Communications
doi.org/10.1002/ejoc.202100060
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Synthesis of Isatin-Hydrazones from 3-Diazo Oxindoles and
Sulfoxonium Ylides under Catalyst- and Additive-Free
Conditions
Yu Tian,[a] Zunting Zhang,[a] and Tao Wang*[a]
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A facile synthesis of isatin-hydrazones from 3-diazo oxindoles
and sulfoxonium ylides under catalyst- and additive-free
conditions is described.
A plausible reaction pathway is
proposed for the transformation, in which diazo compounds
play as electrophiles to react with nucleophilic sulfoxonium
ylides. The reaction mechanism is supported by the experimen-
tal evidence.
Sulfoxonium ylides have been investigated as carbene precur-
sors to undergo a large array of transformations.[1] Relying on
their easy accessibility, moisture-/air-stability, and low explosi-
bility, sulfoxonium ylides are considered as promising substi-
tutes of diazo compounds. For example, distinct achievements
have been gained in the transition-metal-catalyzed CÀ H and
XÀ H functionalizations by using sulfoxonium ylides, instead of
diazo compounds, as carbene precursors.[2] Generally, compared
to diazo compounds, sulfoxonium ylides are more nucleophilic
and show lower decomposition rates to form metal carbenes.
These differences offer chemists opportunities to design new
reactions that are generally difficult to achieve. For example,
the cross-olefination of carbene precursors is challenging due
to the competing homocouplings. In 2018, Maulide et al.
devised a strategy to overcome this problem.[3] Sulfoxonium
ylides and diazoesters were subjected to a ruthenium complex.
Owing to the intrinsic difference in the reactivity, a metal
carbene was generated faster from the diazoester, which was
then attacked by the more nucleophilic sulfoxonium ylide,
resulting in the generation of olefin products with high Z
selectivity. Both N2 and DMSO were eliminated in the reaction
(Scheme 1a). Interestingly, the substituents adjacent to the
carbanion of the diazo dramatically affected the reactivity of
the diazo compounds. In 2019, Fan[4] and Wang[5] individually
reported the Rh(III)-catalyzed cascade reactions of sulfoxonium
ylides with α-diazo-β-ketoesters, which afforded naphthalenone
derivatives bearing a β-ketosulfoxonium ylide unit. Only N2 was
eliminated in this reaction (Scheme 1b). Switching the diazo
compound to a 3-diazoindolin-2-imines, in 2019 Lu and Wang
Scheme 1. Reactions of sulfoxonium ylides with diazo compounds.
successfully realized the synthesis of spiro[cyclopropane-1,3’-
indolin]-2’-imines under copper catalysis. The reaction released
both N2 and DMSO as by-products (Scheme 1c).[6] Our group
also engages in the carbene transfer reactions. For example, we
have reported the gold-catalyzed dimerization of 3-diazo
oxindoles[7] and the gold-catalyzed cross-coupling of 3-diazoox-
indoles with diazoesters,[8] respectively. During our investigation
on the cross-olefination of 3-diazo oxindoles[9] with sulfoxonium
ylides, we surprisingly found that isatin-hydrazones were
formed. A literature screening showed that isatin-hydrazones
are important compounds possessing antimicrobial,[10]
antibacterial,[11] leucine-rich repeat kinase 2 (LRRK2) inhibiting[12]
and β-amyloid aggregation inhibiting activities.[13] Giving the
importance of isatin-hydrazones, herein we want to report their
synthesis from 3-diazo oxindoles and sulfoxonium ylides under
catalyst- and additive-free conditions (Scheme 1d).
In our first entry, we were aiming to realize the cross-
olefination of sulfoxonium ylide 1a with 3-diazo oxindole 2a in
the presence of XPhosAuCl/AgPF6. To our surprise, isatin-
hydrazone 3a rather than a cross-olefination product, 3-
alkylideneoxindole, was obtained (Table 1, entry 1). A control
experiment revealed that the gold catalyst was not essential for
this transformation. The yield of 3a even slightly increased
(entry 2). The product was generated from one 3-diazo oxindole
[a] Y. Tian, Prof. Dr. Z. Zhang, Prof. Dr. T. Wang
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of
Education, School of Chemistry and Chemical Engineering,
Shaanxi Normal University,
No.620 West Chang’an Avenue, Xi’an 710119, China
E-mail: chemtao@snnu.edu.cn
Supporting information for this article is available on the WWW under
Eur. J. Org. Chem. 2021, 1592–1595
1592
© 2021 Wiley-VCH GmbH