Journal of the American Chemical Society
Article
difunctionalized arene (entry 7). In this case, a 4.3/1 ratio of
cross- vs homocoupling was observed. Essentially, this method
allows for 1,2-diarylation of aryl triflates.
ASSOCIATED CONTENT
* Supporting Information
Detailed experimental procedures and characterization data for
new compounds. This material is available free of charge via the
■
S
2.5. Heterocyclic Arynes. Benzyne and its derivatives have
been well-explored.18 In contrast, relatively few heterocyclic
arynes have been investigated. Pyridynes and indolynes have
been employed in the synthesis of complex natural products.19
Several attempts were made to investigate the formation and
reactivity of heterocyclic arynes. The reaction of benzothio-
phene with 2-bromopyridine in the presence of TMPLi
afforded 42% of coupling product (Scheme 3). The
AUTHOR INFORMATION
Corresponding Author
■
Present Address
‡Department of Chemical Engineering, HCMC University of
Technology, VNU-HCM, Ho Chi Minh City, Vietnam.
Scheme 3. Reactions of Heterocyclic Arynes
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank the Welch Foundation (Grant No. E-1571), the
National Institute of General Medical Science (Grant No.
R01GM077635), and the Camille and Henry Dreyfus
Foundation for supporting this research.
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regioselectivity of the reaction is consistent with the one
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3. SUMMARY
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We describe here a method for base-promoted arylation of
arenes and heterocycles by aryl halides and aryl triflates.
Despite the use of lithium amide bases, the reaction is highly
functional-group tolerant, with alkene, ether, dimethylamino,
trifluoromethyl, ester, cyano, halide, hydroxyl, and silyl
functionalities compatible with reaction conditions. Moreover,
NH-containing indole arylation at the 3-position by aryl
chlorides was achieved. Additionally, we describe a general
method for electrophilic trapping of ArLi intermediates that are
generated in the reaction of benzyne with deprotonated arenes
or heterocycles. The trapping provides rapid and easy access to
a wide range of highly functionalized polyaryls from readily
available starting materials. Furthermore, generation and use of
thiophyne is disclosed. The base-promoted arylation method-
ology complements conventional direct arylation processes,
possesses high functional group tolerance, and allows access to
structures that are not easily accessible via other direct arylation
methods.
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H
dx.doi.org/10.1021/ja504886x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX