4
T. Hayase et al. / Journal of Fluorine Chemistry 84 (1997) 1–5
pressure. Purification of the residue by TLC (thin layer chro-
matography) afforded fluorine-containing alcohols.
ysis, Chiralcel OF, eluent 0.5% 2-propanol in hexane, flow
rate 0.2 ml miny1, room temperature, retention time (min)
major 27.4, minor 31.2); m.p. 73.8 8C.
3.2. General procedure for the enantioselective addition of
dialkylzincs to aldehyde (1a) using DPMPM as a chiral
catalyst (Table 2, entry 10 and Table 4, entry 2)
1-(4-Trifluoromethylphenyl)-2-methylpropan-1-ol4e. 1H
NMR (CDCl3) d 0.83 (d, Js6.8 Hz, 3H, CH3), 0.96 (d,
Js6.8 Hz, 3H, CH3), 1.90 (bs, 1H, OH), 1.96 (dqq, Js6.3,
6.8, 6.8 Hz, 1H, CH), 4.46 (d, Js6.3 Hz, 1H, CH), 7.42 (d,
Js8.3 Hz, 2H, 2ph-CH), 7.59 (d, Js8.3 Hz, 2H, 2ph-CH);
IR (neat) (cmy1) 3371.0; HRMS calculated for C11H13F3O
218.0919, found 218.0915; [a]3D0sy20.3 (c 1.10, MeOH),
97% e.e. (by HPLC analysis, Chiralcel OJ, eluent 0.5% 2-
propanol in hexane, flow rate 0.2 ml miny1, room tempera-
ture, retention time (min) major 125.2, minor 141.1].
(S)-1-Pentafluorophenylpropan-1-ol 4f. 1H NMR
(CDCl3) d 0.97 (t, Js7.4 Hz, 3H, CH3), 1.86 (dq, Js7.3,
7.4 Hz, 1H, 1/2CH2), 2.05 (dq, Js7.3, 7.4 Hz, 1H, 1/
2CH2), 2.18 (bs, 1H, OH), 4.97 (dd, Js7.3, 7.3 Hz, 1H,
CH); IR (KBr) (cmy1) 3365.2; HRMS calculated for
C9H7F5O 226.0417, found 226.0417; [a]3D1sq3.0 (c 2.01,
pentane), 96% e.e. (byHPLCanalysis,SumichiralOA-4900,
To a solution of (R)-(q)-DPMPM (0.1 mmol, 0.027 g)
in hexane 3 ml, n-BuLi (1.6 M hexane solution, 0.1 mmol)
was added at 0 8C then hexane solution of dialkylzinc (1 M,
3.0 mmol, 3.0 ml) was added at 0 8C. After 15 min, aldehyde
1a (1 mmol) was added to the solution at 0 8C. The reaction
mixture was stirred for 15 min at 0 8C then stirring was
continued at room temperature for 2–3 h. The reaction was
quenched by adding 1 M HCl (15 ml), then extracted with
CH2Cl2 and dried (Na2SO4). The extract was filtered and the
filtrate was evaporated under reduced pressure. Purification
of the residue by TLC (thin layer chromatography) afforded
optically active alcohols.
(S)-1-Pentafluorophenyl-2-methylpropan-1-ol 4a. 1H
NMR (CDCl3) d 0.80 (d, Js6.8 Hz, 3H, CH3), 1.15 (d,
Js6.8 Hz, 3H, CH3), 2.13 (dqq, Js9.2, 6.8, 6.8 Hz, 1H,
CH), 2.20 (bs, 1H, OH), 4.63 (d, Js9.2 Hz, 1H, CH); IR
(KBr) (cmy1) 3361.3; HRMS calculated for C10H9F5O
240.0574, found 240.0571; [a]2D8sq4.0 (c 1.51, pentane),
97% e.e. (by HPLC analysis, Sumichiral OA-4900, eluent
0.5% 2-propanol in hexane, flow rate 1.0 ml miny1, room
temperature, retention time (min) major 13.7, minor 12.9);
m.p. 44.1 8C.
eluent 0.5% 2-propanol in hexane, flow rate 1.0 ml miny1
,
room temperature, retention time (min) major 18.8, minor
17.5); m.p. 38.5 8C.
1-(2,4,6-Trifluorophenyl)propan-1-ol 4g. 1H NMR
(CDCl3) d 0.92 (t, Js7.4 Hz, 3H, CH3), 1.82(ddq, Js0.88,
7.4, 7.4 Hz, 1H, 1/2CH2), 1.98 (ddq, Js0.88, 7.4, 7.4 Hz,
1H, 1/2CH2), 2.44 (s, 1H, OH), 4.89 (dd, Js7.4, 7.4 Hz,
1H, CH), 6.58–6.71 (m, 2ph-CH); IR (neat) (cmy1
)
3371.0; HRMS calculated for C9H9F3O 190.0606, found
190.0587; [a]2D8sy1.0 (c 3.11, MeOH), 92% e.e. (by
HPLC analysis, Chiralcel OD, eluent 1.0% 2-propanol in
hexane, flow rate 0.3 ml miny1, room temperature, retention
time (min) major 39.7, minor 43.6).
1-(2,4,6-Trifluorophenyl)-2-methylpropan-1-ol 4b. 1H
NMR (CDCl3) d 0.76 (d, Js6.6 Hz, 3H, CH3), 1.12 (d,
Js6.6 Hz, 3H, CH3), 2.12 (dqq, Js9.2, 6.6, 6.6 Hz, 1H,
CH), 2.40 (s, 1H, OH), 4.55 (d, Js9.2 Hz, 1H), 6.58–6.71
(m, 2H); IR (neat) (cmy1) 3401.8; HRMS calculated for
C10H11F3O 204.0762, found 204.0761; [a]3D0sy1.2 (c
1.24, MeOH), 93% e.e. (by HPLC analysis, Chiralcel OD,
1-(2-Trifluoromethylphenyl)propan-1-ol 4h. 1H NMR
(CDCl3) d 0.98 (t, Js7.4 Hz, 3H, CH3), 1.76 (dq, Js6.4,
7.4 Hz, 2H, CH2), 2.09 (s, 1H, OH), 5.02 (t, Js6.4 Hz, 1H,
CH), 7.36 (dd, Js7.7, 7.7 Hz, 1H, ph-CH), 7.54–7.63 (m,
2H, 2ph-CH), 7.75 (d, Js7.7 Hz, 1H, ph-CH); IR (neat)
(cmy1) 3392.2; HRMS calculated for C10H11F3O 204.0762,
found 204.9757; [a]2D5sy31.0 (c 2.48, MeOH), 89% e.e.
(by HPLC analysis, Chiralpak AS, eluent 0.25% 2-propanol
in hexane, flow rate 0.5 ml miny1, room temperature, reten-
tion time (min) major 26.4, minor 24.7).
eluent 1.0% 2-propanol in hexane, flow rate 0.3 ml miny1
room temperature, retention time (min) major 30.2, minor
32.9).
,
1-(2-Trifluoromethylphenyl)-2-methylpropan-1-ol4c. 1H
NMR (CDCl3) d 0.76 (d, Js6.6 Hz, 3H, CH3), 1.11 (d,
Js6.6 Hz, 3H, CH3), 1.95 (s, 1H, OH), 2.04 (dqq, Js7.6,
6.6, 6.6 Hz, 1H, CH), 4.75 (d, Js7.6 Hz, 1H, CH), 7.38
(dd, Js7.5, 7.5 Hz, 1H, ph-CH), 7.55–7.65 (m, 2H, 2ph-
1-[3,5-Bis(trifluoromethyl)phenyl]propan-1-ol 4i. 1H
NMR (CDCl3) d 0.97 (t, Js7.4 Hz, 3H, CH3), 1.81 (dq,
Js6.4, 7.4 Hz, 2H, CH2), 2.07 (bs, 1H, OH), 4.78 (t, Js6.4
Hz, 1H, CH), 7.79 (s, 1H, ph-CH), 7.81 (s, 2H, 2ph-CH);
IR (KBr) (cmy1) 3222.5; HRMS calculated for C11H10F6O
272.0636, found 272.0635; [a]3D2sy21.5 (c 1.51, MeOH),
90% e.e. (by HPLC analysis, Chiralcel OD, eluent 0.5% 2-
propanol in hexane, flow rate 0.5 ml miny1, room tem-
perature, retention time (min) major 40.0, minor 44.6); m.p.
91.5 8C.
CH), 7.72 (d, Js7.5 Hz, 1H, ph-CH); IR (neat) (cmy1
)
3423.0; HRMS calculated for C11H13F3O 218.0919, found
218.0906; 96% e.e. (byHPLCanalysis, ChiralpakAD,eluent
0.5% 2-propanol in hexane, flow rate 1.0 ml miny1, room
temperature, retention time (min) major 18.1, minor 15.6).
1-[3,5-Bis(trifluoromethyl)phenyl]-2-methylpropan-1-
1
ol 4d. H NMR (CDCl3) d 0.89 (d, Js6.8 Hz, 3H, CH3),
0.95 (d, Js6.8 Hz, 3H, CH3), 1.99 (dqq, Js5.9, 6.8, 6.8
Hz, 1H, CH), 2.00 (bs, 1H, OH), 4.59 (d, Js5.9 Hz, 1H,
CH), 7.78 (s, 3H, 3ph-CH); IR (KBr) (cmy1) 3388.3;
HRMS calculated for C12H12F6O 286.0793, found 286.0798;
[a]3D2sy20.5 (c 1.35, MeOH), 94% e.e. (by HPLC anal-
1-(4-Trifluoromethylphenyl)propan-1-ol 4j. 1H NMR
(CDCl3) d 0.88 (t, Js7.4 Hz, 3H, CH3), 1.66–1.78 (m, 2H,
CH2), 2.77 (s, 1H, OH), 4.59 (t, Js6.6 Hz, 1H, CH), 7.39