Thim, L.; Goux-Henry, C.; Skrydstrup, T.; Framery, E.
Tetrahedron Lett. 2008, 49, 6635–6638; (d) Johannesen, S. A.; Glegoła, K.; Sinou,
D.; Framery, E.; Skrydstrup, T. Tetrahedron Lett. 2007, 48, 3569–3573; (e)
Konovets, A.; Glegoła, K.; Penciu, A.; Framery, E.; Jubault, P.; Goux-Henry, C.;
Pietrusiewicz, K. M.; Quirion, J. C.; Sinou, D. Tetrahedron: Asymmetry 2005, 16,
3183–3187; (f) Bauer, T.; Bartoszewicz, A. Pol. J. Chem. 2007, 81, 2115.
4. (a) Borriello, C.; Cucialito, M. E.; Panunzi, A.; Ruffo, F. Inorg. Chim. Acta 2003,
353, 238–244; (b) Brunner, H.; Schönherr, M.; Zabel, M. Tetrahedron:
Asymmetry 2003, 1115–1122.
(R)-enantiomer. These results may be explained by the steric influ-
ence of the methyl substituent in the starting malonate. Finally, we
performed the allylic amination reaction using benzylamine as the
nucleophile. The reaction furnished the desired allylic amine in a
moderate yield of 65% after 96 h at 36 °C and an ee of 35% in favour
of the (R)-enantiomer (Table 2, entry 10). Isopropylamine was
completely unreactive under these conditions (Table 2, entry 11)
and it is possible that complexation of the primary amine to the
metal centre may result in deactivation of the catalyst, or that
the amine may be interfering with the Pd-bound imine functional-
ity of the ligand.3d
To determine the mode of complexation of phosphine–imine
ligands 5 and 6 with palladium, an NMR and IR study of the palla-
dium complex was made using ligand 6 before and after complex-
ation with palladium. The 1H NMR spectra of free ligand 6
displayed the imine proton at 9.00 ppm, which was not shifted
after chelatation with palladium, which excluded the possibility
of chelatation with nitrogen. The IR spectroscopic data of complex
6 with palladium did not reveal a bathochromic shift with respect
to the free ligand,11 with a vC@N stretching vibration band at
1636 cmꢀ1. This also excluded the coordination of the imine nitro-
gen to the palladium metal centre. A significant downfield shift of
the single 31P resonances of ligand 6 to 15.86 ppm after complex-
ation compared to ꢀ16.57 ppm for the free ligand confirmed coor-
dination of the phosphine moiety to the palladium centre. Finally,
the best results were obtained with a Pd/ligand ratio of 2:1
(Table 1), suggesting that the imino ligand binds to the palladium
metal centre in a monodentate fashion (Fig. 2).
5. (a) Wartchow, C. A.; Wang, P.; Bednarski, M. D.; Callstron, M. R. J. Org. Chem.
1995, 60, 2216–2226; (b) Irmak, M.; Groschner, A.; Boysen, M. M. K. Chem.
Commun. 2007, 177–179.
6. Synthesis of 2-amino-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-a-D-galactopyranose
4. To suspension of galactosamine hydrochloride (2.5 g, 11.59 mmol,
a
2
1 equiv) in pyridine (50 mL), HMDS (24.2 mL, 115.9 mmol, 10 equiv) was
added followed by TMSCl (14.7 mL, 115.9 mmol, 10 equiv). The resulting
mixture was stirred at rt and the reaction monitored via TLC (petroleum ether/
ethyl acetate 5:1). During the reaction a lot of salt byproduct precipitated. After
completion of the reaction (approx. 3 h), the mixture was evaporated in vacuo
with a cooling trap between rotary evaporator and pump stand. The residue
was twice co-evaporated with toluene to remove the residual pyridine. The raw
material was then submitted to short column filtration over silica gel
(petroleum ether/ethyl acetate 5:1, Rf = 0.71) to remove the pyridinium salts.
The product can be stored in a refrigerator for several months. Colourless oil,
4.45 g, 82% yield, [a]
20 = +10.0 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3):
D
d = 0.06, 0.07, 0.12, 0.14 (4s, 36H, 4OSi(CH3)3), 1.31 (s, 2H, NH2), 2.94 (dd, 1H,
J = 9.8, 7.6, H-2), 3.31 (dd, 1H, J = 9.8, 2.8, H-3), 3.35 (dd, 1H, J = 6.5, 5.7, H-5),
3.53 (dd, 1H, J = 9.7, 5.7, H-6), 3.61 (dd, 1H, J = 9.7, 7.4, H-60), 3.72 (d, 1H, J = 2.8,
H-4), 4.31 (d, 1H, J = 7.6, H-1). 13C NMR (150 MHz, CDCl3): d = ꢀ0.5, 0.4, 0.6, 0.7
(4OSi(CH3)3), 54.9 (C-2), 61.2 (C-6), 70.3 (C-4), 75.6 (C-5), 76.0 (C-3), 99.6 (C-1).
In conclusion, we have demonstrated that the novel chiral
ligands 5 and 6 are efficient ligands for the asymmetric allylic alky-
lation of racemic 1,3-diphenyl-2-propenyl acetate with malonates,
requiring only 0.5 mol % of the Pd complex to provide a high enan-
tioselectivity (up to 99% ee). These ligands can be prepared in two
C18H45NO5PSi4 (467.90): calcd: C, 46.21; H, 9.69; N, 2.99; found: C, 46.29; H,
9.46; N, 3.01.
7. Synthesis and spectral data for 1,3,4,6-tetra-O-trimethylsilyl-2-deoxy-2-{[2-
(diphenylphosphino)benzoyl]imino}-a-D-glucopyranose 5 see: Olszewska, B.;
Szulc, I.; Kryczka, B.; Kubiak, A.; Porwan´ ski, S.; Zawisza, A. Tetrahedron:
Asymmetry 2013, 24, 212–216.
steps using commercially available
hydrochloride. These P–N types of ligands utilise the chirality of
-gluco and -galactosamine and induce chirality to the coordina-
tion sphere solely by phosphorus atom coordination.
D-gluco and D-galactosamine
8. Synthesis of 1,3,4,6-tetra-O-trimethylsilyl-2-deoxy-2-{[2-(diphenylphosphino)benzoyl]
imino}-
a
-
D-galactopyranose 6. In a Schlenk tube under nitrogen, 2-amino-2-
D
D
deoxy-1,3,3,6-tetra-O-trimethylsilyl-
a-D-galactopyranose (1 g, 2.1 mmol) and
2-(diphenylphosphino)benzaldehyde (621 mg, 2.1 mmol) were stirred in
toluene (40 mL) at 60 °C for 12 h. After concentration, the residue was
purified by flash column chromatography on silica gel, eluting with
hexane/ethyl acetate, 5:1 (Rf = 0.82). Yellow solid, 1.04 g, 67% yield, mp 57.8–
59.8 °C,
20 = +7.5 (c 0.5, CHCl3); IR (KBr): 1636 cmꢀ1 (vC@N); 1H NMR
(600 MHz, CDCl3): d = ꢀ0.08, 0.01, 0.10, 0.13 (4s, 36H, 4OSi(CH3)3), 3.29 (dd, 1H,
J = 9.4, 7.4, H-2), 3.53 (dd, 1H, J = 6.5, 5.6, H-5), 3.65 (dd, 1H, J = 9.7, 5.6, H-6),
3.73 (dd, 1H, J = 9.7, 7.3, H-60), 3.80 (dd, 1H, J = 9.4, 2.6, H-3), 3.83 (d, 1H, J = 2.6,
H-4), 4.80 (d, 1H, J = 7.4, H-1), 6.93–6.95 (m, 1H, C6H5), 7.25–7.35 (m, 12H,
C6H5), 8.13–8.16 (m, 1H, C6H5), 9.00 (d, 1H, J = 5.8, NCH). 13C NMR (150 MHz,
CDCl3): d = ꢀ0.3, 0.5, 0.7, 0.9 (4OSi(CH3)3), 61.7 (C-6), 70.2 (C-4), 74.1 (C-3),
75.0 (C-2), 75.7 (C-5), 97.2 (C-1), 126.9 (d, J = 4.3, C6H5), 128.4, 128.5, 128.6,
a
OTMS
O
TMSO
O
[a]
D
C6H5
C6H5
Pd+
OTMS
TMSO
OTMS
PPh2 Ph2P
TMSO
TMSO
N
OTMS
N
Figure 2. The mode of complexation ligands 5 and 6 with palladium.
Please cite this article in press as: Szulc, I.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.06.031

4
I. Szulc et al. / Tetrahedron Letters xxx (2015) xxx–xxx
128.7, 130.2, 133,6, 133.9, 134.0, 134.1 (C6H5), 136.5 (d, J = 7.1, C6H5), 136.6 (d, 10. Alberico, E.; Gladiali, S.; Taras, R.; Junge, K.; Beller, M. Tetrahedron: Asymmetry
J = 7.7, C6H5), 138.1 (d, J = 20.1, C6H5), 139.6 (d, J = 18.5, C6H5), 161.6 (d, J = 27.9,
NCH). 31P NMR (243 MHz, CDCl3) d = ꢀ16.57. C37H58NO5PSi4 (740.18): calcd: C,
60.04; H, 7.90; N, 1.89; found: C, 59.79; H, 7.85; N, 1.88.
2010, 21, 1406–1410.
11. Mogorosi, M. M.; Mahamo, T.; Moss, J. R.; Mapolie, S. F.; Slootweg, J. C.;
Lammertsma, K.; Smith, G. S. J. Organomet. Chem. 2011, 696, 3585–3592.
9. Feng, J.-Q.; Bohle, D. S.; Li, C.-J. Tetrahedron: Asymmetry 2007, 18, 1043–1047.
Please cite this article in press as: Szulc, I.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.06.031