Mesyloxy-group migration as the stereoselective preparation method of various functionalized olefins and its reaction mechanism

Article abstract of DOI:10.1021/ol007060u

It was demonstrated that mesylation of appropriate γ,γ-difluorinated allylic alcohols under usual conditions furnished the corresponding α,γ-difluorinated allylic mesylates, possibly by way of 1,3-mesyloxy-group migration after formation of the expected "normal" intermediates, γ,γ-difluorinated allylic mesylates. This rearrangement was conveniently applied to the construction of trisubstituted allylic alcohols, α,β-unsaturated esters, amides, or ketones in good to excellent chemical yields with exclusive E selectivities.

Full text of DOI:10.1021/ol007060u

General Methods: Unless otherwise noted, materials were obtained from commercial
suppliers and were used without further purification. All manipulations involving air-sensitive
materials were performed under nitrogen or argon, with such materials being exposed only to
throughly dried and degassed solvents. Anmhydrous ether, THF, and CH Cl were purchased from
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Kanto Kagaku Co., Ltd. And were used as they are.
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H NMR and C NMR spectra were recorded with a Varian Gemini-200 (200 and 50 MHz),
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a Mercury-300 (300 and 75 MHz), and a VXR-500 (500 MHz: only for H) in CDCl unless
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otherwise noted, respectively. Chemical shifts were recorded in parts per million downfield from
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internal tetramethylsilane (Me Si).
F NMR spectra were recorded with a Varian Mercury-300
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(282 MHz) and a VXR-500 (470 MHz) in CDCl unless otherwise noted. Chemical shifts were
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reported in ppm downfield from internal hexafluorobenzene (C F ). Data were tabulated in the
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following order: number of proton, multipilicity (s: singlet; d: doublet; t: triplet; q: quartet; quint:
quintet; sex: sextet; sep: septet; m: multiplet; br: broad peak), coupling constants (in hertz).
Infrared (IR) spectara were obtained on a JASCO FT/IR-500 spectrometer, and all spectra were
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-1
reported in wave numbers (cm ) with the reference at the 1601.4 cm absorptionof a polystyrene
film. Column chromatography was conducted eith silica gel (BW-200, 100-200 mesh) by using
mixture of hexanes and ethyl acetate (v/v).
(2S,3R,6S)-3-Benzoyloxy-6-[(tert-butyldimethylsilyl)oxy]methyl-5-[difluoro-(methane-
sulfonyloxy)metyl]-2-methoxy-3,6-dihydro-2H-pyran (3): To a stirred solution of allylic alcohol
1
1 (0.444 g, 1 mmol) in 10 mL of CH Cl was added methanesulfonyl chloride (0.093 g, 1.2 mmol)
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2
and Et N (0.167 g, 1.2 mmol) at 0 °C. After the mixture was stirred for 1 h at that temperature, the
3
reaction was quenched with aqueous NaHCO , and the mixture was diluted with CH Cl followed
3
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by the separation of the resulting organic layer. The aqueous layer was extracted twice with
CH Cl , and the combined CH Cl layers were washed with H O, dried over MgSO , and
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2
2
2
2
4
evaporated. Purification by silica gel column chromatography afforded the rearranged product 3 in
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91% yield. H NMR δ 0.08 (6 H, s), 0.89 (9 H, s), 3.27 (3 H, s), 3.47 (3 H, s), 3.87 (1 H, dd, J=4.6,
10.5 Hz), 3.96 (1 H, dd, J=2.0, 11.2 Hz), 4.16 (1 H, br s), 5.24 (1 H, d, J=3.7 Hz), 5.50 (1 H, m),
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6.47 (1 H, s), 7.5-8.1 (5 H, m). C NMR δ -5.62, -5.45, 18.1, 25.5, 41.3, 55.8, 63.3, 66.3, 68.9,
95.2, 119.9 (t, J=273.0 Hz), 128.3, 129.0 (t, J=3.0 Hz), 129.1, 129.8, 130.3 (t, J=28.3 Hz), 133.4,
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165.5. F NMR δ 93.9 (d, J=152.6 Hz), 96.9 (d, J=152.6 Hz). IR (neat) ν 2955.1, 2857.4, 1728.0,
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1391.1, 1255.9, 1113.8, 1055.2, 837.7, 776.5, 713.3 cm .
(2S,3R,6S)-3-Benzoyloxy-6-[(tert-butyldimethylsilyl)oxy]methyl-5-(hydroxy-methyl)-2-
methoxy-3,6-dihydro-2H-pyran (4): To an EtOH solution of 3 was added NaBH (0.11 g, 3
4
mmol) at room temperature. After the reaction mixture was stirred for 1.0 h at that temperature, the
reaction was quenched with H O, and the mixture was diluted with Et O, followed by separation of
2
2
the resulting organic layer. The aqueous layer was extracted twice with Et O, and the combined
2
ethereal layers were washed with brine, dried with MgSO and evaporated. Purification by silica
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18.0
gel column chromatography afforded the allylic alcohol 4 in 86% yield. [α]
CHCl ). H NMR δ 0.10 (3 H, s), 0.10 (3 H, s), 0.89 (9 H, s), 2.94 (1 H, t, J=6.2 Hz), 3.45 (3 H, s),
+57.1° (c 0.16,
D
1
3

3.83 (1 H, dd, J=5.1, 11.0 Hz), 3.93 (1 H, dd, J=3.7, 11.0 Hz), 4.12 (2 H, m), 4.25 (1 H, m), 5.19 (1
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H, d, J=4.2 Hz), 5.50 (1 H, m), 5.83 (1 H, s), 7.4-8.1 (5 H, m). C NMR δ -4.77, -4.60, 18.9, 26.4,
56.7, 64.0, 65.4, 68.1, 71.3, 96.4, 121.8, 129.1, 130.3, 130.5, 133.9, 141.0. IR(neat) ν 3516.1,
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2950.8, 1732.0 cm . Anal. Calcd for C H O Si: C, 61.74; H, 7.89. Found: C, 61.31; H, 8.22.
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6
Preparation of exo-difluoromethylenated TBS ether 6.
2-{3-[(tert-Butyldimethylsilyl)oxy]ethyl}-1,1-difluorohept-1-ene (6b): Dibromodifluoro-
methane (4.0 g, 18 mmol) was added to 25 mL of THF at -78 °C and, after addition of hexamethyl-
phosphorous triamide (5.4 g, 36 mmol) and 5b (7.2 mmol) in a successive manner, the mixture was
allowed to warm to room temperature. After 30 min stirring and addition of a mixture of H2O and
pentane (20 and 30 mL, respectively), the usual work-up and chromatographic purification by silica
1
gel (n-hex/ CH2Cl2=8/1) afforded the intermediate 6b in 83% yield. H NMR (CDCl3) δ 0.00 (3 H,
s), 0.04 (3 H, s), 0.86 (9 H, s), 0.87 (3 H, t, J=6.6 Hz), 1.20 (3 H, d, J=6.6 Hz), 1.29 (4 H, m), 1.45
(2 H, m), 1.97 (2 H, m), 4.61 (1 H, qt, J=6.4, 1.8 Hz). 13C NMR (CDCl3) δ -5.2, -5.0, 14.0, 18.1,
22.5, 23.1, 29.1 (t, J=2.6 Hz), 32.0, 64.5 (d, J=6.4 Hz), 94.1 (t, J=13.0 Hz), 153.0 (t, J=286.4 Hz).
19F NMR (CDCl3, from C6F6) δ 66.72 (1 F, d, J=54.9 Hz), 68.15 (1 F, d, J=56.5 Hz). Because of
the intrinsic instability of compounds 6 and 7, they were confirmed only by NMR and/or IR, and
elemental analyses were tried for the final products.
Mesyloxy-group migration of 6.
(E)-1,1-Difluoro-2-ethylidenehept-1-yl methanesulfonate (7b): To a THF solution (10
mL) of 6b (1 mmol) was added tetra-n-butylammonium fluoride (1 mmol) in THF at 0 °C. After
stirring for 2 h, the reaction was quenched with H O and diluted with Et O. The usual work-up
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2
afforded the crude γ,γ-difluorinated allylic alcohol which, without further purification, was
subjected to the next mesylation (1.2 mmol of MsCl and Et3N in 10 mL of CH Cl ) to furnish 7b
2
2
1
after usual work-up and chromatographic purification (n-hex/AcOEt=4/1). H NMR δ 0.88 (3 H, t,
J=7.0 Hz), 1.30 (4 H, m), 1.44 (2 H, m), 1.73 (3 H, dt, J=7.1, 2.6 Hz), 2.16 (2 H, m), 3.21 (3 H, s),
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6.20 (1 H, qt, J=7.0, 1.7 Hz). C NMR δ 13.0, 13.8, 22.2, 25.5, 28.3, 31.7, 41.1, 122.9 (t, J=273.9
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Hz), 129.6 (t, J=7.3 Hz), 131.3 (t, J=24.9 Hz). F NMR δ 92.9 (s).
NaBH reduction of 7 to 8.
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(E)-2-Ethylideneheptanol (8b): 3 mmol of sodium borohydride was added to 7b (1 mmol) in
EtOH (10 mL) at 0 °C. After stirring for 2 h at room temperature, usual work-up and purification
by silica gel column chromatography (n-hex/AcOEt=4/1) furnished the desired allylic alcohol 8b.
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H NMR δ 0.87 (3 H, t, J=4.5 Hz), 1.2-1.5 (6 H, m), 1.63 (3 H, d, J=7.0 Hz), 2.0 (2 H, m), 3.99 (2
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H, s), 5.47 (1 H, q, J=10.2 Hz). C NMR δ 12.9, 14.0, 22.5, 27.5, 27.9, 31.9, 67.1, 120.8, 140.1.
IR (neat) ν 3330.7, 2929.1, 2859.9, 1458.1, 1001.6 cm . Anal. Calcd for C H O: C, 76.00; H,
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9
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12.75. Found: C, 75.72; H, 13.11.
Ester formation from 7 to 9-11.

To a stirred MeOH solution (10 mL) of 7 (1 mmol) was added NaOMe (3 mmol) at room
temperature. After the reaction mixture was stirred for 1 h, the usual work-up and purification by
silica gel column chromatography afforded the desired methyl ester 9.
2 1
Methyl (E)-2-ethylideneheptanoate (9b) : H NMR δ 0.85 (3 H, J=6.2 Hz), 1.30 (6 H, d, J=
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7.5 Hz), 2.26 (2 H, t, J=7.1 Hz), 3.69 (3 H, s), 6.80 (1 H, q, J=7.2 Hz). C NMR δ 13.9, 14.1,
22.4, 26.3, 31.6, 51.4, 133.4, 137.1, 168.4. IR(neat) ν 2954.3, 1716.7, 1435.3, 1258.3, 1197.2,
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1142.8 cm .
Amide formation from 7 to 12-14. To a stirred THF solution (10 mL) of LiNEt (3 mmol),
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prepared from NHEt (0.31 mL, 3 mmol) and n-BuLi (1.88 mL, (a 1.6 M solution in n-hexane)),
2
was added the rearranged product 7 at -78 °C. After the reaction mixture was stirred for 2 h at that
temperature, the usual work-up and purification by silica gel column chromatography afforded the
desired amide 14.
1
N,N-Diethyl-(E)-2-ethylideneheptanmide (14b): H NMR δ 0.86 (3 H, t, J=6.0 Hz), 1.19 (6
H, t, J=7.1 Hz), 1.27 (6 H, m), 1.94 (3 H, d, J=7.1 Hz), 3.24 (4 H, q, J=7.2 Hz), 6.95 (1 H, q, J=7.0
13
Hz).
C NMR δ 14.0, 14.8, 15.3, 22.5, 25.2, 28.3, 31.8, 43.0, 142.7, 143.9, 190.0. IR(neat) ν
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2932.1, 2872.3, 1660.4, 1336.3, 1202.6, 1146.6, 1020.7, 940.0, 785.0 cm . Anal. Calcd for
C H NO : C, 73.88; H, 11.92; N, 6.63. Found: C, 73.80; H, 11.73; N, 6.75.
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(E)-2-(2-Phenylethyl)but-2-enoyl fluoride (15e): To a stirring THF solution of 7e (0.170 g,
0.59 mmol) was added a 1 M THF solution of TBAF (177 µL) at 0 °C. After stirring for 1 h at
room temperature, the reaction mixture was quenched with water. The usual work-up and
purification by silica gel column chromatography (n-hex/CH Cl =8/1) afforded the product 15e
2
2
1
(0.095 g, 0.49 mmol) in 84% yield. H NMR δ 1.67 (3 H, d, J=7.3 Hz), 2.57-2.69 (2 H, m), 2.72-
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2.83 (2 H, m), 7.07 (1 H, q, J=7.3 Hz), 7.15-7.35 (5 H, m). C NMR δ 14.6, 28.7, 34.5, 126.1,
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128.0 (d, J=48.4 Hz), 128.4, 128.6, 140.8, 146.2, 157.8 (d, J=347.9 Hz). F NMR δ 176.37 (s).
IR (neat) ν 2936, 1797, 1015, 727, 699 cm . Anal. Calcd for C H FO : C, 74.98; H, 6.82.
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Found: C, 75.16; H, 7.21.
(E)-3-(2-Phenylethyl)pent-3-en-2-one (16e): MeMgBr (0.68 mmol) was added slowly at –78
°C to a THF (5 ml) solution of 15e (0.100 g, 0.520 mmol) containing CuI (0.08 mmol). The
reaction mixture was stirred for 3 h at -78 to -40 °C and quenched with saturated aqueous NH Cl.
4
Usual work-up and purification by silica gel column chromatography (n-hex/CH Cl =8/1) afforded
2
2
1
16e (0.076 g, 0.404 mmol) in 78% yield. H NMR δ 1.69 (3 H, d, J=7.1 Hz), 2.30 (3 H, s), 2.54-
2.68 (4 H, m), 6.74 (1 H, q, J=7.1 Hz), 7.14-7.30 (5 H, m). C NMR δ 14.5, 25.6, 27.4, 34.9,
125.6, 128.0, 128.4, 139.3, 141.8, 142.0, 198.9. IR (neat) ν 2932, 1665, 1266 cm . Anal. Calcd
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for C H O : C, 82.94; H, 8.57. Found: C, 82.94; H, 8.77.
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2) Basavaiah, D.; Sarma, P. K. S.; Bhavani, A. K. D. J. Chem. Soc., Chem. Commun. 1994,
1091.