ConVersion of Weinreb Amides into Benzene Rings
FTIR (CH2Cl2 cast film microscope) 1055, 1098, 1161, 1446, 1641,
2834, 2931, 3474 cm-1; 1H NMR (CDCl3, 500 MHz) δ 1.59-1.69
(m, 2 H), 2.10-2.25 (m, 2 H), 2.30-2.45 (m, 2 H), 3.14 (dd, J )
3.7, 9.6 Hz, 1 H), 3.31-3.64 (overlapping singlets and multiplets,
16 H), 4.77 (dd, J ) 2.2, 3.7 Hz, 1 H), 4.90-4.96 (m, 1 H), 5.02
(apparent ddq, J ) 1.7, 7.0, 17.1 Hz, 1 H), 5.06-5.14 (m, 2 H),
5.83 (dddd, J ) 6.3, 6.3, 10.3, 16.9 Hz, 1 H), 5.89-6.02 (m, 1 H);
13C NMR (CDCl3, 125 MHz) δ 27.2 (t), 27.7 (t), 35.5 (t), 35.8 (t),
40.7 (t), 41.5 (t), 56.0 (q), 56.1 (q), 58.9 (q), 59.9 (q), 60.0 (q),
60.69 (q), 60.71 (q), 71.4 (d), 72.0 (d), 74.6 (s), 74.7 (s), 80.6 (d),
80.7 (d), 82.0 (d), 84.3 (d), 84.4 (d), 97.4 (d), 97.5 (d), 114.0 (t),
114.1 (t), 117.4 (t), 117.5 (t), 134.1 (d), 134.3 (d), 139.1 (d), 139.2
(d); exact mass (electrospray) m/z calcd for C17H30NaO6 353.1935,
found 353.1934.
1-[[2S-(2r,3ꢀ,4r,5ꢀ,6ꢀ)]-3,4,5,6-Tetramethoxytetrahydro-2H-
pyran-2-yl]cyclohex-3-enol (9e). A solution of 9b (0.030 g, 0.091
mmol) in CH2Cl2 (2 mL) was degassed for 30 min with a stream
of Ar. Grubbs I catalyst (0.0037 g, 0.0045 mmol) was added, and
the Ar stream was continued for 15 min. The mixture was then
refluxed overnight under a static pressure of Ar, cooled, and filtered
through flash chromatography silica gel (1 × 5 cm), using CH2Cl2.
Evaporation of the solvent and flash chromatography of the residue
over silica gel (1 × 20 cm), using Et2O-hexanes, gave 9e (0.0136
g, 90%) as an oil: FTIR (CH2Cl2 cast film) 1058, 1100, 1159, 2835,
2912, 3484 cm-1; 1H NMR (CDCl3, 500 MHz) δ 1.58-1.68 (m, 1
H), 1.78-1.88 (m, 1 H), 1.92-2.14 (m, 2 H), 2.26-2.54 (m, 2 H),
3.03 (d, J ) 1.0 Hz, 0.5 H), 3.17 (apparent dtd, J ) 0.5, 4.2, 9.6
Hz, 1 H), 3.31-3.43 (s overlapping with m, 4 H), 3.47 (dd, J )
2.4, 9.8 Hz, 1 H), 3.52 (two overlapping s, 3 H), 3.55-3.65
(overlapping singlets and m, 7 H), 3.72 (d, J ) 1.4 Hz, 0.5 H),
4.77 (d, J ) 3.8 Hz, 0.5 H), 4.79 (d, J ) 3.7 Hz, 0.5 H), 5.60-5.67
(m, 1 H), 5.71-5.82 (m, 1 H); 13C NMR (CDCl3, 125 MHz) δ
21.7 (t), 22.0 (t), 29.2 (t), 30.6 (t), 33.8 (t), 34.4 (t), 55.2 (q), 55.4
(q), 58.9 (q), 59.8 (q), 60.1 (q), 60.7 (q), 60.8 (q). 71.4 (s), 71.6
(s), 72.8 (d), 72.9 (d), 80.1 (d), 80.6 (d), 82.0 (d), 82.1 (d), 84.4
(d), 84.5 (d), 97.2 (d), 97.3 (d), 123.6 (d), 124.0 (d), 126.1 (d),
127.1 (d); exact mass (electrospray) m/z calcd for C15H26NaO6
325.1622, found 325.1624.
Et2O-petroleum ether (35-60 °C), gave 10a19 (0.270 g, 75%) as
a liquid: [R]20 -43.59 (c 1.28, CHCl3); FTIR (CHCl3 cast film
D
microscope) 914, 1113, 1719, 2934, 2980 cm-1; 1H NMR (CDCl3,
500 MHz) δ 1.37 (d, J ) 6.9 Hz, 3 H), 2.31-2.39 (m, 2 H),
2.60-2.79 (m, 2 H), 3.96 (q, J ) 6.9 Hz, 1 H), 4.55 (AB q, J )
11.7, ∆νAB ) 19.2 Hz, 2 H), 4.98-5.03 (m, 1 H), 5.06 (apparent
dq, J ) 1.6, 17.1 Hz, 1 H), 5.84 (dddd, J ) 6.6, 6.6, 10.3, 16.8 Hz,
1 H), 7.30-7.42 (m, 5 H); 13C NMR (CDCl3, 125 MHz) δ 17.4
(q), 27.2 (t), 36.5 (t), 71.9 (t), 80.6 (d), 115.3 (t), 127.7 (d), 127.9
(d), 128.5 (d), 137.2 (d), 137.6 (s), 212.0 (s); exact mass (electro-
spray) m/z calcd for C14H18NaO2 241.1199, found 241.1199.
4-[(S)-1(Benzyloxy)ethyl]octa-1,7-dien-4-ol (10b). Allylmag-
nesium bromide (1 M in Et2O, 1.0 mL, 1.0 mmol) was added
dropwise to a stirred and cooled (-15 °C) solution of 10a (0.18 g,
0.83 mmol) in THF (8 mL). The cold bath was left in place but
not recharged, and stirring was continued for 2 h. The mixture was
quenched with saturated aqueous NH4Cl, and the aqueous phase
was extracted with Et2O. The combined organic extracts were
washed with brine, dried (MgSO4), and evaporated. Flash chro-
matography of the residue over silica gel (1.5 × 15 cm), using
10% Et2O-petroleum ether (35-60 °C), gave 10b (0.15 g, 71%)
as an oil: FTIR (CH2Cl2 cast) 912, 1095, 1454, 1641, 2871, 2941,
2977, 3471, 3561 cm-1; 1H NMR (CDCl3, 500 MHz) δ 1.19 (d, J
) 6.3 Hz) and 1.21 (d, J ) 6.3 Hz), (3 H in all), 1.40-1.49 (m,
0.5 H), 1.54-1.62 (m, 0.5 H), 1.65-1.73 (m, 1 H), 2.03-2.27 (m,
3 H), 2.28 (s, 0.8 H), 2.36 (d, J ) 0.7 Hz, 0.2 H), 2.40-2.48 (m,
1 H), 3.49 (q, J ) 6.3 Hz) and 3.51 (q, J ) 6.3, Hz), (1 H in all),
4.54 (AB q, J ) 11.5, ∆νAB ) 124.7 Hz) and 4.55 (AB q, J )
11.5, ∆νAB ) 123.3 Hz), (2 H in all), 4.92-5.13 (m, 4 H),
5.77-5.92 (m, 2 H), 7.27-7.39 (m, 5 H); 13C NMR (CDCl3, 125
MHz) δ 13.1 (q), 13.3 (q), 27.6 (t), 33.9 (t), 35.1 (t), 39.5 (t), 40.7
(t), 71.3 (t), 71.4 (t) 75.5 (s), 75.6 (s), 79.12 (d), 79.15 (d), 114.2
(t), 117.6 (t), 117.9 (t), 127.6 (d), 127.65 (d), 127.68 (d), 128.4
(d), 134.0 (d), 134.2 (d), 138.5 (s), 139.0 (d), 139.1 (d); exact mass
(electrospray) m/z calcd for C17H24NaO2 283.1669, found 283.1670.
1-[(S)-1-(Benzyloxy)ethyl]cyclohex-3-enol (10c). A solution of
10b (0.10 g, 0.38 mmol) in CH2Cl2 (9 mL) was degassed for 30
min with a stream of Ar. Grubbs I catalyst (0.019 g, 0.023 mmol)
was added, and the Ar stream was continued for 15 min. The
mixture was then refluxed for 3 h under a static pressure of Ar,
cooled, and filtered through flash chromatography silica gel (1 ×
5 cm), using CH2Cl2. Evaporation of the solvent and flash
chromatography of the residue over silica gel (1.5 × 15 cm), using
10% Et2O-petroleum ether (35-60 °C), gave 10c (0.069 g, 78%)
as an oil: FTIR (CH2Cl2 cast) 1075, 1088, 2916, 2972, 3026, 3467,
Methyl (5R)-2,3,4-Tri-O-methyl-5-C-phenyl-r-D-xylopyrano-
side (9f). SOCl2 (0.015 mL, 0.20 mmol) was added dropwise to a
stirred and cooled (0 °C) solution of 9e (0.015 g, 0.050 mmol) in
pyridine (0.11 mL, 1.39 mmol). Stirring at 0 °C was continued for
3 h, and the mixture was poured onto crushed ice and extracted
with Et2O. The combined organic extracts were washed with water,
saturated aqueous NaHCO3, and brine, dried (Na2SO4), and
evaporated to give the crude intermediate diene as an oil. DDQ
(0.011 g, 0.05 mmol) was added to a stirred solution of this diene
in PhH (1 mL), and the mixture was then stirred and refluxed for
1 h, cooled to room temperature, and filtered through flash
chromatographysilicagel(0.5×30cm),using50%EtOAc-hexanes.
1
3566 cm-1; H NMR (CDCl3, 400 MHz) δ 1.23 (d, J ) 6.4 Hz)
and 1.25 (d, J ) 6.3 Hz), (3 H in all), 1.52-1.74 (m, 1.5 H),
1.80-1.88 (m, 0.5 H), 1.98-2.36 (m, 5 H), 3.43 (q, J ) 6.4 Hz)
and 3.47 (q, J ) 6.4 Hz), (1 H in all), 4.59 (AB q, J ) 11.6, ∆νAB
) 95.0 Hz) and 4.60 (AB q, J ) 11.6, ∆νAB ) 96.7 Hz), (2 H in
all), 5.58-5.66 (m, 1 H), 5.71-5.79 (m, 1 H), 7.29-7.41 (m, 5
H); 13C NMR (CDCl3, 125 MHz) δ 13.0 (q), 13.2 (q), 22.18 (t),
22.20 (t), 28.7 (t), 30.0 (t), 33.1 (t), 34.8 (t), 71.4 (t), 71.5 (t), 72.2
(s), 72.3 (s), 79.6 (d), 80.2 (d), 123.8 (d), 124.3 (d), 126.6 (d),
126.8 (d), 127.62 (d), 127.64 (d), 127.7 (d), 128.36 (d), 128.38
(d), 138.6 (s); exact mass (electrospray) m/z calcd for C15H20NaO2
255.1356, found 255.1356.
Evaporation of the solvent gave 9f (0.012 g, 86%) as an oil: [R]20
D
88.32 (c 0.82, MeOH); FTIR (CH2Cl2 cast film microscope) 1097,
1455, 2833, 2909, 2934 cm-1; 1H NMR (CDCl3, 500 MHz) δ 3.04
(d, J ) 0.5 Hz, 3 H), 3.10 (dd, J ) 9.3, 9.3 Hz, 1 H), 3.35 (ddd,
J ) 0.5, 3.7, 9.6 Hz, 1 H), 3.44 (d, J ) 0.6 Hz, 3 H), 3.58 (d, J )
0.6 Hz, 3 H), 3.62 (dd, J ) 9.2, 9.2 Hz, 1 H), 3.65 (d, J ) 0.6 Hz,
3 H), 4.44 (d, J ) 9.8 Hz, 1 H), 4.91 (d, J ) 3.7 Hz, 1 H),
7.33-7.44 (m, 5 H); 13C NMR (CDCl3, 125 MHz) δ 55.3 (q), 59.1
(q), 60.4 (q), 61.0 (q), 72.8 (d), 81.8 (d), 83.2 (d), 85.8 (d), 97.9
(d), 127.6 (d), 128.2 (d), 128.4 (d), 138.9 (s); exact mass
(electrospray) m/z calcd for C15H22NaO5 305.1359, found 305.1357.
(S)-2-(Benzyloxy)hept-6-en-3-one (10a). 3-Butenylmagnesium
bromide (0.5 M in THF, 4.1 mL, 4.1 mmol) was added dropwise
to a stirred and cooled (-15 °C) solution of 1013 (0.37 g, 1.66
mmol) in THF (12 mL). Stirring at -15 °C was continued for 3 h,
and the mixture was then diluted with Et2O and quenched with
saturated aqueous NH4Cl. The organic phase was washed with water
and brine, dried (MgSO4), and evaporated. Flash chromatography
of the residue over silica gel (1.5 × 15 cm), using 10%
(S)-1-[(1-Phenylethoxy)methyl]benzene (10d). SOCl2 (0.042
mL, 0.58 mmol) was added dropwise to a stirred and cooled (0
°C) solution of 10c (0.03 g, 0.13 mmol) in pyridine (0.33 mL, 4.07
mmol). Stirring at 0 °C was continued for 2 h, and the mixture
was poured onto crushed ice and extracted with Et2O. The combined
organic extracts were washed with hydrochloric acid (2 M), water,
and brine, dried (MgSO4), and evaporated to give the crude
intermediate diene as a colorless liquid. DDQ (0.33 g, 1.45 mmol)
was added to a stirred solution of this diene in PhH (2 mL). The
(19) Matsumoto, K.; Otsuka, K.; Okamoto, T.; Mogi, H. Synlett 2007, 729–
732.
J. Org. Chem. Vol. 74, No. 4, 2009 1689