The Journal of Organic Chemistry
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Hept-1-yn-4-ol, 4f (Table 2, entry 6).6a Following the general
procedure above, 4f was obtained as a clear, colorless oil (0.035 g, 63%
yield). 1H NMR (500 MHz, CDCl3): δ 0.96 (t, J = 7.5 Hz, 3H), 1.35−
1.57 (m, 4H), 2.07 (t, J = 3 Hz, 1H), 2.33 (ddd, J = 2.5, 7.0, 16.5 Hz,
1H), 2.44 (ddd, J = 3.0, 7.5, 17 Hz, 1H), 3.75−3.81 (m, 1H). 13C
NMR (125 MHz, CDCl3): δ 14.1, 18.9, 27.5, 38.5, 69.7, 70.9, 81.1.
Enantiomeric excess was determined to be 74% by chiral GC analysis.
GC conditions: 91 °C isothermal, tR for the (S)-alcohol, 13.41 min; tR
for the (R)-alcohol, 13.87 min.
MHz, CDCl3): 2.09 (t, J = J = 2.5 Hz, 1H), 3.11 (d, J = 2.5 Hz, 1H),
3.12 (d, J = 2.5 Hz, 1H), 7.25−7.43 (m, 3H), 7.57−7.63 (m, 2H).
General Procedure for the Investigation of Additives in the
Propargylation of Acetophenone, 2-Phenylpent-4-yn-2-ol, 6a
and 2-Phenylpenta-3,4-dien-2-ol, 6b (Table 3).6b,29 To a 25 mL
round-bottom flask charged with stir bar, cooled under Ar, were added
indium (1 mmol), (+)-(1S,2R)-2-amino-1,2-diphenylethanol (1
mmol), and anhydrous THF (7 mL). The flask was backfilled with
Ar (3×). Pyridine (1 mmol, where applicable) and propargyl bromide
(1 mmol) were added, and the entire mixture was allowed to mix for
30 min. Dropwise addition of acetophenone (0.5 mmol) and the
appropriate additive (0.1, 0.5, 1, or 2 mmol) occurred, and after 24 h
the reaction was quenched with dilute HCl (6 mL) and transferred to
a separatory funnel with hexanes/Et2O (1:1) solution (6 mL). The
organic phase was washed with hexanes/Et2O (2 × 3 mL). The
combined organic layers were washed with dilute HCl (2 × 6 mL), DI
water (1 × 6 mL), and brine (1 × 6 mL), dried with MgSO4, filtered
through a silica plug, and evaporated in vacuo to provide the alcohol
products, 6a and 6b. Percent conversion was determined by 1H NMR
5-Ethylhept-1-yn-4-ol, 4g (Table 2, entry 7)..27 Following the
general procedure above, 4g was obtained as a clear, colorless oil
1
(0.042 g, 60% yield). H NMR (500 MHz, CDCl3): δ 0.91 (t, J = 5.0
Hz, 3H), 0.92 (t, J = 5.0 Hz, 3H), 1.27−1.51 (m, 5H), 2.06 (t, J = 3.0,
1H), 2.37 (ddd, J = 3.0, 7.5, 17 Hz, 1H), 2.44 (ddd, J = 4.5, 7.5, 16.5
Hz, 1H), 3.77 (dt, J = 5.0, 8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3):
δ 11.4, 11.5, 21.0, 21.8, 24.8, 45.5, 70.7, 71.4, 81.6. Enantiomeric excess
was determined to be 83% by chiral GC analysis of the acetylated
alcohol. GC conditions: 91 °C isothermal, tR for the (S)-alcohol, 35.71
min; tR for the (R)-alcohol, 36.38 min.
2,2-Dimethylhex-5-yn-3-ol, 4h (Table 2, entry 8).6a Following
the general procedure above, 4h was obtained as a clear, colorless oil
spectroscopy. 6a (propargyl isomer) H NMR (500 MHz, CDCl3): δ
1
1.66 (s, 3H), 2.06 (t, J = 2.5 Hz, 1H), 2.71 (dd, J = 2.0, 13.5 Hz, 1H),
2.78 (dd, J = 2.5, 14.5 Hz, 1H), 7.27−7.31 (m, 1H), 7.35−7.40 (m,
1
(0.033 g, 53% yield). H NMR (500 MHz, CDCl3): δ 0.93 (s, 9H),
1
2.07 (t, J = 5.5 Hz, 1H), 2.26 (ddd, J = 3.0, 10.5, 16.5 Hz, 1H), 2.44
(dt, J = 2.5, 17.0 Hz, 1H), 3.46 (dd, J = 3.0, 10.0 Hz, 1H). 13C NMR
(125 MHz, CDCl3): δ 22.7, 25.7, 34.7, 70.6, 77.6, 82.5. Enantiomeric
excess was determined to be 95% by chiral GC analysis of the
acetylated alcohol. GC conditions: 80 °C isothermal, tR for the (S)-
alcohol, 37.98 min; tR for the (R)-alcohol, 42.15 min.
2H), 7.48−7.54 (m, 2H); 6b (allenyl isomer) H NMR (500 MHz,
CDCl3): δ 1.68 (s, 3H), 4.98 (dd, J = 2.0, 4.5 Hz, 2H), 5.58 (t, J = 6.5
Hz, 1H), 7.27−7.31 (m, 1H), 7.35−7.40 (m, 2H), 7.48−7.54 (m, 2H).
Indium Mediated Propargylation of Trifluoroacetophenone
in the Presence of the Additive Ti(i-PrO)4, 1,1,1-Trifluoro-2-
phenylpent-4-yn-2-ol, 5a and 1,1,1-Trifluoro-2-phenylpenta-
3,4-dien-2-ol, 5b (Scheme 3). To a 25 mL round-bottom flask
charged with stir bar, cooled under Ar, were added indium (0.115 g, 1
mmol), (+)-(1S,2R)-2-amino-1,2-diphenylethanol (0.213 g, 1 mmol),
and anhydrous THF (7 mL). The flask was backfilled with Ar (3×).
Pyridine (0.081 mL, 1 mmol) and propargyl bromide (0.11 mL, 1
mmol) were added, and the entire mixture was allowed to mix for 30
min followed by dropwise addition of 2,2,2-trifluoroacetophenone
(0.068 mL, 0.5 mmol). After 24 h, the reaction was quenched with
dilute HCl (6 mL) and transferred to a separatory funnel with
hexanes/Et2O (1:1) solution (6 mL). The organic phase was washed
with hexanes/Et2O (2 × 3 mL). The combined organic layers were
washed with dilute HCl (2 × 6 mL), DI water (1 × 6 mL), and brine
(1 × 6 mL), dried with MgSO4, filtered through a silica plug, and
evaporated in vacuo to provide 5a and 5b as a yellow oil (100%
1-Phenylhex-1-en-5-yn-3-ol, 4i (Table 2, entry 9).24 Following
the general procedure above, 4i was obtained as a clear, yellow-orange
1
oil (0.068 g, 71% yield). H NMR (500 MHz, CDCl3): δ 2.11 (t, J =
3.5 Hz, 1H), 2.55 (ddd, J = 2.5, 6.5, 16.5 Hz, 1H), 2.61 (ddd, J = 2.5,
5.5, 16.5 Hz, 1H), 4.50 (q, J = 6.0 Hz, 1H), 6.31 (dd, J = 6.0, 16.0 Hz,
1H), 6.69 (d, J = 16.0 Hz, 1H), 7.26−7.42 (m, 5H). 13C NMR (125
MHz, CDCl3): δ 27.9, 70.8, 71.3, 80.4, 126.7, 128.0, 128.7, 130.1,
131.5, 136.5. Enantiomeric excess was determined to be 75% by chiral
GC analysis. GC conditions: 151 °C isothermal, tR for the (R)-alcohol,
57.18 min; tR for the (S)-alcohol, 58.94 min.
1-(Furan-2-yl)but-3-yn-1-ol, 4j (Table 2, entry 10).6a Follow-
ing the general procedure above, 4j was obtained as a clear, orange-
1
yellow oil (0.053 g, 78% yield). H NMR (500 MHz, CDCl3): δ 2.08
(t, J = 2.5 Hz, 1H), 2.78 (dd, J = 2.5, 6.0 Hz, 2H), 4.89 (t, J = 6.5 Hz,
1
1H), 6.35 (s, 2H), 7.40 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 26.2,
conversion, 1:1, 5a:5b). 5a (propargyl isomer) H NMR (500 MHz,
66.2, 71.2, 80.0, 106.7, 110.3, 142.4, 154.8. [α]25 = +10.0° c = 6.4 in
CDCl3): δ 2.07 (t, J = 2.5 Hz, 1H), 3.11 (d, J = 2.5 Hz, 1H), 3.12 (d, J
= 2.5 Hz, 1H), 7.23−7.45 (m, 3H), 7.59−7.65 (m, 2H); 5b (allenyl
D
MeOH. Enantiomeric excess was determined to be 78% by chiral GC
analysis. GC conditions: 111 °C isothermal, tR for the (R)-alcohol,
33.41 min; tR for the (S)-alcohol, 34.53 min.
1
isomer) H NMR (500 MHz, CDCl3): δ 5.13 (dd, J = 1.5, 6.5 Hz,
1H), 5.20 (dd, J = 1.5, 6.5 Hz, 1H), 5.86 (t, J = 6.5 Hz, 1H), 7.23−7.45
(m, 3H), 7.59−7.65 (m, 2H).
1-(Furan-3-yl)but-3-yn-1-ol, 4k (Table 2, entry 11).28 Follow-
ing the general procedure above, 4k was obtained as a clear, yellow oil
General Procedure for the Investigation on the Effect of
Reagent Addition and Indium(III) Triflate in the Indium-
Mediated Propargylation of Acetophenone, 2-phenylpent-4-
yn-2-ol, 6a and 2-phenylpenta-3,4-dien-2-ol, 6b (Table 4)..6b,29
To a 25 mL round-bottom flask charged with stir bar, cooled under Ar,
were added indium (1 mmol), In(OTf)3 (0.5 mmol), pyridine (1
mmol), acetophenone (0.5 mmol), and anhydrous THF (7 mL). The
flask was backfilled with Ar (3×). Propargyl bromide (1 mmol) was
added, and the entire mixture was allowed to mix for 24 h. The
reaction was quenched with dilute HCl (6 mL) and transferred to a
separatory funnel with hexanes/Et2O (1:1) solution (6 mL). The
organic phase was washed with hexanes/Et2O (2 × 3 mL). The
combined organic layers were washed with dilute HCl (2 × 6 mL), DI
water (1 × 6 mL), and brine (1 × 6 mL), dried with MgSO4, filtered
through a silica plug, and evaporated in vacuo to provide 6a and 6b as a
clear oil. Table 4, entry 4: (85% conversion, 1:14, 6a:6b). 6a
(propargyl isomer) 1H NMR (500 MHz, CDCl3): δ 1.66 (s, 3H), 2.06
(t, J = 2.5 Hz, 1H), 2.71 (dd, J = 2.0, 13.5 Hz, 1H), 2.78 (dd, J = 2.5,
14.5 Hz, 1H), 7.27−7.31 (m, 1H), 7.35−7.40 (m, 2H), 7.48−7.54 (m,
1
(0.047 g, 69% yield). H NMR (500 MHz, CDCl3): δ 2.09 (t, J = 3.0
Hz, 1H), 2.61−2.70 (m, 2H), 4.85 (t, J = 6.0 Hz, 1H), 6.46 (s, 2H),
7.40 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 28.4, 65.5, 71.3, 80.5,
108.6, 127.5, 139.4, 143.5. Enantiomeric excess was determined to be
78% by chiral GC analysis. GC conditions: 115 °C isothermal, tR for
the (R)-alcohol, 37.76 min; tR for the (S)-alcohol, 40.62 min.
Indium-Mediated Propargylation of a Trifluoroacetophe-
none, 1,1,1-Trifluoro-2-phenylpent-4-yn-2-ol, 5a (Scheme 2).
To a 25 mL round-bottom flask charged with stir bar, cooled under Ar,
were added indium (0.115 g, 1 mmol), and anhydrous THF (7 mL).
The flask was backfilled with Ar (3×). Pyridine (0.081 mL, 1 mmol)
and propargyl bromide (0.11 mL, 1 mmol) were added, and the entire
mixture was allowed to mix for 30 min followed by dropwise addition
of 2,2,2-trifluoroacetophenone (0.068 mL, 0.5 mmol). After 24 h, the
reaction was quenched with dilute HCl (6 mL) and transferred to a
separatory funnel with hexanes/Et2O (1:1) solution (6 mL). The
organic phase was washed with hexanes/Et2O (2 × 3 mL). The
combined organic layers were washed with dilute HCl (2 × 6 mL), DI
water (1 × 6 mL), brine (1 × 6 mL), dried with MgSO4, filtered
through a silica plug, and evaporated in vacuo to provide 5a as a yellow
1
2H); 6b (allenyl isomer) H NMR (500 MHz, CDCl3): δ 1.68 (s,
3H), 4.98 (dd, J = 2.0, 4.5 Hz, 2H), 5.58 (t, J = 6.5 Hz, 1H), 7.27−7.31
(m, 1H), 7.35−7.40 (m, 2H), 7.48−7.54 (m, 2H).
1
oil (80% conversion of 2,2,2-trifluoroacetophenone). H NMR (500
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dx.doi.org/10.1021/jo201980b | J. Org. Chem. 2012, 77, 889−898