The Journal of Organic Chemistry
Article
system was warmed to room temperature; upon warming, the
reactants became a dull tan/gold solution. The reaction was allowed
to proceed for 45 min before an aliquot was abstracted for crude
analysis (performed where noted, with the procedure outlined in
general experimental guidelines). Following yield determination, the
solution was transferred to a scintillation vial and concentrated in
vacuo (at room temperature). The crude material was purified via
flash column chromatography (3% EtOAc/Hex) on deactivated silica
(0.5% triethylamine) to provide an isolable ketene N,O-acetal in
satisfactory yield. Ketene acetals, although isolable, decomposed
throughout the workup/purification process, as evidenced by TLC
and NMR analysis.
as described above, 1-methylindole (2.00 equiv, 271.0 mg, 2.00
mmol) was reacted with n-BuLi (2.00 equiv, 181.8 μL, 2.00 mmol,
11.0 M in hex.) and 2-(octan-2-ylperoxy)tetrahydro-2H-pyran (17,
1.00 equiv, 230.4 mg, 1.00 mmol) to furnish the title ketene N,O-
acetal as a lime-green oil (90.9 mg, 35%). This molecule decomposed
throughout the workup/purification process, as evidenced by TLC
and NMR analysis. Characterization: Rf = 0.58 (3% EtOAc/Hex); 1H
NMR (600 MHz, CDCl3): δ 7.36−7.30 (m, 1H), 7.07−7.02 (m, 1H),
7.00−6.92 (m, 2H), 5.44 (s, 1H), 4.34−4.23 (1H), 3.46 (s, 3H),
1.79−1.69 (m, 1H), 1.59−1.51 (m, 1H), 1.44−1.34 (m, 1H), 1.34−
1.28 (m, 1H), 1.30 (d, J = 6.25 Hz, 3H), 1.28−1.10 (6H), 0.81 (t, J =
7.18 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 152.8, 132.6,
127.5, 119.5, 118.9, 118.4, 107.9, 77.7, 76.5, 36.4, 31.8, 29.3, 27.6,
25.5, 22.7, 19.8, 14.1. HRMS (FT-ICR, ESI+): calcd for C17H25NNaO
(M + Na), 282.1834; found, 282.1829.
2-Decyloxy-1-methylindole (21a). Using the general procedure for
ketene N,O-acetal synthesis via intermolecular etherification as
described above, 1-methylindole (2.00 equiv, 271. mg, 2.00 mmol)
was reacted with n-BuLi (2.00 equiv, 181.8 μL, 2.00 mmol, 11.0 M in
hexanes) and 2-(decylperoxy)tetrahydro-2H-pyran (13a, 1.00 equiv,
258.0 mg, 1.00 mmol) to furnish the title ketene N,O-acetal as a lime-
green oil (216 mg, 75%). The same molecule (21a) was produced
following an incomplete reaction between 1-methylindole (2.00 equiv,
271.0 mg, 2.00 mmol), n-BuLi (2.00 equiv, 181.8 μL, 2.00 mmol, 11.0
M), and 1-(tert-butylperoxy)decane (13b, 1.00 equiv, 230.4 mg, 1.00
mmol) (90.4 mg, 31% by qNMR; 48% of 13b unreacted by qNMR).
This molecule decomposed throughout the workup/purification
process, as evidenced by TLC and NMR analysis. Characterization:
2-(Decyloxy)-4-methoxy-1-methylindole (23a). Using the general
procedure for ketene N,O-acetal synthesis via intermolecular ether-
ification as described above, 4-methoxy-1-methylindole (2.00 equiv,
98.7 mg, 600.0 μmol) was reacted with n-BuLi (2.00 equiv, 54.6 μL,
600.0 μmol, 11.0 M in hex.) and 2-(decylperoxy)tetrahydro-2H-pyran
(13a, 1.00 equiv, 77.5 mg, 300.0 μmol) to furnish the title ketene
N,O-acetal as a lime-green oil (67.9 mg, 71%). This molecule
decomposed throughout the workup/purification process, as
evidenced by TLC and NMR analysis. Characterization: Rf = 0.37
1
(3% EtOAc/Hex); H NMR (600 MHz, CDCl3): δ 6.92 (t, J = 7.95
1
Rf = 0.42 (3% EtOAc/Hex); H NMR (600 MHz, C6D6): δ 7.68−
Hz, 1H), 6.73 (d, J = 7.93 Hz, 1H), 6.45 (d, J = 7.94 Hz, 1H), 5.55 (s,
1H), 4.02 (t, J = 6.58 Hz, 2H), 3.85 (s, 3H), 3.46 (s, 3H), 1.78−1.71
(2H), 1.42−1.34 (2H), 1.31−1.11 (12H), 0.93 (t, J = 7.19 Hz, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 152.4, 151.9, 133.9, 119.7,
117.0, 101.9, 100.2, 73.0, 70.7, 55.4, 32.0, 29.6, 29.4, 29.1, 27.8, 26.0,
22.7, 14.2. HRMS (FT-ICR, ESI+): calcd for C20H31NNaO2 (M +
Na), 340.2253; found, 340.2250.
7.62 (m, 1H), 7.29−7.24 (m, 1H), 7.23−7.18 (m, 1H), 7.01−6.95
4
(m, 1H), 5.53 (d, J = 0.76 Hz, 1H), 3.79 (t, J = 6.42 Hz, 2H), 3.10
(s, 3H), 1.62−1.55 (2H), 1.41−1.16 (14H), 0.94 (t, J = 7.18 Hz,
3H); 13C{1H} NMR (150 MHz, C6D6): δ 153.4, 133.3, 120.0, 119.5,
119.1, 108.2, 76.4, 70.4, 32.2, 29.9, 29.7, 29.6, 29.2, 27.0, 26.2, 23.0,
14.3. HRMS (FT-ICR, ESI+): calcd for C19H29NNaO (M + Na),
310.2147; found, 310.2147.
2-(Octyloxy)-4-methoxy-1-methylindole (23b). Using the general
procedure for ketene N,O-acetal synthesis via intermolecular ether-
ification as described above, 4-methoxy-1-methylindole (2.00 equiv,
98.7 mg, 600.0 μmol) was reacted with n-BuLi (2.00 equiv, 54.6 μL,
600.0 μmol, 11.0 M in hex.) and 2-(octylperoxy)tetrahydro-2H-pyran
(14a, 1.00 equiv, 69.1 mg, 300.0 μmol) to furnish the title ketene
N,O-acetal as a lime-green oil (64.8 mg, 75%). This molecule
decomposed throughout the workup/purification process, as
evidenced by TLC and NMR analysis. Characterization: Rf = 0.38
(3% ETOAc/Hex); 1H NMR (600 MHz, CDCl3): δ 6.93 (t, J = 7.97
Hz, 1H), 6.74 (d, J = 7.94 Hz, 1H), 6.46 (d, J = 7.96 Hz, 1H), 5.56 (s,
1H), 4.03 (t, J = 6.43 Hz, 2H), 3.86 (s, 3H), 3.46 (s, 3H), 1.79−1.72
(tt, J = 7.18, 6.80 Hz, 2H), 1.42−1.35 (tt, J = 7.67, 6.78 Hz, 2H),
1.32−1.10 (8H), 0.82 (t, J = 7.18 Hz, 3H); 13C{1H} NMR (150
MHz, CDCl3): δ 152.4, 151.9, 133.9, 119.7, 117.0, 101.9, 100.2, 73.0,
70.7, 55.4, 31.9, 29.3, 29.3, 29.0, 27.8, 26.0, 22.7, 14.1. HRMS (FT-
ICR, ESI+): calcd for C18H27NNaO2 (M + Na), 312.1940; found,
312.1938.
2-Octyloxy-1-methylindole (21b). Using the general procedure for
ketene N,O-acetal synthesis via intermolecular etherification as
described above, 1-methylindole (2.00 equiv, 176. mg, 1.30 mmol)
was reacted with n-BuLi (2.00 equiv, 181.8 μL, 2.00 mmol, 11.0 M in
hexanes) and 2-(octylperoxy)tetrahydro-2H-pyran (14a, 1.00 equiv,
150.0 mg, 651.0 μmol) to furnish the title ketene N,O-acetal as a lime-
green oil (120 mg, 71%). This molecule decomposed throughout the
workup/purification process, as evidenced by TLC and NMR analysis.
1
Characterization: Rf = 0.50 (3% EtOAc/Hex); H NMR (600 MHz,
C6D6): δ 7.67−7.63 (m, 1H), 7.29−7.24 (m, 1H), 7.24−7.19 (m,
1H), 7.01−6.97 (m, 1H), 5.53 (d, 4J = 0.76 Hz, 1H), 3.78 (t, J = 6.43
Hz, 2H), 3.10 (s, 3H), 1.61−1.54 (2H), 1.34−1.17 (10H), 0.93 (t, J =
7.17 Hz, 3H); 13C{1H} NMR (150 MHz, C6D6): δ 153.4, 133.3,
120.0, 119.5, 119.1, 108.2, 76.5, 70.4, 32.1, 29.5, 29.5, 29.2, 27.0, 26.2,
22.9, 14.2. HRMS (FT-ICR, ESI+): calcd for C17H25NNaO (M +
Na), 282.1834; found, 282.1833.
2-((3,7-Dimethyl-6-en-1-yl)oxy)-1-methylindole (21c). Using the
general procedure for ketene N,O-acetal synthesis via intermolecular
etherification as described above, 1-methylindole (2.00 equiv, 94.9
mg, 702.0 μmol) was reacted with n-BuLi (2.00 equiv, 63.8 μL, 702.0
μmol, 11.0 M in hexanes) and 2-((3,7-dimethyloct-6-en-1-yl)peroxy)
tetrahydro-2H-pyran (15, 1.00 equiv, 90.0 mg, 351.0 μmol) to furnish
the title ketene N,O-acetal as a lime-green oil (72.6 mg, 73%). This
molecule decomposed slightly upon workup and purification, as
detected via TLC/NMR analysis. Characterization: Rf = 0.50 (3%
2-((3,7-Dimethyloct-6-enyl)oxy)-4-methoxy-1-methylindole
(23c). Using the general procedure for ketene N,O-acetal synthesis via
intermolecular etherification as described above, 4-methoxy-1-
methylindole (2.00 equiv, 98.7 mg, 600.0 μmol) was reacted with
n-BuLi (2.00 equiv, 54.6 μL, 600.0 μmol, 11.0 M in hex.) and 2-((3,7-
dimethyloct-6-en-1-yl)peroxy)tetrahydro-2H-pyran (15, 1.00 equiv,
76.9 mg, 300.0 μmol) to furnish the title ketene N,O-acetal as a lime-
green oil (57.2 mg, 78%). This molecule decomposed throughout the
workup/purification process, as evidenced by TLC and NMR analysis.
1
EtOAc/Hex); H NMR (600 MHz, C6D6): δ 7.67−7.63 (m, 1H),
7.29−7.25 (m, 1H), 7.24−7.19 (m, 1H), 7.01−6.97 (m, 1H), 5.53 (d,
4J = 0.76 Hz, 1H), 5.18 (tsept, 3J = 7.18, 4J = 1.52 Hz, 1H), 3.90−3.81
(m, 2H), 3.10 (s, 3H), 2.09−1.96 (m, 2H), 1.72−1.64 (m, 1H), 1.69
(s, 3H), 1.63−1.52 (m, 1H), 1.57 (s, 3H), 1.44−1.38 (m, 1H), 1.38−
1.32 (m, 1H), 1.21−1.13 (m, 1H), 0.84 (d, J = 6.80 Hz, 3H);
13C{1H} NMR (150 MHz, C6D6): δ 153.4, 133.3, 131.1, 125.0, 120.0,
119.5, 119.1, 108.2, 76.5, 68.7, 37.3, 36.0, 29.6, 27.0, 25.8, 25.7, 19.5,
17.6. HRMS (FT-ICR, ESI+): calcd for C19H27NNaO (M + Na),
308.1990; found, 308.1988.
1
Characterization: Rf = 0.60 (3% EtOAc/Hex); H NMR (600 MHz,
CDCl3): δ 6.93 (t, J = 7.98 Hz, 1H), 6.74 (d, J = 8.01 Hz, 1H), 6.46
(d, J = 7.94 Hz, 1H), 5.57 (s, 1H), 5.03 (tsept, 3J = 7.18, 4J = 1.50 Hz,
1H), 4.12−4.04 (m, 2H), 3.86 (s, 3H), 3.46 (s, 3H), 2.02−1.86 (m,
2H), 1.85−1.78 (m, 1H), 1.68−1.55 (m, 2H), 1.61 (s, 3H), 1.54 (s,
3H), 1.37−1.29 (m, 1H), 1.22−1.12 (m, 1H), 0.89 (d, J = 6.43 Hz,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 152.4, 151.9, 133.9,
131.4, 124.6, 119.7, 117.0, 101.9, 100.2, 73.0, 69.0, 55.4, 37.1, 35.8,
29.6, 27.8, 25.8, 25.5, 19.6, 17.7. HRMS (FT-ICR, ESI+): calcd for
C20H29NNaO2 (M + Na), 338.2096; found, 338.2092.
2-(Octan-2-yloxy)-1-methylindole (22). Using the general proce-
dure for ketene N,O-acetal synthesis via intermolecular etherification
2380
J. Org. Chem. 2021, 86, 2369−2384