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Metal-Free Amidation Reactions of Terminal Alkynes with Benzenesulfonamide SACHINTA MAHATO, Sougata Santra, Grigory V Zyryanov, and Adinath Majee J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03065 • Publication Date (Web): 26 Feb 2019 Downloaded from http://pubs.acs.org on February 26, 2019
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The Journal of Organic Chemistry
Metal-Free Amidation Reactions of Terminal Alkynes with Benzenesulfonamide Sachinta Mahato,a Sougata Santra,b Grigory V. Zyryanovbc and Adinath Majeea* a
Department of Chemistry; Visva-Bharati (A Central University), Santiniketan 731235, India. E-mail:
[email protected] b
Department of Organic and Biomolecular Chemistry, Chemical Engineering Institute, Ural Federal University, 19 Mira Street, 620002, Yekaterinburg, Russian Federation. c
I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy Street, 620219 Yekaterinburg, Russian Federation.
R
+ R1 SO2NH2
PIDA
CH3CN, rt R = aryl/heteroaryl 10 h R1 = aryl C-N bond formation
O R
Metal-free Aerobic conditions Wide Substrates Scope Room temperature
H O R1 N S
O 21 examples up to 87% yield
Abstract: A novel and efficient approach has been developed to synthesize α-sulfonylamino ketones through the reaction between terminal alkynes and sulfonamides under ambient air using PIDA (diacetoxy iodobenzene). A library of α-sulfonylamino ketone derivatives having a variety of substituents has been synthesized. A plausible reaction pathway has been predicted. This reaction offers a broad substrate scope, metal-free synthesis, excellent regioselectivity, easily accessible reactants, room temperature reaction conditions under ambient air, and is operationally simple. A gram-scale synthesis demonstrates the potential applications of the
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present method. In addition, we have also synthesized α-acetoxy ketones in case of absence of sulfonamide.
Introduction: α-Amino ketones serve a significant role in organic chemistry as they are found in a large variety of biologically active natural products. Commercial medicines such as mephedrone1 and bupropion2 (Figure 1) contain α-amino ketones as well as the proteasome inhibitor epoxomicin.3 In organic synthesis, this moiety is also very useful for the preparation of 2-amino alcohols4 and nitrogen-containing heterocycles (Figure 2).5 Figure 1: Commercial Medicines Containing α-Amino Ketones O
H N
O CH3
Cl
CH3
H 3C
H N CH3
Mephadrone
CH3 C CH3 CH3
Bupropion
Figure 2: Nitrogen-Containing Heterocycles Synthesized from α-Amino Ketones NC H 2N
R2 O
NC
N R H N 2 S O O R 1 ref 5(a)
R2 O R N R S O O R 1 ref 5(b)
O
Ph
N S O O R 1 ref 5(c)
Scheme 1: Different Strategies for the Synthesis of α-Sulfonylamino Ketones
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The Journal of Organic Chemistry
Previous Works Catalyst, DMSO, heat (ref 6)
R1
O
NBS/CAN, solvent, heat
R3 N
R1
(ref 7)
R
IBX/ -CD,H2O
R2
pyridine N-oxide solvent, heat, (ref 9)
R
N SO2R
2
1
R 3O 2S
N
R2
N
O
cat Rh(II) H2O (ref 11)
R1
R1 = aromatic, aliphatic R2 = Ts, Ms O (ref 12)
2
O
R CN
R2 H NSO2R2
base, solvent
R1
NHTs
R1
solvent (ref 10)
R2 N N
O
catalyst or PIDA, PhI=NTs
R1
R3
2
R1 = aromatic,aliphatic R2 = H, Me, Et R3 = COC6H5NO2, COOEt SO2Ph, Ts
(ref 8)
OTMS
H N
R1
H NSO2R3
R1= ayl, alkyl R2= Ts, Ms, SO2Ph
Our Work O PIDA (0.25 equiv) O S NH2 CH3CN, rt, 10 h R O
+ R1
R 1
2
R = aryl, heteroaryl
H O N S O 3
R1
R1 = H, Me, Cl
Owing to their importance, synthetic organic chemists have attempted various methodologies based on different modifications (Scheme 1). Some of the methodologies are the oxidative ring opening of aziridines by DMSO,6 NBS combined with CAN,7 IBX in the presence of β-cyclodextrin,8 or pyridine N-oxide.9 Another way to synthesize α-amino ketones is through
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umpolung process using silyl enol ethers, followed by nucleophilic addition of amines.10 Additionally, a rhodium-catalyzed denitrogenative hydration of N-sulfonyl-1,2,3-triazoles was reported by Murakami et al.11 Recently, Zhan et al.12 prepared sulfonylamino ketones via Cs2CO3 promoted N-N bond cleavage from hydrazones precursor. As oxidants, hypervalent iodine reagents have recently received much attention due to their low toxicity, mild reactivity, ready availability, high stability, and easy handling.13 They are useful oxidants in various coupling reactions.14 Our group is actively engaged in developing various methodologies15 in organic synthesis involving the chemistry of C-N bond forming/cleavage reactions.16 Herein, we report a fully different approach from the reported methods using
(diacetoxy)iodobenzene
(phenyliodine(III) diacetate, (PIDA)14b to synthesize α-amino ketones under ambient temperature. We have observed that the reaction of terminal alkynes with benzenesulfonamide affords α-amino ketones (α-sulfonylamino ketones) in good to excellent yields in presence of PIDA as oxidant (Scheme 1).
Results and Discussion: We
started
our
study
by
mixing
phenylacetylene
(1a,
0.5
mmol)
and
4-
methylbenzenesulfonamide (2a, 0.5 mmol) using PIDA (1 equiv) as oxidant, at room temperature in acetonitrile solvent. Gratifyingly, benzenesulfonamide (the α-sulfonylamino ketone, 3a) was obtained in 65% yield along with 12% of α-acetoxyacetophenone (4a) after 10 h (Table 1, entry 1). Encouraged by this result, we carried out the reaction in different conditions to optimize the reaction, and the results are summarized in Table 1. At first, we investigated the loading effect of the oxidant (PIDA) and sulfonamide (TsNH2, 2a) in different ratios. Using 0.5 equiv of PIDA and 1 equiv of TsNH2 (2a), the yields of 3a and 4a were 74% and
