Beilstein J. Org. Chem. 2019, 15, 1210–1216.
(
5 mL) was added TFA (0.5 mmol, 5 mol %) dropwise over were reacted in MeOH (5 mL) according to the general proce-
1
0 min, and stirred for 24 h at room temperature. The color of dure A. Flash column chromatography purification (EtOAc/
the solution changed during the reaction from yellow-green to hexane 1:1, v/v) afforded the proline-based peptide 2 as color-
brown then black. The neutralization of the polymerization less oil. Yield: 78%; Rf 0.30 (EtOAc/hexane 1:1, v/v); [α]D23
solution was carried out with a concentrated basic solution. The −6.26 (c 0.0047 g·cm−3, MeOH); 1H NMR (400 MHz, CDCl3)
use of a 1 M NaOH (5 mL) solution requires two washes of δ 1.40 (s, 9H), 1.41–1.75 (m, 9H), 1.94 (m, 3H), 3.26–3.37 (m,
1
0 min each but at the end of the reaction an emulsion may 2H), 4.08–4.11 (m, 2H), 4.59–4.65 (m, 1H), 6.23–6.29 (m, 2H),
appear. In order to avoid this problem an excess of 0.1 M NaOH 7.26–7.40 (m, 4H), 7.53 (m, 2H); 13C NMR (100 MHz, CDCl3)
solution was used. Polymers were isolated by precipitation in δ 19.2, 24.2, 24.4, 26.7, 28.9, 37.2, 47.7, 51.9, 59.3, 64.8, 79.5,
petroleum ether and dried in high vacuum. The resulting dark 106.4, 110.4, 127.4, 128.9, 141.3, 142.8, 152.9, 154.8, 175.4,
solid was ground until the retained material on a 45 µm sieve 175.5.
was lower than 10%.
PFA-supported catalyst 3. Compound 1 (476 mg, 1 mmol,
according to a reported procedure [17].
TFA (38 µL, 0.5 mmol) were reacted in CHCl3 (5 mL) accord-
ing to the general procedure B. After precipitation in petroleum
General procedure C. The nitroolefin (0.25 mmol, 1.0 equiv) ether, polymer 3 was obtained as a black amorphous solid. IR
and the aldehyde (0.75 mmol, 3.0 equiv) were added to a solu- (KBr, cm−1): 3500, 3120, 2930, 2860, 1720, 1680, 1540, 1420,
tion of the prolyl pseudo-peptide catalyst (0.025 mmol, 1320, 1180, 1080, 790. 740, 600; microanalysis: N (2.68%), C
0
.01 equiv) in the solvent of choice (1 mL). The reaction mix- (58.29%), H (5.12%), S (0%); loading = 0.64 mmol·g−1.
ture was stirred for 24 h and then concentrated under reduced
pressure. The resulting crude product was purified by flash PFA-supported catalyst 4. Compound 2 (545 mg, 1 mmol,
column chromatography on silica gel using n-hexane/EtOAc as 1.0 equiv), furfuryl alcohol (860 µL, 10 mmol, 10 equiv) and
eluent. Enantiomeric excess (ee) was determined by chiral TFA (38 µL, 0.5 mmol) were reacted in CHCl3 (5 mL) accord-
HPLC analysis through comparison with the authentic racemic ing to the general procedure B. After precipitation in petroleum
material. Assignment of the stereoisomers was performed by ether, polymer 4 was obtained as a black amorphous solid. IR
comparison with literature data.
(KBr, cm−1): 3500, 3120, 2930, 1720, 1680, 1610, 1550, 1420,
350, 1200, 1160, 1110, 1038, 780, 740, 600; microanalysis: N
(1.36%), C (50.52%), H (3.77%), S (0%); loading =
1
Synthesis and characterization
Prolyl pseudo-peptide 1. Furfurylamine (177 µL, 2 mmol), 0.33 mmol·g−1.
acetone (116 mg, 2 mmol), Boc-L-Pro-OH (431 mg, 2 mmol)
and cyclohexyl isocyanide (249 µL, 2 mmol) were reacted in PFA. Furfuryl alcohol (860 µL, 10 mmol) and TFA (38 µL,
MeOH (5 mL) according to the general procedure A. Flash 0.5 mmol) were reacted in CHCl3 (5 mL) according to the
column chromatography purification (EtOAc/hexane 1:1, v/v) general procedure B. After precipitation in petroleum ether,
afforded the Boc-proline-based peptide 1 as colorless oil. A PFA was afforded as a black amorphous solid. IR (KBr, cm−1):
mixture of conformers was observed by NMR (ratio 3:1). 3480, 2930, 1718, 1420, 1150, 1100, 800, 690, 600; micro-
Assigned signals belong to the mixture of conformers. Yield: analysis: N (0 %), C (56.14%), H (4.10%), S (0%); loading of
8
0
0
9
1
1
1%; Rf 0.34 (EtOAc/hexane 1:1, v/v); [α]D20 − 19.9 (c catalyst = 0 mmol·g−1
.0085 g·cm−3, MeOH); 1H NMR (400 MHz, CDCl3) δ
.99–1.19 (m, 3H), 1.29–1.39 (m, 2H), 1.43 (s, 3H), 1.45 (s, (2R,3S)-2-Ethyl-4-nitro-3-phenylbutanal (5). Prepared by reac-
H), 1.48 (s, 3H), 1.58–2.01 (m, 9H), 2.10 (m, 1H), 3.39 (m, tion of n-butanal with trans-β-nitrostyrene according to the
H), 3.53 (m, 1H), 3.65 (m, 1H); 4.50, 4.52 (2×d, J = 16.0 Hz, general procedure C. The compound was purified by flash
H), 4.60 (m, 1H), 4.77, 5.09 (2×d, J = 18.2 Hz, 1H), 5.70, 5.94 column chromatography (EtOAc/hexane 1:9, v/v). The spec-
(
2×d, J = 7.2 Hz, NH, 1H), 6.39 (m, 1H), 7.40 (d, J = 7.8 Hz, troscopic data are in agreement with the published data [15].
1
2
7
H); 13C NMR (100 MHz, CDCl3) δ 23.1, 24.2, 24.4, 24.9, The enantiomeric excess was determined by chiral-stationary
5.1, 25.5, 28.6, 30.2, 32.7, 32.8, 41.5, 47.2, 48.4, 56.9, 63.3, phase HPLC (Chiralpak OD-H, hexane/iPrOH 99:1, v/v, 25 °C)
9.5, 107.3, 110.8, 141.9, 152.2, 154.7, 173.7, 174.1.
at 1.00 mL/min, UV detection at 210 nm: tR: (syn, major) =
8.4 min, (anti, minor) = 20.9 min; Rf 0.26 (EtOAc/hexane 2:8,
Prolyl pseudo-peptide 2. (S)-(−)-α-Methylbenzylamine v/v); [α]D23 +25.21 (c 0.0046 g·cm−3, MeOH); 1H NMR
2
(
(
257 µL, 2 mmol), acetone (147 µL, 2 mmol), Boc-L-Pro-OH (400 MHz, CDCl3) δ 9.72, 9.49 (2×d, J = 2.6 Hz, 1H, CHO),
431 mg, 2 mmol) and furfuryl isocyanide (216 µL, 2 mmol) 7.36–7.29 (m, 3H, Ph), 7.19–7.17 (m, 2H, Ph), 4.72 (dd, J =
1215