10.1002/adsc.201701581
Advanced Synthesis & Catalysis
addition of the nitrile group to the carbocationic solution of compound 1b (142 mg, 0.60 mmol) and
center of B2 affords C, which could then undergo C-C BF3·OEt2 (43 mg, 0.30 mmol) in CH3CN (2 mL) was
o
bond rotation and intramolecular cyclization to heated at 45 C under argon for 8 hours. Then water
produce oxazoline D.[19] Finally, aromatization of (2 mL) and saturated Na2CO3 solution (1 mL) was
o
oxazoline D to oxazole 2 would occur via the loss of added to quench the reaction at 0 C. The aqueous
HF. In addition, B1 can undergo a 1,2-fluoride layer was separated and extracted with CH2Cl2 (3x3
shift[20,21] and C=O bond formation to afford the 3-BF3 mL). The combined organic extracts were washed
complex. The C-F bond of 3 can be activated by the with brine, dried over MgSO4, filtered and
coordination of a fluorine atom to the boron center of concentrated to give the crude residue, which was
BF3. Subsequent nucleophilic substitution of the α- purified by flash chromatography on silical gel with
fluorine atom of 3 for H2O produces 4. Although in EtOAc/n-hexane (1:10) to afford compound 2b (114
our study the cascade reactions produce oxazole mg, 80% yield) as colorless oil and compound 4b (5
mg, 4% yield) as white solid (mp = 132.0–134.0 oC).
compounds with high regioselectivity, an analogous
substitution of compound 3 with nitrile group give
oxazole E, which in turn can undergo a cyclization
process to generate E cannot be ruled out as the cause
of the formation of 4,5-diphenyloxazole 5a-l.
Acknowledgement
We are grateful to the Ministry of Science and
Technology, Taiwan (MOST 105-2113-M-039-004)
for financial support.
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Scheme 3. Proposed reaction mechanism.
In conclusion, we have developed an unpresented
Lewis
acid-mediated
defluorinative
[3+2]
annulation/aromatization cascade in which the 1,3-
zwitterionic nature of the 2,2-difluoroethanol moiety
was unveiled in situ by an appropriate Lewis acid,
which allowed this moiety to function as a synthon
for the O-C=C unit in the [3+2] cycloaddition. This
transformation represented a rare case of sequential
C-N and C-O bond formation via C-F bond breaking.
We believe that this study is a valuable addition to the
field of C-F bond activation.
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Experimental Section
General procedure for the synthesis of oxazole
compounds
The general procedure is illustrated immediately
below with compound 2b as a specific example. A
5
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