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J. Shah – J. Liebscher · Guanidinium-tagged Organocatalysts for Direct Aldol Reactions
1.27 – 1.16 (m, 6H, N+-CH2-CH-(CH3)2), 0.92 – 0.79 (m, 13 mmol) was added, and the reaction mixture was stirred at
6H, CH3-CH2-N). – 13C NMR (75 MHz, CDCl3): δ = r. t. over night. The reaction mixture was extracted with di-
172.7, 172.01,163.2, 154.6, 154.1, 136.1, 135.3, 128.5 – ethyl ether (3 × 50 mL), giving a quantitative yield of 8. –
127.1, 71.8, 67.2, 66.7, 59.8, 57.6, 52.6, 50.9, 49.9, 44.8, 1H NMR (300 MHz, CDCl3): δ = 7.11 – 6.87 (m, 10H, Ar),
43.6, 36.4, 35.4, 26.8, 26.4, 20.5, 20.3, 20.2, 13.2, 13.0. – 5.10 – 5.02 (m, 4H, Ph-CH2-CO2), 4.95 – 4.77 (m, 1H, CO2-
HRMS ((+)-ESI: m/z = 680.4136 (calcd. 680.4138 for CH-C), 4.16 – 4.02 (m, 1H, N-CH-CO2), 3.83 – 3.76 (m, 2H,
C38H56N4O7, [M+H]+).
N+-CH2-CH2-O), 3.61 – 3.47 (m, 1H, O-CH-CH2), 4.11 –
The guanidinium bromide 3b was transformed into the 4.07 (m, 2H, N+-CH2-(CH2)4-CH3), 3.92 – 3.80 (m, 2H,
corresponding tetrafluoroborate and finally deprotected in N+-CH2-CH2-O), 3.71 – 3.52 (m, 2H, N-CH2-CO), 2.94 –
the same way as described for 4a giving the final product 4b. 2.80 (dd, 4H, N-CH2-CH3), 2.56 – 2.52 (t, 4H, N-CH2-CH2-
Yield: 585 mg (83 %); yellow oil. – 1H NMR (300 MHz, CH3), 2.40 – 2.32 (m, 1H, CO2-CH-CH2-CH), 1.82 – 1.64
CDCl3): δ = 5.28 (m, 1H, CH2-CO2-CH-C), 4.01 (m, 1H, N- (m, 1H, CO2-CH-CH2-CH), 1.77 – 1.69 (m, 2H, N+-CH2-
CH-CO2), 3.98 (m, 2H, N+-CH2-(CH2)3-CO), 3.74 (m, 2H, CH2-(CH2)3-), 1.60 – 1.52 (m, 2H, N+-(CH2)2-CH2-CH2-),
N+-CH2-CH-(CH3)2), 3.38 (m, 2H, N-CH2-CH-O), 3.20 1.29 – 1.20 (m, 2H, N+-(CH2)3-CH2-), 1.18 – 1.14 (m, 2H,
(m, 4H, N-CH2-CH2-O), 2.72 – 2.30 (dd, 4H, N-CH2-CH3), N+-(CH2)4-CH2-), 1.01 – 0.91 (m, 4H, CH3-CH2-CH2-N),
2.40 – 2.31 (m, 4H, N-CH2-CH2-O), 1.76 – 1.43 (m, 1H, 0.78 – 0.72 (m, 6H, CH3-CH2-N), 0.61 – 0.56 (m, 6H, CH3-
CO2-CH-CH2-CH), 1.74 – 1.67 (m, 2H, N+-(CH2)2-CH2- (CH2)2-N), 0.55 – 0.52 (m, 3H, CH3-(CH2)5-N). – 13C NMR
CH2-CO), 1.62 (m, 2H, CO2-CH2), 1.56 (m, 2H, N+-CH2- (75 MHz, CDCl3): δ = 170.4, 159.7, 159.1, 154.1, 142.6,
CH2-(CH2)2-CO), 1.22 (m, 1H, N+-CH2-CH-(CH3)2), 0.87 127.6 – 126.1, 77.1, 63.3, 59.8, 57.6, 50.6, 49.4, 42.3, 41.9,
(m, 6H, N+-CH2-CH-(CH3)2), 0.76 (m, 6H, CH3-CH2-N). – 31.1, 29.4, 22.2, 21.2, 21.1, 20.5, 13.8, 13.0, 12.6, 11,1. –
13C NMR (75 MHz, CDCl3): δ = 175.1, 171.6, 163.1, 133.5, HRMS: ((+)-ESI: m/z = 666.4708 (calcd. 666.4709 for
73.2, 65.8, 65.5, 65.4, 64.5, 57.5, 56.4, 49.8, 48.9, 43.8, 36.1, C39H62N4O5+, [M+H]+).
33.5, 26,3, 25.9, 21.4, 20.2, 12.7. – HRMS: ((+)-ESI: m/z =
In a 50 mL dry round bottom flask the bromide 8 (0.5 g,
0.67 mmol) was dissolved in 15 mL of dry methanol (15 mL).
AgBF4 (0.13 g, 0.67 mmol) was dissolved in dry methanol
(15 mL) under the exclusion of light. This AgBF4 solution
was added dropwise to the solution of 8 until no more pre-
cipitate (AgBr) was formed. After the precipitate had settled
down the supernatant clear solution was separated, dried and
evaporated to give a quantitative yield of the correspond-
ing guanidinium tetrafluoroborate as a yellow oil. It was
dissolved in dry methanol (1.00 g, 1.3 mmol in 15 mL),
and Pd/C (80 mg) was added. The mixture was pressur-
ized under H2 at 5 bar. After stirring over night the Pd/C
was filtered off, and the filtrate was concentrated under
vacuum giving the unprotected tetrafluoroborate 9 (0.62 g,
91 %) as a yellow oil. – 1H NMR (300 MHz, CDCl3):
δ = 4.25 (m, 2H, N+-CH2-CH2-O), 4.08 (m, 1H, N-CH-
CO2), 3.95 – 3.88 (m, 1H, O-CH-CH2), 4.11 – 4.07 (m, 2H,
N+-CH2-(CH2)4-CH3), 3.92 – 3.78 (m, 2H, N+-CH2-CH2-
O), 3.91 – 3.76 (m, 2H, N-CH2-CO), 2.67 – 2.61 (dd, 4H,
N-CH2-CH3), 2.56 – 2.52 (t, 4H, N-CH2-CH2-CH3), 2.40 –
2.32 (m, 1H, CO2-CH-CH2-CH), 2.04 – 1.97 (m, 1H, CO2-
CH-CH2-CH), 1.87 – 1.69 (m, 2H, N+-CH2-CH2-(CH2)3-
), 1.60 – 1.52 (m, 2H, N+-(CH2)2-CH2-CH2-), 1.25 – 1.19
(m, 2H, N+-(CH2)3-CH2-), 1.39 – 1.29 (m, 2H, N+-(CH2)4-
CH2-), 1.39 – 1.35 (m, 4H, CH3-CH2-CH2-N), 0.96 – 0.94
(m, 6H, CH3-CH2-N), 0.81 – 0.78 (m, 6H, CH3-(CH2)2-N),
0.66–.59 (m, 3H, CH3-(CH2)5-N). – 13C NMR (75 MHz,
CDCl3): δ = 172.1, 148.6, 77.2, 61.4, 60.7, 56.5, 52.9,
51.4, 45.5, 43.3, 32.5, 31.2, 28.6, 26.9, 22.2, 19.3, 13.7,
8.1. – HRMS: ((+)-ESI: m/z = 442.3870 (calcd. 442.3872
for C24H50N4O3+, [M+H]+)
456.3300 (calcd. 456.3301 for C23H44N4O5, [M+H]+).
N-(2-Bromoethyl)-N-((diethylamino)(dipropylamino)-
methylene)hexane-1-aminium bromide (6)
1,1-Diethyl-2-hexyl-3,3-dipropylguanidine (2a) (1.00 g,
3.7 mmol) was mixed with 1,2-dibromoethane (1.09 g,
5.5 mmol). The reaction mixture was stirred at r. t. over night.
The resulting sticky matarial was washed with diethyl ether
(3×25 mL). After keeping under vacuum for 1 h product 6
was obtained as a colorless oil; yield 1.3 g (64 %). – 1H NMR
(300 MHz CDCl3): δ = 4.09 – 3.91 (m, 2H, N+-CH2-
CH2-O), 3.79 – 3.58 (m, 2H, N+-CH2-CH2-O), 3.41 – 2.91
(m, 10H, N(CH2-CH2-CH3)2, N(CH2-(CH2)4CH3), N(CH2-
CH3)2), 1.79 – 1.43 (m, 6H, N(CH2-CH3)2), 1.22 – 1.27
(m, 12H, N-(CH2)-(CH2)4-CH3), N-((CH2)-(CH2)-CH3)2),
0.86 – 0.96 (m, 9H, N(CH2-CH2-CH3)2, N-(CH2)5-CH3). –
13C NMR (75 MHz CDCl3): δ = 163.78, 53.24, 53.15, 51.69,
51.56, 51.07, 31.26, 27.40, 27.22, 26.46, 22.48, 20.97, 13.93,
13.55, 13.26, 12.97, 11.37.
N-(2-((3R,5S)-5-Carboxypyrrolidin-3-yloxy)ethyl)-N-
((diethylamino)(dipropylamino)methylene)hexan-1-aminium
tetrafluoroborate (9)
A solution of the diprotected 4-hydroxyproline 7 (3.2 g,
9 mmol) in dry DMF (25 mL) was added to a suspension
of sodium hydride (0.3 g, 13 mmol) in dry DMF (25 mL)
at −20 ◦C under argon. The reaction mixture was stirred
for 20 min. N-(2-Bromoethyl)-N-((diethylamino)(dipropyl-
amino)methylene)hexan-1-aminium bromide (6) (6.12 g,
Unauthenticated
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