SPECIAL TOPIC
Superior Non-Symmetrical NCP Pincer Type Palladacycle Catalyst Precursor
2895
Scheme 1 Synthesis of palladacycle 5 from the chloropalladation of (5-dimethylamino-pent-3-ynyl) diisopropyl phosphinite
isopropyl phosphinite, efficiently promotes the Suzuki the best reported systems in the literature. The applica-
cross-coupling reaction of aryl chlorides without the need tions of non-symmetrical pincer palladacycles such as 5 as
for the addition of external phosphines.
catalyst precursors for the Suzuki coupling of sterically
demanding substrates and for other coupling reactions are
currently under investigation in our Laboratory.
The phosphinite ligand has been easily obtained in 86%
yield from the reaction of 5-dimethylamino-pent-3-yn-1-
ol with diisopropylchlorophosphine. The simple addition
of (5-dimethylamino-pent-3-ynyl) diisopropyl phosphin-
ite to a methanolic solution of Li2PdCl4 at 0 °C generates
palladacycle 5 in 58% yield as a light-yellow air and wa-
ter-stable solid.
All reactions were carried out under an Ar atmosphere in an oven-
dried resealable Schlenk tube. PdCl2 was purchased from Degussa.
Aryl chlorides, CsF, and i-Pr2PCl were purchased from Acros. 4-
NCC6H4B(OH)2 and 4-CH3C(O)C6H4B(OH)2 were purchased from
Combi-Blocks, Inc. C6H5B(OH)2, 4-MeOC6H4B(OH)2, 4-
MeC6H4B(OH)2, 2-MeOC6H4B(OH)2 and 1-naphthylboronic acid
were prepared according to the previously published procedures.10
Chemicals were used without further purification. Dioxane was
dried over metallic Na. NMR spectra were recorded on a Varian In-
ova 300 spectrometer. IR spectra were measured on a Bomem B-
102 spectrometer. Mass spectra were obtained on a GC/MS Shi-
madzu QP-5050 (EI, 70 eV). GC analyses were performed on a
Hewlett-Packard-5890 GC with a FID and 30 meter capillary col-
umn with a dimethylpolysiloxane stationary phase.
An initial optimisation of the reaction conditions such as
solvent (dioxane, THF, DMF, and DMA), base (K3PO4,
K2CO3, KF, CsCO3 and CsF) and temperature showed
that dioxane/CsF mixture at 130 °C gave the best results
for the coupling of aryl chlorides with aryl boronic acids
catalysed by 5 (Equation 1 and Table 1).
Synthesis of (5-Dimethylamino-pent-3-ynyl) Diisopropyl Phos-
phinite; Typical Procedure
Diisopropylchlorophosphine (720 mg, 4.7 mmol) was added slow-
ly, under Ar, to a stirred mixture of 5-dimethylamino-pent-3-yn-1-
ol (600 mg, 4.7 mmol), DMAP (10 mg) and Et3N (480 mg, 4.7
mmol) in anhyd Et2O (20 mL). After addition, stirring was contin-
ued for additional 24 h. The reaction mixture was washed with aq
10% Na2CO3 solution (2 × 20 mL), then dried with Na2CO3 and the
solvent was evaporated, affording the desired amino phosphinite as
a pale yellow oil (988 mg, 86% yield), sufficiently pure for further
work.
Equation 1
For example, the coupling reaction of chlorobenzene and
2-tolylboronic acid in the presence of palladacycle 5 gave
the corresponding biphenyl in 98% isolated yield (entry
1). It is clear from Table 1 that both electron-rich and elec-
tron-poor aryl chlorides are efficiently coupled in the
presence of 5 to furnish the corresponding biaryl products
in excellent yields, and a wide variety of functional groups
are tolerated in both aryl chloride and aryl boronic acid.
1H NMR (CDCl3): d = 3.81 (dt, 3JPH = 9.0 Hz, 3JHH = 7.1 Hz, 2 H,
5
CH2OP), 3.21 (t, JHH = 2.2 Hz, 2 H, CH2N), 2.49 (dtt, 3JHH = 7.1
5
4
Hz, JHH = 2.2 Hz, JPH = 0.7 Hz, 2 H, CH2C≡C), 2.29 (s, 6 H,
NMe2), 1.71 (dheptet, 3JHH = 7.1 Hz, 2JPH = 1.2 Hz, 2 H, CH), 1.09
(dd, 3JHH = 7.1 Hz, 3JPH = 10.5 Hz, 6 H, CH3), 1.03 (dd, 3JHH = 7.1
Hz, 3JPH = 15.9 Hz, 6 H, CH3).
Interestingly, palladacycle 5 is also a highly efficient cat-
alyst precursor for the coupling of sterically demanding
substrates such as 1,3,5-trimethyl-2-bromobenzene. Thus,
the reaction of 2-tolylboronic acid with 1,3,5-trimethyl-2-
bromobenzene under the same reactions employed in
Table 1 (using 0.5% of 5) affords the cross-coupled prod-
uct in 78% yield (Equation 2).
13C {1H} NMR (CDCl3): d = 81.8, 75.9 (C≡C), 70.5 (d, 2JPC = 20.0
1
Hz, CH2OP), 48.0 (CH2N), 44.0 (NMe2), 27.9 (d, JPC = 16.0 Hz,
3
2
CH), 21.6 (d, JPC = 6.6 Hz, CH2C≡C); 17.8 (d, JPC = 20.0 Hz,
CH3), 16.8 (d, 2JPC = 8.0 Hz, CH3).
31P {1H} NMR (CDCl3): d = –93.3.
Synthesis of the Pincer Palladacycle 5; Typical Procedure
A Li2PdCl4 solution was prepared by dissolving PdCl2 (720 mg,
4.06 mmol) and LiCl (432 mg, 10.2 mmol) in MeOH (20 mL) with
gentle heating. (5-Dimethylamino-pent-3-ynyl) diisopropyl phos-
phinite (988 mg, 4.06 mmol), dissolved in MeOH (5 mL), was add-
ed under stirring to the former solution, which had been cooled to 0
ºC. The stirring was continued at the same temperature for 3 h. The
solvent was evaporated under reduced pressure and CH2Cl2 (20 mL)
was added. The resulting suspension was stirred at r.t. for 3 h. The
Equation 2
In conclusion we have prepared a highly efficient catalyst
precursor for the coupling of boronic acids with aryl chlo-
rides and, from the standpoint of yields, it ranks amongst solvent was evaporated and the residue was extracted with hot hex-
anes (2 × 20 mL). Drying of the combined extract with MgSO4 and
Synthesis 2003, No. 18, 2894–2897 © Thieme Stuttgart · New York