Organic Letters
Letter
In conclusion, we have presented an efficient strategy for
bifunctional-ligand-enabled gold-catalyzed intermolecular hy-
droarylation of alkynes under soft reaction conditions. The
WangPhos ligand, which was installed with a remote amide
group, is shown to be enabling in this transformation. This
chemistry exhibits gentle reaction conditions, furnishes excellent
yields, and tolerates a broad substrate scope.
Scheme 6. Mechanism Studies
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
employed naphthol as the nucleophile. Encouragingly, the
expected compoud 2a was indeed formed in a good yield of 92%
when L1AuCl was used as the catalyst and NaBARF was used as
the chloride abstractor (Table 1, entry 1). Subsequent catalyst
screenings revealed that our previously designed amine-
functionalized ligands L2−L5 were largely ineffective (entries
2−5). It should be mentioned that the use of common
PPh3AuCl, IPrAuCl, or JohnPhosAuCl in the presence of
exogeneous Et3N or its absence resulted in no reaction at all
(entries 6 and 7). Both the gold precatalyst and NaBARF were
required for the reaction (entries 8 and 9).10 Replacing NaBARF
by AgOTf (entry 10) or AgNTf2 (entry 11) generated lower
yields of the formation of 2a. Besides, DCE was also found to be
very significant for the optimal reaction conditions. With PhF or
PhCF3 as the reaction solvent, the yields of 2a would reduce to
only 77 and 82% (entries 12 and 13).
Then, the scope of this chemistry was examined. First, various
aliphatic terminal alkynes were explored. As summarized in
Scheme 3, when the terminal alkynes were installed by an alkyl
group including 1-decanyl (2b), phenethyl (2c), isobutyl (2d),
cyclohexyl (2e), or cyclopropyl (2f), the reactions all proceeded
smoothly. Functionalized alkyl groups including OTBS (2g,
2h), benzyloxy (2i), chloro (2j), and even C−C double bonds
(2k) are also readily tolerated, highlighting the exceptionally
mild nature of this chemistry. Several substituted phenyl-
acetylenes were also examined. Substituents such as CF3, OMe,
Me, Br, or F at the different positions on the benzene ring were
tolerated, and the corresponding 1,1-diarylethylenes 2l−2p
were generated in excellent yields. Besides, 2-naphthol function-
alized by a 7-OTBS group underwent reactions with different
terminal alkynes smoothly to afford the desired products 2q, 2r,
and 2s in 90, 92, and 88% yields, respectively. With these results
in hand, then the challenging internal alkynes were also tested.
Early results revealed that replacing the terminal alkynes with
internal alkynes including 6-dodecyne and diphenylacetylene
resulted in no reaction at this point, even at a higher reaction
temperature (90 °C).
Experimental procedures, characterization data for all new
products, and NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
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Ting Li − College of Chemistry and Pharmaceutical Engineering,
Nanyang Normal University, Nanyang, Henan 473061, P. R.
China; Department of Chemistry and Biochemistry, University of
California, Santa Barbara, Santa Barbara, California 93106,
Liming Zhang − Department of Chemistry and Biochemistry,
University of California, Santa Barbara, Santa Barbara,
Authors
Yuhan Yang − College of Chemistry and Pharmaceutical
Engineering, Nanyang Normal University, Nanyang, Henan
473061, P. R. China
Baomin Luo − College of Chemistry and Pharmaceutical
Engineering, Nanyang Normal University, Nanyang, Henan
473061, P. R. China
Bo Li − College of Chemistry and Pharmaceutical Engineering,
Nanyang Normal University, Nanyang, Henan 473061, P. R.
China
Luyi Zong − College of Chemistry and Pharmaceutical
Engineering, Nanyang Normal University, Nanyang, Henan
473061, P. R. China
Weiguang Kong − College of Chemistry and Pharmaceutical
Engineering, Nanyang Normal University, Nanyang, Henan
473061, P. R. China
Hao Yang − College of Chemistry and Pharmaceutical
Engineering, Nanyang Normal University, Nanyang, Henan
473061, P. R. China
Xinpeng Cheng − Department of Chemistry and Biochemistry,
University of California, Santa Barbara, Santa Barbara,
California 93106, United States
A gram-scale formation of 2a was also carried out under
standard conditions, and 1.2 g of the desired product was
furnished on a 10 mmol scale (Scheme 4). Moreover, when the
reaction was performed with the catalyst loading lowered to 0.1
mol %, 86% yield of the desired product could be generated,
albeit a longer reaction time was needed.
The synthetic utilities of this chemistry are also demonstrated
by one-step conversions of 2a to versatile naphtho[2,1-b]furan
derivatives, as outlined in Scheme 5.11 In addition, an additional
function handle (i.e., iodo) was readily installed into 2a in an
excellent yield upon routine iodination.12
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
It shoud be noted that the hydroarylation transformation did
not happen to provide the product at all when the naphthol
hydroxyl group was transformed to acetoxy or methoxy (Scheme
6). This result is consistent with the mechanism we proposed.
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T.L. thanks NSFC 21602120 and the Science and Technology
Department of Henan Province 202102310331 for financial
support.
C
Org. Lett. XXXX, XXX, XXX−XXX