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different functional groups were tested for InCl3 catalyzed O–H
insertion reaction (Table 3). To our delight, all the alcohols 11–16
are efficiently converted into their respective ethers 11a–16a17,18
in good yields and in shorter reaction time. In most of the cases,
the BF3ÁOEt2 failed to catalyze the reaction, excepting the prolinol
derivative 15. Acid sensitive groups like Boc, C-TMS, O-Silyl,
MOM–ethers, acetonide groups remained unscathed during this
transformation.
In summary, we have demonstrated a facile InCl3 catalyzed
insertion of :CHCO2Et fragment (from EDA) into the O–H bond un-
der solvent-free conditions with remarkable chemoselectivity
(high yielding ethers) and in case of unsaturated alcohols high reg-
ioselectivity (only insertion products were obtained) to afford the
corresponding ethers. Furthermore, this methodology proved bet-
ter than the reported ones, was general, and displayed good func-
tional group tolerance and versatility. Overall, a facile synthesis of
ethers from alcohols has been accomplished that may find varied
applications in synthetic organic chemistry.3
17. General experimental procedure: To a mixture of alcohol (1.5 mmol) and EDA
(1.0 mmol), InCl3 (0.2 mmol) was added and stirred under neat at ambient
temperature until the completion of the reaction as indicated by TLC. To the
reaction mixture, water (5.0 mL) was added and the product was extracted
with ethyl acetate (2 Â 10 mL). The combined organic layers were washed with
brine (10 mL), dried (Na2SO4) and purified by column chromatography (Silica
gel, 60–120 mesh, EtOAc:n-hexane, 1:9–2:8) to afford products.
18. Analytical and spectral data of selected compounds: Compound 2a: 1H NMR
(300 MHz, CDCl3): d 7.28–7.14 (m, 5H, Ar–H), 4.17 (q, 2H, J = 6.86 Hz, O–CH2),
4.00 (s, 2H, O–CH2), 3.72 (t, 2H, J = 6.86 Hz, O–CH2), 2.91 (t, 2H, J = 6.86 Hz,
CH2), 1.27 (t, 3H, J = 7.84 Hz, CH3). 13C NMR (100 MHz, CDCl3): d = 170.2, 138.2,
128.8, 128.2, 126.1, 72.4, 68.3, 60.9, 36.0, 13.9. IR (neat): 3440, 2930, 1750,
1260, 1157, 1055, 810, 775 cmÀ1 ESI–MS: 231 [M+Na]+. Anal. Calcd for
.
C
12H16O3: C, 69.21, H, 7.74. Found: 69.19, H, 7.70. Compound 6a: 1H NMR
(300 MHz, CDCl3): d 4.21 (q, 2H, J = 7.18 Hz, O–CH2), 3.99 (s, 2H, O–CH2), 3.48
(t, 2H, J = 6.61 Hz, O–CH2), 1.35–1.26 (m, 19H), 0.88 (t, 3H, J = 6.42 Hz, CH3). 13
NMR (100 MHz, CDCl3): d 170.6, 71.9, 68.3, 64.9, 31.9, 29.5, 29.4, 29.3, 29.2,
28.5, 25.9,25.8, 22.6, 14.1. IR (neat): 3440, 2930, 1690, 1510, 1257, 1036 cmÀ1
C
.
Acknowledgements
ESI–MS: 267 [M+Na]+. Anal. Calcd for C14H28O3: C, 68.81, H, 11.55. Found:
68.84, H, 11.51. Compound 9a: 1H NMR (300 MHz, CDCl3): d 8.20 (d, 2H,
J = 7.18 Hz, Ar–H), 7.51 (d, 2H, J = 8.31 Hz, Ar–H), 4.71 (s, 2H, O–CH2), 4.21 (q,
2H, J = 7.55 Hz, O–CH2), 4.13 (s, 2H, CH2), 1.31 (t, 3H, J = 7.55 Hz, CH3). 13C NMR
(100 MHz, CDCl3): d 169.8, 147.3, 144.8, 127.8, 123.4, 71.8, 67.7, 60.9, 14.0. IR
(neat): 3450, 2830, 1690, 1410, 1257, 1036, 850, 770 cmÀ1. ESI–MS: 262
[M+Na]+. Anal. Calcd for C11H13NO5: C, 55.23, H, 5.48, N, 5.86. Found: 55.21, H,
5.52, N, 5.83. Compound 10a: 1H NMR (300 MHz, CDCl3): d 7.34–7.15 (m, 10H,
Ar–H), 5.54 (s, 1H, CH), 4.18 (q, 2H, J = 6.80 Hz, O–CH2), 4.04 (s, 2H, O–CH2),
1.28 (t, 3H, J = 7.55 Hz, CH3). 13C NMR (75 MHz, CDCl3): d 170.5, 141.0, 128.3,
127.7, 127.2, 83.4, 65.9, 60.7, 14.1. IR (neat): 3450, 2830, 1695, 1250, 1157,
1050, 834, 776 cmÀ1. ESI–MS: 293 [M+Na]+. Anal. Calcd for C17H18O3: C, 75.53,
H, 6.71. Found: 75.55, H, 6.75. Compound 11a: 1H NMR (300 MHz, CDCl3): d
4.70 (d, 1H, J = 2.26 Hz, O–CH), 4.28–4.11 (m, 4H, 2 Â O–CH2), 3.54–3.24 (m,
3H), 2.26–1.65 (m, 4H, 2 Â CH2), 1.45 (s, 9H, 3 Â CH3), 1.28 (t, 3H, J = 6.79 Hz,
CH3), d = 0.16 (s, 9H, 3 Â CH3). 13C NMR (75MHz, CDCl3): d 169.5, 168.6, 102.3,
96.2, 79.1, 70.8, 65.9, 60.5, 60.4, 47.0, 28.2, 26.0, 24.5, 14.4, À0.26. IR (neat):
3451, 2856, 1739, 1254, 1040, 700 cmÀ1. ESI–MS: m/z 407 [M+Na]+. Anal. Calcd
for C19H34NO5Si: C, 59.34, H, 8.91, N, 3.64. Found: C, 59.36, H, 8.94, N, 3.66.
Compound 12a: 1H NMR (300 MHz, CDCl3): d 4.15 (q, 2H, J = 7.18 Hz, O–CH2),
3.98 (s, 2H, O–CH2), 3.59 (t, 2H, J = 6.04 Hz, O–CH2), 3.49 (t, 2H, J = 6.23 Hz, O–
CH2), 1.29–1.16 (m, 4H, 2 Â CH2), 1.26 (t, 3H, J = 7.17 Hz), 0.85 (s, 9H, 3 Â CH3),
0.00 (s, 6H, 2 Â CH3). 13C NMR (100 MHz, CDCl3): d 170.1, 96.2, 71.6, 68.3, 62.8,
29.8, 29.4, 26.1, 22.9, 14.3, À5.1. IR (neat): 3078, 2932, 2858, 1711, 1433, 1254,
1090, 834 cmÀ1. ESI–MS: m/z 313 [M+Na]+. Anal. Calcd for C14H30O4Si: C, 57.89,
H, 10.41. Found: 57.92, H, 10.44. Compound 13a: 1H NMR (300 MHz, CDCl3): d
5.79–5.49 (m, 2H, olefinic), 4.54 (s, 1H, O–CH), 4.18 (m, 2H, O–CH2), 3.99–3.97
(m, 4H, 2 Â O–CH2), 3.82–3.64 (m, 2H, O–CH2), 3.47–3.27 (m, 2H, O–CH2), 2.17
Two of the authors (Y.L.P. and M.A.) acknowledge the financial
support from the UGC and the CSIR, New Delhi in the form of
fellowships.
References and notes
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(t, 2H, J = 6.04 Hz, CH2), 1.82–1.39 (m, 8H, 4 Â CH2), 1.31–1.25 (m, 3H, CH3). 13
C
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NMR (100 MHz, CDCl3): d 170.1, 135.1, 125.5, 98.6, 71.8, 66.6, 66.5, 62.0, 60.5,
30.5, 28.8, 28.7, 25.2, 19.4, 13.9. IR (neat): 3050, 2952, 1720, 1455, 1260,
1065 cmÀ1. ESI–MS: m/z 309 [M+Na]+. Anal. Calcd for C15H26O5: C, 62.91, H,
9.15. Found: 62.93, H, 9.19. Compound 14a: 1H NMR (300 MHz, CDCl3): d 4.80–
4.56 (m, 6H, 3 Â O–CH2), 4.24–4.05 (m, 3H), 4.01 (s, 2H, O–CH2), 3.87 (t, 1H,
J = 7.93 Hz), 3.78–3.55 (m, 3H), 3.33 (s, 3H, O–CH3), 3.33 (s, 3H, O–CH3), 1.41 (d,
15H, J = 8.9 Hz, 5 Â CH3), 1.24 (t, 3H, J = 6.94 Hz, CH3). 13C NMR (75 MHz,
CDCl3): d 169.4, 151.6, 98.2, 95.9, 93.0, 79.6, 71.5, 70.9, 68.3, 63.2, 60.2, 58.5,
57.8, 55.9, 55.3, 28.2, 14.0. IR (neat): 3120, 2965, 2870, 1730, 1460, 1250,
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Perkin Trans. 1 2000, 3015–3019; (b) Fringuelli, F.; Piermatti, O.; Pizzo, F.;
Vaccaro, L. Curr. Org. Chem. 2003, 7, 1661–1689; (c) Frost, C. G.; Hartley, J. P.
1050, cmÀ1. ESI–MS: m/z 481 [M+H]+, 503 [M+Na]+. Anal. Calcd for C22H42NO10
:
C, 54.98, H, 8.81, N, 2.91. Found: C, 54.96, H, 8.78, N, 2.94. Compound 15a: 1H
NMR (300 MHz, CDCl3): d 4.62 (s, 1H), 4.28–4.15 (m, 4H, 2 Â O–CH2), 4.03 (br.
s, 1H), 3.62 (d, J = 6.9 Hz, 1H) 3.31 (br. s, 2H), 2.15–1.82 (m, 4H, 2 Â CH2), 1.45
(s, 9H), 1.29 (t, 3H, J = 6.9 Hz, O–CH3). 13C NMR (75 MHz, CDCl3): d 169.6, 153.8,
78.5, 71.4, 67.9, 63.2, 60.0, 56.0, 46.5, 28.2, 23.5, 13.9. ESI–MS: m/z 288 [M+H]+,
310 [M+Na]+. Anal. Calcd for C14H25NO5: C,58.52, H, 8.77, N, 4.87. Found: C,
58.54, H, 8.75, N, 4.89.