Gold-catalyzed intermolecular oxidation of o-alkynylbiaryls: An easy and practical access to functionalized fluorenes

Article abstract of DOI:10.1039/c4cc05115g

A novel gold-catalyzed intermolecular oxidation of o-alkynylbiaryls has been developed. A variety of functionalized fluorenes are readily accessed by utilizing this non-diazo approach, thus providing a viable alternative to synthetically useful fluorenes. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc05115g

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Gold-catalyzed intermolecular oxidation of
o-alkynylbiaryls: an easy and practical access
to functionalized fluorenes†
Cite this: Chem. Commun., 2014,
50, 10726
Received 3rd July 2014,
Accepted 23rd July 2014
Fei Pan, Shuang Liu, Chao Shu, Rong-Kun Lin, Yong-Fei Yu, Jin-Mei Zhou and
Long-Wu Ye*
DOI: 10.1039/c4cc05115g
www.rsc.org/chemcomm
A novel gold-catalyzed intermolecular oxidation of o-alkynylbiaryls of N-arylynamides.7d Despite these significant achievements,
has been developed. A variety of functionalized fluorenes are readily these oxidative cyclizations, presumably involving the intra-
accessed by utilizing this non-diazo approach, thus providing a molecular trapping of the a-oxo gold carbenoids by the aryl
viable alternative to synthetically useful fluorenes.
ring, are limited to terminal alkynes or electron-deficient internal
alkynes, as electron-rich internal alkynes often suffer the competing
Among the polycyclic aromatic hydrocarbons (PAH), fluorenes overoxidation of the carbene center by the very oxidant.9,7d Recently,
are core structures employed in a variety of practical applications Chang and co-workers described a general route for the synthesis
in materials chemistry as dyes and optical brightening agents.1 of fluorenes that involves a rhodium- or copper-catalyzed intra-
In addition, fluorenyl functions have also played important roles molecular aromatic carbenoid insertion of biaryldiazoacetates
in the field of organic synthesis, mainly as unique protecting (Scheme 1a).10 Inspired by these studies and our recent findings
groups in peptide synthesis.2 Somewhat surprisingly, however, on the gold-catalyzed synthesis of polycyclic aromatic hydro-
only a few preparative methods have been reported.3 Therefore, carbons,11 we envisioned that these synthetically useful fluorene
the development of novel strategies, especially those based on skeletons might be accessed directly from o-alkynylbiaryls through a
assembling structures directly from readily available and easily gold-catalyzed intermolecular alkyne oxidation (Scheme 1b). In this
diversified building blocks, is highly desirable.
communication, we describe herein the realization of such a gold-
In recent years, significant progress has been made in the catalyzed oxidative protocol, providing a flexible and alternative way
gold-catalyzed intermolecular alkyne oxidation to make alkynes for the preparation of versatile fluorene derivatives.
as equivalents of a-diazo ketones.4–6 For example, this non-diazo
Ynamide 1a was chosen as a model substrate for our initial
approach offers a viable alternative for the transition metal- study and some of the results are outlined in Table 1.12 The
catalyzed intramolecular aromatic carbenoid insertion of diazo screening of different gold catalysts was first performed (Table 1,
compounds.7,8 In this regard, L. Zhang and co-workers reported entries 1–8). In most cases, diketone compound 3a was detected
an elegant protocol for the synthesis of variously substituted as a major product (Table 1, entries 1–6). To our delight, the use of
chroman-3-ones involving a gold-catalyzed intermolecular oxida- the bulky gold catalysts could dramatically suppress the undesired
tion of propargyl aryl ethers.7a Later, J. Zhang and co-workers
realized a gold-catalyzed oxidation/C–H functionalization reaction
of electron-deficient N-arylpropiolamides for the construction of
3-acyloxindoles.7b The group of Gagosz disclosed a gold-catalyzed
oxidative cyclization of propynyl arenes, allowing rapid and practical
access to a variety of functionalized indan-2-ones.7c Recently,
Li and co-workers reported that the preparation of oxindoles
could be achieved via a gold-catalyzed intermolecular oxidation
State Key Laboratory for Physical Chemistry of Solid Surfaces, The Key Laboratory
for Chemical Biology of Fujian Province and Department of Chemistry, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian,
P R China. E-mail: longwuye@xmu.edu.cn; Fax: +86 592-218-5833
† Electronic supplementary information (ESI) available. CCDC 1015243. For ESI
Scheme 1 Formation of functionalized fluorenes through gold-catalyzed
intermolecular alkyne oxidation.
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4cc05115g
10726 | Chem. Commun., 2014, 50, 10726--10729
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Table 1 Optimization of reaction conditionsa
Table 2 Reaction scope studya
Entry Substrate
1
Product
2
Yield (%)
77
Yieldb (%)
Entry
L
Oxidant (R)
2a
3a
1
2
3
4
5
6
7
8
9
Et3P
Ipr
PPh3
P(4-CF3C6H4)3
Cy-JohnPhos
Xphos
4a (Et)
4a (Et)
4a (Et)
4a (Et)
4a (Et)
4a (Et)
4a (Et)
4a (Et)
4b (Me)
o5
21
495
65
1
1a
2a
o5
o5
o5
18
78
62
495
495
495
75
o2
o2
25
BrettPhos
t
Me4 BuXPhos
BrettPhos
50
2
3
4
5
1b
1c
1d
1e
2b
2c
2d
2e
75
56
67
58
10
11
12
BrettPhos
BrettPhos
BrettPhos
BrettPhos
BrettPhos
BrettPhos
BrettPhos
4c (iPr)
60
o5c
o5d
30
47
62
o2
5a (R0 = 2-Br)
5b (R0 = 2,6-Br2)
5c (R0 = 3,5-Cl2)
4a (Et)
4a (Et)
—
12
10
14
o2
o2
0
13
14e
15 f
16g
0
a
Reaction conditions: [1a] = 0.05 M, oxidant (2.0 equiv.); DCE: 1,2-
b
1
dichloroethane. Estimated by H NMR using diethyl phthalate as the
internal reference. 70% of 1a remained unreacted. 75% of 1a
remained unreacted. Reaction was run in H2O. Reaction was run
in H2O–DCE
c
d
e
f
g
=
1 : 1. The corresponding phenanthrene 3a0 was
obtained in 85% yield (see ESI for details).
overoxidation (Table 1, entries 7 and 8) and the desired fluorene
2a was obtained in 78% yield when using BrettPhosAuNTf2 as the
gold catalyst (Table 1, entry 7). Here, the bulky ligand likely
prevents the overoxidation of the carbene center by the very
oxidant via intermolecular reactions as the carbene center is
sterically shielded.7a Attempts to improve the yield of this reaction
by the screening of other quinoline N-oxides and pyridine
N-oxides were unsuccessful (Table 1, entries 9–13). As water could
assist some gold-catalyzed oxidative reactions,6a water was used as
the solvent or mixture solvent to further improve this reaction but
resulted in a decrease of the yield (Table 1, entries 14 and 15).
Of note, without a gold catalyst, the reaction failed to give even
a trace of fluorene 2a, and PtCl2 and AgNTf2 could not catalyze
this reaction. Finally, it should be specially mentioned that the
corresponding phenanthrene 3a0 was obtained in 85% yield
without the addition of N-oxide (Table 1, entry 16), indicating
that the gold-catalyzed 6-endo-dig cycloisomerization can be
suppressed by the oxidant.13
6
7
1f
2f
64
86
1g
2g0
8b
1h
1i
2h
2i
72
88
With the optimized reaction conditions in hand (Table 1,
entry 7), we subsequently investigated the substrate scope of
this oxidative cyclization. Different functional groups such as
9
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substrate 1m, the reaction could lead to a respectable 71% yield
(Table 2, entry 13).
Table 2 (continued)
In summary, we have developed a gold-catalyzed intermolecular
oxidation of o-alkynylbiaryls, allowing the convenient synthesis of
functionalized fluorenes in generally moderate to good yields. In
comparing our method with literature protocols, this non-diazo
approach offers a convenient and viable alternative for the pre-
paration of synthetically useful fluorenes. Other notable features of
this method include widespread availability of the substrates, a
simple procedure, and mild reaction conditions and, in particular,
no need to exclude moisture or air (‘‘open flask’’). Further studies
on the mechanism and synthetic application of the current reaction
are ongoing in our group.
Entry Substrate
1
Product
2
Yield (%)
54
10
1j
2j
We are grateful for the financial support from the National
Natural Science Foundation of China (No. 21102119 and 21272191),
the Program for Changjiang Scholars and Innovative Research Team
in University (PCSIRT) and NFFTBS (No. J1310024).
11
12
1k
1l
2k
2l
o10c
o10c
Notes and references
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1m
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14
ynamide 1g only afforded spiro compound 2g0 through a gold-
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