The ligands can be synthesized in two steps from the easily
available planar chiral ferrocenyl boronic acid 1 (Scheme
1).7-8 The Suzuki cross-coupling between 1 and aryl iodide
Table 1. Room-Temperature Suzuki Cross-Coupling of
4-Chloro-acetophenone and Phenyl Boronic Acid
Scheme 1. Ligand Synthesis
entrya
ligand 3
3a
3b
3c
[Pd]
conv. [%]b,c
yield [%]
1
2
3
4
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2dba3
99 (98)
>99 (>99)
96 (92)
>99 (>99)
<1
84
91
73
85
3d
3a ,b,c, or d
a Conditions: 1.0 equiv of aryl chloride (0.07 M in THF), 2.0 equiv of
aryl boronic acid, 5 mol % [Pd], 6 mol % ligand 3, 3.0 equiv of K3PO4, 8
equiv of H2O, 24 h. b Measured by GC to an internal standard. c Conversion
after 1 h in parenthesis.
At the outset, the catalytic performance of Pd(OAc)2:3b
was tested in the cross-coupling of various activated aryl
chlorides and aryl boronic acids, as summarized in Table
2.9-10 The yield of the coupling products were good to very
2a-d affords moderate to good yields of the aryl ferrocenyl
sulfoxides 3a-d using previously reported optimized condi-
tions.
Table 2. Suzuki Cross-Coupling of Activated Aryl Chlorides
Using Ligand 3b and Pd(OAc)2
Standard sulfoxide cleavage with t-BuLi generates the
optically pure ferrocenyl anions, which were trapped with
chlorodicyclohexylphosphine to give aryl-MOPFs 3a-d. The
phosphines were borane protected to prevent oxidation during
aqueous workup. Concomitant DABCO deprotection af-
forded the free phosphine ligands in 58-68% yield (cf.
Scheme 1). In contrast to tricyclohexylphosphine and tri-
tert-butylphosphine, these phosphines turned out to be air
stable and could be stored for month without any precautions
taken.
Initially, the performances of the aryl-MOPFs (3a-d) were
tested in the Suzuki cross-coupling of commercially available
4-chloro-acetophenone and phenyl boronic acid. Applying
Pd(OAc)2 as a palladium source and a Pd:ligand ratio of 1:1.2
afforded smooth cross-couplings at room temperature, af-
fording the corresponding biaryl compound in good to
excellent yield, as outlined in Table 1.
A variety of different bases and solvents were tested, but
the superior combination turned out to be K3PO4 in THF.
Notably, Pd2dba3 and aryl-MOPFs 3a-d did not catalyze
the reaction (entry 5, Table 1). As already mentioned, ligands
3a-d were effective under the exact same reaction condi-
tions, yet the highest yield (91%) was obtained when the
palladium complex of 3b was employed. This indicated that
ligand 3b could function as a model for other substrate
couplings (vide infra).
a Conditions: 1.0 equiv of aryl chloride (0.07 M in THF), 2.0 equiv of
aryl boronic acid, 5 mol % Pd(OAc)2, 6 mol % ligand 3b, 3.0 equiv of
K3PO4, 8 equiv of H2O. Reaction time: 24 h at room temperature. Reaction
time not optimized. b Measured by GC to an internal standard. c Isolated
yield.
good but highly dependent on the Pd:ligand ratio. This was
reflected in the outcome from entry 4, where the Pd:ligand
ratio was 1:2.5 and the conversion only was 3%. The strong
(9) For ferrocene based monophosphine ligands in Suzuki cross-coupling
of aryl chlorides, see: (a) Pickett, T. E.; Richards, C. J. Tetrahedron Lett.
2001, 42, 3767. (b) Liu, S. Y.; Choi, M. J.; Fu, G. C. Chem. Commun.
2001, 2408. (c) Kataoka, N.; Shelby, Q.; Stambuli, J. P. Hartwig, J. F. J.
Org. Chem. 2002, 67, 5553. (d) Pickett, T. E.; Roca, F. X.; Richards, C. J.
J. Org. Chem. 2003, 68, 2592.
(10) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1998, 120, 9722. (b) Gsto¨ttmayr, C. W. K.; Bo¨hm, V. P. W.; Herdtweck,
E.; Grosche, M.; Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1363.
(c) Wolfe, J. P.; Buchwald, S. P. Angew. Chem., Int. Ed. 1999, 38, 2413.
(d) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. 2000, 39,
4153. (e) Andreu, M. G.; Zapf, A.; Beller, M. Chem. Commun. 2000, 2475.
(f) Botella, L.; Na´jera, C. Angew. Chem., Int. Ed. 2002, 41, 179.
(7) For the synthesis of optically pure (Sp,Ss)-1, see also ref 6c.
(8) The ferrocene sulfoxide chemistry was originally developed by Kagan
et al.: (a) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. B. J.
Org. Chem. 1997, 62, 6733. (b) Riant, O.; Argouarch, G.; Guillaneux, D.;
Samuel, O.; Kagan, H. B. J. Org. Chem. 1998, 63, 3511. See also: (c)
Hua, D. H.; Lagneau, N. M.; Chen, Y.; Robben, P. M.; Clapham, G.;
Robinson, P. D. J. Org. Chem. 1996, 61, 4508. For the azaferrocenyl series,
see: (d) Hansen, J. G.; Søtofte, I.; Johannsen, M. Org. Lett. 2001, 3, 499.
(e) Hansen. J. G.; Johannsen, M. J. Org. Chem. 2002, 68, 1266.
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