Li et al.
1,2-Diphenylethanone (5a): White solid; Mp 59–60 °C (Lit.11
59–60 °C); 1H NMR (300 MHz, CDCl3; δ, ppm) 7.91 (d, J ) 7.2
Hz, 2H), 7.46 (t, J ) 7.2 Hz, 1H), 7.33 (t, J ) 7.2 Hz, 2H),
7.26-7.16 (m, 5H), 4.19 (s, 2H); 13C NMR (75 MHz, CDCl3; δ,
ppm) 197.1, 136.9, 134.6, 133.2, 129.5, 128.7, 128.7, 128.7, 126.9,
45.5; IR (neat; cm-1) V 2962, 1685, 1076, 801, 699. HRMS (EI):
calcd for C14H12O (M+), 196.0888; found, 196.0894.
to give similar experimental results. Cyclic ꢀ-bromo alcohol
10e afforded the desired ring-contractive product 11e in only
30% yield. The lower yield of this reaction may be accounted
for by the formation of polymers that are insolvable in organic
solvent. No reaction was found when 2-bromo-1-phenylethanol
10f was submitted to 0.6 equiv of Et2Zn or EtZnCH2I under
the typical reaction conditions.
It is notable that when bromohydrins derived from electron-
deficient olefins were submitted to the reaction the rearrange-
ment products were not detected, but olefins were obtained
(Scheme 5). For example, treatment of substrate 12a with 2.0
equiv of Et2Zn in CH2Cl2 at room temperature for 5 h gave
4′-methoxychalcone 13a in 60% isolated yield. The high
stereochemistry (E) of the product olefin was determined by
comparison of the NMR spectrum of the authentic olefin. It
seems likely that the pathway of the formation of olefins might
proceed through the reductive elimination of HBrO from the
bromohydrins.10 Reaction of bromohydrin 12b with 0.6 equiv
of Et2Zn afforded the corresponding ethyl (E)-cinnamate 13b
in 15% yield along with the recovered starting 12b. The yield
of 13b increased to 50% when 2.0 equiv of Et2Zn was used
and the reaction time was prolonged to 24 h.
Ethyl 7-(4-Methoxyphenyl)-6-oxoheptanoate (5m): Colorless
1
oil (128.0 mg, 92% yield); H NMR (300 MHz, CDCl3; δ, ppm)
7.11 (d, J ) 8.4 Hz, 2H), 6.87 (d, J ) 8.4 Hz, 2H), 4.11 (q, J )
7.2 Hz, 2H), 3.79 (s, 3H), 3.60 (s, 2H), 2.44 (t, J ) 6.6 Hz, 2H),
2.25 (t, J ) 6.6 Hz, 2H), 1.57-1.52 (m, 4H), 1.22 (t, J ) 7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3; δ, ppm) 208.3, 173.3, 158.7,
130.4, 126.3, 114.2, 60.2, 55.2, 49.2, 41.2, 34.0, 24.3, 23.1, 14.2;
IR (neat; cm-1) V 2936, 1713, 1512, 1032, 812. HRMS (EI): calcd
for C16H22O4 (M+), 278.1518; found, 278.1511.
General Procedure for Furukawa Reagent (EtZnCH2I)
Promoted Rearrangement of Bromohydrins. A 25 mL round-
bottom flask was equipped with a stir bar and charged with freshly
distilled methylene chloride (3 mL) and diethyl zinc (30 µL, 0.3
mmol) under an atmosphere of nitrogen at 0 °C. Methylene iodide
(24 µL, 0.3 mmol) was added dropwise via syringe under nitrogen,
and the resulting white suspension was stirred for 20 min.
Bromohydrins (0.5 mmol) were added rapidly, and the ice bath
was removed. The mixtures were allowed to stir at room temper-
ature for 2 h until TLC indicated complete consumption of the
starting bromohydrins. The reaction mixtures were quenched by
saturated aqueous ammonium chloride solution and extracted with
diethyl ether (3 × 10 mL). The combined organic layers were
washed with brine and then dried over anhydrous magnesium
sulfate, filtered, and concentrated in vacuo to give the crude
products, which were purified by column chromatography packed
with silica gel using petroleum ether/ethyl acetate (20:1) as eluent
to afford the corresponding products.
Conclusions
In summary, we have described a new procedure of synthe-
sizing carbonyl compounds from ꢀ-bromo alcohols using
organozinc species Et2Zn or EtZnCH2I. The rearrangement
reaction involves mild conditions, high efficiency, functionality
tolerance, and using a substoichiometric amount of Et2Zn (60
mol %). This method is general for bromohydrins and permits
regioselective syntheses of R-aryl ketones. A variety of ring-
expansive and -contractive carbonyl compounds were also
obtained with good to excellent isolated yields.
1-Phenyl-1H-inden-2(3H)-one (9f): White solid (90.5 mg, 87%
yield); Mp 49-51 °C (Lit.12 49-50 °C); H NMR (300 MHz,
1
CDCl3; δ, ppm) 7.27-7.03 (m, 9H), 4.60 (s, 1H), 3.60 (s, 2H);
13C NMR (75 MHz, CDCl3; δ, ppm) 213.9, 141.4, 138.2, 137.4,
128.9, 128.6, 128.1, 128.0, 127.4, 126.2, 125.0, 59.9, 43.1; IR (KBr;
cm-1) V 1753.
Experimental Section
General Procedure for Et2Zn-Mediated Rearrangement of
Bromohydrins. Et2Zn (30 µL, 0.3 mmol) was added to a solution
of bromohydrins (0.5 mmol) in dry dichloromethane (3 mL) at 0
°C under nitrogen. After stirring at room temperature for 2 h, the
mixture was quenched by saturated aqueous ammonium chloride
solution and extracted with diethyl ether (3 × 10 mL). The
combined organic layers were washed with brine and then dried
over anhydrous magnesium sulfate, filtered, and concentrated in a
vacuum to give the crude products, which were purified by column
chromatography packed with silica gel using petroleum ether/ethyl
acetate (20:1) as eluent to afford the corresponding products.
Acknowledgment. We are grateful to the National Natural
Science Foundation of China (20572104) and the Program of
NCET (060551) for financial support.
Supporting Information Available: Detailed experimental
procedures and characterization data for all products. This
material is available free of charge via the Internet at
JO800231S
(10) Cho, S.; Kang, S.; Keum, G.; Kang, S. B.; Han, S. Y.; Kim, Y. J. Org.
Chem. 2003, 68, 180.
(11) Ye, C. F.; Twamley, B.; Shreeve, J. M. Org. Lett. 2005, 7, 3961.
(12) Blomquist, A. T.; Moriconi, E. J. J. Org. Chem. 1961, 26, 3761.
3522 J. Org. Chem. Vol. 73, No. 9, 2008