in smaller batches also may mitigate a potentially violent
situation. 2-Furaldehyde (300 mL, 348 g 3.62 mol) was added
to NH2NH2‚H2O (600 mL, 619 g, 12.4 mol) over 30 min with a
water bath to moderate the resulting exothermic reaction. After
stirring at ambient temperature for 0.5 h, 50 g of sodium
carbonate was added. The liquid phase was decanted from the
sodium carbonate. The crude reaction mixture was distilled at
atmospheric pressure, then under a partial vacuum (100 mm)
to remove the water and excess hydrazine, and finally distilled
under vacuum (0.1 mm, bp 90-105 °C) to give 1 as an oil (263
g, 66% yield): 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.39
(br d, J ) 1.1 Hz, 1H), 6.43 (d, J ) 3.3 Hz, 1H), 6.39 (dd, J )
1.8, 3.7 Hz, 1H), 5.55 (br s, 2H).
for 18 h, the reaction mixture was transferred to a separatory
funnel with CH2Cl2 (10 mL) and H2O (10 mL). The organic phase
was separated, and the aqueous was extracted with additional
CH2Cl2 (10 mL). The combined organic phases were washed with
brine (10 mL) and dried over Na2SO4, and the volatiles were
removed on a rotary evaporator. The crude product was purified
by flash chromatography (25 g silica gel; 10% ethyl acetate in
hexanes) to give 4b (0.443 g, 96% yield) as a yellow oil: IR 3400,
1600 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.27-7.40 (m, 6H), 6.32
(dd, J ) 1.8, 2.9 Hz, 1H), 6.09 (d, J ) 3.3 Hz, 1H), 5.03 (dt, J )
1.8, 6.6 Hz, 1H), 3.08 (d, J ) 6.6 Hz, 2H), 2.47 (br s, 1H); 13C
NMR (100 MHz) δ 152.3, 143.3, 141.6, 128.4, 127.6, 125.7, 110.3,
107.3, 72.8, 38.2.
(R)-1-(2-Furyl)undecan-2-ol ((R)-4c; Entry 5, Table 1). To
4 Å molecular sieves (0.50 g) in ether (10 mL) were added (S)-
1,1′-bi-2-naphthol (0.286 g, 0.998 mol) and titanium(IV) isopro-
poxide (0.143 mL, 0.138 g, 0.484 mmol). The reaction mixture
was refluxed for 1 h and was allowed to cool to room tempera-
ture. Decanal (0.94 mL, 0.78 g, 5.0 mmol) was added, the mixture
was stirred for 5 min, and 2 (1.30 mL of a 1.3:1 mixture of 2/2-
methylfuran, approximately 8.2 mmol of 2) was added over 5
min. The reaction mixture was stirred at room temperature for
15 min. Saturated sodium bicarbonate solution (1 mL) was
added, and the reaction mixture was stirred for 1 h at room
temperature. The reaction mixture was filtered through a Celite
bed, which was washed with additional ether (75 mL). The ether
solution was washed with 1.0 M NaOH (2 × 60 mL) and dried
over Na2SO4, and the volatiles were removed on the rotary
evaporator. The crude product was purified by flash chroma-
tography (60 g of silica gel; 10% ethyl acetate in hexanes) to
give (R)-4c (0.781 g, 65% yield; 94% ee) as a white solid: mp
2-Methylene-2,3-dihydrofuran (2). The following is a typi-
cal run for the preparation of 2, following the procedure
described by Kishner5a and Rice.7 Moist potter’s clay (1.5 g) was
placed in a 25 mL Schlenk flask with a magnetic stirring bar. A
2.5% H2PtCl6 solution (3 mL) was added and stirred until the
mixture was homogenized. The catalyst was dried at 100 °C for
1 h with a gentle stream of air passing over it. A balloon of H2
was put on the reaction vessel, and the catalyst was heated to
150 °C for 2 h. After the reaction vessel had cooled to room
temperature, the hydrogen balloon was replaced with a balloon
of CO2. The catalyst and KOH (1.5 g) were then placed in a 500
mL three-neck RB flask, which had been previously flushed with
Ar, fitted with a dropping funnel, a distillation apparatus in
which the receiving vessel was cooled in dry ice/acetone, and a
stopper. The distillation apparatus was connected to a trap that
also was cooled in dry ice/acetone. The reaction vessel was heated
to 130 °C with an oil bath, and 5-10 mL portions of 2-furylhy-
drazone-half hydrate (281 g, 2.39 mol) were added. The decom-
position of 1, especially during the addition of the first two or
three portions, was extremely violent, leading to the loss of some
product even with the cooling system described. The oil bath
temperature was increased in order to induce the rapid decom-
position of 1; slow decomposition invariably meant poor selectiv-
ity for 2, with almost exclusive formation of 2-methylfuran. As
the addition progressed, the oil bath temperature was raised to
210-220 °C. Under these conditions, the amount of 1 added in
each portion was limited by the associated foaming. The
combined collected distillate was washed with 2% Na2CO3 (200
mL), water (2 × 200 mL), and brine (200 mL) and then dried
over Na2CO3. The crude product (165 g; approximately 1:1.4 2/2-
methylfuran; 35% crude yield of 2) was distilled under Ar at
atmospheric pressure to give six fractions: fraction 1 (54-65
°C; 31.1 g, 1:5 2/2-methylfuran), fraction 2 (65-67 °C; 21.5 g,
1:4 2/2-methylfuran), fraction 3 (67-68 °C; 23.8 g, 1:3 2/2-
methylfuran), fraction 4 (68-74 °C; 38.0 g, 1.3:1 2/2-methylfu-
ran), fraction 5 (74-75 °C; 20.2 g, 4:1 2/2-methylfuran), and
fraction 6 (75-76 °C; 9.8 g, 10:1 2/2-methylfuran); IR (CH2Cl2)
35-36 °C; IR 3443, 1642 cm-1 1H NMR (400 MHz, CDCl3) δ
;
7.33 (d, J ) 1.4 Hz, 1H), 6.30 (dd, J ) 2.0, 3.1 Hz, 1H), 6.10 (d,
J ) 2.9, 1H), 2.84 (dd, J ) 4.0, 15.0 Hz, 1H), 2.71 (dd, J ) 8.1,
15.0 Hz, 1H), 1.78 (d, J ) 4.0 Hz, 1H), 1.47 (m, 2H), 1.26 (br s,
14H), 0.87 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
153.0, 141.6, 110.3, 107.0, 70.5, 36.7, 36.1, 31.9, 29.57 (2 C),
29.53, 29.3, 25.6, 22.7, 14.1. Anal. Calcd for C15H26O2: C, 75.58;
H, 10.99. Found: C, 75.53; H, 11.20. The enantiomeric excess
was determined by the use of the chiral shift reagent Eu(hfc)3.
The methine proton bonded to the carbon adjacent to the
hydroxy group for the two enantiomers resonates as broad
singlets at δ 6.06 for (R)-4c and δ 5.86 for (S)-4c (0.10 M of 4c
with 33 mol % Eu(hfc)3 in CDCl3). The assignment of the
absolute stereochemistry of the major enantiomer in this reac-
tion was based on the comparison of the 1H NMR spectra of the
(+)-MTPA esters of 4c and the structurally similar (+)-MTPA
esters of 2-methyl-1-nonen-4-ol.19 The alkenyl protons of (+)-
MTPA ester of (R)-2-methyl-1-nonen-4-ol resonated downfield
(δ 4.83 and 4.76) from the (+)-MTPA ester of (S)-2-methyl-1-
nonen-4-ol (δ 4.72 and 4.65). The 1H NMR spectra of the (+)-
MTPA ester of the major enantiomer of the above reaction
resonates at δ 6.29 (dd, 1H, J ) 2.0, 3.1 Hz) and 6.07 (d, 1H, J
) 2.9 Hz, H3), downfield from the minor isomer at δ 6.22 (dd,
1H, J ) 2.0, 3.1 Hz) and 5.53 (d, 1H, J ) 2.9 Hz, H3).
1680, 1622 cm-1 1H NMR (400 MHz, CDCl3) δ 6.41 (m, 1H),
;
5.12 (m, 1H), 4.54 (m, 1H), 4.19 (m, 1H), 3.33 (app pentet, J )
2.7 Hz, 2H); 13C NMR (100 MHz) 161.7 (C), 144.5 (CH), 102.1
(CH), 83.8 (CH2), 32.7 (CH2); UV-vis (λmax ) 239 nm, ꢀ ) 6800,
after correcting for purity as determined by 1H NMR). The
signals associated with 2-methylfuran resonated at δ 7.27, 6.41,
1
Acknowledgment. We thank the Petroleum Re-
search Foundation, administered by the American
Chemical Society, and Lafayette College’s Academic
Research Committee for financial support. We gratefully
acknowledge a grant from the Kresge Foundation for
the purchase a 400 MHz NMR spectrometer.
5.96, and 2.29 in the H NMR and δ 152.1, 140.7, 110.3, 105.4,
and 13.4 in the 13C NMR. The use of kaolin instead of moist
potter’s clay gave similar yields of 2. Smaller scale reactions gave
lower yields (20-30%) of 2. When mixtures of 2 and 2-methyl-
furan were stored over potassium carbonate in the freezer for
several months, there was slow isomerization of 2, with fractions
containing a high proportion (>90%) of 2 undergoing more rapid
isomerization.
Supporting Information Available: Experimental de-
(()-2-(2-Furyl)-1-phenylethan-1-ol18 (4b; Entry 2, Table
1). To a solution of benzaldehyde (0.250 mL, 0.261 g, 2.46 mmol)
in CH2Cl2 (2 mL) were added 2 (1.0 mL of a 1:2 mixture of 2/2-
methylfuran, approximately 3.7 mmol of 2), NaHCO3 (0.050 g,
0.60 mmol), and Yb(fod)3 (0.132 g, 0.125 mmol). After stirring
1
tails and characterization data for 4-6; copies of H and 13C
NMR for 2 and 4-6. This material is available free of charge
JO0479112
(18) Solladie´-Cavallo, A.; Roje, M.; Isarno, T.; Sunjic, V.; Vinkovic,
V. Eur. J. Org. Chem. 2000, 1077-1080.
(19) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.;
Yamamoto, H. J. Am. Chem. Soc. 1993, 115, 11490-11495.
J. Org. Chem, Vol. 70, No. 7, 2005 2865