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J. S. Yadav et al.
PAPER
tography (silica gel, EtOAc–PE, 1:9; Rf = 0.8) afforded 12 (3.3 g,
90%) as a magenta-colored liquid; [α]D25 +1.7 (c 1.0, CHCl3).
IR (KBr): 3449, 2925, 2855, 1455, 1101, 772 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.18–7.34 (m, 5 H), 6.34 (t,
J = 7.36 Hz, 1 H), 4.45 (s, 2 H), 3.40–3.50 (m, 2 H), 2.03–2.13 (m,
2 H), 1.54–1.69 (m, 2 H), 1.21–1.46 (m, 7 H), 0.87 (d, J = 6.4 Hz, 3
H).
(R)-3-Methylnon-8-yn-1-ol (15)
To a soln of Na (0.50 g, 19.8 mmol) in liquid NH3 (25 mL) was add-
ed compound 14 (0.8 g, 3.31 mmol) in anhyd THF (8 mL) at –33
°C. The mixture was stirred for 15 min and quenched with solid
NH4Cl (1.5 g). NH3 was allowed to evaporate and Et2O was added
to the residual mixture and it was filtered through a pad of celite.
The filtrate was dried (anhyd Na2SO4). The solvent was removed in
vacuo to give a residue (0.473 g, 94%) that was used for the next re-
action without purification. Li wire (0.63 g, 90 mmol) was added to
1,3-diaminopropane (4 mL) in a 100-mL two-necked pear-shaped
flask. The soln was heated at 80 °C for 2 h until the blue color had
discharged and the white lithium salt was evident. The mixture was
cooled to r.t., and NaNH2 (0.58 g, 64.8 mmol) was added in one por-
tion. The resulting yellow soln was stirred for 15 min. A soln of the
internal alkyne (0.47 g, 3.0 mmol) in 1,3-diaminopropane (5 mL)
was added dropwise, and the blood-red soln was heated at 65 °C for
6 h. The resulting brown soln was cooled to r.t. and then in an ice
bath and quenched with sat. aq NH4Cl. The resulting mixture was
poured into H2O (10 mL) and acidified with concd HCl (10 mL).
This mixture was then extracted with CHCl3. Evaporation of the
CHCl3, addition of benzene (10 mL), and subsequent evaporation
afforded a tan solid that was adsorbed onto silica gel and added to
the top of a chromatography column. Flash chromatography (10%
EtOAc–hexanes) gave 15 (0.32 g, 68%) as colorless oil; Rf = 0.2
(EtOAc–PE, 1:9).
13C NMR (75 MHz, CDCl3): δ = 138.6, 138.4, 128.2, 127.4, 127.3,
96.2, 72.9, 68.4, 68.3, 36.8, 33.0, 29.8, 28.4, 28.4, 26.5, 25.7, 19.8.
(R)-[(3-Methylnon-8-ynyloxy)methyl]benzene (6)
To soln of dibromo compound 12 (3.3 g, 8.34 mmol) in anhyd THF
(24 mL), 1.6 M BuLi in THF (1.2 mL, 12.5 mmol) was added at
–78 °C over 0.5 h; the mixture was stirred for 2 h. The mixture was
quenched with sat. NaHCO3 (5 mL) and extracted with CH2Cl2 (3 ×
30 mL). The combined organic layers were washed with sat. NaCl
(10 mL) and H2O (10 mL), dried (Na2SO4), and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy (silica gel, EtOAc–PE, 1:9, Rf = 0.85) to afford pure 6 (1.79
g, 90%) as a colorless liquid; [α]D25 +0.3 (c 1.00, CHCl3).
IR (KBr): 3305, 2928, 2858, 1456, 1365, 1101, 737 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.18–7.34 (m, 5 H), 4.45 (s, 2 H),
3.40–3.50 (m, 2 H), 2.12–2.19 (dt, J = 6.8, 1.9 Hz, 1 H), 1.82 (s, 1
H), 1.55–1.67 (m, 2 H), 1.07–1.53 (m, 8 H), 0.88 (d, J = 6.83 Hz, 3
H).
13C NMR (75 MHz, CDCl3): δ = 138.6, 128.2, 127.5, 127.4, 72.8,
68.5, 68.2, 36.7, 36.4, 29.7, 29.3, 28.6, 26.0, 19.6, 18.3.
IR (KBr): 3305, 2931, 2860, 2117, 1727, 1462, 1433, 1378, 1056,
629 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.61–3.73 (m, 2 H), 2.19 (dt,
J = 6.7, 1.2 Hz, 2 H), 2.02–2.08 (br, 1 H), 1.94 (t, J = 2.5 Hz, 1 H),
1.12–1.65 (m, 9 H), 0.90 (d, J = 6.6 Hz, 3 H).
MS (ESI): m/z = 267 [M + Na]+.
13C NMR (75 MHz, CDCl3): δ = 84.6, 68.13, 61.1, 39.8, 36.5, 29.3,
28.6, 26.0, 19.5, 18.3.
(R)-[(7,7-Dibromo-3-methylhept-6-enyloxy)methyl]benzene
(13)
To a soln of aldehyde 9 (1.0 g, 4.60 mmol) in CH2Cl2 (50 mL) were
added CBr4 (3.8 g, 11.5 mmol) and Ph3P (4.8 g, 18.4 mmol) and the
mixture was stirred at r.t. for 1 h. The mixture was concentrated un-
der reduced pressure to leave a crude oil. Purification by chroma-
tography (silica gel, EtOAc–PE, 1:9, Rf = 0.7) afforded 13 (1.6 g,
90%) as a magenta-colored liquid.
MS (EI): m/z = 155 [M + H]+.
2-[(R)-16-(Benzyloxy)-14-methylhexadec-8-ynyloxy]tetra-
hydro-2H-pyran (16)
Into a suitable flask fitted with an NH3 condenser at –40 °C, NH3
(45 mL) was collected and to this was added a catalytic amount of
Fe2(NO3)3 (20 mg, 0.17 mmol) followed by Li (0.33 g, 47.14 mmol)
over a period of 20 min. The contents were stirred for 30 min to
form LiNH2. Then (R)-[(3-methylnon-8-ynyloxy)methyl]benzene
(6, 1.0 g, 4.09 mmol) was added in THF (8 mL) followed by HMPA
(3 mL) as co-solvent. The contents were stirred for 2 h and then
compound 7A (1.2 gm) in THF (5 mL) was added. The mixture was
stirred for 6 h and quenched with NH4Cl (1 g). The mixture was
warmed to r.t. for evaporation of NH3. The residue was dissolved in
Et2O (20 mL) and sat. NH4Cl soln (10 mL) was added. The organic
layer was separated and washed with brine (10 mL). The organic
layer was concentrated under reduced pressure and the residue was
subjected to column chromatography to give 16 (1.53 g, 85%) as a
IR (KBr): 3449, 3029, 2925, 2855, 1455, 1101, 772 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.18–7.34 (m, 5 H), 6.34 (t,
J = 7.36 Hz, 1 H), 4.45 (s, 2 H), 3.40–3.50 (m, 2 H), 2.03–2.13 (m,
2 H), 1.54–1.69 (m, 2 H), 1.21–1.46 (m, 3 H), 0.87 (d, J = 6.4 Hz, 3
H).
13C NMR (75 MHz, CDCl3): δ = 138.6, 138.4, 128.2, 127.4, 96.2,
72.9, 68.4, 36.8, 33.0, 29.0, 28.19, 19.8.
(R)-[(3-Methylnon-6-ynyloxy)methyl]benzene (14)
To a soln of dibromo compound 13 (1.6 g, 4.14 mmol) in anhyd
THF (15 mL), 1.6 M BuLi in THF (10 mL, 10.31 mmol) was added
at –78 °C. Then slowly EtI (0.4 mL, 2.5 mmol) was added at –78 °C
and the mixture was stirred for 2 h. The mixture was quenched with
sat. NaHCO3 (5 mL) and extracted with CH2Cl2 (2 × 30 mL). The
combined organic layers were washed with sat. NaCl (10 mL) and
H2O (10 mL), dried (Na2SO4), and concentrated under reduced
pressure. The residue was purified by column chromatography (sil-
ica gel, EtOAc–PE, 1:9, Rf = 0.75) to afford pure 14 (0.80 g, 80%)
as a colorless liquid.
25
colorless liquid; Rf = 0.6 (EtOAc–PE, 1:9); [α]D +0.3 (c 0.6,
CHCl3).
IR (KBr): 3305, 3030, 2930, 2858, 1638, 1456, 1364, 1103, 1029,
908, 737, 631 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.22–7.37 (m, 5 H), 4.57 (t,
J = 3.39 Hz, 1 H), 4.45 (s, 2 H), 3.81–3.90 (m, 1 H), 3.67–3.76 (m,
1 H), 3.45–3.54 (m, 3 H), 3.31–3.41 (m, 1 H), 2.09–2.16 (m, 4 H),
1.22–1.87 (m, 25 H), 0.88 (d, J = 6.42 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 138.6, 128.2, 127.5, 127.4, 98.7,
80.18, 80.13, 72.8, 68.6, 67.5, 62.2, 62.9, 36.7, 36.5, 30.7, 29.7,
29.6, 29.3, 29.0, 28.9, 28.7, 26.1, 25.4, 19.6, 19.5, 18.7.
IR (KBr): 2926, 2858, 1722, 1455, 1366, 1273, 1103, 737 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.27–7.33 (m, 5 H), 4.47 (s, 2 H),
3.48 (dt, J = 6.7, 1.5 Hz, 2 H), 2.06–2.18 (m, 4 H), 1.36–1.79 (m, 2
H), 1.21–1.35 (m, 3 H), 1.10 (t, J = 7.3 Hz, 2 H), 0.94–1.0 (m, 1 H),
0.89 (d, J = 6.6 Hz, 3 H).
MS (ESI): m/z = 465 [M + Na]+.
13C NMR (75 MHz, CDCl3): δ = 129.4, 128.2, 127.5, 127.3, 72.8,
68.4, 36.3, 29.6, 19.4, 19.1, 16.3, 14.2, 12.3.
MS (ESI): m/z = 267 [M + Na]+.
(3R)-3-Methyl-16-(tetrahydro-2H-pyran-2-yloxy)hexadec-8-
yn-1-ol (17)
To a soln of Na (0.80 g, 34.78 mmol) in liquid NH3 (25 mL) was
added compound 16 (1.50 g, 3.40 mmol) in anhyd THF (8 mL) at
Synthesis 2013, 45, 1513–1518
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