Tetrahedron
ortho-Difunctionalization of arynes by LiZnEt2(TMP)-mediated
deprotonative zincation/elimination of aryl triflates
Seoyoung Cho, Qiu Wang*
Department of Chemistry, Duke University, Durham, NC 27708, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Generation of arynes from aryl triflates has been achieved using lithium diethyl(tetramethylpiperidyl)-
zincate base LiZnEt2(TMP), via a directed ortho-deprotonative zincation and subsequent elimination of
the triflate group. The aryne formation has been demonstrated by the cycloaddition reaction with diene
and insertion reactions with ureas. Furthermore, the nucleophilic addition of LiZnEt2(TMP) to arynes was
observed in the absence of external aryne partners, offering a new cascade strategy for diverse difunc-
tionalization of arynes.
Received 29 January 2018
Received in revised form
15 March 2018
Accepted 20 March 2018
Available online xxx
© 2018 Elsevier Ltd. All rights reserved.
Keywords:
Arynes
Deprotonative zincation
ortho-Difunctionalization
Insertion
Tandem reaction
1. Introduction
elimination of the leaving group. In 2002, Uchiyama reported the
use of lithium dimethyl(tetramethylpiperidyl)-zincate to promote
Aryne chemistry has received great attention in organic chem-
istry, mechanistic studies, and synthesis of versatile functionalized
arene derivatives, such as natural products and functional mate-
rials.1 Aryne is a highly reactive intermediate2 and its synthesis3,4
commonly starts from difunctionalized arene precursors,5
including commonly used 2-(trimethylsilyl)phenyl triflates
(Scheme 1, a).5a However, access to highly functionalized and
elaborate arynes remains limited due to the lengthy synthesis
required to introduce bis-functional groups onto their precursors.
Alternatively, ortho-CeH deprotonative metalation/elimination has
been reported for aryne formation from arenes bearing a leaving
group, such as halides,6 triflates,6d iodonium salts,7 and carboxylic
acids8 (Scheme 1, b). Thus, from the aspects of the availability of
precursors and general applicability, the preparation of arynes from
mono-functionalized arene precursors is attractive and advanta-
geous. Yet in most cases, a strong base (e.g., LiR) is required for the
deprotonative metalation step, which would limit the substrate
scope, and result in side reactions (e.g., thia-Fries rearrangement).9
When multiple functionalities or leaving groups are present, che-
moselectivity arises for both CeH deprotonation and the selective
the ortho-CeH zincation/elimination of aryl halides toward the
aryne formation.10 Encouragingly, the arylzincate intermediates
were found to be compatible with sensitive substituents such as
ester, amide, and cyano groups.
Recently, we have investigated the use of a related zincate base
LiZnEt2(TMP) 1 to achieve selective CeH zincation for an extensive
scope of functionalized arenes.11 During our studies, no aryne for-
mation was detected from fluoro-, bromo- or chloro-substituted
arenes when LiZnEt2(TMP) was used, in contrast to the aryne for-
mation from aryl halides reported in Uchiyama's studies where
LiZnMe2(TMP) was used.10 Furthermore, the analogous LiZ-
n(tBu)2(TMP) in Uchiyama's studies was effective for promoting the
CeH zincation similar to LiZnMe2(TMP) for aryl halides, but
without forming the aryne intermediates from the resulting aryl-
zincate intermediate. As both the nature of alkyl ligands in the
arylzincate intermediates and the leaving group strongly influence
the aryne formation, we became interested whether the zincate
base LiZnEt2(TMP) 1 may promote the formation of aryne in-
termediates via deprotonative zincation/elimination starting from
aryl triflates. Note the triflate group (OTf) is expected to be a better
leaving group than halides to facilitate the aryne formation, while
aryl triflates were much less explored than aryl halides due to
common side reactions of thia-Fries rearrangement. Herein, we
report our findings regarding LiZnEt2(TMP)-mediated aryne
* Corresponding author.
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Cho S, Wang Q, ortho-Difunctionalization of arynes by LiZnEt2(TMP)-mediated deprotonative zincation/