was quenched with H2O. The aqueous layer was extracted with
Et2O, and washed with brine. The combined organic layers were
dried over anhydrous MgSO4. After concentration in vacuo, the
residue was purified by flash chromatography on silica gel or
preparative TLC to afford arylamine 3.
were 0.18, 0.40, 0.42, and 0.47 (mol L¹1). Conditions B: twice
amounts of [Pd(dba)2]/2XPhos: 1a (0.50 mmol), 2c (0.55
mmol), [Pd(dba)2] (10 ¯mol), XPhos (20 ¯mol), CsF (0.75
mmol), and DMI (0.50 mL). Average concentrations (3 times)
of 3ac after 10, 20, 30, and 60 min were 0.31, 0.40, 0.40,
and 0.45 (mol L¹1). Conditions C: twice amounts of 1a: 1a
(1.0 mmol), 2c (0.55 mmol), [Pd(dba)2] (5.0 ¯mol), XPhos (10
¯mol), CsF (0.75 mmol), and DMI (0.50 mL). Average con-
centrations (3 times) of 3ac after 10, 20, 30, and 60 min were
0.20, 0.45, 0.46, and 0.48. Conditions D: twice amounts of 2c:
1a (0.30 mmol), 2c (0.66 mmol), [Pd(dba)2] (3.0 ¯mol), XPhos
(6.0 ¯mol), CsF (0.45 mmol), and DMI (0.30 mL). Average
concentrations (3 times) of 3ac after 10, 20, 30, and 60 min
were 0.40, 0.51, 0.54, and 0.59. Conditions E: twice amounts
of CsF: 1a (0.30 mmol), 2c (0.33 mmol), [Pd(dba)2] (3.0 ¯mol),
XPhos (6.0 ¯mol), CsF (0.90 mmol), and DMI (0.30 mL).
Average concentrations (3 times) of 3ac after 10, 20, 30, and
60 min were 0.79, 0.80, 0.81, and 0.89.
Reaction of p-Bromotoluene with Tris(trimethylsilyl)-
amine (eq 5). To a mixture of p-bromotoluene (387 mg, 2.3
mmol), CsF (343 mg, 2.3 mmol), [Pd(dba)2] (3.0 mg, 5.2 ¯mol),
XPhos (4.9 mg, 10 ¯mol), and DMI (0.50 mL) in a screw vial
were added tris(trimethylsilyl)amine (116 mg, 0.49 mmol) and
decane as an internal standard, and the mixture was stirred at
140 °C for 48 h. The reaction mixture was quenched with H2O.
The aqueous layer was extracted with Et2O, and washed with
brine. The combined organic layers were dried over anhydrous
MgSO4. After concentration in vacuo, the residue was purified
by flash chromatography on silica gel or preparative TLC to
afford arylamine tri(p-tolyl)amine (63 mg, 0.22 mmol) in 44%
yield.
Time Course Experiment: The Reaction of p-Bromo-
toluene (1a) with N-Trimethylsilylamine 2 (Figure 1).
General procedure: To a mixture of p-bromotoluene (1a, 0.20
mmol), CsF (0.30 mmol), [Pd(dba)2] (2.0 ¯mol), XPhos (4.0
¯mol), DMF (20 ¯L, an internal standard) and DMI (0.20 mL)
in a screw vial was added N-trimethylsilylamine 2 (0.22 mmol).
The vial was closed with a screw cap and taken outside the
dry box. The reaction was monitored by 1H NMR at 90 °C. The
reaction with 2a: Average yields (3 times) of 3aa after 10, 20,
and 30 min were 90%, 91%, and 91%. The reaction with 2b:
Average yields (3 times) of 3ab after 10, 20, 30, 40, 50, and
60 min were 10%, 39%, 62%, 79%, 79%, and 82%. The reac-
tion with 2c: Average yields (3 times) of 3ac after 10, 20, 30,
40, 50, and 60 min were 18%, 40%, 42%, 43%, 47%, and 47%.
The reaction with 2d: Average yields (3 times) of 3ad after 10,
20, 30, 40, 50, and 60 min were 4%, 5%, 6%, 7%, 8%, and 9%.
Treatment of N-TMS-Diphenylamine (2a) with CsF
(eq 8). General procedure: (N-Trimethylsilyl)diphenylamine
(24 mg, 0.098 mmol) was added to a mixture of CsF (23 mg,
0.15 mmol) in DMI (0.10 mL) prepared in a 3 mL-vial in a dry
box. The vial was closed with a screw cap and taken outside
the dry box. The mixture was heated at 100 °C for 30 min and
subjected to hydrolysis by CDCl3. The crude product was
Competition Experiment between (N-Trimethylsilyl)-
diphenylamine (2a) and N-Trimethylsilyl-N-methylaniline
(2b) toward p-Bromotoluene (1a) (eq 11). To a mixture of
1a (34 mg, 0.20 mmol), CsF (45 mg, 0.30 mmol), [Pd(dba)2]
(1.1 mg, 1.9 ¯mol), XPhos (1.9 mg, 4.0 ¯mol), and DMI (0.20
mL) in a screw vial were added 2a (54 mg, 0.22 mmol) and 2b
(39 mg, 0.22 mmol), and the resulting mixture was stirred at
100 °C for 3 h. The reaction mixture was analyzed by 1H NMR
to determine the formation of 3aa and to estimate yields of
3ab (17%). Finally, the reaction mixture was diluted with Et2O,
and washed with brine. The combined organic layers were
dried over anhydrous MgSO4 and concentrated in vacuo. The
residue was purified by preparative TLC to afford 3aa (36 mg,
0.14 mmol, 70%).
Competition Experiment between (N-Trimethylsilyl)-
diphenylamine (2a) and (N-Trimethylsilyl)morpholine (2d)
toward p-Bromotoluene (1a) (eq 12). To a mixture of 1a (34
mg, 0.20 mmol), CsF (90 mg, 0.59 mmol), [Pd(dba)2] (1.5 mg,
2.6 ¯mol), XPhos (2.4 mg, 5.0 ¯mol), and DMI (0.20 mL) in a
screw vial were added 2a (55 mg, 0.23 mmol) and 2d (37 mg,
0.23 mmol) and the mixture was stirred at 100 °C for 0.5 h.
1
Assay of the reaction mixture by H NMR confirmed the for-
mation of 3aa and showed that the yield of 3ad was 5%.
The reaction mixture was diluted with Et2O, and washed with
brine. The combined organic layers were dried over anhydrous
MgSO4 and concentrated in vacuo. This crude was purified by
preparative TLC to afford 3aa (46 mg, 0.18 mmol, 89% yield).
Competition Experiment between (N-Trimethylsilyl)-
diphenylamine (2a) and (N-Trimethylsilyl)aniline (2c) to-
ward p-Bromotoluene (1a) (eq 13). To a mixture of 1a (86
mg, 0.50 mmol), CsF (85 mg, 0.56 mmol), [Pd(dba)2] (3.7
mg, 6.4 ¯mol), XPhos (5.0 mg, 11 ¯mol), decane (an internal
standard, 5.0 ¯L, 0.051 mmol), and DMI (0.50 mL) in a screw
vial were added 2a (14 mg, 0.56 mmol) and 2c (110 mg, 0.56
mmol), and the mixture was stirred at 100 °C for 1 h. The
reaction mixture was quenched with H2O. The aqueous layer
was extracted with Et2O (three times), and washed with brine.
The combined organic layers were dried over anhydrous
MgSO4. After concentration in vacuo, the residue was analyzed
1
analyzed by H NMR to determine the yield of diphenylamine
(30%).
Reaction of p-Bromotoluene (1a) with Diphenylamine
(13a) (eq 10). To a mixture of p-bromotoluene (1a, 38 mg,
0.22 mmol), CsF (45 mg, 0.30 mmol), [Pd(dba)2] (1.2 mg, 2.1
¯mol), XPhos (1.9 mg, 4.0 ¯mol), and DMI (0.20 mL) in a
screw vial was added diphenylamine (40 mg, 0.24 mmol). The
vial was closed with a screw cap and taken outside the dry box.
The mixture was heated at 100 °C for 30 min and analyzed by
1H NMR to determine the yield of diphenyl(p-tolyl)amine (7%
yield). When the mixture was heated for 18 h, the yield was
about 30%.
Concentration Effect of Palladium Catalysts, CsF, 1a,
or 2c (Figure 3). Conditions A: Normal conditions (same
data as shown in Figure 1): 1a (1.0 mmol), 2c (1.1 mmol),
[Pd(dba)2] (10 ¯mol), XPhos (20 ¯mol), CsF (1.5 mmol), DMF
(20 ¯L, an internal standard), and DMI (1.0 mL). Average
concentrations (3 times) of 3ac after 10, 20, 30, and 60 min
1
by H NMR to confirm the formation of 3aa, 3ac, and 6, and
separated by HPLC to afford 3aa (63 mg, 0.24 mmol, 48%),
© 2015 The Chemical Society of Japan
Minami, Yasunori
