equiv) in dry DCM. After cooling to -95 °C in a MeOH/
liquid N2 bath, catalytic trimethylsilyl triflate (less than 10
mol %) was added slowly and without interruption (method
A). In some experiments it was found that the starting furan
component had not entirely been consumed. In this case we
added the enol ether (1.2 equiv) to a mixture of trimethylsilyl
triflate (10 mol %) and furan component (1 equiv) in dry
DCM at -95 °C (method B). Thus, better yields were
obtained.
Remarkably, all reactions without exception were complete
after the first sample for TLC was taken (less than 5 min).
Further addition of either trimethylsilyl triflate or of one of
the starting components gave no increase in yield. Workup
and column chromatography provided enantiopure cycload-
ducts.16 Side products resulting from electrophilic substitu-
tion, including ipso substitution, of the heteroatom-substituted
furan were not detected or were formed only in neglible yield.
Dilution plays an important role: after initial experiments
at a concentration of 0.1 M, all experiments were conducted
at higher dilution (0.005 M). Selectivities remained un-
changed, but yields increased by about 20% (Table 1).
Compatibility with functional groups such as stannyl (G
) Bu3Sn), silyl (G ) Et3Si), and bromine (G ) Br) was
high, and stable enantiopure oxabicyclic vinylic adducts were
obtained. 3-(tert-Butyldimethylsilyl)furan (G ) SiButMe2),
however, gave only decomposed materials indicated early
on by a yellow or light brown reaction solution. In all other
experiments the mixture remained colorless. For silylated
furan (G ) SiButMe2), we assume that the steric bulk will
obstruct approach of allyl cations in the preferred compact
mode.
Three minor isomers 13B-D were obtained in 8% yield
altogether. The high regioselectivity observed for G ) Br
(10:1) and G ) SCOPh (17:1) is unprecedented for inter-
molecular 4 + 3 cycloadditions to 3-substituted furans. The
observed anti-orientation is in accord with a class B reaction18
which passes through a short-lived cationic intermediate or
transition state equivalent (Scheme 4).
Partial positive charge developing at carbon C3 is stabi-
lized by bromonium resonance and especially thionium
resonance. π-Facial discrimination11a,c is attributed to the
W-configurated allyl cation intermediate which is rigidified
by silicon-oxygen chelation and sandwiched by the aryl
group of the chiral auxiliary and diene moiety (Scheme 5).19
2,5- and 3,4-Disubstituted Furans. 3,4-Dibromofuran20
showed a comparable, even slightly higher facial selectivity
phenylethoxy}-8-oxabicyclo[3.2.1]oct-6-en-6-yl] Ester (11A) and Ben-
zenecarbothioic Acid, S-[(1R,2S,5R)-3-Oxo-2-{(1R)-phenylethoxy}-8-
oxabicyclo[3.2.1]oct-6-en-6-yl] Ester (11B). Benzenecarbothioic acid S-(3-
furanyl) ester (63 mg, 0.311 mmol) and silyl enol ether 1a were allowed to
react according to the general procedure (method B) to afford 11A (43 mg,
37%) and 11B (35 mg, 30%). Data for 11A: crystalline solid, mp 105 °C,
[R]25 ) +31.2° (c ) 1, CHCl3); IR (CHCl3) ν 3064, 3000, 2980, 2928,
D
2864, 1724, 1680, 1448, 1176, 1104, 896 cm-1; 1H NMR δ 8.00-7.25 (m,
10 H, Ar), 6.68 (d, J ) 1.8 Hz, 1 H, H7), 5.35 (d, J ) 5.0 Hz, 1 H, H5),
4.85 (q, J ) 6.4 Hz, 1 H, H8), 4.81 (dd, J ) 5.1, 1.8 Hz, 1 H, H1), 3.95
(d, J ) 5.1 Hz, 1 H, H2), 2.68 (dd, J ) 16, 5.0 Hz, 1 H, H4ax), 2.55 (d, J
) 16 Hz, 1 H, H4eq), 1.51 (d, J ) 6.4 Hz, 3 H, H9); 13C NMR δ 205.22
(4°, C3), 188.42 (4°, C10), 143.05 (4°, C6), 136.29 (3°, C7), 136.08, 135.60
(4°, Ar), 134.17, 128.90, 128.72, 128.09, 127.76, 126.44 (3°, Ar), 81.36,
80.83, 79.66, 79.51 (3°, C1, C2, C5, C8), 44.91 (2°, C4), 24.11 (1°, C9);
MS (120 °C) m/z 276 (5), 195 (1), 153 (5), 138 (9), 123 (1), 105 (100), 77
(14); HRMS calcd for C14H12O4S 276.0456, found 276.0455. Crystal
structure analysis: C22H20O4S, M ) 380.46, monoclinic, space group P21
(No. 4), a ) 6.342(1), b ) 7.256(1), and c ) 20.630(2) Å, R ) 90°, â )
91.48(1)°, γ ) 90°, V ) 949.0(2) Å3, Z ) 2, Fcalcd ) 1.332 g cm-3, F(000)
) 400, crystal size 0.54 × 0.66 × 0.20 mm, T ) 300 K, µ(Mo KR) ) 2.0
cm-1. Data for 11B: crystalline solid, mp 105-110 °C, [R]25 ) +90.1°
D
Given equatorial substituents in the three-carbon bridge
and compact transition states, four possible single isomers,
A, B, C, and D, can be envisaged in principle (Scheme 3
and Table 1). We were pleased to find that 3-thiobenzoyl-
furan (mp 49-50 °C)15c reacted cleanly. It was hoped that
the cycloadducts were crystalline, and this proved to be the
case. With simple acetal 1a two major products were
obtained. Rather than being regioisomers, they were anti
adducts with R and S configuration at carbon C2 (11A:11B
) 1.2:1). X-ray diffraction furnished the relative and also
absolute configuration directly, without recourse to the chiral
auxiliary (sulfur as heavy atom). Terminally methylated
acetal 1c and 3-thiobenzoylfuran reacted with high anti-
selectivity (17:1) and perfectly matched stereoselectivity
(17:1), giving 13A (67% yield, X-ray crystal structure).17
(c ) 1, CHCl3); IR (CHCl3) ν 3064, 3000, 2980, 2928, 2872, 1728, 1680,
1448, 1176, 1100, 900 cm-1; 1H NMR δ 8.0-7.25 (m, 10 H, Ar), 6.71 (d,
J ) 1.9 Hz, 1 H, H7), 5.43 (dd, J ) 4.4, 1.4 Hz, 1 H, H5), 5.19 (dd, J )
4.9, 1.9 Hz, 1 H, H1), 4.78 (q, J ) 6.4 Hz, 1 H, H8), 4.10 (d, J ) 4.9 Hz,
1 H, H2), 2.65 (dd, J ) 16, 4.5 Hz, 1 H, H4ax), 2.53 (dd, J ) 16, 1.4 Hz,
1 H, H4eq), 1.52 (d, J ) 6.4 Hz, 3 H, H9); 13C NMR δ 202.38 (4°, C3),
188.34 (4°, C10), 142.31 (4°, C6), 136.08 (3°, C7), 136.01, 135.86 (4°,
Ar), 134.19, 128.91, 128.57, 127.92, 127.59, 126.40 (3°, Ar), 81.25, 79.58,
79.40, 77.40 (3°, C1, C2, C5, C8), 44.75 (2°, C4), 23.69 (1°, C9); MS (140
°C) m/z 279 (1), 276 (2), 219 (1), 167 (2), 149 (6), 138 (3), 105 (100), 77
(9); HRMS calcd for C14H12O4S 276.0456, found 276.0445. Crystal structure
analysis: C22H20O4S, M ) 380.46, monoclinic, space group P21 (No. 4), a
) 10.547(1), b ) 8.792(1), and c ) 11.535(2) Å, R ) 90°, â )
115.88(1)°, γ ) 90°, V ) 962.4(2) Å3, Z ) 2, Fcalcd ) 1.313 g cm-3, F(000)
) 400, crystal size 0.44 × 0.74 × 1.2 mm, T ) 300 K, µ(Mo KR) ) 1.9
cm-1. (1S,2R,5S)-Benzenecarbothioic Acid, S-[4-Methyl-3-oxo-2-{(1R)-
phenylethoxy}-8-oxabicyclo[3.2.1]oct-6-en-6-yl] Ester (13 A). Benzene-
carbothioic acid S-(3-furanyl) ester (60 mg, 0.29 mmol) and silyl enol ether
1a were allowed to react according to the general procedure (method B) to
afford 13A (78 mg, 67%), colorless solid, mp 70 °C, [R]25D ) +104.7° (c
) 1, CHCl3); IR (CHCl3) ν 3064, 2980, 2932, 2876, 1724, 1676, 1448,
1228, 1176, 1132, 1084, 904, 880 cm-1; 1H NMR δ 8.00-7.20 (m, 10 H,
Ar), 6.75 (d, J ) 2.0 Hz, 1 H, H7), 5.24 (d, J ) 4.5 Hz, 1 H, H5), 4.82 (dd,
J ) 5.1, 2.0 Hz, 1 H, H1), 4.81 (q, J ) 6.5 Hz, 1 H, H9), 4.02 (dd, J ) 5.1,
0.6 Hz, 1 H, H2), 2.86 (ddq, J ) 7.2, 4.5, 0.6 Hz, 1 H, H4), 1.51 (d, J )
6.5 Hz, 3 H, H10), 1.10 (d, J ) 7.2 Hz, 3 H, H8); 13C NMR δ 206.73 (4°,
C3), 188.24 (4°, C11), 143.13 (4°, C6), 137.75 (3°, C7), 136.21, 134.51
(4°, Ar), 134.08, 128.89, 128.70, 128.02, 127.50, 126.40 (3°, Ar), 83.64,
81.59, 81.45, 79.22 (3°, C1, C2, C5, C9), 50.55 (2°, C4), 24.12 (1°, C10),
9.15 (1°, C8); MS (120 °C) m/z 290 (3), 271 (1), 232 (1), 204 (2), 167 (7),
152 (13), 139 (2), 105 (100), 91 (2), 77 (16); HRMS calcd for C15H14O4S
290.0613, found 290.0615. Crystal structure analysis: C23H22O4S, M )
394.49, monoclinic, space group P21 (No. 4), a ) 7.397(2), b ) 6.217(2),
and c ) 22.032(5) Å, R ) 90°, â ) 96.68(2)°, γ ) 90°, V ) 1006.3(5) Å3,
Z ) 2, Fcalcd ) 1.302 g cm-3, F(000) ) 416, crystal size 0.37 × 0.28 ×
(16) The chiral auxiliaries remain configurationally stable under the
reaction conditions (ref 11c). Products are obtained as single isomers (ee
> 98%). See also: X-ray crystal structure of cycloadducts 11A, 11B, and
13A (Table 1).
(17) Selected Spectroscopic Data. 4 + 3 Cycloaddition, Method A.
To a solution of furan component (1.0 equiv) and silyl enol ether (1.0 equiv)
in DCM (0.005 M solution) was added TMSOTf (0.1 equiv) at -95 °C.
After 5 min a saturated aqueous NaHCO3 solution was added and the
mixture was allowed to reach room temperature. The aqueous layer was
extracted with DCM (3×), and the combined organic phase was dried
(MgSO4) and concentrated. The crude product was purified by column
chromatography (silica gel, PE/MTBE). Method B. To a solution of furan
component (1.0 equiv) in DCM (0.005 M solution) was added TMSOTf
(0.1 equiv) at -95 °C. A solution of acetal component (1.2 equiv) in DCM
(25 mL/mmol) was then added slowly. Workup after 5 min as described
for method A. Benzenecarbothioic Acid, S-[(1S,2R,5S)-3-Oxo-2-{(1R)-
0.04 mm, T ) 300 K, µ(Mo KR) ) 1.9 cm-1
.
(18) Hoffmann, H. M. R. Angew. Chem. 1984, 96, 29; Angew. Chem.,
Int. Ed. Engl. 1984, 23, 1.
Org. Lett., Vol. 2, No. 7, 2000
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