Palladium-catalysed asymmetric allylic alkylation using new chiral phosphinite-nitrogen ligands derived from D-glucosamine

Article abstract of DOI:10.1039/a810041a

Novel phosphinite-nitrogen chiral ligands synthesized from D-glucosamine furnish a high level of enantiomeric excess (up to 96% ee] in palladium-catalysed allylic alkylation.

Full text of DOI:10.1039/a810041a

Palladium-catalysed asymmetric allylic alkylation using new chiral
phosphinite–nitrogen ligands derived from d-glucosamine
Koji Yonehara, Tomohiro Hashizume, Kenji Mori, Kouichi Ohe* and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku,
Kyoto 606-8501, Japan. E-mail: uemura@scl.kyoto-u.ac.jp
Received (in Cambridge, UK) 24th December 1998, Accepted 25th January 1999
Novel phosphinite–nitrogen chiral ligands synthesized from
d-glucosamine furnish a high level of enantiomeric excess
(up to 96% ee) in palladium-catalysed allylic alkylation.
with the palladium complex generated in situ by mixing chiral
3
ligand 1 and [Pd(h -C3H5)Cl]2. The results are summarized in
Table 1. In the presence of only 0.25 mol% Pd complex, the
reaction proceeded very smoothly with high enantioselectivity.
The best result was obtained when the reaction was carried out
in toluene at 0 °C (entries 1–5).
Palladium-catalysed allylic alkylation is known as a powerful
synthetic tool for the construction of carbon–carbon bonds.1
Enantioselective versions of the reaction have been explored
and large enantiomeric excesses have been achieved using
various C2- and C1-symmetric bidentate chiral ligands.2 While
they are excellent ligands, expensive chiral sources and tedious
synthetic steps are sometimes needed for their synthesis.
Recently carbohydrates have attracted a great deal of interest as
a source of chiral ligands, because they exist widely in nature
and have many chiral centres in their skeletons.3,4 Now, we
report the synthesis of novel phosphinite–nitrogen chiral
ligands from commercial d-glucosamine hydrochloride
(2-amino-2-deoxy-d-glucopyranoside hydrochloride), which
have been less frequently used as chiral ligands,4,5 and their
application to the Pd-catalysed allylic alkylation.
First, we prepared compound 1 according to the procedures
illustrated in Scheme 1. N-Acylation of d-glucosamine hydro-
chloride with (PriCO)2O and NaOMe, and the protection of both
4,6- and 1,3-positions by benzylidene and acetyl groups gave d-
glucopyranoside 2 in good yield. This compound could be
readily converted into oxazoline derivative 3 using SnCl4
without removing the benzylidene protecting group.6 Deacetyl-
ation of the 3-position followed by treatment with Ph2PCl and
Et3N gave phosphinite–nitrogen chiral ligand 1. This ligand was
easily oxidized by air in solution, but was relatively stable in the
solid state.
Next, we synthesized phosphinite–nitrogen ligands 5–9† by
the procedure described in Scheme 1 using anhydrides or acid
chlorides such as BnCOCl, (ButCO)2O, PhCOCl, (BuiCO)2O
and Ac2O, and applied them to the palladium-catalysed
asymmetric allylic alkylation under the previously determined
optimum conditions (entries 6–10).‡ As can be seen in Table 1,
a dramatic substituent effect on the enantiomeric excess was
observed. The use of the ligand 5 (R = Bn) or 6 (R = But)
(entries 6 and 7) gave lower enantioselectivities compared with
the case of ligand 1. On the contrary, the use of the ligand 7 (R
= Ph) or 8 (R = Bui) increased the selectivity (entries 8 and 9).
Furthermore, it was noted that the highest enantiomeric excess
(96% ee) was achieved using ligand 9 (R = Me) (entry 10).
We suppose that nucleophilic attack occurs predominantly at
the allyl terminus trans to the Pd–P bond in the p-allyl-
palladium complex.8 Since the (S)-product was obtained as the
major enantiomer, the reaction probably proceeds through endo
intermediate A rather than exo intermediate B, as shown in
Table 1 Palladium-catalysed asymmetric allylic alkylation with chiral
ligands 1 and 5–9a
Asymmetric allylic substitution of 1,3-diphenyl-3-acetoxy-
prop-1-ene with dimethyl malonate in the presence of N,O-
bis(trimethylsilyl)acetamide (BSA) and KOAc was carried out
Entry
L*
Solvent T/°C
t/h
Ee (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
5
6
7
8
9
CH2Cl2 room temp.
1
85 (S)
THF
room temp.
0.5 86 (S)
88 (S)
0.5 84 (S)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
room temp.
60
0
0
0
0
0
0
1
6
18
6
6
6
90 (S)
78 (S)
83 (S)
94 (S)
95 (S)
96 (S)
10
6
a
The reaction was carried out under Ar using 1,3-diphenyl-3-acetoxy-
prop-1-ene (1.0 mmol), dimethyl malonate (3.0 mmol), BSA (3.0 mmol),
Scheme 1 Reagents and conditions: i, (PriCO)2O, MeONa, MeOH, room
temp., 24 h, 82%; ii, PhCHO, ZnCl2, room temp., 5 h, then Ac2O, pyridine,
room temp., 24 h, 43% (2 steps); iii, SnCl4, CH2Cl2, room temp., 1 h, 52%;
iv, K2CO3, MeOH, room temp., 1 h, 73%; v, Ph2PCl, Et3N–THF (1:1), cat.
DMAP, room temp., 15 min, 46%.
3
KOAc (0.05 mmol), solvent (2.0 ml), [Pd(h -C3H5)Cl]2 (0.25 mol%) and
L* (0.55 mol%). Product was isolated in quantitative yield. b Measured by
HPLC; the absolute configuration was determined by optical rotation (ref.
7).
Chem. Commun., 1999, 415–416
415

toluene was added ligand 9 (2.62 mg, 5.5 3 1023 mmol) under Ar
atmosphere. After 30 min, racemic 1,3-diphenyl-3-acetoxyprop-1-ene (0.25
g, 1.0 mmol) was added and the solution was stirred for 30 min. N,O-
Bis(trimethylsilyl)acetamide (0.74 ml, 3.0 mmol), dimethyl malonate (0.35
ml, 3.0 mmol) and KOAc (4.8 mg, 0.05 mmol) were then added at 0 °C and
the solution was stirred at this temperature. After the reaction was
completed (6 h), the solvent was evaporated in vacuo and column
chromatography on silica gel (hexane–EtOAc 5:1) of the residue yielded
the pure product. The enantiomeric excess was determined to be 96% ee by
HPLC (Daicel Chiralcel AD column, 1.0 ml min21, hexane–PriOH
95:5).
1 J. Tsuji, Palladium Reagents and Catalysis, Innovations in Organic
Synthesis, Wiley, New York, 1995.
2 For an overview see: B. M. Trost and D. L. Van Vranken, Chem. Rev.,
1996, 96, 395.
Scheme 2
3 N. Nomura, Y. C. Mermet-Bouvier and T. V. RajanBabu, Synlett, 1996,
745; P. Barbano, A. Currao, J. Herrmann, R. Nesper, P. S. Pregosin and
R. Salzmann, Organometallics, 1996, 15, 1879; A. Albinati, P. S.
Pregosin and K. Wick, Organometallics, 1996, 15, 2419; K. Boog-Wick,
P. S. Pregosin and G. Trabesinger, Organometallics, 1998, 17, 3254; K.
Boog-Wick, P. S. Pregosin, M. Wo¨rle and A. Albinati, Helv. Chim. Acta,
1998, 81, 1622.
4 B. Gla¨ser and H. Kunz, Synlett, 1998, 53.
5 T. V. RajanBabu, T. A. Ayers, G. A. Halliday, K. K. You and J. C.
Calabrese, J. Org. Chem., 1997, 62, 6012.
Scheme 2. In the transition state, the steric repulsion in A
between the phenyl group on phosphorous and the substrate
appears smaller than that in B.
In summary, we have demonstrated that the novel chiral
ligands 1 and 5–9 are very efficient ligands for asymmetric
allylic alkylation, using only 0.25 mol% Pd complex to provide
a high enantioselectivity (up to 96% ee). These ligands can be
prepared in six steps using commercial d-glucosamine hydro-
chloride as an inexpensive natural chiral source. They are a new
type of P–N ligands using only the chirality of d-glucosamine,
which is communicated to the coordination sphere built with
both phosphorous and nitrogen. To the best of our knowledge,
this is the first example of the application of phosphinite–
nitrogen chiral ligands9 to asymmetric allylic alkylation.
Application of these ligands to other asymmetric reactions is
now in progress.
6 V. K. Srivastava, Carbohydr. Res., 1982, 103, 286.
7 J. Sprinz and G. Helmchen, Tetrahedron Lett., 1993, 34, 1769.
8 The phosphorous atom is a better p-acceptor than the nitrogen atom in p-
allyl–palladium complexes bearing a P–N bidentate ligand. For exam-
ples, see: B. Åkermark, B. Krakenberger, S. Hansson and A. Vitagliano,
Organometallics, 1987, 6, 620; P. E. Blo¨chl and A. Togni, Organome-
tallics, 1996, 15, 4125; E. Pen˜a-Cabrera, P.-O. Norrby, M. Sjo¨gren, A.
Vitagliano, V. De Felice, J. Oslob, S. Ishii, D. O’Neill, B. Åkermark and
P. Helquist, J. Am. Chem. Soc., 1996, 118, 4299; H. Steinhagen, M.
Reggelin and G. Helmchen, Angew. Chem., Int. Ed. Engl., 1997, 36,
2108.
Notes and references
9 Some imino-phosphinite ligands and their application to other asym-
metric reactions have been reported: C. G. Arena, F. Nicolo, D. Drommi,
G. Bruno` and F. Faraone, J. Chem. Soc., Chem. Commun., 1994, 2251; R.
Sablong, C. Newton, P. Dierkes and J. A. Osborn, Tetrahedron Lett.,
1996, 37, 4933; R. Sablong and J. A. Osborn, Tetrahedron Lett., 1996, 37,
4937.
† Selected data for 9; dH 2.05 (d, J 1.1, 3H), 3.61–3.69 (m, 2H), 3.76 (t, J
8.5, 1H), 4.23–4.32 (m, 2H), 4.36 (dd, J 3.3, 8.5, 1H), 5.35 (s, 1H), 5.98 (d,
J 7.4, 1H), 7.23–7.53 (m, 15H); dC 14.3, 62.9, 68.6, 69.4 (d, J 5.2), 79.6 (d,
J 3.6), 82.3 (d, J 20.2), 101.2, 102.2, 126.0–136.9 (16 C), 141.9 (d, J 21.3),
142.2 (d, J 16.4), 165.0; dP 114.5; [a2D0 275.7 (c 0.25, CHCl3).
‡ Procedure for the Pd-catalysed enantioselective allylic alkylation: To a
3
stirring solution of [Pd(h -C3H5)Cl]2 (0.91 mg, 2.5 3 1023 mmol) in
Communication 8/10041A
416
Chem. Commun., 1999, 415–416