A. Perosa et al.
carried out to ensure complete degassing of the mixture and air removal.
The empty volume was then filled with nitrogen. The autoclave was
heated for 20 h at 1408C with magnetic stirring, after which time it was
cooled and vented. Methanol and residual DMC were removed from the
2.25 (br, 6H; P-CH2), 1.79 (d, J
1.26 (br, 6H), 1.11 (br, 24H), 0.70 ppm (brt, 9H); 13C{1H} NMR (neat,
608C, 100 MHz, [D6]DMSO): d=30.9 (3C; C6), 29.8 (d, J(P,C)=15 Hz,
3C; C3), 28.1 (3C; C5), 28.0 (3C; C4), 21.7 (3C; C7), 20.5 (3C; C2), 19.0
(d, J(P,C)=49 Hz, 3C; C1), 13.0 (C3, C8), 2.5 ppm (d, J(P,C)=51 Hz, 3C;
P-CH3); IR (neat): n˜max =2930, 2856, 1467, 1340 cmꢀ1
[TOMA][NO3] (6): Compound 6 (2.8 g, >95%) was synthesised using
the same procedure as for [TOMP]
[NO3]. 1H NMR (neat, 608C,
ACHTUNGTERN(NNUG P,H)=13 Hz, 3H; P-CH3), 1.43 (br, 6H),
AHCTUNGTRENNUNG
mixture by rotary evaporation, to give [TOMP]ACHTUNRGTNEUNG[CH3OCOO] (27.5 g,
G
ACHTUNGTRENNUNG
100%) as a viscous clear colourless liquid (m.p. <08C). A small amount
(<1 equiv) of methanol may remain incorporated in the sample even
after it has been subjected to prolonged high vacuum; it can be identified
.
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1
in the H NMR spectrum by an HMBC experiment. It does not, however,
400 MHz, [D6]DMSO): d=3.30 (br, 6H; N-CH2), 3.01 (3H; N-CH3), 1.58
(br, 6H), 1.17 (br, 6H), 1.11 (br, 24H), 0.71 ppm; 13C{1H} NMR (neat,
608C, 100 MHz, [D6]DMSO): d=60.4 (3C; C1), 46.8 (1C; N-CH3), 30.9
(3C; C6), 28.2 (6C; C5-C4), 25.6 (3C; C3), 21.7 (3C; C7), 21.2 (3C; C2),
affect future transformations. 1H NMR (neat, 608C, 400 MHz,
[D6]DMSO): d=3.15 (s, 3H; CH3OCOO), 2.33 (brt, 6H; P-CH2), 1.88
(d, JACHTUNGTRENNUNG(P,H)=14 Hz, 3H; P-CH3), 1.42 (br, 6H), 1.27 (br, 6H), 1.11 (br,
24H), 0.70 ppm (brt, 9H); 13C{1H} NMR (neat, 608C, 100 MHz,
[D6]DMSO, CH2 assigned by 2D INADEQUATE): d=155.8 (1C; C=O),
12.9 ppm (3C; C8); IR (neat): n˜max =2930, 2856, 1467, 1377 cmꢀ1
[TOMA]
[TOMA][CH3OCOO] (1.28 g, 2.9 mmol). The mixture was stirred at
.
A
ACHTUNGTREN[NUNG l-Phe] (9): l-Phenylalanine (0.585 g, 2.9 mmol) was added to
50.0 (1C; CH3O), 30.9 (3C; C6), 29.9 (d, J
(3C; C5), 28.0 (3C; C4), 21.6 (3C; C7), 20.7 (d, J
19.0 (d, J(P,C)=48 Hz, 3C; C1), 12.8 (3C; C8), 2.6 ppm (d, J
53 Hz, 3C; P-CH3); IR (neat): n˜max =2900, 2856, 1669 cmꢀ1
[TOMA][CH3OCOO] (2): TOA (20 mL, 16.2 g, 45.7 mmol), DMC
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
708C under air for 1 h, and then for an additional 3 h under vacuum to
A
ACHTUNGTRENNUNG
1
eliminate co-products (e.g., methanol, CO2); yield: 1.48 g, 96%. H NMR
.
(neat, 608C, 400 MHz, [D6]DMSO): d=6.96 (2H), 6.84 (2H), 6.73 (2H),
3.01 (br, 6H; N-CH2), 2.93 (3H; N-CH3), 2.27 (1H), 1.33 (br, 6H), 0.96
(br, 30H), 0.56 ppm; 13C{1H} NMR (neat, 608C, 100 MHz, [D6]DMSO):
d=175.6, 141.1, 128.5, 126.6, 124.0, 59.9 (3C; C1), 57.4, 42.7, 47.4 (1C; N-
CH3), 30.9 (3C; C6), 28.2 (6C; C5-C4), 25.6 (3C; C3), 21.6 (3C; C7), 21.3
(3C; C2), 12.9 ppm (3C; C8); IR (neat): n˜max =3411, 2927, 2857, 1599,
A
ACHTUNGTRENNUNG
(30 mL, 32.1 g, 356 mmol) and methanol (20 mL) were combined (two
phases) in a sealed 200 mL steel autoclave fitted with a pressure gauge
and a thermocouple for temperature control. Three vacuum-nitrogen
cycles were carried out to ensure complete removal of air. The empty
volume was then filled with nitrogen. The autoclave was heated for 20 h
at 1408C with magnetic stirring, after which time it was cooled and
vented. Methanol and residual DMC were removed from the mixture by
1380 cmꢀ1
[TOMP][HOCOO] (10): [TOMP]ACHTNUTRGNENG[U CH3OCOO] (3.0 g, 6.5 mmol) was
.
A
U
stirred under air with water (1 mL) at 408C for 2 h. Excess water and
methanol were removed under reduced pressure to yield [TOMP]-
AHCTUNGERTG[NNUN HOCOO] (2.9 g, 100%) as a viscous clear liquid that tends to solidify
rotary evaporation to give [TOMA]ACHTNUGTRENUNG[CH3OCOO] (20.0 g, 99%) as a vis-
cous clear pale yellow liquid (m.p. <08C). A small amount (<1 equiv) of
methanol may remain incorporated in the sample even after it has been
subjected to prolonged high vacuum; it does not, however, affect future
transformations. 1H NMR (neat, 608C, 400 MHz, [D6]DMSO): d=3.36
(6H; N-CH2), 3.11 (6H; N-CH3 and CH3O), 1.54 (br, 6H), 1.08 (br,
30H), 0.67 ppm (9H); 13C{1H} NMR (neat, 608C, 100 MHz, [D6]DMSO,
CH2 assigned by 2D INADEQUATE): d=155.5 (1C; C=O), 59.9 (3C;
C1), 50.0 (1C; CH3O), 46.8 (1C; N-CH3), 30.9 (3C; C6), 28.2 (6C; C5-C4),
25.7 (3C; C3), 21.6 (3C; C7), 21.3 (3C; C2), 12.8 ppm (3C; C8); IR (neat):
with time (m.p. ꢁ258C). 1H NMR (neat, 608C, 400 MHz, [D6]DMSO):
d=2.33 (br, 6H; P-CH2), 1.84 (brd, 3H; P-CH3), 1.33 (br, 6H), 1.23 (br,
6H), 1.05 (br, 24H), 0.64 ppm (brt, 9H); 13C{1H} NMR (neat, 608C,
100 MHz, [D6]DMSO): d=158.9 (1C; C=O), 31.0 (3C; C6), 29.8 (d,
JACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
.
n˜max =2900, 2857, 1669 cmꢀ1
[TOMP][CF3COO] (3): TFA (0.80 g, 7.0 mmol) was added dropwise
over 5 min to [TOMP][CH3OCOO] (1.52 g, 3.3 mmol), and the solution
.
A
R
ACHTUNGTRENNUNG
stirred under air with water (1 mL) at 408C for 2 h. Excess water and
methanol were removed under reduced pressure to yield [TOMP]-
AHCTUNGERTG[NNUN HOCOO] (2.9 g, 100%) as a viscous clear liquid that tends to solidify
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
was stirred at 508C for 2 h. Excess TFA was removed under reduced
pressure, and any residual TFA can be removed by dissolving the result-
ing liquid in 30 mL of CH2Cl2, washing with 2ꢄ25 mL aliquots of 10%
NaHCO3, followed by drying over Na2SO4, filtering, and removal of the
with time (m.p. ꢁ258C). 1H NMR (neat, 608C, 400 MHz, [D6]DMSO):
d=5.14 (s, OH), 3.14 (br, 6H; N-CH2), 2.96 (br, 3H; N-CH3), 1.45 (br,
6H), 1.12 (br, 6H), 1.35 (br, 24H), 0.62 ppm (brt, 9H); 13C{1H} NMR
(neat, 608C, 100 MHz, [D6]DMSO): d=160.3 (1C; C=O), 59.9 (3C; C1),
47.8 (1C; N-CH3), 30.9 (3C; C6), 28.1 (6C; C5-C4), 25.3 (3C; C3), 21.6
(3C; C7), 21.1 (3C; C2), 12.8 ppm (3C; C8); IR (neat): n˜max =3406, 2500,
solvent. [TOMP]
liquid (m.p. 23–248C). 1H NMR (neat, 608C, 400 MHz, [D6]DMSO): d=
2.25 (br, 6H; P-CH2), 1.84 (d, J(P,H)=14 Hz, 3H; P-CH3), 1.39 (br, 6H),
1.23 (br, 6H), 1.09 (br, 24H), 0.68 ppm (brt, 9H); 13C{1H} NMR (neat,
608C, 100 MHz, [D6]DMSO): d=158.9 (q, J(F,C)=37 Hz, 1C; C=O),
115.3 (q, J(F,C)=290 Hz, 1C; CF3), 30.6 (3C; C6), 29.4 (d, J(P,C)=
14 Hz, 3C; C3), 27.8 (3C; C5), 27.6 (3C; C4), 21.4 (3C; C7), 20.2 (d,
(P,C)=5 Hz, 3C; C2), 19.1 (d, J(P,C)=48 Hz, 3C; C1), 12.6 (C3, C8),
2.4 ppm (d, J(P,C)=53 Hz, 3C; P-CH3); IR (neat): n˜max =2900, 1688,
1467, 1199, 1164, 1122 cmꢀ1
[TOMA][CF3COO] (4): Compound 4 (3.2 g, 96%) was synthesised using
the same procedure as for [TOMP]
[CF3COO]. 1H NMR (neat, 608C,
ACHTUNGTRENNUNG[CF3COO] (1.64 g, 97%) was obtained as a viscous clear
AHCTUNGTRENNUNG
2856, 1650, 1631 cmꢀ1
[TOMP][NTf2] (12): An aqueous solution of LiNTf2 (2.33 g. 8.13 mmol
in 50 mL) was added to [TOMP][CH3OCOO] (4.0 g, 8.13 mmol) dis-
.
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
solved in water (70 mL). The mixture was stirred at 708C for 2 h. The re-
sulting white precipitate was preferably extracted (but can be isolated by
J
N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
decanting as well) with CH2Cl2 to afford pure dry [TOMP]ACHTUNGTRENNUNG
1
.
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
400 MHz, [D6]DMSO): d=3.21 (br, 6H; N-CH2), 3.00 (3H; N-CH3), 1.51
AHCTUNGTRENNUNG
(br, 6H), 1.14 (br, 6H), 1.09 (br, 24H), 0.68 ppm (brt, 9H);
13C{1H} NMR (neat, 608C, 100 MHz, [D6]DMSO): d=158.2 (q, J
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
31 Hz, 1C; C=O), 116.9 (q, JACHTGNUTRENNUNG
.
(1C; N-CH3), 30.7 (3C; C6), 28.0 (3C; C5), 27.9 (3C; C4), 25.3 (3C; C3),
21.5 (3C; C7), 21.1 (3C; C2), 12.7 ppm (3C; C8); IR (neat): n˜max =2900,
G
ACHTUNGTRENNUNG
2858, 1688, 1378, 1199, 1170, 1125 cmꢀ1
.
AHCTUNGTRENNUNG
400 MHz, [D6]DMSO): d=2.98 (br, 6H; N-CH2), 2.73 (3H; N-CH3), 1.45
(br, 6H), 1.12 (br, 6H), 1.07 (br, 24H), 0.67 ppm (t, J=7.2 Hz, 9H);
ACHTUNGTRENNUNG[TOMP]ACHTUNGTRENNUNG[NO3] (5): [TOMP]ACHTNGUTNER[NUNG CH3OCOO] (4.0 g, 8.13 mmol) was treated
with aqueous concentrated HNO3 (0.60 mL, 9.2 mmol) at 508C for 2 h.
The mixture was cooled and extracted with dichloromethane. The organic
extract was washed twice with saturated NaHCO3 (25 mL) and the sol-
13C{1H} NMR (neat, 608C, 100 MHz, [D6]DMSO): d=119.1 (q, J
ACHTUNGTRENNUNG(F,C)=
322 Hz, 1C; CF3), 60.8 (3C; C1), 46.9 (1C; N-CH3), 30.5 (3C; C6), 27.8
vent was removed under vacuum to afford [TOMP]
[NO3] (3.5 g, >95%)
(6C; C5-C4), 25.0 (3C; C3), 21.4 (3C; C7), 21.0 (3C; C2), 12.6 ppm (3C;
as a colourless liquid. 1H NMR (neat, 608C, 400 MHz, [D6]DMSO): d=
C8); IR (neat): n˜max =2929, 2859, 1469, 1378, 1353 cmꢀ1
.
12280
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12273 – 12282