A. Arnone, P. Bravo, M. Frigerio, A. Mele, B. Vergani, F. Viani
FULL PAPER
Table 3. NMR data for compounds 11, 12 and 13
Compound
1H NMR (CDCl3/TMS)
δ, J (Hz)
19F NMR (CDCl3/C6F6)
δ, J (Hz)
31P NMR (CDCl3/
H3PO4)
δ, J (Hz)
(2S,3S,RS)-11
1.37 (br. t, J ϭ 7.1 Hz, 6 H, 2 ϫ OCH2CH3), 1.38 Ϫ118.82 (br. ddd, J ϭ 308.7, 101.0 and 5.00 (br. dd, J ϭ 101.0
and 1.62 (br. s, 6 H, 2 ϫ 6-CH3), 2.17 and 2.40 (m, 16.6 Hz, 1 F, 1a-F), Ϫ117.32 (br. ddd, and 99.4 Hz, 1 P, P-1)
2 H, 4-H2), 2.41 (br. s, 3 H, ArCH3), 3.29 (br. dd, J ϭ 308.7, 99.4 and 13.7 Hz, 1 F, 1b-F)
J ϭ 11.3 and 3.8 Hz, 1 H, 3-H), 4.2Ϫ4.4 (m, 4 H, 2
ϫ OCH2CH3), 4.95 (m, 1 H, 5-H), 5.95 (br. dd, J ϭ
16.6 and 13.7 Hz, 1 H, 2-H), 7.33 and 7.58 (m, 4 H,
p-TolH), 7.49, 7.59 and 8.25 (m, 5 H, ArH)
1.29 and 1.38 (br. t, J ϭ 7.2 Hz, 6 H, 2 ϫ Ϫ118.13 (br. ddd, J ϭ 308.4, 100.8 and 4.81 (br. dd, J ϭ 100.8
(2R,3S,RS)-11
(2S,3R,RS)-11
(2S,3S)-12
OCH2CH3), 1.62 and 1.65 (br. s, 6 H, 2 ϫ 6-CH3), 14.9 Hz, 1 F, 1a-F), Ϫ117.52 (br. ddd, and 100.4 Hz, 1 P, P-1)
2.10 (br. s, 3 H, ArCH3), 2.58 and 2.88 (m, 2 H, 4- J ϭ 308.4, 100.4 and 14.1 Hz, 1 F, 1b-F)
H2), 3.75 (br. ddd, J ϭ 7.8, 5.4 and 2.0 Hz, 1 H, 3-
H), 4.1Ϫ4.4 (m, 2 H, 2 ϫ OCH2CH3), 5.29 (m, 1 H,
5-H), 6.06 (br. dd, J ϭ 14.9 and 14.1 Hz, 1 H, 2-H),
and 7.1Ϫ7.9 (m, 9 H, ArH)
1.22 and 1.25 (br. t,
J ϭ 7.1 Hz, 6 H, 2 ϫ Ϫ119.82 (br. ddd, J ϭ 308.4, 100.8 and 4.65 (br. dd, J ϭ 102.4
OCH2CH3), 1.62 and 1.67 (br. s, 6 H, 2 ϫ 6-CH3), 15.9 Hz, 1 F, 1a-F), Ϫ117.82 (br. ddd, and 100.8 Hz, 1 P, P-1)
2.40 (br. s, 3 H, ArCH3), 2.80 (m, 2 H, 4-H2), 3.34 J ϭ 308.4, 102.4 and 14.4 Hz, 1 F, 1b-F)
(br. dd, J ϭ 7.3 and 6.0 Hz, 1 H, 3-H), 4.0Ϫ4.3 (m,
2 H, 2 ϫ OCH2CH3), 5.22 (m, 1 H, 5-H), 6.05 (br.
dd, J ϭ 15.9 and 14.4 Hz, 1 H, 2-H), 7.3Ϫ8.2 (m,
9 H, ArH)
1.28 and 1.31 (br. t,
J ϭ 7.2 Hz, 6 H, 2 ϫ Ϫ118.62 (br. ddd, J ϭ 311.5, 103.8 and 5.69 (br. dd, J ϭ 103.8
OCH2CH3), 1.52 and 1.68 (br. s, 6 H, 2 ϫ 6-CH3), 15.8 Hz, 1 F, 1a-F), Ϫ115.48 (br. ddd, and 102.6 Hz, 1 P, P-1)
2.29 (br. s, 3 H, ArCH3), 2.40 and 2.50 (m, 2 H, 4- J ϭ 311.5, 102.6 and 11.7 Hz, 1 F, 1b-F)
H2), 3.75 (dt, J ϭ 4.0 and 6.8 Hz, 1 H, 3-H), 4.1Ϫ4.3
(m, 4 H, 2 ϫ OCH2CH3), 5.24 (m, 1 H, 5-H), 5.83
(dddd, J ϭ 15.8, 11.7, 4.0, 3.2 Hz, 1 H, 2-H), 7.05
and 7.36 (m, 4 H, p-TolH), 7.42, 7.58, and 8.08 (m,
5 H, ArH)
(2S,3R)-12
(R)-13
1.18 and 1.20 (br. t,
J
ϭ
7.1 Hz, 6 H,
2
ϫ
Ϫ118.78 (br. ddd, J ϭ 310.6, 102.3 and 5.30 (br. t,
J
ϭ
OCH2CH3), 1.67 and 1.75 (br. s, 6 H, 2 ϫ 6-CH3), 14.4 Hz, 1 F, 1a-F), Ϫ117.23 (br. ddd, 102.3 Hz, 1 P, P-1)
2.31 (br. s, 3 H, ArCH3), 2.38 and 2.85 (m, 2 H, 4- J ϭ 310.6, 102.3 and 15.6 Hz, 1 F, 1b-F)
H2), 3.73 (br. d, J ϭ 10.5 Hz, 1 H, 3-H), 3.9Ϫ4.3 (m,
4 H, 2 ϫ OCH2CH3), 5.41 (m, 1 H, 5-H), 5.77 (dddd,
J ϭ 15.6, 14.4, 1.9, 1.7 Hz, 1 H, 2-H), 7.13 and 7.44
(m, 4 H, p-TolH), 7.47, 7.60, and 8.11 (m, 5 H, ArH)
1.29 and 1.34 (t, J ϭ 7.2 Hz, 6 H, 2 ϫ OCH2CH3), Ϫ121.30 (br. ddd, J ϭ 310.0, 104.7 and 6.10 (br. dd, J ϭ 104.7
1.53 and 1.62 (br. s, 6 H, 2 ϫ 6-CH3), 1.6Ϫ2.2 (m, 13.2 Hz, 1 F, 1a-F), Ϫ118.66 (br. ddd, and 103.4 Hz, 1 P, P-1)
4 H, 3-H2 and 4-H), 4.2Ϫ4.4 (m, 4 H,
2
ϫ J ϭ 310.0, 103.4 and 12.3 Hz, 1 F, 1b-F)
OCH2CH3), 5.10 (m, 1 H, 5-H), 5.64 (m, 1 H, 2-H),
7.46, 7.59 and 8.11 (m, 5 H, ArH)
tion of the appropriate compound (1.1 mmol) and DCC (1.0 mmol)
in CH2Cl2 (8 mL). After 5 min, DMAP (0.1 mmol) was added, and
1.6Ϫ1.9 (m, 4 H, 3- and 4-H2), 3.81 (br. q, J ϭ 7.3 Hz, 1 H, 2Ј-H),
4.28 (m, 4 H, 2 ϫ OCH2CH3), 4.93 (m, 1 H, 5-H), 5.37 (m, 1 H,
after 30 min the white precipitate was filtered off. The clear filtrate 2-H), 7.2Ϫ7.4 (m, 5 H, ArH). Ϫ 19F NMR (CDCl3): δ ϭ Ϫ121.51
was concentrated in vacuo and the residue was directly subjected,
without further chemical manipulation, to 1H-NMR analysis.
Comparison of the spectra of the two diastereomeric esters allowed
assessment of the enantiopurity. In all examined cases, the phenyl-
propionic esters were obtained as the sole reaction products and in
yields Ն 95%.
(br. ddd, J ϭ 307.0, 103.3 and 14.5 Hz, 1 F, F-1a), Ϫ119.63 (br.
ddd, J ϭ 307.0, 101.0 and 10.8 Hz, 1 F, F-1b).
(b) Starting from (S)-6 (0.067 mmol, 20 mg) and (Ϫ)-(R)-phenyl-
propionic acid (0.072 mmol, 8.2 µL), (2S,2ЈR)-14 was obtained.
Yield: 28 mg (97%).
Ϫ Using (ϩ)-(S)-phenylpropionic acid,
(2S,2ЈS)-14 was obtained. Yield: 28 mg (97%). Ϫ The 1H-NMR
spectra of (2S,2ЈR)-14 and (2S,2ЈS)-14 were superimposable on
those of (2R,2ЈS)-14 and (2R,2ЈR)-14, respectively, described above.
(a) Starting from (R)-6 (0.053 mmol, 16 mg) and (Ϫ)-(R)-phenyl-
propionic acid (0.053 mmol, 6.0 µL), (2R,2ЈR)-14 was obtained.
Yield: 22 mg (95%). Ϫ 1H NMR (CDCl3): δ ϭ 1.30 and 1.33 (t,
J ϭ 7.0 Hz, 6 H, 2 ϫ OCH2CH3), 1.50 and 1.66 (br. s, 6 H, 2 ϫ 6-
Me), 1.56 (d, J ϭ 7.3 Hz, 3 H, 2Ј-CH3), 1.7Ϫ2.1 (m, 4 H, 3- and
4-H2), 3.82 (br. q, J ϭ 7.3 Hz, 1 H, 2Ј-H), 4.19 (m, 4 H, 2 ϫ
OCH2CH3), 5.04 (m, 1 H, 5-H), 5.37 (m, 1 H, 2-H), 7.2Ϫ7.4 (m,
5 H, ArH). Ϫ 19F NMR (CDCl3): δ ϭ Ϫ120.72 (br. ddd, J ϭ 307.5,
103.3 and 14.0 Hz, 1 F, F-1a), Ϫ119.41 (br. ddd, J ϭ 307.5, 103.5
and 10.6 Hz, 1 F, F-1b). Ϫ From (ϩ)-(S)-phenylpropionic acid,
(2R,2ЈS)-14 was obtained. Yield: 23 mg (97%). Ϫ 1H NMR
(CDCl3): δ ϭ 1.34 and 1.60 (br. s, 6 H, 2 ϫ 6-Me), 1.39 (br. t, J ϭ
7.0 Hz, 6 H, 2 ϫ OCH2CH3), 1.54 (d, J ϭ 7.3 Hz, 3 H, 2Ј-Me),
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