1
222
R. Yamaguchi et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 3 Preparation of Dialkylamines by Cp*Ir-Catalyzed N-Alky-
lation of Ammonium Tetrafluoroborate with Secondary Alcohols
5.0 mol% Ir), and NaHCO (251 mg, 3.00 mmol, 30 mol%). Hexan-
3
1
-ol (5.145 g, 50.4 mmol) was added by syringe and the flask was
sealed with a glass stopper. The mixture was stirred at r.t. for 30 min
and then at 140 °C for 17 h. Then, aq 2 M NaOH (20 mL) was added
to the mixture and the product was extracted with CH Cl (45 mL).
[
Cp*IrCl2]2 (cat.)
NaHCO3
NH4BF4
+
R R CH OH
1
2
(R R CH) NH
1 2
2
2
2
2
1
40 °C, 17 h
Evaporation of the solvent followed by Kugelrohr distillation (180
Entry
Alcohol
[Cp*IrCl2]2
Yielda
(%)
°C/133 mbar) gave the product; yield: 1.599 g (60%).
1
(
mol% Ir)
H NMR (270 MHz, CDCl ): d = 2.43–2.36 (t, J = 7 Hz, 6 H), 1.51–
3
1
.21 (m, 24 H), 0.98–0.85 (t, J = 7 Hz, 9 H).
1b
2b
3.0
2.0
81
84
13
C NMR (67.8 MHz, CDCl ): d = 54.3, 31.9, 27.3, 27.1, 22.6, 14.0.
OH
3
Procedure 2
Dihexylamine;
12a,13
OH
Typical Procedure
To a heavy-walled glass tube (15 mL) under an atmosphere of argon
was added NH BF (1.050 g, 10.0 mmol), [Cp*IrCl ] (80 mg, 0.10
4
4
2 2
3c
3.0
78
mmol, 2.0 mol% Ir), and NaHCO (252 mg, 3.00 mmol, 30 mol%).
OH
3
Hexan-1-ol (2.254 g, 22.1 mmol) was added by syringe and the
glass tube was sealed with a Teflon stopper. The mixture was stirred
at r.t. for 30 min and then at 140 °C for 17 h. Then, aq 2 M NaOH
(20 mL) was added to the mixture and the product was extracted
with CH Cl (45 mL). The GC yields of dihexylamine and trihexyl-
4c,d
PhCH(OH)Me
Me(CH ) CH(OH)Me
3.0
3.0
77e
5c
54f
2
5
2
2
a
Isolated yield.
amine were 75% and 9%, respectively. Evaporation of the solvent
followed by column chromatography (Florisil, hexane) gave a mix-
ture of dihexylamine and trihexylamine (1.567 g). From this mix-
ture, pure dihexylamine was isolated by further column
chromatography (Florisil, hexane); yield: 1.01 g (55%).
1
b
c
d
e
f
NH BF (10 mmol), alcohol (30 mmol), NaHCO (30 mol%).
NH BF (1.0 mmol), alcohol (3.0 mmol), NaHCO (30 mol%).
NH OAc was used instead of NH BF .
Ratio meso/dl 62:38 ( H NMR).
4
4
3
4
4
3
4
4
4
1
A mixture of diastereomers.
H NMR (270 MHz, CDCl ): d = 2.62–2.55 (t, J = 7 Hz, 4 H), 1.50–
3
1
.29 (m, 16 H), 0.90–0.85 (t, J = 7 Hz, 6 H).
In summary, we have developed a new atom-economical
and selective synthetic method for secondary and tertiary
13
C NMR (67.8 MHz, CDCl ): d = 50.1, 31.7, 30.1, 27.0, 22.5, 13.9.
3
alkylamines by (pentamethylcyclopentadienyl)iridium Procedure 3
9
,14
Dicyclohexylamine; Typical Procedure
To a 100-mL flask under an atmosphere of argon was added
NH BF (1.050 g, 10.0 mmol), [Cp*IrCl ] (81 mg, 0.10 mmol, 2.0
(Cp*Ir) complex catalyzed multiple N-alkylation of am-
monium salts with primary and secondary alcohols.
4
4
2 2
mol% Ir), and NaHCO (251 mg, 2.99 mmol, 30 mol%). Cyclohex-
3
All reactions and manipulations were carried out in a glovebox or
anol (3.015 g, 30.1 mmol) was added by syringe and the flask was
sealed with a glass stopper. The mixture was stirred at r.t. for 30 min
and then at 140 °C for 17 h. Then, aq 2 M NaOH (20 mL) was added
using standard Schlenk techniques under an atmosphere of N or ar-
2
1
13
gon. H and C NMR spectra were recorded on Jeol A-500 and EX-
70 spectrometers. Gas chromatography (GC) analyses were per-
2
to the mixture and the product was extracted with CH Cl (45 mL).
2 2
formed on a GL-Sciences GC353B gas chromatograph with a cap-
illary column (GL-Sciences TC-17). Column chromatography was
carried out by using Florisil. Solvents were dried by standard proce-
dures and distilled prior to use. The catalyst [Cp*IrCl ] was pre-
Evaporation of the solvent followed by Kugelrohr distillation (175
°C/133 mbar) gave the product; yield: 1.529 g (84%).
1
H NMR (270 MHz, CDCl ): d = 2.55 (m, 2 H), 1.88–1.83 (m, 4 H),
3
2
2
1.75–1.69 (m, 4 H), 1.63–1.57 (m, 2 H), 1.33–0.95 (m, 10 H).
1
0
pared according to the literature method. All other reagents are
commercially available and were used after distillation.
1
3
C NMR (67.8 MHz, CDCl ): d = 52.5, 33.9, 25.7, 24.8.
3
Procedure 1
Acknowledgment
Tribenzylamine;2 Typical Procedure
d,11
To a 100-mL flask under an atmosphere of argon was added
This work was supported by KAKENHI (No. 19550106).
NH OAc (766 mg, 9.94 mmol), [Cp*IrCl ] (40 mg, 0.050 mmol,
4
2 2
1
.0 mol% Ir), and NaHCO3 (250 mg, 2.97 mmol, 30 mol%).
PhCH OH (3.797 g, 35.1 mmol) was added by syringe and the flask References
2
was sealed with a glass stopper. The mixture was stirred at r.t. for
(
1) For example: (a) Salvatore, R. N.; Yoon, C. H.; Jung, K. W.
3
0 min and then at 130 °C for 17 h. Then, aq 2 M NaOH (20 mL)
Tetrahedron 2001, 57, 7785. (b) Chiappe, C.; Pieraccini, D.
Green Chem. 2003, 5, 193.
was added to the mixture and the product was extracted with
CH Cl (45 mL). Evaporation of the solvent followed by Kugelrohr
distillation (200 °C/0.4 mbar) gave the product; yield: 2.358 g
2
2
(
2) (a) Fujita, K.; Li, Z.; Ozeki, N.; Yamaguchi, R. Tetrahedron
Lett. 2003, 44, 2687. (b) Fujita, K.; Fujii, T.; Yamaguchi, R.
Org. Lett. 2004, 6, 3525. (c) Fujita, K.; Enoki, Y.;
Yamaguchi, R. Org. Synth. 2006, 83, 217. (d) Fujita, K.;
Enoki, Y.; Yamaguchi, R. Tetrahedron 2008, 64, 1943.
3) (a) Fujita, K.; Yamaguchi, R. Synlett 2005, 560. (b) Fujita,
K.; Yamaguchi, R. In Iridium Complexes in Organic
Synthesis; Oro, L. A.; Claver, C., Eds.; Wiley-VCH:
Weinheim, 2009, Chap 5, 107–143.
(
83%).
1
H NMR (270 MHz, CDCl ): d = 7.43–7.19 (m, 15 H), 3.56 (s, 6 H).
3
1
3
C NMR (67.8 MHz, CDCl ): d = 139.6, 128.7, 128.2, 126.8, 57.9.
3
(
Trihexylamine;12 Typical Procedure
To a 100-mL flask under an atmosphere of argon was added
NH OAc (762 mg, 9.89 mmol), [Cp*IrCl ] (199 mg, 0.250 mmol,
4
2 2
Synthesis 2009, No. 7, 1220–1223 © Thieme Stuttgart · New York