Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones

Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones

Accepted Manuscript Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones Vinod K. Yadav, Vi...

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Accepted Manuscript Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones Vinod K. Yadav, Vishnu P. Srivastava, Lal Dhar S. Yadav PII: DOI: Reference:

S0040-4039(16)30368-9 http://dx.doi.org/10.1016/j.tetlet.2016.04.018 TETL 47518

To appear in:

Tetrahedron Letters

Received Date: Accepted Date:

22 March 2016 7 April 2016

Please cite this article as: Yadav, V.K., Srivastava, V.P., Yadav, L.D.S., Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones, Tetrahedron Letters (2016), doi: http:// dx.doi.org/10.1016/j.tetlet.2016.04.018

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Graphical Abstract

Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones Vinod K. Yadav, Vishnu P. Srivastava, Lal Dhar S. Yadav* AcO R1

NaO

O S

O S 2 R2 CH3CN/H2O R1 R O (4:1) 12 examples 70 oC, 10-12 h 79-93% yields I2

O

1

Tetrahedron Letters

Molecular iodine mediated oxidative coupling of enol acetates with sodium sulfinates leading to β-keto sulfones Vinod K. Yadav, Vishnu P. Srivastava, Lal Dhar S. Yadav* Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India  Corresponding author. Tel.: +91 532 2500652; fax: +91 532 2460533; E-mail address: [email protected] (L.D.S. Yadav)

A RT I C L E I N F O

A BS T RA C T

Article history: Received Received in revised form Accepted Available online

An efficient, transition metal-free protocol for direct oxidative sulfonylation of enol acetates with readily available sodium sulfinates has been developed using molecular iodine as an oxidant. The reaction follows a free radical pathway and offers a more practical, economical, safer and environmentally benign approach to a variety of β-keto sulfones in a one-pot procedure.

Keywords: Enol acetates Radical addition Sulfonylation Molecular iodine β-Keto sulfones Sodium sulfinates

Now a days, organic reactions promoted by molecular iodine have attracted much interest because it is mild, inexpensive, cheap, easily available in solid form and easy to handle compared to molecular bromine and chlorine. Chemists have been credited to develop green and sustainable methods using eco-friendly iodine or iodide catalysts/reagents in the current synthetic chemistry.1 Iodide or hypervalent iodine promoted organic reactions have received considerable attention and experienced impressive advancement during the past few years.2 Recently, few reactions have been reported using the molecular iodine for the formation of carbon-sulfur,3,4 nitrogen-sulfur5 and oxygensulfur6 bonds. Yuan and co-workers have efficiently utilized molecular iodine for decarboxylative cross-coupling reactions of sodium sulfinates with cinnamic acids.7 β-Keto sulfones constitute an important class of organic compounds, which have strongly attracted chemists owing to their interesting biological properties8 and diverse synthetic applications including the synthesis of natural products9 and various organic compounds.9 Recently, Timoshenko and coworkers have elegantly reviewed the methods of synthesis, chemical properties and application of β-ketosulfones.8 The general methods for the preparation of β-keto sulfones include the alkylation of metallic arens sulfinates with α-halo or αtosyloxy ketones,11 the acylation of alkyl sulfones with carboxylic acid derivatives such as chlorides, esters or Nacylbenzotriazoles,12 and the oxidation of β-hydroxy sulfones or β-keto sulfides.13 The recent approaches for the synthesis of βketo sulfones involve the addition of sulfonyl radicals to carboncarbon multiple bonds.14 However, most of the above methods suffer from one or more limitations such as the requirement of pre-functionalized substrates, expensive and toxic metals, relatively complicated or harsh reaction conditions, and formation of undesired by-products. Thus, the development of a

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mild, convenient and environmentally benign method to access β-ketosulfones would be an interesting target of research. α-Funtionalization of ketones is one of the most important and synthetically useful reactions,15 which has been recently achieved under metal-free conditions by employing easily synthesized enol acetates of ketones as nucleophiles.16 Only few reports are available on α-funtionalization of ketones via enol acetates, viz. α-arylation using aryl diazonium salts,15a α-trifluromethylation of using CF3SO2Cl,15b or CF3SO2Na,15c and αalkyl/arylsulfonylation using RSO2Cl15b or RSO2NHNH215d,17 as a radical source. However, alkyl/arylsulfonyl chlorides are not easy to handle due to their air and moisture sensitivity, and they generate corrosive by-products, whereas RSO2NHNH2 is generally prepared from RSO2Cl and requires an additional step. On other hand, sodium sulfinates are advantageous because they are readily available, easy to handle and are not sensitive to air and moisture. To the best of our knowledge, only three methods are available for the synthesis of β-keto sulfones through enol acetates. One of these methods uses sulfonyl chloride (Scheme 1a)15b and the other two methods use sulfonylhydrazide (Scheme 1b).15d,17 Keeping the above point of view and in continuation of our work on functionalization of alkenes18 and alkynes,13c,19 we report herein a new metal-free and environmentally benign friendly approach for the synthesis of β-keto sulfones as depicted in (Scheme 1c). At the beginning of our strategy, a model reaction was performed using aryl enol acetate 1a as a substrate, sodium sulfinate 2a as a sulfonaylating agent and I2 as an oxidant (Table 1). Most gratifyingly, the desired product 3a was obtained in an excellent yield in the presence of this metal-free oxidant (Table 1, entry 4). Initially, the desired product 3a was obtained in 26%

2

Tetrahedron from 1 mmol to 1.5 mmol, there was no effect on the yield of the product 3a (Table 1, entry 4 vs 11).

Previous work ref. 15b O

R2SO2Cl

(a)

AcO

O S

R1

R1

(b)

O

R2

ref. 15d,17 R2SO2NHNH2

Present work AcO (c)

NaO

Ar

O S

O

I2 Metal-free Ar'

O S

CH3CN/H2O Ar (4:1)

O

Ar'

Scheme 1. Synthesis of β-keto sulfones from enol acetates.

Next, we screened several solvents, viz. CH3CN, C2H5OH, THF, DMF, DCM, H2O and CH3CN/H2O (4:1) and CH3CN/H2O (4:1) was found to be the best solvent (Table 1, entry 4 vs 12-17). When 2 equiv. of TEMPO (2,2,6,6-tetramethyl-1piperidinyloxy), a well known radical-trapping reagent, was added to the reaction mixture, no β-keto sulfone 3a was formed, indicating that the reaction presumably involves a radical intermediate (Table 1, entry 18). Consequently, the synthesis of 3a was conducted under the optimized reaction conditions with 1a (1 mmol), 2a (1.2 mmol), I2 (1 mmol) in CH3CN/H2O (4:1) at 70 oC for 10 h to afford 90% yield of the product 3a (Table 1, entry 4).

Entry

Solvent

Temp. ( oC)

Time (h)

Yield (%)b

1

CH3CN+H2O (4:1)

rt

10

26

2

CH3CN+H2O (4:1)

45

10

53

3

CH3CN+H2O (4:1)

60

10

69

With the optimized reaction conditions in hand, we surveyed the functional group compatibility and scope of the present I2 mediated synthesis of β-keto sulfones 3 using a variety of aryl enol acetates 1 and sodium sulfinates 2 and the results are summarized in Table 2. Arylenol acetates 1 as well as sodium sulfinates 2 bearing different electron-donating and electronwithdrawing substituents reacted to give good to excellent yields of the desired products 3. However, arylenol acetates 1 or sodium sulfinates 2 with an electron-donating group afforded slightly higher yields (Table 2, entries 3d, 3e, 3f, 3g and 3h) as compared to those bearing an electron-withdrawing group (Table 2, entries 3b, 3c, 3i, 3j and 3l).This is probably because an electron-rich aromatic ring stabilizes benzylic radical 5 formed upon addition of the sulfonyl radical and the ensuing radical intermediate 6 (Scheme 2). Similarly, the sulfonyl radical 5 bearing an electronrich aromatic ring might be stabilized by resonance.

4

CH3CN+H2O (4:1)

70

10

90

Table 2

5

CH3CN+H2O (4:1)

80

10

90

6

CH3CN+H2O (2:1)

70

10

71

Substrate scope for the conversion of enol acetates into β-keto sulfonesa

7

CH3CN+H2O (5:1)

70

10

78

8

CH3CN+H2O (4:1)

70

13

90

9

CH3CN+H2O (4:1)

70

10

n.d.c

10

CH3CN+H2O (4:1)

70

10

72

11

CH3CN+H2O (4:1)

70

10

90

12

CH3CN

70

10

67

13

C2H5OH

70

10

59

14

THF

70

10

56

15

DMF

70

10

63

16

DCM

70

10

53

17

H2 O

70

10

61

18

CH3CN+H2O (4:1)

70

12

n.d.d

Table1 Optimization of reaction conditionsa AcO NaO

Ph

O S

O Ph

I2, solvent o

Ph

70 C, time (h)

1a

2a

O S O 3a

Ph

AcO NaO

R1 1

yield, when reaction was conducted at rt for 10 h (Table 1, entry 1). Moreover, when the reaction was performed at 45 oC, the yield was slightly increased (Table 1, entry 2). Thus, we tried the reaction at relatively higher temperatures and found that the optimum yield (90%) was obtained 70 oC (Table 1, entry 3-5). It was noted that the product 3a was not formed in the absence of an I2 (Table 1, entry 9). A decrease in the loading of I2 from 1 mmol to 0.5 mmol resulted in a lower yield of the product (Table 1, entry 4 vs 10), whereas and on increasing the amount of I2

F

O

O

O S

O

O

O

3b 12 h, ( 82%) O

O

F

Cl 3c 11.5 h, (86%) O

O

O

S

S

S

O

O

O

3d 10 h, (91%) O

MeO

S 2 R CH3CN/H2O R1 O (4:1) b 3a-l 70 oC, 10-12 h (79-93%)c S

3a 10 h, (90%)) O

O

S

Me

3e 10 h, (92%) O

O

a

Reaction conditions: enol acetate 1a (1 mmol), sodium sulfinate 2a (1.2 mmol), I2 (1 mmol) and solvent (3 mL) at rt to 80 oC for 10-13 h. b Isolated yield of 3a; n.d .= not detected. c In the absence of I2. d The reaction was quenched with TEMPO (2.5 equiv).

R2

O

O

O

I2

2

O

Me

O S

Me

O

3f 10 h, ( 93%) O

O

S

S

S

O

O

O

3g 10 h, (92%)

3h 10 h, (91%)

O

O

O

Me

3i 11.5 h, (87%) O

O S

S

O

O

O

Br

3k 11 h, (88%)

Cl

O

S

3j 12 h, (79%)

OMe

Br

Me 3l 12 h, (84%)

a

For experimental procedure, see ref. 21. All compounds are known and were characterized by comparison of their spectral data with those reported in the literature.13b,14g,18g,d,20 c Yields of isolated pure compounds 3. b

A verity of functional groups, such as methyl, methoxyl, fluoro, chloro and bromo were well tolerated in the present

3 protocol. In the case of aliphatic enol acetates and sodium sulfinates the reaction did not work to produce the expected βketo sulfones. This is possibly because in the case of aliphatic enol acetates far less stable alkyl free radicals are formed after the attack of the sulfony radical on the aliphatic enol acetates as compared to the benzyl free radicals formed in the case of aromatic enol acetates. As demonstrated by the exclusive formation of products 3a-l (Table 2), the present sulfonylation reaction is highly regioselective.

2.

On the basis of the above observations and the literature reports,4,7,15 a plausible mechanism for the formation of β-keto sulfones 3 is depicted in Scheme 2. Initially, molecular iodine reacts with sodium sulfinate 2 to give sulfonyl iodide 4, which undergoes homolysis to generate sulfonyl radical 5 and iodine radical. The addition of 5 to arylenol acetate 1 forms radical intermediate 6. The iodine radical combines with 6 to give intermediate 7, which undergoes hydrolysis to afford the desired β-keto sulfones 3 through the intermediate 7. 3.

O S R ONa 2 2

I2, 1,

O I2

R2 S NaI

O I

4 O

R AcO

CH3CN/H2O (4:1)

R1 3

H 2O OAc O O I S 2 S 2 R1 R R O 7 O AcOH + HI

S 5 O

I

R1 1

70 oC, 10-12 h O

2

4.

OAc O

I

S

R1 6

O

5.

R2

Scheme 2. A plausible mechanism for the formation of β-keto sulfones.

6. 7. 8. 9.

In summary, we have developed a novel protocol for direct one-pot synthesis of β-keto sulfones using readily available, stable and diversified arylenol acetates as substrates, sodium sulfinates as sulfonaylating agents and iodine as an oxidizing reagent. The present base-free and transition metal-free efficient protocol offers a superior alternative and eco-compatible approach to β-keto sulfones.

Acknowledgments We sincerely thank SAIF, Punjab University, Chandigarh, for providing microanalyses and spectra. V.K.Y. is grateful to the CSIR, New Delhi, for the award of a Junior Research Fellowship (Ref. No: 22/06/2014 (i) EU-V). V.P.S. is grateful to the Department of Science and Technology (DST) Govt. of India, for the award of a DST-Inspire Faculty position (Ref. IFA-11CH-08) and financial support.

10. 11.

12. 13.

14.

References and notes 1.

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Tetrahedron 17. Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. S. Synlett 2016, 27, 427. 18. (a) Yadav, A. K.; Yadav, L. D. S. Green. Chem. 2015, 17, 3515; (b) Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. S. Tetrahedron Lett. 2015, 56, 2892; (c) Singh, A. K.; Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2015, 56, 653; (d) Singh, A. K.; Chawla, R.; Keshari, T.; Yadav; V. K.; Yadav, L. D. S. Org. Biomol. Chem. 2014, 12, 8550; (e) Keshari, T.; Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. S. Green. Chem. 2014, 16, 3986; (f) Singh, A. K.; Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2014, 55, 4742; (g) Chawla, R.; Singh, A. K.; Yadav, L. D. S. Eur. J. Org. Chem. 2014, 2032. 19. Singh, A. K.; Chawla, R.; Yadav, L. D. S. Synlett 2013, 24, 1558. 20. Kamigata, N.; Udodaira, K.; Shimizu, T. J. Chem. Soc. Perkin Trans. 1, 1997, 783. 21. General procedure for the synthesis of β-keto sulfones 3: A mixture of enol acetate 1 (1 mmol), sodium sulfinate 2 (1.2 mmol), I2 (1 mmol) and CH3CN + H2O (4:1, 3 mL) was taken in a flask and stirred at 70 oC for 10 - 12 h (Table 2). After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with ethyl acetate (3 × 5 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The resulting crude product was purified by column chromatography using a mixture of hexane/ethyl acetate (4:1) as eluent to afford an analytically pure sample of product 3. All the compounds are known and were characterized by comparison of their spectral data with those reported in the literature.12b,13g,18g,d,20 Characterization data of representative compounds 3 are given below: Compound 3a: 13b,18g Solid; 90% yield; 1H NMR (400 MHz, CDCl3) δ 7.98-7.90 (m, 4H), 7.66-7.58 (m, 2H), 7.53 (t, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 4.76 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 187.97, 138.85, 135.81, 134.36, 134.26, 129.29, 129.24, 128.85, 128.61, 63.50. EIMS (m/z): 260 (M+). Anal. Calcd for C14H12O3S: C, 64.60; H, 4.65; S, 12.32. Found: C, 64.79; H, 4.94; S, 12.08. Compound 3e:18d,20 Solid; 92% yield, 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.297.25 (m, 2H), 7.24-7.20 (m, 2H), 4.71 (s, 2H), 2.46 (s, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 187.66, 145.39, 145.16, 136.11, 133.47, 129.69, 129.39, 129.36, 128.51, 63.55, 21.60, 21.49. EIMS (m/z): 288 (M+); Anal. Calcd for C16H16O3S: C, 66.64; H, 5.59; S, 11.12; Found: C, 66.83; H, 5.32; S, 11.40. Compound 3k:14g,18g Solid; 88% yield; 1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 6.8, 1.9 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 4.66 (s, 2H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 187.29, 145.59, 135.65, 134.53, 132.23, 130.83, 129.97, 129.90, 128.57, 63.79, 21.75. EIMS (m/z): 351, 353 (M+, M+ + 2). Anal. Calcd for C15H13BrO3S: C, 51.00; H, 3.71; S, 9.08. Found: C, 51.16; H, 3.43; S, 9.32.

Highlights

• Base- and transition metal-free eco-compatible efficient synthetic approach. • Molecular iodine mediated radical cross coupling. • One-pot synthesis of β-keto sulfones from enol acetates and sodium sulfinates. • Sodium sulfinates as operationally simple sulfonating agents.