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CHO
O2CCF3
aryl migration
H migration
Zn
R2
Ar
Ar
R1
O
Br
O
H
HO Br
R2
CF3CO2ZnEt
R2
Ar
Ar
R1
R1
H
R2
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13. General reaction procedure: A 25 mL round-bottom flask was charged with dry
methylene chloride (2 mL), and diethylzinc (0.3 ml, 0.3 mmol) was added via
syringe under an atmosphere of nitrogen at 0 °C. Then trifluoroacetic acid
8
R1
Scheme 4. A possible mechanism for the rearrangement reaction.
report.9 When 2-bromo-1-(4-methoxyphenyl)ethanol 6b was
submitted to the reaction, 60% yield of 7b was obtained under
similar conditions. The reaction process involves an initial rear-
rangement of bromohydrin to arylacetaldehyde, followed by self
aldol condensation to form
a
,b-unsaturated aldehyde.11
A possible mechanism for this pinacol-type rearrangement
mediated by CF3CO2ZnEt is shown in Scheme 4. CF3CO2ZnEt reacts
with bromohydrin to afford zinc complex 8, followed by the migra-
tion of aryl group to form the desired aldehyde and an elimination
of CF3CO2ZnBr. Hydrogen migration in intermediate 8 will give ke-
tone isomer.9,12 The aryl group containing electron-donating sub-
stitutions on the aromatic ring is beneficial to generate aldehyde.
On the other hand, the steric feature of groups R1 and R2 has effect
on the regioselectivity. Bulky R1 and R2 obstruct the aryl migration
and prefer the formation of ketone.
In summary, we have described a highly efficient and selective
rearrangement reaction of bromohydrins to aldehydes. The reac-
tion mediated by 0.6 equiv of CF3CO2ZnEt under mild conditions
gave the secondary and tertiary aldehydes in high yields (85–
99%) and with good to excellent regioselectivity. The electron-
donating substitutions on the aromatic ring are beneficial to gener-
ate aldehyde. The presented procedure leads to building of useful
aldehydes for organic chemicals.
(22.5 lL, 0.3 mmol) was added dropwise via syringe under nitrogen and the
resulting mixture was stirred for additional 30 min. Bromohydrin (0.5 mmol)
was added to the reaction mixture and then the ice bath was removed. The
solution was allowed to stir at room temperature until TLC indicated complete
consumption of the starting bromohydrin. The reaction mixture was
concentrated in vacuo, and purified by column chromatograph packed with
silica gel using petroleum ether/ethyl acetate (10:1) as eluent to afford the
pure product. Compound 5h: 1H NMR (400 MHz, CDCl3; d, ppm): 9.60 (s, 1H),
7.22 (s, 1H), 6.50 (s, 1H), 3.91 (s, 3H), 3.83 (s, 3H), 3.68 (t, J = 7.2 Hz, 1H), 2.06–
Acknowledgments
1.97 (m, 1H), 1.68–1.59 (m, 1H), 1.33–1.23 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H); 13
C
We are grateful to the National Natural Science Foundation of
China (21072152) and the Tianjin Natural Science Foundation
(09JCZDJC24400) for financial supports.
NMR (100 MHz, CDCl3; d, ppm): 201.3, 157.8, 156.0, 133.5, 119.2, 102.1, 96.7,
56.4, 55.8, 52.0, 30.5, 20.4, 14.0; IR (neat; cmÀ1): 2959, 1723, 1600, 1499, 1460,
1296, 1207, 1029, 819; HRMS (EI): calcd for C13H17BrO3 (M+H)+, 301.0434;
found, 301.0426. Compound 5p14 1H NMR (400 MHz, CDCl3; d, ppm): 9.44 (s,
:
1H), 7.46 (d, J = 2.3 Hz, 1H), 7.16 (dd, J = 8.6, 2.3 Hz, 1H), 6.9 (d, J = 8.6 Hz, 1H),
3.89 (s, 3H), 1.44 (s, 6H); 13C NMR (100 MHz, CDCl3; d, ppm): 201.6, 155.1,
134.7, 131.7, 127.0, 112.1, 112.0, 56.3, 49.6, 22.5; IR (neat; cmÀ1): 3428, 2970,
1727, 1600, 1262, 1055, 810.
Supplementary data
Supplementary data associated with this article can be found, in
14. Kromann, H.; Larsen, M.; Boesen, T.; Schonning, K.; Nielsen, S. F. Eur. J. Med.
Chem. 2004, 39, 993.
References and notes
1. (a) Smith, M. B.; March, J. Advanced Organic Chemistry, 5th ed.; Wiley-
Interscience: New York, 2001. and references cited therein; (b) Boukhris, S.;