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(R)-2-Phenyloctan-1-ol (4c). Purification by column chromatog-
raphy (SiO2, 5−20% Et2O/pentane, gradient) afforded 4c (33 mg,
determined for the benzoate ester of the alcohol. Enantiomeric excess
was determined by chiral HPLC analysis, Chiralcel OD-H column, n-
heptane/i-PrOH 98:2, 40 °C, 232 nm, retention times (min): 8.43
(minor) and 9.06 (major).
yield = 70%) as a colorless oil: 99% ee, [α]20 = −14.2 (c = 1 in
D
CHCl3); [lit.26 (S)-enantiomer (92% ee): [α]21 = +15.1 (c = 0.99 in
D
1
CHCl3)]; H NMR (400 MHz, CDCl3) δ 7.37−7.18 (m, 5H), 3.81−
(S)-3-Bromo-2-methylpropan-1-ol (4i). Purification by column
chromatography (SiO2, 10−30% Et2O/pentane, gradient) afforded 4i
(22.5 mg, yield = 30%) as a colorless oil: 72% ee, [α]20D = +1.6 (c = 1
in CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.67−3.56 (m, 2H), 3.54−
3.45 (m, 2H), 2.08−1.97 (m, 1H), 1.43 (s, 1H), 1.03 (d, J = 6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 65.4, 37.6, 37.3, 15.5. The
enantiomeric excess was determined for the benzoate ester of the
alcohol. Enantiomeric excess was determined by chiral HPLC analysis,
Chiralcel OB-H column, n-heptane/i-PrOH 100:0, 40 °C, 226 nm,
retention times (min): 27.92 (major) and 31.4 (minor).
3.66 (m, 2H), 2.82−2.72 (m, 1H), 1.77−1.63 (m, 1H), 1.62−1.50 (m,
1H), 1.34−1.11 (m, 8H), 0.85 (t, J = 6.9 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 142.5, 128.6, 128.0, 126.6, 67.6, 48.7, 32.0, 31.7, 29.3,
27.3, 22.6, 14.0; HRMS (APCI+, m/z) calcd for C14H21 [M − H2O]+
189.16378, found 189.16372. Enantiomeric excess was determined by
chiral HPLC analysis, Chiralcel OJ-H column, n-heptane/i-PrOH 95:5,
40 °C, 220 nm, retention times (min): 10.63 (major) and 11.33
(minor).
(R)-4-Methyl-2-phenylpentan-1-ol (4d). Purification by column
chromatography (SiO2, 5−20% Et2O/pentane, gradient) afforded 4d
(30 mg, yield = 70%) as a colorless oil: 84% ee, [α]20D = −10.2 (c = 1
in CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.38−7.19 (m, 5H), 3.76−
3.64 (m, 2H), 2.95−2.84 (m, 1H), 1.64−1.51 (m, 1H), 1.49−1.36 (m,
3H), 0.86 (t, J = 6.7 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 142.4,
128.6, 128.1, 126.7, 68.0, 46.4, 41.1, 25.2, 23.5, 21.8; HRMS (APCI+,
m/z) calcd for C12H17 [M − H2O]+ 161.13248, found 161.13238.
Enantiomeric excess was determined by chiral HPLC analysis,
Chiralcel AD-H column, n-heptane/i-PrOH 95:5, 40 °C, 212 nm,
retention times (min): 12.26 (major) and 13.04 (minor).
(S)-2-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)octan-1-ol (4j). Purifica-
tion by column chromatography (SiO2, 10−40% Et2O/pentane,
gradient) afforded 4j (25 mg, yield = 65%) as a colorless oil: anti:syn
1
= >99:1, [α]20 = +22.0 (c = 1 in CHCl3); H NMR (400 MHz,
D
CDCl3) δ 4.10 (dd, J = 7.9, 6.1 Hz, 1H), 4.02 (dd, J = 14.0, 7.7 Hz,
1H), 3.75 (dd, J = 11.2, 3.1 Hz, 1H), 3.69−3.60 (m, 3H), 1.71−1.61
(m, 1H), 1.41 (s, 3H), 1.35 (s, 3H), 1.33−1.18 (m, 10H), 0.87 (t, J =
6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 109.1, 80.0, 68.8, 64.6,
44.0, 31.7, 29.5, 28.1, 27.0, 26.6, 25.5, 22.6, 14.0; HRMS (ESI+, m/z)
calcd for C13H26O3Na [M + Na]+ 253.17742, found 253.17761. The
1
(R)-2-(4-Bromophenyl)propan-1-ol (4e). Purification by column
chromatography (SiO2, 10−20% Et2O/pentane, gradient) afforded an
inseparable mixture of 4e and p-bromobenzyl alcohol in a ratio of
90:10 (27 mg, yield = 84%) as a colorless oil: 99% ee, [α]20D = +8.6 (c
diastereomeric ratio was determined by H NMR.
(S)-2-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)propan-1-ol (4k). Purifi-
cation by column chromatography (SiO2, 10−40% Et2O/pentane,
gradient) afforded 4k (23 mg, yield = 50%) as a colorless oil: anti:syn =
1
>99:1, [α]20 = +15.2 (c = 1 in CHCl3) [lit.27 (anti:syn = >20:1):
= 1 in CHCl3); H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.4 Hz,
D
[α]25D = +15.8 (c = 0.88 in CHCl3)]; 1H NMR (400 MHz, CDCl3) δ
4.10 (dd, J = 7.9, 6.1 Hz, 1H), 3.98−3.90 (m, 1H), 3.71−3.56 (m,
3H), 2.77 (br s, 1H), 1.91−1.78 (m, 1H), 1.41 (s, 3H), 1.35 (s, 3H),
0.82 (d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 109.4, 80.9,
68.8, 67.5, 39.2, 26.6, 25.7, 13.1; HRMS (ESI+, m/z) calcd for
C8H16O3Na [M + Na]+ 183.09917, found 183.09885. The
2H), 7.44 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.5
Hz, 2H), 4.64 (s, 2H), 3.72−3.62 (m, 2H), 2.96−2.86 (m, 1H), 1.25
(d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 142.7, 139.8,
131.6, 131.6, 129.2, 128.6, 121.4, 120.4, 68.4, 64.5, 41.9, 17.5; HRMS
(APCI+, m/z) calcd for C9H10Br [M − H2O]+ 196.99604, found
196.99617. Enantiomeric excess was determined by chiral HPLC
analysis, Chiralcel OB-H column, n-heptane/i-PrOH 95:5, 40 °C, 224
nm, retention times (min): 14.37 (minor) and 14.9 (major).
(R)-2-(4-Bromophenyl)hexan-1-ol (4f). Purification by column
chromatography (SiO2, 10−20% Et2O/pentane, gradient) afforded
4f (34 mg, yield = 75%) as a colorless oil. 97% ee, [α]20D = −13.8 (c =
1 in CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H),
7.09 (d, J = 8.4 Hz, 2H), 3.77−3.64 (m, 2H), 2.78−2.68 (m, 1H),
1.80−1.60 (m, 1H), 1.58−1.45 (m, 1H), 1.38−1.04 (m, 2H), 0.84 (t, J
= 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 141.6, 131.7, 129.8,
120.4, 67.4, 48.2, 31.6, 29.4, 22.7, 13.9; HRMS (APCI+, m/z) calcd for
C12H16Br [M − H2O]+ 239.04299, found 239.04261. Enantiomeric
excess was determined by chiral HPLC analysis, Chiralcel AD-H
column, n-heptane/i-PrOH 95:5, 40 °C, 230 nm, retention times
(min): 15.04 (major) and 16.01 (minor).
1
diastereomeric ratio was determined by H NMR.
(S)-1-Hydroxyhexan-2-yl Benzoate (4l). Purification by column
chromatography (SiO2, 10−30% Et2O/pentane, gradient) afforded 4l
(51 mg, yield = 53%) as a colorless oil: 97% ee, [α]20D = −23.0 (c = 1
in CHCl3); [lit.28 (94% ee): [α]23 = −24 (c = 0.4 in CHCl3)]; H
1
D
NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.3 Hz, 2H) 7.56 (t, J = 7.5
Hz, 1H), 7.43 (t, J = 7.9 Hz, 2H), 5.20−5.12 (m, 1H), 3.85−3.71 (m,
2H), 2.29 (br s, 1H), 1.82−1.62 (m, 2H), 1.47−1.29 (m, 4H), 0.90 (t,
J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9, 133.1, 130.2,
129.7, 128.4, 76.4, 64.9, 30.4, 27.5, 22.6, 13.9; HRMS (ESI+, m/z)
calcd for C13H18O3Na [M + Na]+ 245.11482, found 245.11461.
Enantiomeric excess was determined by chiral HPLC analysis,
Chiralcel OB-H column, n-heptane/i-PrOH 95:5, 40 °C, 225 nm,
retention times (min): 15.08 (major) and 15.91 (minor).
(R)-2-(4-Bromophenyl)octan-1-ol (4g). Purification by column
chromatography (SiO2, 10−20% Et2O/pentane, gradient) afforded
4g (38 mg, yield = 90%) as a colorless oil: 99% ee, [α]20D = −13.2 (c =
1 in CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 2H),
7.08 (d, J = 8.4 Hz, 2H), 3.77−3.60 (m, 2H), 2.78−2.68 (m, 1H),
1.74−1.61 (m, 1H), 1.60−1.47 (m, 1H), 1.38−1.07 (m, 8H), 0.85 (t, J
= 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 141.7, 131.7, 129.8,
120.4, 67.4, 48.2, 31.9, 31.7, 29.3, 27.2, 22.6, 14.0; HRMS (APCI+, m/
z) calcd for C14H20Br [M − H2O]+ 267.07429, found 267.07391.
Enantiomeric excess was determined by chiral HPLC analysis,
Chiralcel AD-H column, n-heptane/i-PrOH 95:5, 40 °C, 226 nm,
retention times (min): 14.20 (major) and 14.90 (minor).
General Procedure for the Synthesis of γ-Alkyl-Substituted
Alcohols through Cu-Catalyzed Asymmetric Allylic Alkylation
of Allyl Bromides with Organolithium Reagents Followed by a
Hydroboration/Oxidation. To a solution of the alkene (0.2 mmol)
in dry THF (1 mL) was added 9-BBN in THF (0.5 M, 0.6 mmol, 3
equiv), and the mixture was stirred at room temperature for 2 h. Then
the mixture was cooled to 0 °C, ethanol (2.0 mL), an aq. solution of
NaOH (6.0 M, 1.2 mL), and H2O2 (30% in water, 4 mL) were added,
and the mixture was warmed to room temperature while being stirred
overnight. The reaction was quenched with an aqueous solution of
Na2S2O3 (5 mL) and the mixture extracted with dichloromethane (3 ×
5 mL). The organic layer was dried with MgSO4 and filtered and the
solvent evaporated in vacuo. The crude product was purified by flash
chromatography on silica gel using various mixtures of n-pentane/
Et2O as eluent.
(S)-2-(Bromomethyl)octan-1-ol (4h). Purification by column
chromatography (SiO2, 10−30% Et2O/pentane, gradient) afforded
4h (15 mg, yield = 60%) as a colorless oil: 97% ee, [α]20D = −9.4 (c =
1
(S)-3-Phenylheptan-1-ol (6a). Purification by column chromatog-
1 in CHCl3); H NMR (400 MHz, CDCl3) δ 3.50 (dd, J = 10.5, 5.8
raphy (SiO2, 5−20% Et2O/pentane, gradient) afforded 6a (29 mg,
Hz, 2H), 3.41 (dd, J = 10.5, 6.5 Hz, 2H), 1.68−1.53 (m, 1H), 1.39−
1.34 (m, 1H), 1.33−1.19 (m, 8H), 1.16−1.02 (m, 1H), 0.88 (t, J = 6.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 68.4, 35.7, 33.1, 31.8, 29.6,
26.9, 22.7, 16.7, 14.1; HRMS (ESI+, m/z) calcd for C9H20BrO [M +
H]+ 223.09752, found 223.09707. The enantiomeric excess was
yield = 67%) as a colorless oil: 99% ee, [α]20 = −1.6 (c = 1 in
D
CHCl3); [lit.29 (94% ee): [α]20 = −1.28 (c = 1.02 in CHCl3)]; H
1
D
NMR (400 MHz, CDCl3) δ 7.30−7.05 (m, 5H), 3.52−3.37 (m, 2H),
2.68−2.58 (m, 1H), 1.97−1.85 (m, 1H), 1.83−1.70 (m, 1H), 1.69−
E
dx.doi.org/10.1021/jo401536u | J. Org. Chem. XXXX, XXX, XXX−XXX