Bu4NI-Catalyzed Cross-Coupling between Sulfonyl Hydrazides and Diazo Compounds to Construct β-Carbonyl Sulfones Using Molecular Oxygen

Article abstract of DOI:10.1021/acs.orglett.6b02532

A new cross-coupling reaction between sulfonyl hydrazides and diazo compounds has been established, leading to a variety of β-carbonyl sulfones in good yields. This methodology was distinguished by simple manipulation, easily available starting materials, and wide substrate scope. A plausible mechanism involving a radical process was proposed based upon the experimental observations and literature.

Full text of DOI:10.1021/acs.orglett.6b02532

Letter
pubs.acs.org/OrgLett
Bu4NI-Catalyzed Cross-Coupling between Sulfonyl Hydrazides and
Diazo Compounds To Construct β‑Carbonyl Sulfones Using
Molecular Oxygen
Yaxiong Wang,† Liang Ma,† Meihua Ma,† Hao Zheng,‡ Ying Shao,*,†,‡ and Xiaobing Wan*,†
†Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science,
Soochow University, Suzhou 215123, China
‡Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Advanced Catalysis and Green Manufacturing
Collaborative Innovation Center, Changzhou University, Changzhou 213164, China
S
* Supporting Information
ABSTRACT: A new cross-coupling reaction between sulfonyl hydrazides and diazo compounds has been established, leading to
a variety of β-carbonyl sulfones in good yields. This methodology was distinguished by simple manipulation, easily available
starting materials, and wide substrate scope. A plausible mechanism involving a radical process was proposed based upon the
experimental observations and literature.
transformation (Scheme 1b).4 In 2015, we reported a tandem
iazo compounds are highly useful and versatile substrates
Dthat have been widely applied to various reactions in the reaction for the synthesis of β-ester-γ-amino ketones from diazo
past few decades.1 Generally, there are four patterns in the
compounds, olefins, and tertiary amines via a cross-coupling of a
cobalt-based carbene radical and α-aminoalkyl radical (Scheme
1c).5 Recently, Jiang and co-workers reported a three-
component reaction between N-hydroxyphthalimide, diazo
compounds, and N,N-dimethylanilines to construct α-amino-
oxy-β-amino ketones catalyzed by PhI(OAc)2, which involved
the addition of α-aminoalkyl radicals to diazo compounds in this
transformation.6 The sulfonyl radical, an excellent segment to
introduce sulfonyl groups, has huge synthetic potential in
chemical and biomedical fields.7 In general, a simple and efficient
synthetic strategy that merges both diazo compounds and
radicals into a one-pot reaction under metal-free conditions is
still sparse and highly desirable. Recently, sulfonylation reactions
via sulfonyl radicals generated in situ from sulfonyl hydrazides
were developed by several groups using external oxidants.8
Herein, we describe the successful execution of this cross-over
reaction between sulfonyl radicals and diazo compounds, which
resulted in the efficient formation of β-carbonyl sulfones without
employing any metal catalysts (Scheme 1d).
process of the dinitrogen elimination of diazo compounds,
leading to different reactive intermediates involved in organic
transformation.2,3b In most cases, diazo compounds are used as
metal carbene precursors, which have been proven to be highly
efficient intermediates in numerous reactions, such as cyclo-
propanation of alkenes, X−H insertion reactions (X = C, N, O, S,
Si, etc.), and ylide reactions (Scheme 1a).3 In addition, it could
also be attacked by some electrophilic reagents, including
aldehyde, imine, etc., to form zwitterion intermediates for further
Scheme 1. Various Reactivity of Diazo Compounds
Tosyl hydrazide 1a and ethyl diazoacetate 2a were chosen as
the reactants to identify this coupling process for the synthesis of
ethyl 2-tosylacetate 3a. Initially, several metal catalysts and
oxidants were screened to identify the reaction conditions.
Unfortunately, all of these systems were inert and ineffective for
this transformation (see Table S1 of the Supporting
Information). Notably, a combination of tetrabutylammonium
Received: August 24, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02532
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Organic Letters
Letter
a
iodide (TBAI) and tert-butyl hydroperoxide (TBHP), a well-
established system for the in situ generation of sulfonyl radicals,9
also did not provide the desired product 3a (Table 1, entry 1).
Scheme 2. Scope of Sulfonyl Hydrazides
a
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
TBAI
oxidant
solvent
yield (%)
1
2
TBHP
air
CH3CN
CH3CN
PhH
<5
69
77
74
68
33
85
<5
69
82
52
80
<5
65
48
<5
<5
82
<5
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
3
air
4
air
DMSO
cyclohexane
H2O
5
air
6
air
7
air
air
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
8
9
I2
air
10
11
12
13
14
15
16
17
18
19
NaI
air
NH4I
air
NIS
air
PhI(OAc)2
TBAB
TBAC
18-crown-6
air
air
a
Reaction conditions: 1 (0.5 mmol, 1.0 equiv), 2a (1.0 mmol, 2.0
equiv), TBAI (0.1 mmol, 20 mol %), and i-PrOH (2 mL) for 24 h
under air. Isolated products.
air
air
c
SDS
air
TBAI
TBAI
O2
N2
The exact structure of representative product 3o has been
conclusively confirmed by the single-crystal X-ray diffraction.
To further explore the diversity of this transformation, a
representative selection of diazo compounds was subjected to
this process, and the results are presented in Scheme 3. A series of
a
Reaction conditions: 1a (0.5 mmol, 1.0 equiv), 2a (1.0 mmol, 2.0
equiv), catalyst (0.1 mmol, 20 mol %), oxidant (1.5 mmol, 3.0 equiv),
b
c
and solvent (2 mL) for 24 h under air. Isolated yields. SDS: sodium
dodecyl sulfate.
a
Scheme 3. Scope of Diazo Compounds
Gratifyingly, when air was used instead of TBHP as the oxidant,
the reaction proceeded smoothly and gave the desired ethyl 2-
tosylacetate 3a in moderate yield (Table 1, entry 2). Further
screenings of solvents (Table 1, entries 3−7) found that i-PrOH
was particularly effective for this transformation, resulting in the
formation of product 3a in a high 85% yield (Table 1, entry 7). It
is noteworthy that no product 3a could be obtained in the
absence of TBAI (Table 1, entry 8). Continuously, we examined
several iodine reagents and phase transfer catalysts and found
there were no obvious improvement in yields compared with
TBAI (Table 1, entries 9−17). In addition, the results replacing
air with O2 or N2 showed that molecular oxygen is essential as an
oxidant for this transformation (Table 1, entries 18 and 19).
With the optimized reaction conditions in hand, a series of
sulfonyl hydrazides were used to assess the scope of the reaction
(Scheme 2). Pleasingly, various ortho-, meta-, and para-
substituted arylsulfonyl hydrazides underwent smooth sulfony-
lations and provided the desired products in good to excellent
yields (3a−3m). Notably, both electron-withdrawing and
electron-donating groups hardly affected the reactivity of the
reaction. Furthermore, the steric effect was inconspicuous, both
4-Me-phenylsulfonyl hydrazide and 2-Me-phenylsulfonyl hydra-
zide could be converted into the corresponding β-carbonyl
sulfones in 85 and 84% yields (3a and 3m), respectively. To our
delight, the heteroaryl sulfonyl hydrazides, including quinolone
and thiophene, resulted in the formation of corresponding
products (3n and 3p) in satisfactory yields. In addition, both
benzylsulfonyl hydrazide and alkylsulfonyl hydrazides afforded
the corresponding products (3q−3s) in moderate to high yields.
a
Reaction conditions: 1a (0.5 mmol, 1.0 equiv), 2 (1.0 mmol, 2.0
equiv), TBAI (0.1 mmol, 20 mol %), and i-PrOH (2 mL) for 24 h
under air. Isolated products.
α-diazocarbonyl compounds 2 reacted with TsNHNH2 1a,
leading to the corresponding products in moderate to high yields
(4a−4l). It is noteworthy that the diazoacetamides were also
found to be reactive in this transformation, providing the desired
products (4i−4k) in high yields. Notably, reaction of 1a and 2-
diazo-1-phenylethan-1-one also afforded the desired product 1-
phenyl-2-tosylethan-1-one (4l), albeit in a low 35% yield.
B
DOI: 10.1021/acs.orglett.6b02532
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Letter
Several control experiments were designed to understand the
mechanism of this process. The addition of the radical inhibitor
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) prohibited the
reaction, which implies that a radical process was involved in this
transformation. At the same time, the sulfonyl radical
intermediate was captured by TEMPO, leading to the radical
adduct 5a (see Scheme S1 in the Supporting Information). Next,
we tried to react TsNHNH2 1a with 1,1-diphenylethylene
instead of ethyl diazoacetate in our conditions. As desired, the
product (2-tosylethene-1,1-diyl)dibenzene 6a was isolated in
29% yield, which indicated that a sulfonyl radical participated in
the reaction (Scheme 4a).7i,10 When ethyl diazoacetate was
Scheme 5. Proposed Reaction Mechanism
Scheme 4. Probe for the Possible Mechanism
detection of product 8a), another pathway could be put forward,
in which the diazo compound 2 decomposed to generate free
carbene B under thermal conditions. Its subsequent coupling
with sulfonyl radical A also afforded radical intermediate INT2.
Finally, INT2 underwent H-abstraction and delivered the
desired β-carbonyl sulfone 3.
In conclusion, we have successfully developed an efficient
approach for the construction of β-carbonyl sulfones from the
coupling between sulfonyl hydrazides and diazo compounds
catalyzed by TBAI. A radical mechanism has been proposed to
account for this reaction, which possibly undergoes two routes
and proceeds under metal-free conditions. This methodology
allows a wide substrate scope, utilizes readily available starting
materials, and provides operational simplicity. Efforts to develop
other metal-free cross-coupling reactions between radicals and
diazo compounds are in progress in our laboratory.
added to the reaction simultaneously, products 6a−8a could be
detected by LC−MS (Scheme 4b). Based upon the above results,
we suspected three radical species 6b−8b as key intermediates
were involved in this transformation (Figure 1). Notably, the use
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b02532.
■
S
Experimental procedures and full spectroscopic data for all
new compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: yingshao@cczu.edu.cn.
*E-mail: wanxb@suda.edu.cn.
Notes
The authors declare no competing financial interest.
Figure 1. Three radical intermediates.
ACKNOWLEDGMENTS
of ethyl diazoiodoacetate I-2a11 or ethyl 2-diazo-2-tosylacetate 9
as substrates failed to afford the desired product 3a (Scheme
4c,d), which suggested that both were not the reactive
intermediates in this process.
Based upon the above results and literature, a plausible
mechanism was proposed, as shown in Scheme 5. Initially, the
iodine anion was oxidized to iodine by air. Next, the iodine
radical could be generated from iodine upon heating.12 The
sulfonyl radical A was formed in situ from sulfonyl hydrazides 1
through the continuous exchange of an iodine radical.13
Subsequently, the addition of sulfonyl radicals A to diazo
compound 2 afforded radical intermediate INT1, which
underwent radical-triggered dediazotization with the release of
N2 to form radical intermediate INT2.6 According to the
previous work14 and our experiment observations (Figure 1,
■
This project is funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions (PAPD),
NSFC (21302015, 21272165), the Jiangsu Planned Projects for
Postdoctoral Research Fund (No. 1501094B), and the China
Postdoctoral Science Foundation.
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