J. D. Rosen et al. / Tetrahedron Letters 44 (2003) 365–368
367
The reaction was quenched with 1N NaOH (50 mL)
and transferred to a separatory funnel. The aqueous
layer was collected and the organic extracted again with
1N NaOH (50 mL). The combined aqueous cuts were
re-acidified with 2N HCl (70 mL) and extracted with
EtOAc (75 mL). The organic layer was washed with
water (50 mL) and then concentrated in vacuo to an
oil.
Scheme 3. Reagents and conditions: (a) NBS, AIBN, CCl4,
80°C, 6, h; (b) Hu¨nig’s base, THF, 60°C, 24 h, 76% yield over
both steps.
The oil was redissolved in THF (50 mL), treated with
DBU (3.74 mL, 25.0 mmol) and heated to 60°C for 18
h. The resultant slurry was cooled to room tempera-
ture, diluted with EtOAc (50 mL) and filtered through
a sintered glass funnel. The wet cake was rinsed with
EtOAc (2×25 mL) and the combined filtrates concen-
trated in vacuo (at or below 25°C). The crude lactone
was purified by flash chromatography (SiO2, hexanes:
EtOAc=1:3).
affording crystalline 7 in 76% yield (from saturated
lactone).
Interestingly, when this reaction was performed without
a radical initiator, complete bromination was observed
(as expected) on very small scale, but the reaction
would stall at various points on larger scale. Once the
progress of the 3-bromination was halted, thermal elim-
ination would occur (resulting in a visible release of
HBr) and bromination at the newly formed allylic
position was detected. Again, thermal elimination
occurred leading to the formation of pyran-2-one 9.
Hence, without AIBN the bromination reaction led to a
complex mixture of 6–9.
5-Chloro-2-(4-fluorophenyl)pentanoic acid (4b): IR
(neat): 1707 cm−1; 1H NMR (400 MHz, CDCl3): l
10.87 (br s, 1H), 7.32–7.27 (m, 2H), 7.07–7.01 (m, 2H),
3.58 (t, J=7.6 Hz, 1H), 3.53 (t, J=6.4 Hz, 2H), 2.21
(m, 1H), 1.96 (m, 1H), 1.84–1.65 (m, 2H); 13C NMR
(100 MHz, CDCl3): l 179.7, 162.2 (d, J=246.7 Hz),
133.4 (d, J=3.2 Hz), 129.5 (d, J=8.0 Hz), 115.5 (d,
J=21.6 Hz), 50.0, 44.2, 30.2, 30.1.
This discovery led us to examine a controlled conver-
sion of dihydropyran-2-one 7 to pyran-2-one 913
(Scheme 4). The same conditions used in the initial
bromination/elimination sequence were repeated, and
except for minor rate differences the results were nearly
identical. Hence, the potential for utilizing 3-aryl-d-lac-
tones as precursors to 3-aryl-5,6-dihydropyran-2-ones
or 3-arylpyran-2-ones has been demonstrated.
3-(4-Fluorophenyl)tetrahydropyran-2-one (3b): mp 62.3–
62.5°C; IR (neat): 1733 cm−1; 1H NMR (400 MHz,
CDCl3): l 7.24–7.19 (m, 2H), 7.07–7.01 (m, 2H), 4.51–
4.41 (m, 2H), 3.76 (dd, J=10.4, 6.8 Hz, 1H), 2.29 (m,
1H), 2.10–1.97 (m, 3H); 13C NMR (100 MHz, CDCl3):
l 172.3, 161.9 (d, J=245.9 Hz), 134.5 (d, J=3.2 Hz),
129.7 (d, J=8.0 Hz), 115.5 (d, J=21.6 Hz), 69.0, 46.2,
28.1, 21.9. Anal. calcd for C11H11FO2: C, 68.03; H,
5.71; F, 9.78. Found: C, 67.99; H, 5.68; F, 9.80.
In conclusion, we have successfully demonstrated a
novel route for the synthesis of 3-aryl-d-lactones. This
chemistry utilizes inexpensive and readily available
reagents, and has been shown to accommodate a wide
variety of aryl substituents. In addition, the saturated
lactones have the potential to serve as synthons for
both 5,6-dihydropyran-2-ones and pyran-2-ones.
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Scheme 4. Reagents and conditions: (a) NBS, AIBN, CCl4,
80°C, 4 h; (b) Hu¨nig’s base, THF, 60°C, 2 h, 68% yield over
both steps.
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