excess of 90 and 91%. By changing the PPh
2
group of 1c to
i
the P Pr
2
0%, probably partly owing to the P Pr moiety being a
2
group (ligand 1e), the ee was lowered from 90 to
Scheme 1. Enantioselective Allylic Alkylation of 2
i
7
weaker π-acceptor leading to a decrease in regioselectivity
of the nucleophilic attack. The observed results indicate, that
the steric control also has to be fine-tuned. Since nucleophilic
attack is preferred cis to the S-donor group, this should be
even more favorable the smaller the thioether unit is.
i
Changing the SMe group of 1d to the S Pr group (ligand 1f)
decreases the ee from 91 to 80%. The steric influence is
demonstrated with P,S-ligand 1g, which yields the racemic
product, since the thioether group is connected to the bulky
ferrocenyl core.
2
f 3 shown in Scheme 1 demonstrated that S,S- and Se,S-
Owing to the high reactivity of the Pd-allyl complexes
with ligands 1c and 1d, it was possible to run the reaction
at -20 °C to enhance the stereoselectivity. Subsequently,
we concentrated on ligand 1c, despite 1d giving slightly
better results, since the former can be obtained in much
higher yields and it is far less air sensitive. The extraordinary
air sensitivity of 1d is quite surprising, as the structural
difference between 1c and 1d is very small. The product
could be isolated in quantitative yield and with an ee of 97%
by simultaneous decrease of the amount of catalyst from x
ligands 1a and 1b displayed low reactivity and selectivity
Table 1).
(
Table 1. Reaction Conditions, Yields, and Enatiomeric Excess
Values in 2 f 3
1
E1
E2
R
T (°C)
x
y
t (h) yield (%)a ee (%)b
a
b
c
c
d
e
f
SiPr STol Et
SiPr SePh Et
SMe PPh2 Et
SMe PPh2 Et
SMe PPh2 Me
SMe P Pr2 Et
SiPr PPh2 Me
PPh2 SMe Me
20 2.5 5.5 100
20 2.5 5.5 100
84
65
99
99
98
99
99
99
20
44
90
97
91
70
80
0
1
1
)
2.5 to x ) 1.0 mol % (y ) 2.2 mol % 1c). The high
20 2.5 5.5
0.16
selectivities are noteworthy, since ligands 4 bearing the
-20 1.0 2.2 24
20 2.5 5.5
20 2.5 5.5
20 2.5 5.5
20 2.5 5.5
0.16
i
1
1
1
g
1
a Yield of isolated 3. b Determined by H NMR (CDCl3) with chiral
shift reagent Eu(tfc)3. (R) Configuration determined by the sign of optical
rotation.
stereogenic center in R-position yield the product with an
ee of only 34% (R ) ethyl) or 67% (R ) cyclohexyl). By
changing the alkyl group of the sulfur donor atom to a chiral
sugar moiety an ee of 88% was reached.
To the best of our knowledge, an enantiomeric excess of
By employing P,S-ligands, we found a completely different
situation. The Pd-π-allyl complex is enourmously activated
by the phosphorus group as a strong π-acceptor. In combina-
tion with the thioether unit as a good donor and weak
acceptor, we have a hybrid system that allows electronic
control of the nucleophilic attack to the allylic system. As
is well-known, the nucleophilic attack is expected to proceed
10c
7
9
7% is the best value in this reaction so far reported for a
P,S-ligand. Compared to N,S-ligands, P,S-ligands have the
trans to the better π-acceptor (here the PR
the electronic density of the allylic system is lowest at this
2
group), since
(9) Selected Papers: (a) Boog-Wick, K.; Pregosin, P. S.; Trabesinger,
G. Organometallics 1998, 17, 3254-3264. (b) Koning, B.; Meetsma, A.;
Kellogg, R. M. J. Org. Chem. 1998, 63, 5533-5540. (c) Anderson, J. C.;
James, D. S.; Mathias, J. P. Tetrahedron: Asymmetry 1998, 9, 753-756.
(d) Chesney, A.; Bryce, M. R.; Chubb, R. W. J.; Batsanov, A. S.; Howard,
J. A. K. Tetrahedron: Asymmetry 1997, 8, 2337-2346.
position. This strategy has previously been successfully
8
9
10
applied by the use of P,N-, N,S-, and P,S-Pd chelates.
When ligands 1c and 1d were used, the reaction proceeded
quantitatively within 10 min at room temperature in CH Cl
y ) 99 and 98%), yielding the product with an enantiomeric
(10) (a) Albinati, A.; Eckert, J.; Pregosin, P.; R u¨ egger, H.; Salzmann,
2
2
R.; St o¨ ssel, C. Organometallics 1997, 16, 579-590. (b) Barbaro, P.; Currao,
A.; Herrmann, J.; Nesper, R.; Pregosin, P. S.; Salzmann, R. Organometallics
(
1
996, 15, 1879-1888. (c) Albinati, A.; Pregosin, P. S.; Wick, K.
Organometallics 1996, 15, 2419-2421. (d) Herrmann, J.; Pregosin, P. S.;
Salzmann, R. Organometallics 1995, 14, 3311-3318.
(
7) (a) M u¨ ller, A.; Diemann, E. Thioethers. In ComprehensiVe Coordina-
tion Chemistry; Wilkinson, G., Ed.; Pergamon Press: Oxford, 1987; Vol.
(11) A mixture of (π-allyl)palladium chloride dimer (3.7 mg, 0.01 mmol)
and ligand 1c (10.4 mg, 0.022 mmol) in 1.5 mL CH2Cl2 was stirred at
room temperature for 1 h. The solution was cooled to -20 °C and 1.0
mmol of acetate 2 (252 mg) in 0.5 mL of CH2Cl2 was added, followed by
the nucleophile [alkylation: 3.0 mmol dimethylmalonate (0.34 mL) and
3.0 mmol N,O-bis(trimethylsilyl)acetamide (BSA, 0.74 mL); amination: 2.5
mmol benzylamine (0.27 mL)] and KOAc (1.0 mg, 0.01 mmol) sequentially.
After completion (TLC analysis) or after a certain time elapsed, the reaction
mixture was diluted with 20 mL of Et2O, quenched with 20 mL of saturated
aqueous NH4Cl, and washed with 20 mL of saturated brine. The organic
layer was dried over MgSO4. After evaporation of the solvent in vacuo,
the crude product was purified by column chromatography (eluant: 20%
diethyl ether in hexane).
2
, pp 551-558. (b) Hutton, A. T. Palladium(II): Sulfur Donor Complexes.
In ComprehensiVe Coordination Chemistry; Wilkinson, G., Ed.; Pergamon
Press: Oxford, 1987; Vol. 5, pp 551-558.
(8) Selected papers: (a) Lee, S.; Lim, C. W.; Song, C. E.; Kim, K. M.;
Jun, C. H. J. Org. Chem. 1999, 64, 4445-4451. (b) Ahn, K. H.; Cho, C.-
W.; Park, J.; Lee, S. Tetrahedron: Asymmetry 1997, 8, 1179-1185. (c)
Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.; Salzmann, R. J.
Am. Chem. Soc. 1996, 118, 1031-1037. (d) Sprinz, J.; Helmchen, G.
Tetrahedron Lett. 1993, 34, 1769-1772. (e) Von Matt, P.; Pfaltz, A. Angew.
Chem. 1993, 105, 614-615; Angew. Chem. Int. Ed. 1993, 32, 566-568.
(
f) Dawson, G. J.; Frost, C. G.; Williams, J. M. J.; Coote, S. J. Tetrahedron
Lett. 1993, 34, 3149-3152.
1864
Org. Lett., Vol. 1, No. 11, 1999