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Grignard reagent/CuCl was rinsed twice with 5 mL por-
tions of THF, and was placed under argon while the THF
was added. After stirring for 1 h at rt, the consumption of
the Grignard reagent was complete (as determined by GC
analysis). The reaction was quenched by pouring it directly
into an Erlenmeyer flask that contained 300 mL of ice.
Ethyl acetate (100 mL) and conc. NH4OH (3 mL) were then
added, and the mixture was stirred for 10 min, filtered
through celite, and transferred to a separatory funnel. The
aqueous layer was separated and the organic layer washed
with brine. The combined washings were then extracted
with ethyl acetate, and the extract was washed with addi-
tional brine. The organic layers were combined, dried
(Na2SO4), filtered, and concentrated. Ethyl acetate (12 mL)
was added to the residue, which was stirred and cooled in
an ice bath. Methanol (72 mL) was added, the mixture stir-
red for 1.5 h at 0 °C, and filtered on a Buchner funnel. The
white solid was rinsed with 30 mL of cold methanol, and
dried under vacuum. The yield of the title compound was
5.9 g (58%).
was filtered and dried under vacuum. The yield of the title
compound was 3.86 g.
An additional crop of crystals was obtained by concentrat-
ing the mother liquor from the third crystallization, adding
5 mL of methanol to the residue, and stirring for 4 h at rt.
An additional 200 mg of the title compound was obtained.
The combined yield was 4.1 g (47%).
An identical experiment gave 3.8 g (43%) of the title com-
pound.
Synthesis of 2-Methyl-2'-dicyclohexylphosphino-
biphenyl (3) with in situ Prepared ClPCy2 and
without CuCl
A 5 L, 4-necked flask was equipped with an overhead stirrer,
a 500 mL addition funnel, a thermocouple and a Claisen
adapter fitted with a septum and an N2 inlet. The apparatus
was flushed with N2. After the flask was charged with 1 L
THF and PCl3 (65.5 mL, 750 mmol), it was cooled to an inter-
nal temperature of ca. 14 °C with an ice/salt slurry bath.
The 500 mL addition funnel was charged with CyMgCl
(770 mL, 2 M in Et2O) in 2 portions (500 mL then 270 mL).
The CyMgCl solution was added into the 5 L flask over ca.
2 h via rapid dropwise addition with periodic breaks to pre-
vent the internal temperature from rising above 0 °C. To
help control the exotherm, the ice/salt slurry was refreshed
periodically. After addition was completed, the ice/salt bath
was removed and the reaction was allowed to warm to ambi-
ent temperature with stirring over 2 h.
A 1 L, 3-necked flask was equipped with a stirrer, a reflux
condenser and a 60 mL addition funnel and was flushed with
N2. The 1 L flask was charged with oven-dried Mg turnings
(12 g) and o-tolyl magnesium chloride (500 mL, 1 M in THF)
and was placed in a 60 °C oil bath. After the solution was al-
lowed to equilibrate for 10 15 min, the 60 mL addition fun-
nel was charged with 2-bromochlorobenzene (53.5 mL,
458 mmol). The 2-bromochlorobenzene was added to the
1 L flask dropwise (~30 45 min). After ca. one third of the
2-bromochlorobenzene had been charged, an exotherm oc-
curred inducing vigorous reflux for the remainder of the ad-
dition. Upon complete addition of 2-bromochlorobenzene,
the reaction mixture was maintained in the oil bath for 2 h.
The flask was removed from the oil bath and allowed to cool
to ambient temperature with stirring (~1 h). This solution
was transferred into the crude Cy2PCl solution via vacuum-
assisted cannula transfer. The resulting mixture was al-
lowed to stir at ambient temperature for 14 h and then
quenched with 500 mL water over ca. 20 min in order to
control the exotherm. The organic phase was removed and
filtered through a pad of Celite with an EtOAc wash
(300 mL). After the organic phase was reduced under va-
cuum to ca. 250 mL total volume, it was transferred with
minimal EtOAc to a 2 L, 3-necked, round-bottom flask fitted
with an overhead stirrer and a 500 mL addition funnel. The
solution was seeded with crystals (seeding is not necessary
but tends to produce a first batch product of higher purity)
and cooled with an ice bath, initiating crystallization. The
addition funnel was charged with 2 Â 500 mL MeOH, which
was added dropwise (~30 45 min) to complete product pre-
cipitation. The solid was isolated via vacuum filtration with
one wash (200 mL cold MeOH) and was dried under va-
cuum. Yield: 85 g (51%).
An identical experiment gave 5.3 g (53%) of the title com-
pound.
2-Dimethylamino-2'-di-tert-butylphosphino-
biphenyl (2b)
A dry, 100-mL round-bottomed flask was charged with Mg
turnings (1.37 g, 56.4 mmol) and stirrer and was equipped
with a gas inlet adapter with a septum.[18] The apparatus
was evacuated and backfilled with argon. THF (25 mL) was
added and the mixture was stirred and heated in a bath at
70 °C. 2-Bromo-N,N-dimethylaniline (6.0 g, 3.8 mL, 30 mmol)
was then added in 4 equal portions over the course of 15 min
and, after the reflux caused by Grignard formation had sub-
sided, the temperature of the oil bath was lowered to 60 °C (it
took ca. 30 min for the bath to cool). 2-Bromochlorobenzene
(4.9 g, 3.0 mL, 26 mmol) was then added in 4 equal portions
over the course of ca. 20 min, the mixture was stirred for 2 h
15 min at 60 °C and subsequently cooled to rt (an aliquot was
quenched with MeOH and analyzed by GC: no chloroben-
zene remained). CuCl (450 mg, 4.5 mmol) was then added,
and the mixture stirred for 15 min. Di-tert-butylchlorophos-
phine (5.4 g, 5.6 mL, 30 mmol) was then added via syringe
over the course of 5 min, and the mixture was heated in an
oil bath at 60 °C for 20 h. The reaction was quenched with
water (ca. 80 mL), and transferred to an Erlenmeyer flask
with 80 mL of ethyl acetate and 80 mL of hexane. Conc.
NH4OH (25 mL) was added, and the mixture was stirred for
10 min, filtered through celite, and transferred to a separa-
tory funnel. The aqueous layer was separated, and the or-
ganic layer was washed twice with water. The combined
washings were extracted with ethyl acetate, and the extract
was washed twice with water. The organic layers were com-
bined, dried (Na2SO4), filtered, and concentrated. The resi-
due was suspended in 17 mL of methanol, which was stirred
while cooling in an ice bath for 2 h. A spatula was used to
break any large pieces. A solid was filtered on a Buchner
funnel, and transferred to a round-bottomed flask. Methanol
(10 mL) was added, the suspension was stirred for 1 h while
cooled in an ice bath, and the solid was again filtered and
transferred back to the 100 mL flask. Additional methanol
(10 mL) was added, the suspension was stirred for 1.5 h at
rt and then for 1.5 h while cooled in an ice bath. Awhite solid
Adv. Synth. Catal. 2001, 343, 789±794
793