P. Beier et al. / Tetrahedron: Asymmetry 15 (2004) 2447–2449
2449
7. OÕHagan, D.; Rzepa, H. S. J. Chem. Soc., Chem. Commun.
1997, 645.
8. (a) Seebach, D. Angew. Chem. Int., Ed. Engl. 1990, 29,
1320; (b) Bott, G.; Field, L. D.; Sternhill, S. J. Am. Chem.
Soc. 1980, 102, 5618.
9. Everet, T. S.; Purrington, S. T.; Bumgardner, C. L. J. Org.
Chem. 1984, 49, 3702.
10. Buxton, M. W.; Stacey, M.; Tatlow, J. C. J. Chem. Soc.,
1954, 366.
were dissolved in hexane (200cm3). The CRL (7.5g) was
added and the mixture shaken at 250rpm/37ꢁC for 20h.
The reaction was terminated by the addition of MgSO4
(5g) and the mixture filtered. The solid was washed with
diethyl ether (3 · 15cm3), the solvent removed under
reduced pressure and the residue dissolved in diethyl ether
(50cm3). The unreacted acid was isolated by extraction
with aq NaHCO3 (0.8M, 3 · 40cm3), acidification and
extraction into diethyl ether (3 · 20cm3). Drying and
solvent removal gave (2S)-1 (1.111g, 74%, ee >98%).
11. 3,3,3-Trifluoro-2-methylpropanoic acid, 1:2 (16.1g,
9.7mmol) was dissolved in 1,4-dioxane (100cm3) and HCl
(36%, 70cm3) added. The mixture was heated under
reflux for 15h, cooled and DCM (200cm3) then added.
The two phases were separated and the aqueous was
extracted into DCM (3 · 100cm3). The combined organic
extracts were washed with aq NaHCO3 (0.8M,
3 · 100cm3). The aqueous phase was acidified (conc.
HCl), the product isolated by extraction into diethyl ether
(3 · 100cm3), drying over MgSO4 and removal of the
solvent under reduced pressure. Distillation (80ꢁC/20mm
Hg) gave 1 as a colourless liquid (8.205g, 61%). MS (CI):
m/z = 143.0316 [M+H]+ C4H6O2F3 requires 143.0320. IR
(film) 2923, 2853, 2689, 1701 (CO), 1471, 1327, 1083, 1043,
19
½aꢀD ¼ ꢁ0:8 (c 1.23, MeOH).
14. Compagnone, R. S.; Rapoport, H. J. Org. Chem. 1986, 51,
1713.
15. (2S)-3,3,3-Trifluoro-2-methyl-N-[(1R)-1-phenyl]-propana-
mide, 6: (2S)-1 (ee >98%, 106mg, 0.746mmol) was
dissolved in dry THF (12cm3) and cooled to ꢁ10ꢁC
under nitrogen. 4-Methylmorpholine (81mg, 0.8mmol)
and methyl chloridocarbonate (75mg, 0.8mmol) were
added and after 1min of stirring (1R)-1-phenylethanamine
(113mg, 0.93mmol) then added. The solution was stirred
at ꢁ5 to ꢁ10ꢁC for 40min and then an aqueous solution
of citric acid (5%, 150cm3) added. The mixture was
extracted with ethyl acetate (3 · 40cm3), the organic phase
washed with aqueous solution of sodium hydrogen
carbonate (1M, 3 · 20cm3), dried over MgSO4 and the
solvent removed under reduced pressure. The residue (de
98%) was purified using silica gel column chromatography
to give the major diastereomer as a white solid (de 100%,
165mg, 90%) mp 138.5–139ꢁC (from hexane).
1
965, 702cmꢁ1. H NMR (300MHz, CDCl3; Me4Si): d 9.9
(br s, 1H), 3.33–3.18 (m, 1H), 1.47 (d, 3H, J = 7.2Hz). 19
F
NMR (282MHz, CDCl3; CFCl3): d ꢁ70.5 (d, J = 6.9Hz).
13C NMR (75MHz, CDCl3):
d
173.3, 124.7 (q,
J = 279Hz), 44.4 (q, J = 29Hz), 11.0. MS (EI): m/z (rel
int.) = 142 [M]+ (1), 125 (30), 122 [MꢁF]+ (20), 102 (35),
78 (70), 77 (100), 69 [CF3]+ (20), 45 (35).
25
½aꢀD ¼ þ88:7 (c 0.345, CHCl3). MS (CI): m/z = 246.1107
12. (2R)-3,3,3-Trifluoro-2-methylpropanoic acid, (2R)-1: 1-
Decanol (6.708g, 42.38mmol) and 1 (3.009g, 21.19mmol)
were dissolved in hexane (200cm3). The CRL (7.5g) was
added and the mixture shaken at 250rpm/37ꢁC for 4h.
The reaction was terminated by the addition of MgSO4
(5g) and the mixture filtered. The solid was washed with
diethyl ether (3 · 15cm3), the solvent removed under
reduced pressure and the residue dissolved in diethyl ether
(50cm3). The solution was washed with aq NaHCO3
(0.8M, 3 · 40cm3), the solvent removed from the organic
phase and the residue hydrolyzed (HCl in 1,4-dioxane).
Similar work-up as for the racemic acid afforded (2R)-1
[M+H]+ C12H15OF3N requires 246.1107. IR (KBr) 3308,
3093, 2987, 2972, 1651 (CO), 1560, 1268, 1239, 1175, 1125,
1006, 754, 701cmꢁ1. 1H NMR (300MHz, CDCl3; Me4Si):
d 7.38–7.25 (m, 5H), 5.9 (br s, 1H), 5.19–5.09 (m, 1H),
3.09–2.93 (m, 1H), 1.51 (d, 3H, J = 6.8Hz), 1.39 (d, 3H,
J = 7.2Hz). 19F NMR (282MHz, CDCl3; CFCl3): d ꢁ69.9
(d, J = 8.6Hz). 13C NMR (75MHz, CDCl3): d 165.6,
142.4, 128.8, 127.6, 126.0, 125.6 (q, J = 280Hz), 49.2, 46.3
(q, J = 28Hz), 21.5, 11.0. MS (EI): m/z (rel int.) = 245
[M]+ (60), 230 [MꢁMe]+ (50), 120 (20), 106 (100), 105 (40),
77 (30). MS (ESI): m/z = 244 [MꢁH]ꢁ.
16. (a) Engel, K. H. Tetrahedron: Asymmetry 1991, 2, 165;
(b) Berglund, P.; Holmquist, M.; Hedenstro¨m, E.; Hult,
K.; Ho¨gberg, H. E. Tetrahedron: Asymmetry 1993, 4,
1869.
19
(541mg, 36%, ee 90%), ½aꢀD < þ1 (c 1.12, MeOH).
13. (2S)-3,3,3-Trifluoro-2-methylpropanoic acid, (2S)-1: 1-
Decanol (6.708g, 42.38mmol) and 1 (3.009g, 21.19mmol)