Asymmetric Organocatalysis
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(m, 3H), 6.79 (s, 1H), 6.43 (s, 1H), 5.98 (dd, J=0.8 Hz, 1.2 Hz, 1H),
3.75 ppm (s, 3H); 13C NMR (101 MHz, CDCl3): d=165.5, 160.7, 139.3,
137.2, 128.5, 128.4, 127.5, 126.3, 77.3, 52.1 ppm; HRMS: m/z: calcd for:
357.9780; found: 357.9778 [M+Na]+.
stirred at 408C and monitored by TLC. Upon completion the solvent was
evaporated and the crude product was directly purified by FC.
Method D: The imidate (1, 1 equiv) was weighed in a 4 mL vial, solvent
(5.0 mL dioxane) and catalyst (0.1 equiv) were added. The reaction was
stirred at room temperature and monitored by TLC. Upon completion
the solvent was evaporated and the crude product was directly purified
by FC.
2-[(4-Nitrophenyl)-(2,2,2-trichloroacetimidoyloxy)methyl]acrylic
acid
methyl ester (1b): Synthesised according to known literature procedur-
e.[10a] Rf =0.26 (pentane/Et2O1:1).
2-[Phenyl-(2,2,2-trichloroacetylamino)methyl]acrylic acid methyl ester
(2a): This imidate was obtained according to the general procedure
(Method A, overnight) and isolated as a white solid (77% yield). Rf =
0.31 (pentane/Et2O3:1); m.p. 81 8C. [a]D =À22.78 (c=0.98, CHCl3) (90%
2-[Pyridin-2-yl-(2,2,2-trichloroacetimidoyloxy)methyl]acrylic acid methyl
ester (1c): Rf =0.15 (pentane/Et2O1:1); 1H NMR (400 MHz, CDCl3,
TMS): d=8.62–8.59 (m, 1H), 8.50 (brs, 1H), 7.73 (dt, J=1.3 Hz, 7.6 Hz,
1H), 7.56 (d, J=7.9 Hz, 1H), 7.27–7.22 (m, 1H), 6.89 (s, 1H), 6.52 (s,
1H), 5.97 (s, 1H), 3.74 ppm (s, 3H); 13C NMR (101 MHz, CDCl3): d=
165.4, 160.9, 156.6, 149.3, 137.7, 136.6, 127.9, 123.0, 122.0, 91.0, 78.0,
52.0 ppm; HRMS: m/z: calcd for: 358.9733; found: 358.9724 [M+Na]+.
ee); HPLC (OD, 250 mm, hexane/iPrOH 98:2): tmajor =8.7 min, tminor
=
1
10.4 min; H NMR (400 MHz, CDCl3, TMS): d=8.16 (d, J=8.4 Hz, 1H),
7.39–7.32 (m, 2H), 7.33–7.27 (m, 3H), 6.44 (brs, 1H), 6.02 (brs, 1H),
5.92 (d, J=8.8 Hz, 1H), 3.73 ppm (s, 3H); 13C NMR (101 MHz, CDCl3):
d=166.1, 161.1, 137.9, 137.4, 128.8, 128.7, 128.0, 126.0, 92.5, 56.9,
52.3 ppm; HRMS: m/z: calcd for: 357.9780; found: 357.9792 [M+Na]+.
2-[Naphthalen-2-yl-(2,2,2-trichloroacetimidoyloxy)methyl]acrylic
acid
methyl ester (1d): Rf =0.50 (pentane/Et2O1:1); m.p. 65 8C (off-white
solid); 1H NMR (400 MHz, CDCl3, TMS): d=8.47 (brs, 1H), 7.96 (brs,
1H), 7.89–7.81 (m, 3H), 7.58 (dd, J=1.7 Hz, 8.6 Hz, 1H), 7.53–7.46 (m,
2H), 6.98 (s, 1H), 6.49 (brs, 1H), 6.07 (brs, 1H), 3.75 ppm (s, 3H);
13C NMR (101 MHz, CDCl3): d=165.5, 160.7, 139.2, 134.4, 133.2, 132.9,
128.2, 128.2, 127.7, 127.1, 126.4, 126.2, 125.0, 91.3, 77.4, 52.1 ppm; HRMS:
m/z: calcd for: 407.9937; found: 407.9932 [M+Na]+.
2-[(4-Nitrophenyl)-(2,2,2-trichloroacetylamino)methyl]acrylic acid methyl
ester (2b): This imidate was obtained according to the general procedure
(Method D, 1 d) and isolated as a slightly yellow, clear oil (89% yield).
Rf =0.42 (pentane/Et2O1:1); [ a]D =À34.08 (c=7.7, CHCl3) (74% ee);
HPLC (OD, 250 mm, hexane/iPrOH 90:10): tmajor =16.5 min, tminor
=
1
21.6 min; H NMR (400 MHz, CDCl3, TMS): d=8.35 (d, J=8.4 Hz, 1H),
8.20 (dd, J=2.0 Hz, 7.2 Hz, 2H), 7.48 (d, J=8.6 Hz, 2H), 6.50 (s, 1H),
6.14 (s, 1H), 5.97 (d, J=8.8 Hz, 1H), 3.75 ppm (s, 3H); 13C NMR
(101 MHz, CDCl3): d=166.1 161.6, 147.7, 145.5, 136.5, 130.7, 127.1, 124.2,
92.4, 56.9, 52.8 ppm; HRMS: m/z: calcd for: 402.9631; found: 402.9629
[M+Na]+.
2-[Phenyl-(2,2,2-trichloroacetimidoyloxy)methyl]acrylic acid tert-butyl
ester (1e): Synthesised according to known literature procedure.[10a] Rf =
0.50 (pentane/Et2O1:4).
2-Methylene-3-(2,2,2-trichloroacetimidoyloxy)pentanoic acid methyl ester
(1 f): The compound was slightly yellow liquid. Rf =0.54 (pentane/Et2O
1:1); 1H NMR (400 MHz, CDCl3, TMS): d=8.32 (s, 1H), 6.32 (s, 1H),
5.93 (s, 1H), 5.67 (dd, J=4.1 Hz, 7.6 Hz, 1H), 3.79 (s, 3H), 2.01–1.88 (m,
1H), 1.85–1.72 (m, 1H), 1.01 ppm (t, J=7.4 Hz, 3H); 13C NMR
(101 MHz, CDCl3): d=165.8, 161.2, 139.2, 124.9, 91.5, 77.4, 52.0, 27.7,
9.6 ppm; HRMS: m/z: calcd for: 309.9780; found: 309.9795 [M+Na]+.
2-[Pyridin-2-yl-(2,2,2-trichloroacetylamino)methyl]acrylic acid methyl
ester (2c): This imidate was obtained according to the general procedure
(Method C, 2d) and isolated as a slightly yellow, clear oil (64% yield).
Rf =0.22 (pentane/Et2O1:1); [ a]365nm Hg =+14.88 (c=1.00, CHCl3) (80%
ee); HPLC (OD, 250 mm, hexane/iPrOH 95:5): tmajor =10.1 min, tminor
=
12.5 min; 1H NMR (400 MHz, CDCl3, TMS): d=8.83 (brd, J=6.8 Hz,
1H), 8.55 (ddd, J=0.9 Hz, 1.8 Hz, 4.9 Hz, 1H), 7.70 (d, J=1.8 Hz,
7.7 Hz, 1H), 7.43 (d, J=7.9 Hz, 1H), 7.24 (dddd, J=0.4 Hz, 1.1 Hz,
4.9 Hz, 7.5 Hz, 1H), 6.40 (s, 1H), 6.03 (brs, 1H), 5.95 (d, J=7.5 Hz, 1H),
3.74 ppm (s, 3H); 13C NMR (101 MHz, CDCl3): d=165.9, 161.0, 155.9,
149.0, 138.2, 137.2, 127.8, 123.1, 122.1, 92.5, 56.0, 52.2 ppm; HRMS: m/z:
calcd for: 358.9733; found: 358.9727 [M+Na]+.
4-Methyl-2-methylene-3-(2,2,2-trichloroacetimidoyloxy)pentanoic
acid
methyl ester (1g):[10a] Rf =0.57 (pentane/Et2O1:1); 1H NMR (400 MHz,
CDCl3, TMS): d=8.30 (s, 1H), 6.36 (d, J=0.8 Hz, 1H), 5.89 (brs, 1H),
5.57 (d, J=4.4 Hz, 1H), 3.80 (s, 3H), 2.17–2.07 (m, 1H), 1.03 (d, J=
6.9 Hz, 3H), 0.99 ppm (d, J=6.8 Hz, 3H);13C NMR (101 MHz, CDCl3):
d=165.9, 161.3, 138.4, 125.5, 80.4, 52.1, 32.2, 19.0, 16.6 ppm; HRMS:
m/z: calcd for: 323.9937; found: 323.9943 [M+Na]+.
2,2,2-Trichloroacetimidic acid 2-cyano-1-isopropyl-allyl ester (1h): The
compound was a slightly yellow liquid. Rf =0.49 (pentane/Et2O1:1);
1H NMR (400 MHz, CDCl3, TMS): d=8.45 (brs, 1H), 6.13 (s, 1H), 6.07–
6.06 (m, 1H), 5.15 (d, J=7.3 Hz, 1H), 2.25 (octet, J=6.8 Hz, 1H), 1.08
(d, J=6.7 Hz, 3H), 1.03 ppm (d, J=6.9 Hz, 3H); 13C NMR (101 MHz,
CDCl3): d=161.3, 133.3, 121.0, 116.4, 82.0, 31.4, 18.5, 17.4 ppm; HRMS:
m/z: calcd for: 290.9835; found: 290.9840 [M+Na]+.
2-[Naphthalen-2-yl-(2,2,2-trichloroacetylamino)methyl]acrylic acid methyl
ester (2d): This imidate was obtained according to the general procedure
(Method A, overnight) and isolated as a slightly yellow, clear oil (74%
yield). Rf =0.42 (pentane/Et2O1:1); [ a]D =+4.58 (c=0.98, CHCl3) (74%
ee); HPLC (OD, 250 mm, hexane/iPrOH 95:5): tmajor =10.2 min, tminor
=
1
15.0 min; H NMR (400 MHz, CDCl3, TMS): d=8.26 (d, J=8.7 Hz, 1H),
7.88–7.81 (m, 3H), 7.76 (brs, 1H), 7.54–7.46 (m, 2H), 7.42 (dd, J=
1.9 Hz, 8.5 Hz, 1H), 6.50 (brs, 1H), 6.12–6.08 (m, 1H), 3.73 ppm (s, 3H);
13C NMR (101 MHz, CDCl3): d=166.1, 161.1, 143.8, 137.4, 135.3, 133.1,
132.8, 128.8, 128.0, 127.6, 126.4, 126.3, 125.0, 124.0, 92.6, 57.0, 52.3 ppm;
HRMS: m/z: calcd for: 407.9937; found: 407.9953 [M+Na]+.
2,2,2-Trichloroacetimidic acid (2-oxo-5,6-dihydro-2H-pyran-3-yl)phenyl-
methyl ester (1i): Rf =0.18 (pentane/Et2O1:1); m.p. 123 8C (white solid);
1H NMR (400 MHz, CDCl3, TMS): d=8.45 (s, 1H), 7.51–7.46 (m, 2H),
7.40–7.28 (m, 3H), 6.97 (t, J=4.4 Hz, 1H), 6.84 (s, 1H), 4.44–4.30 (m,
2H), 2.55–2.49 ppm (m, 2H); 13C NMR (101 MHz, CDCl3): d=162.7,
160.4, 140.3, 137.2, 132.2, 128.4, 128.4, 127.1, 91.2, 76.1, 66.0, 24.2 ppm;
HRMS: m/z: calcd for: 369.9780; found: 369.9790 [M+Na]+.
2-[Phenyl-(2,2,2-trichloroacetylamino)methyl]acrylic acid tert-butyl ester
(2e):[10a] This imidate was obtained according to the general procedure
(Method B, 5 d) and isolated as a clear, colourless oil (89% yield). Rf =
0.39 (pentane/Et2O4:1);
[
a]D =À33.38 (c=1.00, CHCl3) (92% ee);
General procedure for asymmetric syntheses of allylic trichloroaceta-
mides (2)
HPLC (OD, 250 mm, hexane/iPrOH 98:2): tmajor =5.5 min, tminor
=
6.1 min; 1H NMR (400 MHz, CDCl3, TMS) d=7.99 (d, J=8.2 Hz, 1H),
7.4–7.2 (m, 5H), 6.37 (s, 1H), 5.9–5.8 (m, 2H), 1.36 ppm (s, 9H);
13C NMR (101 MHz, CDCl3): d=164.7, 161.1, 139.0, 138.3, 128.7, 128.1,
127.8, 125.9, 92.7, 82.3, 56.8, 27.8 ppm.
Method A: The imidate (1, 1 equiv) was weighed in a 4 mL vial, solvent
(0.5 mL dioxane) and catalyst (0.1 equiv) were added. The reaction was
stirred at 408C and monitored by TLC. Upon completion the solvent was
evaporated and the crude product was directly purified by FC.
2-Methylene-3-(2,2,2-trichloroacetylamino)pentanoic acid methyl ester
(2 f): This imidate was obtained according to the general procedure
(Method B, 4 d) and isolated as a clear, colourless oil (83% yield). Rf =
Method B: The imidate (1, 1 equiv) was weighed in a 4 mL vial, solvent
(0.5 mL dioxane) and catalyst (0.1 equiv) were added. The reaction was
stirred at room temperature and monitored by TLC. Upon completion
the solvent was evaporated and the crude product was directly purified
by FC.
0.28 (pentane/Et2O3:1);
[
a]D =À20.28 (c=1.01, CHCl3) (46% ee);
HPLC (OJ, 500 mm, hexane/iPrOH 98:2): tmajor =23.9 min, tminor
=
1
25.6 min; H NMR (400 MHz, CDCl3, TMS): d=7.82 (d, J=7.2 Hz, 1H),
6.27 (s, 1H), 5.83 (s, 1H), 4.55 (q, J=7.8 Hz, 1H), 3.79 (s, 3H), 1.85–1.65
(m, 2H), 0.92 ppm (t, J=7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=
Method C: The imidate (1, 1 equiv) was weighed in a 4 mL vial, solvent
(5.0 mL dioxane) and catalyst (0.1 equiv) were added. The reaction was
Chem. Eur. J. 2008, 14, 1464 – 1471
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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