The Journal of Organic Chemistry
Note
vigorous stirring. The mixture was stirred for 2 h, then water (2.5 mL)
was added dropwise, followed by 15% NaOH (5.25 mL) and more
water (7.4 mL). The resulting salts were washed with diethyl ether (3
× 50 mL), and the combined extracts were dried over sodium sulfate
and concentrated under reduced pressure to give fairly pure (E)-3-
bromoprop-2-en-1-ol as a yellow liquid (4.16 g, 57%).
removed and the reaction mixture left to warm to 20 °C over 3 h. An
accurately weighed amount of tetradecane (∼0.2 mL) was added as a
standard to enable GC determination of the amount of desired
product formed following workup. The reaction mixture was cooled to
0 °C, then oxidized by dropwise addition of excess NaOH (0.6 g in 5
mL of H2O), followed by hydrogen peroxide (30% by weight, 3 mL).
Once the initial exothermic reaction subsided, the cooling bath was
removed and the mixture left to stir overnight at room temperature.
Diethyl ether (10 mL) was added, the aqueous layer saturated with
sodium chloride, and a small aliquot taken from the organic phase for
GC analysis. The mixture was extracted with diethyl ether (2 × 25
mL). The extract was washed with water (10 mL) and brine (10 mL),
then dried over MgSO4 to give a crude product containing the desired
3-alkylprop-1-en-3-ol 9 or 14, which was estimated by GC. In some
cases (see below), mixtures were separated by column chromatog-
raphy on silica (prewashed with 3% triethylamine in petroleum ether,
petroleum ether/ethyl acetate 95:5 through 85:15) to provide the pure
products.
Synthesis of (E)-1-bromo-3-chloroprop-1-ene11,12 (5): A 50 mL
round-bottomed flask equipped with a magnetic stirrer bar was
charged with (E)-3-bromoprop-2-en-1-ol (3.52 g, 25.7 mmol) and
cooled using an ice bath. Hexachloroacetone (7.79 mL, 51.4 mmol)
was added and the solution stirred for 5 min. Powdered triphenyl-
phosphine (6.74 g, 25.7 mmol) was added portionwise over a period
of 25 min. The mixture was stirred for 2 h at 0 °C, then fractionally
distilled under reduced pressure to give 90% pure (E)-1-bromo-3-
chloroprop-1-ene, which was fractionally distilled a second time to give
pure (E)-1-bromo-3-chloroprop-1-ene (5) as a colorless liquid (0.52 g,
1
13%): H (500 MHz, CDCl3) δ 6.48 (1H, dt, J = 13.5, 1.1 Hz), 6.34
(1H, dt, J = 13.5, 7.1 Hz), 4.02 (2H, dd, J = 7.1, 1.1 Hz); 13C (125
MHz, CDCl3) δ 133.1 (CH), 110.8 (CH), 43.6 (CH2).
4,4,5-Trimethylhex-1-en-3-ol (9, R = 1,1,2-Trimethylpropyl, i.e.,
Thexyl): From 3 (R = thexyl) (0.564 g, 2.66 mmol), 5 (0.416 g, 2.68
mmol), THF (15 mL), and t-BuLi in hexanes (1.9 M, 1.41 mL, 2.68
mmol) (note that the excess of 5 and organolithium reagent was
Synthesis of Boronate Esters. Boronate esters 3 where R = Bn
and 4-MeOBn were purchased from Sigma-Aldrich and TCI,
respectively, and used without further purification. Boronate esters 3
where R = Bu, i-Pr, and cyclohexyl were prepared from the reaction of
their corresponding boronic acids with pinacol in pentane in 73, 36,
and 32% yields, respectively. Boronate ester 3 where R = tert-Bu was
prepared by the literature method from pinacolborane and tert-
BuMgCl in 40% yield.24 Boronate ester 3 where R = thexyl was
prepared by the method previously described from the monohydro-
boration of 2,3-dimethyl-2-butene and subsequent reaction with
pinacol, while boronate esters 11 and 12 were also prepared as
described previously.6
1
smaller in this example); colorless oil (0.105 g, 28%); H (400 MHz,
CDCl3) δ 5.94 (1H, ddd, J = 17.2, 10.5, 6.7 Hz), 5.23 (1H, d, J = 17.2
Hz), 5.18 (1H, d, J = 10.5 Hz), 4.01 (1H, d, J = 6.7 Hz, CHOH), 1.73
(1H, app sept, J = 7.0 Hz), 1.47 (1H, br s), 0.87 (3H, d, J = 6.9 Hz),
0.85−0.82 (6H, m), 0.73 (3H, s); 13C (125 MHz, CDCl3) δ 138.5
(CH), 116.5 (CH2), 78.1 (CH), 39.6 (quat C), 32.9 (CH), 19.0
(CH3), 18.6 (CH3), 17.5 (CH3), 17.4 (CH3); HRMS (EI+) m/z calcd
for C9H18O 124.1252, found 124.1252 (M+ − H2O).
4,4-Diethylhex-1-en-3-ol (14, RC = RD = Et): From 13 (RC = RD =
Et) (0.335 g, 1.58 mmol), 5 (0.274 g, 1.76 mmol), dry THF (10 mL),
and t-BuLi in hexanes (1.6 M, 1.09 mL, 1.74 mmol); colorless liquid
Boronate esters 13 were prepared by the DCME reaction with the
appropriate trialkylboranes. The procedure for preparation of 13 (RC =
c-Hex, RD = PhCHCH) is typical. Characterization details of the
other boronate esters 13 can be found in our previous publication.6
Boronate Ester 13 (RC = c-Hex, RD = PhCHCH): Dicyclohexyl-
borane was prepared by the dropwise addition of cyclohexene (2.12
mL, 20.9 mmol) to borane dimethyl sulfide complex (10 M, 1.00 mL,
10.0 mmol). The mixture was stirred at room temperature for 2 h, dry
THF (10 mL) was added, then the mixture was kept at 0 °C during
the dropwise addition of phenylacetylene (1.15 mL, 10.5 mmol). The
mixture was stirred for 1 h at 0 °C and 1 h at room temperature then
recooled to 0 °C. Dichloromethyl methyl ether (1.36 mL, 15.0 mmol)
was added dropwise, followed by a freshly prepared solution of lithium
triethylcarboxide (dropwise addition of n-BuLi (1.6 M in hexanes, 9.38
mL, 15.0 mmol) to a solution of 3-ethyl-3-pentanol (2.12 mL, 15.0
mmol) in THF (10 mL)) dropwise via a cannula over a 20 min period.
The ice bath was removed and the mixture left to stir for a further 1 h.
2,2-Dimethyl-1,3-propanediol (1.57 g, 15.0 mmol) in dry THF (5 mL)
was added and the reaction mixture left to stir overnight at room
temperature. The crude product following workup was separated by
column chromatography on silica (petroleum ether) to give pure (E)-
2-(1,1-dicyclohexyl-3-phenylallyl)-5,5-dimethyl-1,3,2-dioxaborinane
1
(0.042 g, 17%); H (500 MHz, CDCl3) δ 6.02 (1H, ddd, J = 17.2,
10.5, 6.6 Hz), 5.24 (1H, app dt, J = 17.2, 1.6 Hz), 5.16 (1H, app dt, J =
10.5, 1.6 Hz), 4.00−3.96 (1H, m), 1.41−1.28 (6H, m), 0.84 (9H, t, J =
7.6 Hz); 13C (125 MHz, CDCl3) δ 138.8 (CH), 115.9 (CH), 78.4
(CH), 41.7 (quat C), 26.0 (CH2), 8.5 (CH3); HRMS (EI+) m/z calcd
for C10H20O 156.1514, found 156.1509 (M+).
1-Phenylbut-3-en-2-ol (9, R = Benzyl):25 From 3 (R = Bn) (0.280
g, 1.28 mmol), 5 (0.226 g, 1.45 mmol), dry THF (10 mL), and t-BuLi
in hexanes (1.5 M, 0.97 mL, 1.46 mmol); colorless oil (0.097 g, 52%);
1H (400 MHz, CDCl3) δ 7.24 (2H, app t, J = 6.9 Hz), 7.19−7.15 (3H,
m), 5.86 (1H, ddd, J = 17.2, 10.5, 5.8 Hz), 5.18 (1H, app dt, J = 17.2,
1.4 Hz), 5.06 (1H, app dt, J = 10.5, 1.3 Hz), 4.31−4.24 (1H, m), 2.82
(1H, dd, J = 13.6, 5.1 Hz), 2.72 (1H, dd, J = 13.6, 8.0 Hz), 1.64 (1H,
br s); 13C (125 MHz, CDCl3) δ 140.2 (CH), 137.8 (quat C), 129.7
(CH), 128.6 (CH), 126.7 (CH), 115.1 (CH2), 73.8 (CH), 43.9
(CH2); LRMS (EI+) m/z 148 (M+, 4%).
1-(4-Methoxyphenyl)but-3-en-2-ol (9, R = 4-Methoxybenzyl):26
From 4-methoxybenzylboronic acid pinacol ester (0.292 g, 1.18
mmol), 5 (0.210 g, 1.35 mmol), dry THF (10 mL), and t-BuLi in
hexanes (1.5 M, 0.84 mL, 1.26 mmol); colorless oil (0.185 g, 52%); 1H
(400 MHz, CDCl3) δ 7.15 (2H, d, J = 8.7 Hz), 6.86 (2H, d, J = 8.7
Hz), 5.93 (1H, ddd, J = 17.2, 10.5, 5.8 Hz), 5.24 (1H, app dt, J = 17.2,
1.4 Hz), 5.13 (1H, app dt, J = 10.5, 1.4 Hz), 4.34−4.27 (1H, m), 3.79
(3H, s), 2.83 (1H, dd, J = 13.7, 5.1 Hz), 2.73 (1H, dd, J = 13.7, 7.9
Hz), 1.65 (1H, br s); 13C (125 MHz, CDCl3) δ 158.4 (quat C), 140.3
(CH), 130.5 (CH), 129.7 (quat C), 114.8 (CH2), 114.0 (CH), 73.7
(CH), 55.3 (CH3), 42.9 (CH2); LRMS (EI+) m/z 178 (M+, 45%).
Synthesis of GC Standards from Aldehydes and Vinyl-
magnesium Bromide: General Procedure. An oven-dried 50 mL
round-bottomed flask equipped with a magnetic stirrer bar and septum
was flushed with N2. Vinylmagnesium bromide solution in THF (0.7
M, 1.2 equiv) was added, and the mixture was cooled to 0 °C. The
appropriate aldehyde (1 equiv) was added dropwise, and the mixture
was stirred for 15 min. Distilled water (10 mL) was added and the
product extracted with diethyl ether (3 × 20 mL). The combined
organic extracts were washed with water (2 × 10 mL), dried over
1
(1.19 g, 20%) as cubic crystals: mp 188−189 °C; H (400 MHz,
CDCl3) δ 7.40 (2H, d, J = 7.2 Hz), 7.29 (2H, app t, J = 7.6 Hz), 7.16
(1H, t, J = 7.3 Hz), 6.36 (1H, d, J = 16.7 Hz), 6.25 (1H, d, J = 16.7
Hz), 3.65 (4H, s), 0.91−1.82 (22H, m), 1.01 (6H, s); 13C (125 MHz,
CDCl3) (quat C next to boron not seen) δ 139.4 (quat C), 135.9 (CH),
129.0 (CH), 128.4 (CH), 126.2 (CH), 126.1 (CH), 71.9 (CH2), 41.1
(CH), 31.4 (quat C), 30.5 (CH2), 29.2 (CH2), 27.7 (CH2), 27.4
(CH2), 27.3 (CH2), 22.6 (CH3); 11B{1H} (96.2 MHz, CDCl3) δ 29.3;
HR-EI+ MS m/z (%) calcd for C26H3911BO2 394.3043, found 394.3049
(M+, 39%).
Reactions of Alkylboronic Esters with 5 and tert-BuLi:
General Procedure. A mixture of the appropriate boronic ester 3,
11, 12, or 13 (1 equiv), 1-bromo-3-chloroprop-1-ene (5, 1.1 equiv),
and dry THF in a dry 50 mL round-bottomed flask equipped with a
magnetic stirrer bar and septum was cooled to −78 °C, and t-BuLi in
hexanes (1.1 equiv) was added dropwise with vigorous stirring, and the
mixture was stirred for an additional 30 min. The cooling bath was
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dx.doi.org/10.1021/jo4018028 | J. Org. Chem. 2013, 78, 9526−9531