Copper(I)-mediated synthesis of β-hydroxysulfones from styrenes and sulfonylhydrazides: an electrochemical mechanistic study

Abstract

Copper(I) halides were used as mediators in the synthesis of β-hydroxysulfones via the oxysulfonylation of styrenes using sulfonylhydrazides. The feature of the developed process lies in the combination of a copper(I) salt with oxygen—the stoichiometric oxidant. Copper(II) species are responsible for the oxidation of sulfonylhydrazides, they are generated in small amounts in the O₂/Cu(I)/Cu(II) redox system, which is formed during the reaction. The combination of these three components enables one to obtain in the case of α-methylstyrenes only β-hydroxysulfones and in the case of α-unsubstituted styrenes, β-hydroxysulfones as the main products and β-ketosulfones as the by-products. With good yields β-hydroxysulfones were prepared by reduction of the reaction mixture containing both products β-hydroxysulfones and β-ketosulfones with NaBH₄. An electrochemical study revealed that the Cu(I)/Cu(II) pair can serve as an effective mediator of β-hydroxysulfones formation via redox processes.

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Introduction

β-Hydroxysulfones are of great interest as structural units of antifungal¹ and antitumor² compounds, they are known as intermediates in the synthesis of lactones³ and unsymmetrical alkenes.⁴ Traditionally β-hydroxysulfones are obtained through the nucleophilic addition of sulfinates to epoxides,^5–8 reduction of β-ketosulfones^9,10 and hydroxylation of α,β-unsaturated sulfones.¹¹ Over the last few years, several oxidative strategies to prepare β-hydroxysulfones from olefins have been established. In these reports air and low thermally stable sulfinic acids^12–14 in combination with O₂ and PPh₃ (Scheme 1, eqn (1))¹⁵ or sulfonylhydrazides with O₂ and Fe(III) salts are required.

Scheme 1 Recent works for the oxysulfonylation of styrenes.

The latter method was applied for the synthesis of structures containing the β-hydroxysulfone moiety predominantly at a tertiary carbon atom, which cannot be further oxidized (Scheme 1, eqn (2)).¹⁶

For the sulfonylation of unsaturated compounds without additional insertion of oxygen into the molecule, a number of oxidants have been exploited: Cu(OAc)₂,^17,18 CAN,¹⁹ NBS,²⁰ K₂S₂O₈,²¹ peroxides,²² I₂/TBHP²³ and TBAI/TBHP^24,25 systems. It is well-known that oxygen is an ideal environmentally friendly oxidant, which offers fascinating industrial and academic prospects. In oxidative transformations, in most cases, it is used in combination with transition metals salts and complexes.^26–29

In this context, we have disclosed a process for the oxysulfonylation of styrenes utilizing sulfonylhydrazides in the presence of a O₂/Cu(I) system, leading to β-hydroxysulfones. During the reaction the O₂/Cu(I)/Cu(II) system is formed with a small amount of Cu(II) as confirmed by the near absence of the specific colour of Cu(II) species. As a result, β-hydroxysulfones 3 as main products and β-ketosulfones 4 as by-products are formed (Scheme 2).

Scheme 2 The oxysulfonylation of styrenes 1a–1j using sulfonylhydrazides 2a–2e (in the codification of 3 and 4 the first letter index refers to the styrene 1 moiety, the second letter index to the hydrazide 2 moiety).

Results and discussion

The synthesis of β-hydroxysulfones 3aa–3fe and β-ketosulfones 4aa–4ab from styrenes 1a–1j with the use of sulfonylhydrazides 2a–2e was conducted in CH₃CN, CH₃CN–H₂O, THF and THF–H₂O using a O₂/Cu(I)/Cu(II) redox system. This system was a result of the transformation of CuCl, CuBr and CuI under aerobic conditions (Scheme 2).

Our preliminary studies were focused on the reaction of styrene 1a with sulfonylhydrazide 2a, leading to the formation of 1-phenyl-2-tosylethanol 3aa and 1-phenyl-2-tosylethanone 4aa. We examined the influence of the Cu(I) salt counter-ion, oxygen source (air oxygen or 98% oxygen) and solvent type (Table 1) on the yield of 3aa.

Table 1 Screening of the reaction conditions^a

Entry	Time (h)	Ratio (mole Cu(I)/mole 1a)	Oxygen source	Solvent	Yield 3aa^b (%)	Yield 4aa^b (%)	Total yield 3aa and 4aa^b (%)
a General procedure: to a solution of styrene 1a (300 mg, 2.88 mmol) in 25 mL of (CH3CN–H2O (5 : 1), CH3CN, THF, THF–H2O (5 : 1)), the Cu(I) salt (0.58–14.4 mmol, molar ratio 0.2–5 mol of salt/mol 1a) and sulfonylhydrazide 2a (537 mg, 2.88 mmol, molar ratio 1 mol 2a/mol 1a) were added. The mixture was stirred for 7 h at 40 °C. b The yield was determined by ^1H NMR using 1,4-dinitrobenzene as an internal standard, the isolated yield after reduction with NaBH4 is reported in the parentheses. c 7 h at 40 °C, then 12 h at 20–25 °C. d 7 h at 80 °C, then 12 h at 20–25 °C.
1	7	CuBr (2)	Air	CH3CN–H2O	28	14	42
2	7	CuCl (2)	Air	CH3CN–H2O	25	15	40
3	7	CuI (2)	Air	CH3CN–H2O	17	10	27
4^c	7 + 12	CuBr (2)	Air	CH3CN–H2O	38 (61)	27	65
5^d	7 + 12	CuBr (2)	Air	CH3CN–H2O	30	16	46
6	7 + 12	CuBr (0.2)	Air	CH3CN–H2O	10	5	15
7	7 + 12	CuBr (5)	Air	CH3CN–H2O	36	17	53
8	7 + 12	CuBr (2)	Air	CH3CN	20	12	32
9	7 + 12	CuBr (2)	Air	THF	28	13	41
10	7 + 12	CuBr (2)	Air	THF–H2O	18	10	28
11	7 + 12	CuBr (2)	O2	CH3CN–H2O	55 (85)	36	91
12	7 + 12	CuBr (0.2)	O2	CH3CN–H2O	15	8	23
13	7	CuBr (2)	O2	CH3CN–H2O	43 (71)	35	78
14^d	7 + 12	CuBr (2)	O2	CH3CN–H2O	50 (77)	30	80

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Entries 1–3 indicated that among the copper(I) halides (CuBr, CuCl and CuI), the use of CuBr afforded the highest total yield of oxysulfonylation products and the yield of the desired product 3aa after 7 h. When the reaction was performed for a more prolonged time (entry 4) the yield of 3aa reached 38%. Heating the reaction mixture for the first 7 h to 80 °C (entry 5) didn't increase the yield of 3aa. Decreasing (entry 6) or increasing (entry 7) the molar ratio of CuBr per mol of 1a in comparison with the previous entries resulted in a reduced yield of the desired product. Employing CH₃CN, THF or THF–H₂O (5 : 1) in place of CH₃CN–H₂O (5 : 1) negatively influenced the reaction efficiency (entries 8–10). In entry 11, air oxygen was replaced with 98% oxygen and as a result the yield of 3aa was improved to 55%, the total yield of oxysulfonylation products in this case reached 91%. Attempts failed (entries 12–14) to increase the yield of desired product through modification of the molar ratio of CuBr per mol of 1a, temperature and reaction time when compared to the conditions of entry 11, in which the best result was obtained; the total yield of 3aa and 4aa in these experiments didn't exceed 80%.

With the optimized reaction conditions in hand (entry 11, Table 1), the scope of the copper-mediated oxysulfonylation reaction was investigated. A number of β-hydroxysulfones 3aa–3ab were formed in 32–65% yield with β-ketosulfones 4aa–4ab observed as the by-products of the reaction in 18–33% yield (Table 2).

Table 2 The structure and yield of β-hydroxysulfones 3 and β-ketosulfones 4^a

a The yield was determined by ^1H NMR using 1,4-dinitrobenzene as an internal standard; the isolated yield after reduction with NaBH4 is reported in the parentheses.

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In all the examples, hydroxysulfone was predominantly formed independently of the properties of the substituents on the benzene ring. In most cases, the molar ratio of β-hydroxysulfone 3/ketosulfone 4 was 2 : 1. It is well-known that ketones can be easily reduced into their corresponding alcohols.^30–32 That's why in order to transform the β-ketosulfones 4 by-products into the desired β-hydroxysulfones 3 we filtered the reaction mixture from the CuBr after the reaction was complete and then carried out the reduction of the ketosulfones using NaBH₄ (Scheme 3). As a result, the desired β-hydroxysulfones 3 were obtained in a 52–89% overall yield over two steps (Table 2 and entries 4, 11, 13, 14 in Table 1).

Scheme 3 The reduction of β-ketosulfones using NaBH₄.

The oxysulfonylation reaction was also examined by applying of α-methylstyrenes (Table 3). A variety of α-methylstyrenes bearing either electron withdrawing or electron donating substituents on the aryl ring worked well under the conditions of entry 11 (Table 1) and the target β-hydroxysulfones were formed in most cases in good yield. It is important to note that in the reactions of methylsulfonylhydrazide with styrene 1a and octene-1 or cyclohexene with sulfonylhydrazide 2a the oxysulfonylation products were not observed in measurable yield.

Table 3 The structure and yield of β-hydroxysulfones 3^a

a Isolated yield.

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The structures of all the synthesized hydroxysulfones 3 and ketosulfones 4 were confirmed by ¹H and ¹³C NMR spectroscopy, elemental analysis, HRMS and IR spectroscopy.

Proposed reaction mechanism

To study the plausible reaction mechanism, an investigation of the redox properties of oxygen, styrene 1a, p-toluenesulfonylhydrazide 2a and CuBr in CH₃CN–H₂O (5 : 1) with the use of cyclic voltammetry (CV) was carried out. Tetrabutylammonium perchlorate was chosen as a supporting electrolyte. The obtained CV curves are shown in Fig. 1.

Fig. 1 The CV curves obtained for 2.0 mmol L⁻¹ solutions of CuBr (red), p-toluenesulfonylhydrazide 2a (blue), styrene 1a (black) and aerated supporting solution (grey) in 0.1 M Bu₄NClO₄ in CH₃CN–H₂O (5 : 1) on a working glassy-carbon electrode (d = 1.7 mm) at a scan rate of 100 mV s⁻¹.

The oxidizing properties of oxygen are evidenced in reducing at the relatively early potentials, the peak on the CV curve with potential −1.10 V was responsible for its reduction. The chemically irreversible oxidation of styrene 1a takes place in the far region with a maximum at 1.90 V and runs into the discharge of the background. A chemically irreversible peak at 1.35 V was responsible for the oxidation of p-toluenesulfonylhydrazide 2a. Therefore, we can conclude that its oxidation goes rather more easily than the oxidation of styrene.

A chemically and electrochemically reversible peak at E_1/2 = 0.55 V corresponds to the oxidation of Cu(I) into Cu(II), which takes place in the potential range between oxygen reduction and p-toluenesulfonylhydrazide 2a oxidation. This means that under experimental conditions the Cu(I)/Cu(II) couple can serve as an effective mediator of p-toluenesulfonylhydrazide 2a oxidation using oxygen.

On the basis of the obtained experimental data and previous studies of reactions proceeding through the generation of S-centered radicals from sulfonylhydrazides,^33–35 we proposed the pathway of the oxysulfonylation process (Scheme 4). Cu(I) ions are oxidized to Cu(II)^36–40 in the presence of oxygen, as confirmed by numerous kinetic studies of this process.^41–44 An almost colourless solution during the reaction is evidence for a small amount of Cu(II). Afterwards, as a result of the successive oxidation of hydrazide 2a under the action of Cu(II),^16,33,34 oxygen or peroxyradical C, an S-centered tosyl radical A (Ts) is generated, which reacts with styrene 1a to form a C-centered benzyl radical B.¹⁶ In the next step, radical B is trapped with oxygen forming peroxyradical C. Then, after abstraction of an hydrogen atom from a hydrogen donor X–H (NH and CH) the peroxyradical C transforms into hydroperoxide D,⁴⁵ which gives the main product 3aa after reduction.^46–51 Alcohol 3aa can also be formed due to C-centered benzyl radical B oxidation by Cu(II) species to the intermediate cation E followed by its hydroxylation.^52–54 Ketone 4aa is formed after the fragmentation of the species generated from the reaction of peroxyradical C with Cu(I) ions⁵⁵ or oxygen.^56–58

Scheme 4 A plausible oxysulfonylation mechanism using the example of the reaction of styrene 1a and p-toluenesulfonylhydrazide 2a.

The fact that using of octene-1 and cyclohexene as starting reagents didn't lead to the formation of oxysulfonylation products can be explained by the low stability of the C-centered alkyl radical generated after addition of tosyl radical A to their double bonds.

Conclusions

In summary, we have demonstrated a novel copper-mediated oxysulfonylation of styrenes using sulfonylhydrazides for the synthesis of β-hydroxysulfones in 32–93% yield. In the case of α-unsubstituted styrenes, β-ketosulfones are formed as the by-products. Applying α-methylstyrenes in this methodology gives β-hydroxysulfones as single products in high yield. Moreover, using cyclic voltammetry, experimental data and previous reports, a plausible reaction pathway was proposed. Coupling of two starting reagents proceeds under the action of the O₂/Cu(I)/Cu(II) redox system. The distinguishing feature of the work lies in the combination of oxygen and a copper(I) salt, which is oxidized to copper(II) on a limited scale, which makes it possible to obtain β-hydroxysulfones as the main products.

Experimental

NMR spectra were recorded on a Bruker Avance II 300 MHz instrument. Chemical shifts are measured relative to the residual solvent peaks as an internal standard set to δ 7.25 and δ 77.0 (CDCl₃), and δ 2.50 and δ 39.51 (DMSO-d₆). IR spectra were recorded on a FT-IR spectrometer. High resolution mass spectra (HRMS) were measured using electrospray ionization (ESI).⁵⁹ The measurements were carried out in positive ion mode (interface capillary voltage 4500 V); the mass ratio was from m/z 50 to 3000 Da; external/internal calibration was performed using an electrospray calibrant solution. Syringe injection was used for solutions in CH₃CN (flow rate 3 µL min⁻¹). Nitrogen was applied as a dry gas and the interface temperature was set at 180 °C. TLC analyses were carried out on standard silica-gel chromatography plates. Melting points were determined on a Kofler hot-stage apparatus. Chromatography was performed on silica gel (63–200 mesh).

Vinylbenzene (1a), 1-methyl-2-vinylbenzene (1b), 1-tert-butyl-4-vinylbenzene (1d), 1-chloro-4-vinylbenzene (1e), isopropenyl-benzene (1f), p-toluenesulfonohydrazide (2a), 4-iso-propylbenz-aldehyde, 4-chloroacetophenone, 4-bromoacetophenone, 4-nitroacetophenone, 4-methoxyacetophenone, 4-iodobenzene-sulfonylchloride, 4-bromobenzenesulfonylchloride, 4-methoxy-benzenesulfonylchloride, 4-nitrobenzenesulfonylchloride, methyltri-phenylphosphonium bromide, t-BuOK, Na₂SO₄, tetra-butyl-ammonium perchlorate, CuBr, CH₃CN, THF, CHCl₃, CH₂Cl₂, MeOH, petroleum ether (PE, 40/70), ethyl acetate (EA) and hydrazine hydrate (64% w/w water solution of hydrazine) were purchased from commercial sources and were used as received. 1-Iso-propyl-4-vinylbenzene (1c), 1-chloro-4-isopropenylbenzene (1g), 1-bromo-4-isopropenylbenzene (1h), 1-nitro-4-isopropenylbenzene (1i) and 1-methoxy-4-isopropenylbenzene (1j) were synthesized via the Wittig reaction according to the literature.⁶⁰ 4-Iodobenzenesulfono-hydrazide (2b), 4-bromobenzenesulfonohydrazide (2c), 4-methoxy-benzenesulfonohydrazide (2d) and 4-nitrobenzenesulfonohydrazide (2e) were synthesized according to the literature.⁶¹

Cyclic voltammetry (CV) was implemented on an IPC-Pro computer-assisted potentiostat manufactured by Econix (scan rate error 1.0%; potential setting 0.25 mV). The experiments were performed in a 10 mL five-neck glass conic electrochemical cell with a water jacket for thermostatting. CV curves were recorded using a three-electrode scheme. The working electrode was a disc glassy-carbon electrode (d = 1.7 mm). A platinum wire served as an auxiliary electrode. A saturated calomel electrode was used as the reference electrode and was linked to the solution by a bridge with a porous ceramic diaphragm filled with background electrolyte. The tested solutions were thermostatted at 25 ± 0.5 °C. In a typical case, 5 mL of solution was utilized and the depolarizer concentration was 2 mmol L⁻¹. The working electrode was polished before recording each CV curve.

Synthesis of styrenes 1c, 1g–1j

Following a literature procedure⁶⁰ to a solution of methyltriphenylphosphonium bromide (14.3–19.1 g, 39.9–53.4 mmol) in THF (50 mL), t-BuOK (4.8–6.5 g, 43.1–57.7 mmol) was added with vigorous stirring under an Ar atmosphere for 10 min. The mixture was stirred for 1 h at room temperature. Then, the corresponding carbonyl compound (4-iso-propylbenzaldehyde, 4-chloroacetophenone, 4-bromoacetophenone, 4-nitroaceto-phenone or 4-methoxyacetophenone, 3.0 g, 15.1–20.2 mmol) was added. The mixture was stirred for 24 h at room temperature. Then, the mixture was diluted with CH₂Cl₂ (180 mL), washed with water (3 × 15 mL) and dried over Na₂SO₄. The solvent was removed under reduced pressure (10–20 Torr). Styrenes 1c, 1g–1j were isolated by chromatography on SiO₂ with elution using PE–EA with a linear gradient of the latter from 0 to 10 vol%.

1-Isopropyl-4-vinylbenzene (1c)⁶². 4-Iso-propylbenzaldehyde (3.0 g, 20.2 mmol) gave the title compound as a colourless oil (2.2 g, 15.2 mmol, 75%). ¹H NMR (CDCl₃), δ: 1.24 (d, J = 6.9 Hz, 6H), 2.80–2.96 (m, 1H), 5.17 (dd, J = 10.9, 1.1 Hz, 1H), 5.69 (dd, J = 17.6, 1.1 Hz, 1H), 6.68 (dd, J = 17.6, 10.9 Hz, 1H), 7.17 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H). ¹³C NMR (CDCl₃), δ: 23.9, 33.9, 112.8, 126.2, 126.6, 135.2, 136.7, 148.6.

1-Chloro-4-isopropenylbenzene (1g)⁶³. 4-Chloroacetophenone (3.0 g, 19.4 mmol) gave the title compound as a colourless oil (2.3 g, 15.1 mmol, 78%). ¹H NMR (CDCl₃), δ: 2.13 (s, 3H), 5.10 (s, 1H), 5.36 (s, 1H), 7.29 (d, J = 8.6 Hz, 2H), 7.39 (d, J = 8.6 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.7, 112.9, 126.8, 128.3, 133.1, 139.6, 142.1.

1-Bromo-4-isopropenylbenzene (1h)⁶⁴. 4-Bromoacetophenone (3.0 g, 15.1 mmol) gave the title compound as a colourless oil (2.1 g, 10.6 mmol, 70%). ¹H NMR (CDCl₃), δ: 2.13 (s, 3H), 5.11 (s, 1H), 5.36 (s, 1H), 7.33 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.6, 113.0, 121.3, 127.1, 131.2, 140.1, 142.2.

1-Isopropenyl-4-nitrobenzene (1i)⁶⁵. 4-Nitroacetophenone (3.0 g, 18.2 mmol) gave the title compound as a yellow oil (1.9 g, 11.8 mmol, 65%). ¹H NMR (CDCl₃), δ: 2.17 (s, 3H), 5.28 (s, 1H), 5.51 (s, 1H), 7.57 (d, J = 8.9 Hz, 2H), 8.15 (d, J = 8.9 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.5, 116.3, 123.5, 126.2, 141.5, 146.9, 147.6.

1-Isopropenyl-4-methoxybenzene (1j)⁶⁶. 4-Methoxyacetophenone (3.0 g, 20.0 mmol) gave the title compound as a white solid (2.4 g, 16.0 mmol, 80%). Mp = 30.5–31.0 °C (lit.⁶⁶ mp = 32.0–32.5 °C). ¹H NMR (CDCl₃), δ: 2.15 (s, 3H), 3.82 (s, 3H), 5.01 (s, 1H), 5.30 (s, 1H), 6.88 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.9, 55.2, 110.6, 113.5, 126.6, 133.7, 142.5, 159.1.

Synthesis of sulfonylhydrazides 2b–2e

Following a literature procedure⁶¹ a THF (20 mL) solution containing the corresponding arylsulfonyl chloride (4-iodobenzene-sulfonylchloride, 4-bromobenzenesulfonylchloride, 4-methoxy-benzenesulfonylchloride, 4-nitrobenzenesulfonylchloride, 5.0 g, 16.5–24.2 mmol) was cooled using an ice-water bath to 5 °C. Hydrazine hydrate (64% w/w water solution of hydrazine, 2.1–3.0 g; 41.2–60.5 mmol) was slowly added with stirring. Then, the reaction mixture was stirred at 5 °C for 30 min, diluted with THF (20 mL), washed with water (3 × 5 mL) and dried over Na₂SO₄. The solvent was removed under reduced pressure (10–20 Torr) to give the pure products 2b–2e.

4-Iodobenzenesulfonohydrazide (2b)⁶⁷. 4-Iodobenzenesulfonyl-chloride (5.0 g, 16.5 mmol) gave the title compound as a white solid (4.3 g, 14.5 mmol, 88%). Mp = 173.0–175.0 °C (lit.⁶⁷ mp = 162.0 °C). ¹H NMR (DMSO-d₆), δ: 4.16 (br s, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.9 Hz, 2H), 8.46 (s, 1H). ¹³C NMR (DMSO-d₆), δ: 100.7, 129.4, 137.8, 137.9. Calculated for C₆H₇IN₂O₂S C: 24.17%, H: 2.37%, I: 42.57%, N: 9.40%, S: 10.76%. Found C: 24.23%, H: 2.45%, I: 42.18%, N: 9.21%, S: 10.57%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₆H₇IN₂NaO₂S]⁺: 320.9171. Found: 320.9167. IR (KBr), ν, cm⁻¹: 3366, 3291, 1571, 1321, 1158, 1085, 1007, 933, 814, 737, 642, 556.

4-Bromobenzenesulfonohydrazide (2c)⁶⁸. 4-Bromobenzene-sulfonylchloride (5.0 g, 19.6 mmol) gave the title compound as a white solid (4.5 g, 18.0 mmol, 92%). Mp = 114.0–116.0 °C (lit.⁶⁸ mp = 113.0–114.0 °C).¹H NMR (DMSO-d₆), δ: 4.20 (br s, 2H), 7.73 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 8.50 (s, 1H). ¹³C NMR (DMSO-d₆), δ: 126.5, 129.7, 132.0, 137.5.

4-Methoxybenzenesulfonohydrazide (2d)⁶⁹. 4-Methoxybenzene-sulfonylchloride (5.0 g, 24.2 mmol) gave the title compound as a white solid (4.6 g, 23.0 mmol, 95%). White solid, mp = 107.0–109.0 °C (lit.⁶⁹ mp = 105.0–110.0 °C). ¹H NMR (DMSO-d₆), δ: 3.83 (s, 3H), 3.92 (br s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.74 (d, J = 8.8, 2H), 8.21 (s, 1H). ¹³C NMR (DMSO-d₆), δ: 55.7, 114.2, 129.5, 129.8, 162.4.

4-Nitrobenzenesulfonohydrazide (2e)⁶⁹. 4-Nitrobenzenesulfonyl-chloride (5.0 g, 22.6 mmol) gave the title compound as a yellow solid (3.7 g, 16.9 mmol, 75%). Mp = 150.0–152.0 °C (lit.⁶⁹ mp = 152.0–157.0 °C). ¹H NMR (DMSO-d₆): δ 4.34 (br s, 2H), 8.05 (d, J = 8.9 Hz, 2H), 8.42 (d, J = 8.9 Hz, 2H), 8.75 (s, 1H). ¹³C NMR (DMSO-d₆): δ 124.2, 129.2, 144.2, 149.7.

General procedure 1. Preparation of 3aa and 4aa. Optimization of the reaction conditions for oxysulfonylation of styrene 1a with sulfonylhydrazide 2a (Table 1)

To a solution of styrene 1a (300 mg, 2.88 mmol) in 25 mL of (CH₃CN–H₂O (5 : 1), CH₃CN, THF, THF–H₂O (5 : 1)), Cu(I) salt (0.58–14.4 mmol, molar ratio 0.2–5 mol of salt/mol 1a) and p-toluenesulfonylhydrazide 2a (537 mg, 2.88 mmol, molar ratio 1 mol 2a/mol 1a) were added. The mixture was stirred in the air or an oxygen atmosphere for 7 h at 40 °C, for 7 h at 80 °C, then for 12 h at room temperature.

Treatment of the reaction mixture containing 3aa and 4aa

The solvent was removed under reduced pressure (10–20 Torr). The reaction residue was diluted with a mixture of solvents PE/CHCl₃/EA in a volume ratio of 1/2/2 (50 mL) and then filtered from the precipitate using SiO₂ (d = 20 mm, h = 80 mm). The precipitate was washed with a mixture of solvents PE/CHCl₃/EA in a volume ratio of 1/2/2 (3 × 30 mL). The combined organic phases were concentrated under reduced pressure (10–20 Torr). The yields of 3aa and 4aa were determined by ¹H NMR using 1,4-dinitrobenzene as an internal standard.

General procedure 2. Synthesis of β-hydroxysulfones 3aa–3ab and β-ketosulfones 4aa–4ab (Table 2)

To a solution of styrene 1a–1e (300 mg, 1.87–2.88 mmol) in 25 mL of CH₃CN–H₂O (5 : 1), CuBr (3.74–5.76 mmol, molar ratio 2 mol mol⁻¹1a–1e) and sulfonylhydrazide 2a–2b (1.87–2.88 mmol, molar ratio 1 mol 2/mol 1a–1e) were added. The mixture was stirred under an oxygen atmosphere for 7 h at 40 °C, then for 12 h at room temperature. Then, the reaction mixture was treated as described above (General procedure 1). The yields of 3aa, 3ba, 3ca, 3da, 3ea, 3ab and 4aa, 4ba, 4ca, 4da, 4ea, 4ab were determined by ¹H NMR using 1,4-dinitrobenzene as an internal standard. The products 3aa, 3ba, 3ca, 3da, 3ea, 3ab and 4aa, 4ba, 4ca, 4da, 4ea, 4ab were isolated by chromatography on SiO₂ with elution using PE–EA in a linear gradient of the latter from 10 to 40 vol%.

General procedure 3. Synthesis of β-hydroxysulfones 3aa–3ab using NaBH₄ (Table 2, yield in parentheses)

The reaction mixture was treated as described above (General procedure 1). Then, the residue was diluted with 10 mL of THF-MeOH (1 : 1) mixture and NaBH₄ (molar ratio 3 mol mol⁻¹4aa, 4ba, 4ca, 4da, 4ea, 4ab) was added with vigorous stirring. The mixture was stirred for 3 h at 0–5 °C. The solvent was removed under reduced pressure (10–20 Torr). The residue was diluted with EA (50 mL) and washed with water (2 × 5 mL), brine (3 × 5 mL) and again water (2 × 5 mL), dried over Na₂SO₄ and concentrated under reduced pressure (10–20 Torr). The desired products 3aa, 3ba, 3ca, 3da, 3ea, 3ab were isolated by chromatography on SiO₂ with elution using PE–EA in a linear gradient of the latter from 10 to 40 vol%.

2-[(4-Methylphenyl)sulfonyl]-1-phenylethanol (3aa)⁷⁰. White solid, mp = 68.5–70.0 °C (lit.⁷⁰ mp = 68.5–69.5 °C). Yield 85%. R_f = 0.26 (TLC, PE : EA, 5 : 1). ¹H NMR (CDCl₃), δ: 2.45 (s, 3H, CH₃), 3.31 (dd, J = 14.3, 1.8 Hz, 1H), 3.47 (dd, J = 10.0, 14.3 Hz, 1H), 3.76 (d, J = 2.0 Hz, 1H), 5.23 (ddd, J = 10.3, 2.0, 1.8 Hz, 1H), 7.23–7.32 (m, 5H), 7.37 (d, J = 8.1 Hz, 2H), 7.82 (d, J = 8.1 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.6, 63.9, 68.4, 125.6, 127.9, 128.2, 128.6, 130.0, 136.1, 140.7, 145.1. Calculated for C₁₅H₁₆O₃S C: 65.19%, H: 5.84%, S: 11.60%. Found C: 65.12%, H: 5.78%, S: 11.66%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₅H₁₆NaO₃S]⁺: 299.0718. Found: 299.0712. IR (KBr), ν, cm⁻¹: 3496, 1391, 1286, 1167, 1137, 1087, 1064, 1020, 998, 834, 818, 779, 747, 706, 640, 555, 537, 514, 500, 462.

1-(2-Methylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanol (3ba)⁷⁰. White solid, mp = 118.0–120.0 °C (lit.⁷⁰ mp = 116.1–118.0 °C). Yield 54%. R_f = 0.34 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 2.08 (s, 3H), 2.46 (s, 3H), 3.22 (dd, J = 14.5, 1.3 Hz, 1H), 3.39 (dd, J = 14.5, 9.8 Hz, 1H), 3.69 (s, 1H), 5.42 (d, J = 9.8 Hz, 1H), 7.07 (dd, J = 7.2, 2.0 Hz, 1H), 7, 11–7.24 (m, 2H), 7.38 (d, J = 8.1 Hz, 2H), 7.48 (dd, J = 7.2, 1.7 Hz, 1H), 7.85 (d, J = 8.1 Hz, 2H). ¹³C NMR (CDCl₃), δ: 18.5, 21.6, 62.9, 65.0, 125.2, 126.5, 127.9, 128.0, 130.0, 130.5, 133.6, 136.0, 138.7, 145.2. Calculated for C₁₆H₁₈O₃S C: 66.18%, H: 6.25%, S: 11.04%. Found C: 66.15%, H: 6.21%, S: 10.89%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₈NaO₃S]⁺: 313.0874. Found: 313.0869. IR (KBr), ν, cm⁻¹: 3517, 1299, 1287, 1247, 1236, 1199, 1189, 1170, 1158, 1142, 1086, 1047, 857, 803, 758, 749, 721, 638, 564, 518, 506, 456.

1-(4-Isopropylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanol (3ca). White solid, mp = 92.5–95.0 °C. Yield 72%. R_f = 0.39 (TLC, PE : EA, 3 : 1). ¹H NMR (DMSO-d₆), δ: 1.16 (d, J = 6.9 Hz, 6H), 2.39 (s, 3H), 2.83 (m, J = 6.9 Hz, 1H), 3.50 (dd, J = 14.5, 3.7 Hz, 1H), 3.67 (dd, J = 14.5, 8.5 Hz, 1H), 4.96 (ddd, J = 8.5, 4.7, 3.7 Hz, 1H), 5.52 (d, J = 4.7 Hz, 1H), 7.13 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 21.0, 23.9, 33.1, 63.0, 67.8, 126.0, 126.1, 127.8, 129.4, 137.6, 140.5, 143.7, 147.6. Calculated for C₁₈H₂₂O₃S C: 67.89%, H: 6.96%, S: 10.07%. Found C: 67.87%, H: 7.01%, S: 10.14%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₈H₂₂NaO₃S]⁺: 341.1187. Found: 341.1178. IR (KBr), ν, cm⁻¹: 3500, 2966, 1410, 1302, 1287, 1253, 1170, 1140, 1086, 1052, 1001, 862, 851, 822, 776, 734, 635, 597, 568, 547, 532, 509, 471, 449.

1-(4-tert-Butylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanol (3da). White solid, mp = 106.0–107.0 °C. Yield 89%. R_f = 0.40 (TLC, PE : EA, 3 : 1). ¹H NMR (DMSO-d₆), δ: 1.24 (s, 9H), 2.39 (s, 3H), 3.50 (dd, J = 14.6, 3.8 Hz, 1H), 3.67 (dd, J = 14.6, 8.5 Hz, 1H), 4.96 (ddd, J = 8.5, 4.7, 3.8 Hz, 1H), 5.52 (d, J = 4.7 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 21.0, 31.1, 34.1, 62.9, 67.7, 124.8, 125.8, 127.7, 129.4, 137.6, 140.0, 143.6, 149.8. Calculated for C₁₉H₂₄O₃S C: 68.64%, H: 7.28%, S: 9.64%. Found C: 68.57%, H: 6.94%, S: 9.51%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₉H₂₄NaO₃S]⁺: 313.0874. Found: 313.0869. IR (KBr), ν, cm⁻¹: 3521, 2962, 1303, 1289, 1242, 1174, 1140, 1113, 1087, 1057, 864, 844, 823, 773, 737, 636, 579, 543, 528, 506.

1-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonyl]ethanol (3ea)⁷⁰. White solid, mp = 89.5–92.5 °C (lit.⁷⁰ mp = 88.0–91.0 °C). Yield 52%. R_f = 0.28 (TLC, PE : EA, 3 : 1). ¹H NMR (DMSO-d₆), δ: 2.40 (s, 3H), 3.55 (dd, J = 14.6, 4.0 Hz, 1H), 3.67 (dd, J = 14.6, 8.2 Hz, 1H), 4.97 (ddd, J = 8.2, 5.0, 4.0 Hz, 1H), 5.70 (d, J = 5.0 Hz, 1H), 7.32 (s, 4H), 7.39 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H). ¹³C NMR (DMSO-d₆), δ: 21.0, 62.6, 67.3, 127.8, 128.0, 128.1, 129.4, 131.9, 137.5, 141.9, 143.8. Calculated for C₁₅H₁₅ClO₃S C: 57.97%, H: 4.86%, Cl: 11.41%, S: 10.32%. Found C: 57.95%, H: 4.93%, Cl: 11.34%, S: 10.25%. HRMS (ESI) m/z [M + Na]⁺: calculated for: [C₁₅H₁₅ClNaO₃S]⁺: 333.0328. Found: 333.0323. IR (KBr), ν, cm⁻¹: 3485, 1311, 1300, 1287, 1160, 1145, 1138, 1087, 1076, 1064, 1013, 813, 714, 562, 511, 502.

2-[(4-Iodophenyl)sulfonyl]-1-phenylethanol (3ab). White solid, mp = 108.0–112.0 °C. Yield 62%. R_f = 0.32 (TLC, PE : EA, 5 : 1). ¹H NMR (DMSO-d₆), δ: 3.55 (dd, J = 14.6, 3.3 Hz, 1H), 3.76 (dd, J = 14.6, 9.2 Hz, 1H), 5.00 (ddd, J = 9.2, 4.8, 3.3 Hz, 1H), 5.62 (d, J = 4.8 Hz, 1H), 7.19–7.34 (m, 5H), 7.65 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 62.6, 67.9, 101.9, 126.1, 127.4, 128.2, 129.5, 137.8, 140.3, 142.9. Calculated for C₁₄H₁₃IO₃S C: 43.31%, H: 3.38%, I: 32.69%, S: 8.26%. Found C: 43.28%, H: 3.31%, I: 32.32%, S: 8.09%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₄H₁₃INaO₃S]⁺: 410.9528. Found: 410.9522. IR (KBr), ν, cm⁻¹: 3464, 1384, 1303, 1270, 1135, 1083, 1061, 1003, 993, 817, 745, 701, 566, 549, 531.

2-[(4-Methylphenyl)sulfonyl]-1-phenylethanone (4aa)⁷¹. White solid, mp = 102.5–104.5 °C (lit.⁷¹ mp = 102.0–103.0 °C). Yield 36%. R_f = 0.73 (TLC, PE : EA, 2 : 1). ¹H NMR (CDCl₃), δ: 2.43 (s, 3H), 4.73 (s, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.46 (dd, J = 7.5, 7.3 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.94 (d, J = 7.3 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.6, 63.5, 128.5, 128.7, 129.2, 129.7, 134.2, 135.7, 135.8, 145.2, 188.1. Calculated for C₁₅H₁₄O₃S C: 65.67%, H: 5.14%, S: 11.69%. Found C: 65.57%, H: 5.34%, S: 11.59%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₅H₁₄NaO₃S]⁺: 297.0561. Found: 297.0556. IR (KBr), ν, cm⁻¹: 1680, 1596, 1320, 1271, 1150, 1087, 993, 750, 739, 686, 590, 535, 503.

1-(2-Methylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (4ba)⁷². White solid, mp = 108–110 °C (lit.⁷² mp = 109–111 °C). Yield 18%. R_f = 0.37 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 2.45 (s, 6H), 4.70 (s, 2H), 7.23–7.31 (m, 2H), 7.31–7.36 (m, 2H), 7.39–7.46 (m, 1H), 7.71–7.79 (m, 3H). ¹³C NMR (CDCl₃), δ: 21.4, 21.6, 65.5, 125.8, 128.4, 129.7, 130.3, 132.2, 132.7, 135.7, 136.0, 139.9, 145.1, 190.5. Calculated for C₁₆H₁₆O₃S C: 66.64%, H: 5.59%, S: 11.12%. Found C: 66.38%, H: 5.80%, S: 11.29%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₆NaO₃S]⁺: 311.0718. Found: 311.0714. IR (KBr), ν, cm⁻¹: 2956, 2910, 1685, 1314, 1291, 1142, 1084, 978, 823, 761, 747, 556, 517.

1-(4-Isopropylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (4ca). White solid, mp = 127.0–129.5 °C. Yield 23%. R_f = 0.43 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 1.26 (d, J = 7.0 Hz, 6H), 2.43 (s, 3H), 2.97 (m, J = 7.0 Hz, 1H), 4.69 (s, 2H), 7.32 (2d, J = 8.2, 8.4 Hz, 4H), 7.76 (d, J = 8.2 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.6, 23.5, 34.3, 63.5, 126.9, 128.6, 129.6, 129.7, 133.7, 135.8, 145.2, 156.1, 187.6. Calculated for C₁₈H₂₀O₃S C: 68.33%, H: 6.37%, S: 10.13%. Found C: 67.86%, H: 6.82%, S: 9.70%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₈H₂₀NaO₃S]⁺: 339.1031. Found: 339.1025. IR (KBr), ν, cm⁻¹: 2953, 1686, 1311, 1290, 1183, 1142, 1084, 828, 549.

1-(4-tert-Butylphenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (4da). White solid, mp = 98.5–101.0 °C. Yield 31%. R_f = 0.49 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 1.34 (s, 9H), 2.44 (s, 3H), 4.69 (s, 2H), 7.32 (d, J = 7.9 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.76 (d, J = 7.9 Hz, 2H), 7.88 (d, J = 8.2 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.7, 31.0, 35.2, 63.6, 125.8, 128.6, 129.3, 129.8, 133.3, 135.9, 145.2, 158.3, 187.6. Calculated for C₁₉H₂₂O₃S C: 69.06%, H: 6.71%, S: 9.70%. Found C: 69.01%, H: 6.65%, S: 9.59%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₉H₂₂NaO₃S]⁺: 353.1187. Found: 353.1182. IR (KBr), ν, cm⁻¹: 1681, 1314, 1290, 1141, 1083, 828, 768, 590, 549, 516.

1-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonyl]ethanone (4ea)⁷¹. White solid, mp = 128.0–130.5 °C (lit.⁷¹ mp = 137.0–138.0 °C). Yield 24%. R_f = 0.46 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 2.45 (s, 3H), 4.68 (s, 2H), 7.34 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.90 (d, J = 8.6 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.7, 63.7, 128.5, 129.2, 129.9, 130.7, 134.1, 135.6, 141.0, 145.5, 187.0. Calculated for C₁₅H₁₃ClO₃S C: 58.35%, H: 4.24%, Cl: 11.48%, S: 10.38%. Found C: 58.37%, H: 4.31%, Cl: 10.98%, S: 9.93%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₅H₁₃ClNaO₃S]⁺: 331.0172. Found: 331.0166. IR (KBr), ν, cm⁻¹: 1679, 1589, 1315, 1290, 1277, 1148, 1091, 1083, 1004, 784, 759, 724, 537, 507.

2-[(4-Iodophenyl)sulfonyl]-1-phenylethanone (4ab). White solid, mp = 125.0–127.0 °C. Yield 25%. R_f = 0.38 (TLC, PE : EA, 5 : 1). ¹H NMR (CDCl₃), δ: 4.73 (s, 2H), 7.49 (t, J = 7.2 Hz, 2H), 7.56–7.68 (m, 3H), 7.87–7.95 (m, 4H). ¹³C NMR (CDCl₃), δ: 63.2, 102.5, 128.9, 129.2, 129.9, 134.5, 135.5, 138.3, 138.4, 187.8. Calculated for C₁₄H₁₁IO₃S C: 43.54%, H: 2.87%, I: 32.86%, S: 8.30%. Found C: 43.58%, H: 3.01%, I: 32.65%, S: 8.25%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₄H₁₁INaO₃S]⁺: 408.9371. Found: 408.9366. IR (KBr), ν, cm⁻¹: 1677, 1563, 1379, 1314, 1273, 1151, 1002, 756, 741, 727, 565, 516.

General procedure 4. Synthesis of β-hydroxysulfones 3fa–3fe (Table 3)

To a solution of styrene 1f–1j (300 mg, 1.52–2.54 mmol) in 25 mL of CH₃CN–H₂O (5 : 1), CuBr (3.04–5.08 mmol, molar ratio 2 mol mol⁻¹1f–1j) and sulfonylhydrazide 2a–2e (1.52–2.54 mmol, molar ratio 1 mol 2/mol 1f–1j) were added. The mixture was stirred under an oxygen atmosphere for 7 h at 40 °C, then for 12 h at room temperature. Then, the reaction mixture was treated as described above (General procedure 1). The desired products 3fa, 3ga, 3ha, 3ia, 3ja, 3fc, 3fd, 3fe were isolated by chromatography on SiO₂ with elution using PE–EA in a linear gradient of the latter from 10 to 40 vol%.

1-[(4-Methylphenyl)sulfonyl]-2-phenylpropan-2-ol (3fa)⁷³. White solid, mp = 99.5–100.5 °C (lit.⁷³ mp = 103–104 °C). Yield 92%. R_f = 0.64 (TLC, PE : EA, 2 : 1). ¹H NMR (CDCl₃), δ: 1.71 (d, J = 1.1 Hz, 3H), 2.39 (s, 3H), 3.61 (dd, J = 14.6, 1.1 Hz, 1H), 3.72 (d, J = 14.6, 1.1 Hz, 1H), 4.66 (br s, 1H), 7.14–7.24 (m, 5H), 7.26–7.34 (m, 2H), 7.49 (dd, J = 8.2, 1.0 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.5, 30.7, 66.6, 73.0, 124.5, 127.0, 127.4, 128.1, 129.6, 137.3, 144.4. Calculated for C₁₆H₁₈O₃S C: 66.18%, H: 6.25%, S: 11.04%. Found C: 66.23%, H: 6.06%, S: 11.12%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₈NaO₃S]⁺: 313.0874. Found: 313.0879. IR (KBr), ν, cm⁻¹: 3500, 2973, 1451, 1355, 1300, 1268, 1247, 1182, 1155, 1119, 1081, 1036, 1024, 1017, 947, 858, 813, 767, 707, 637, 570, 555, 532, 509, 477.

2-(4-Chlorophenyl)-1-[(4-methylphenyl)sulfonyl]propan-2-ol (3ga). White solid, mp = 142–144 °C. Yield 90%. R_f = 0.68 (TLC, PE : EA, 2 : 1). ¹H NMR (CDCl₃), δ: 1.62 (s, 3H), 2.39 (s, 3H), 3.55 (d, J = 14.8 Hz, 1H), 3.69 (d, J = 14.8 Hz, 1H), 7.07 (d, J = 8.7 Hz, 2H) 7.15 (d, J = 8.7 Hz, 2H) 7.15 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.5, 30.9, 66.3, 72.7, 126.2, 127.5, 128.2, 129.7, 133.1, 137.0, 142.8, 144.7. Calculated for C₁₆H₁₇ClO₃S C: 59.16%, H: 5.28%, Cl: 10.91%, S: 9.87%. Found C: 58.99%, H: 5.29%, Cl: 11.04%, S: 9.98%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₇ClNaO₃S]⁺: 347.0485. Found: 347.0479. IR (KBr), ν, cm⁻¹: 3496, 1308, 1302, 1252, 1158, 1128, 1082, 1044, 849, 771, 645, 543, 522, 460.

2-(4-Bromophenyl)-1-[(4-methylphenyl)sulfonyl]propan-2-ol (3ha)¹⁶. Light-brown solid, mp = 160.5–163 °C (lit.¹⁶ mp = 164.0–166.0 °C). Yield 93%. R_f = 0.29 (TLC, PE : EA, 3 : 1).¹H NMR (DMSO-d₆), δ: 1.55 (s, 3H), 2.37 (s, 3H), 3.77 (d, J = 14.8 Hz, 1H), 3.84 (d, J = 14.8 Hz, 1H), 7.24–7.35 (m, 6H), 7.52 (d, J = 8.0 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 21.0, 30.0, 66.0, 71.5, 119.8, 127.5, 127.6, 129.2, 130.3, 138.2, 143.4, 145.4. Calculated for C₁₆H₁₇BrO₃S C: 52.04%, H: 4.64%, Br: 21.64%, S: 8.68%. Found C: 52.14%, H: 4.73%, Br: 21.12%, S: 8.47%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₇BrNaO₃S]⁺: 390.9979. Found: 390.9974. IR (KBr), ν, cm⁻¹: 3489, 1251, 1158, 1127, 1081, 771, 639, 585, 540, 522, 486.

1-[(4-Methylphenyl)sulfonyl]-2-(4-nitrophenyl)propan-2-ol (3ia)¹⁶. White solid, mp = 137.5–138.5 °C (lit.¹⁶ mp = 140.0–142.0 °C). Yield 89%. R_f = 0.40 (TLC, PE : EA, 2 : 1). ¹H NMR (DMSO-d₆), δ: 1.57 (s, 3H), 2.33 (s, 3H), 3.84 (d, J = 14.8 Hz, 1H), 4.01 (d, J = 14.8 Hz, 1H), 5.71 (s, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 8.9 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 21.0, 30.5, 65.7, 71.8, 122.6, 126.7, 127.7, 129.2, 138.1, 143.6, 146.1, 153.7. Calculated for C₁₆H₁₇NO₅S C: 57.30%, H: 5.11%, N: 4.18%, S: 9.56%. Found C: 57.28%, H: 5.08%, N: 4.16%, S: 9.48%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₇NNaO₅S]⁺: 358.0725. Found: 358.0713. IR (KBr), ν, cm⁻¹: 3480, 1520, 1349, 1310, 1301, 1291, 1268, 1147, 1121, 1084, 855, 815, 757, 537, 518.

1-[(4-Methylphenyl)sulfonyl]-2-(4-methoxyphenyl)propan-2-ol (3ja)¹⁶. White solid, mp = 90–93 °C (lit.¹⁶ mp = 94.5–95.5 °C). Yield 90%. R_f = 0.25 (TLC, PE : EA, 3 : 1). ¹H NMR (CDCl₃), δ: 1.66 (s, 3H), 2.37 (s, 3H), 3.54 (d, J = 14.5 Hz, 1H), 3.67 (d, J = 14.5 Hz 1H), 3.74 (s, 3H), 6.68 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H). ¹³C NMR (CDCl₃), δ: 21.5, 30.7, 55.2, 66.8, 72.8, 113.5, 125.8, 127.5, 129.6, 136.6, 137.4, 144.3, 158.7. Calculated for C₁₇H₂₀O₄S C: 63.73%, H: 6.29%, S: 10.01%. Found C: 63.88%, H: 6.29%, S: 10.01%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₇H₂₀NaO₄S]⁺: 343.0980. Found: 343.0975. IR (KBr), ν, cm⁻¹: 3472, 1607, 1598, 1514, 1309, 1292, 1251, 1183, 1146, 1120, 1083, 1032, 832, 823, 810, 766, 676, 557, 536, 513.

1-[(4-Bromophenyl)sulfonyl]-2-phenylpropan-2-ol (3fc)¹⁶. Yellow solid, mp = 153–156 °C (lit.¹⁶ mp = 153.0–153.5 °C). Yield 52%. R_f = 0.40 (TLC, PE : EA, 3 : 1). ¹H NMR (DMSO-d₆), δ: 1.60 (s, 3H), 3.86 (s, 2H), 4.75 (br s, 1H), 7.11–7.23 (m, 3H), 7.33–7.39 (m, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.70 (d, J = 8.6 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 29.9, 66.1, 71.7, 125.0, 126.4, 127.1, 127.6, 129.8, 131.7, 140.6, 146.5. Calculated for C₁₅H₁₅BrO₃S C: 50.71%, H: 4.26%, Br: 22.49%, S: 9.03%. Found C: 50.78%, H: 4.31%, Br: 22.48%, S: 9.02%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₅H₁₅BrNaO₃S]⁺: 376.9823. Found: 376.9821. IR (KBr), ν, cm⁻¹: 3507, 1576, 1392, 1312, 1295, 1270, 1149, 1122, 1084, 1067, 1010, 942, 821, 775, 765, 714, 701, 579, 545, 528, 411.

1-[(4-Methoxyphenyl)sulfonyl]-2-phenylpropan-2-ol (3fd)¹⁶. White solid, mp = 87.5–89 °C (lit.¹⁶ mp = 90.5–92.5 °C). Yield 85%. R_f = 0.45 (TLC, PE : EA, 2 : 1). ¹H NMR (CDCl₃), δ: 1.68 (s, 3H), 3.58 (d, J = 14.7 Hz, 1H), 3.70 (d, J = 14.7 Hz, 1H), 3.82 (s, 3H), 6.81 (d, J = 8.9 Hz, 2H), 7.11–7.24 (m, 3H), 7.25–7.31 (m, 2H), 7.50 (d, J = 8.9 Hz, 2H). ¹³C NMR (CDCl₃), δ: 30.8, 55.6, 66.7, 73.0, 114.2, 124.6, 127.1, 128.2, 129.7, 131.8, 144.5, 163.5. Calculated for C₁₆H₁₈O₄S C: 62.72%, H: 5.92%, S: 10.47%. Found C: 62.81%, H: 5.95%, S: 10.46%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₆H₁₈NaO₄S]⁺: 329.0824. Found: 329.0813. IR (KBr), ν, cm⁻¹: 3501, 1594, 1497, 1307, 1295, 1261, 1249, 1151, 1117, 1079, 1026, 830, 758, 697, 570, 529, 480, 468.

1-[(4-Nitrophenyl)sulfonyl]-2-phenylpropan-2-ol (3fe)¹⁶. White solid, mp = 177.5–179.5 °C (lit.¹⁶ mp = 187–190 °C). Yield 36%. R_f = 0.25 (TLC, PE : EA, 3 : 1). ¹H NMR (DMSO-d₆), δ: 1.61 (s, 3H), 3.93–4.05 (m, 2H), 5.44 (s, 1H), 7.08–7.23 (m, 3H), 7.31–7.39 (m, 2H), 7.96 (d, J = 8.7 Hz, 2H), 8.29 (d, J = 8.7 Hz, 2H). ¹³C NMR (DMSO-d₆), δ: 29.9, 65.8, 71.6, 123.7, 124.9, 126.4, 127.5, 129.4, 146.3, 146.6, 149.7. Calculated for C₁₅H₁₅NO₅S C: 56.06%, H: 4.70%, N: 4.36%, S: 9.98%. Found C: 56.04%, H: 4.85%, N: 4.21%, S: 9.96%. HRMS (ESI) m/z [M + Na]⁺: calculated for [C₁₅H₁₅NNaO₅S]⁺: 344.0569. Found: 344.0563. IR (KBr), ν, cm⁻¹: 3492, 1525, 1350, 1305, 1148, 1121, 1083, 849, 771, 742, 579, 525.

Acknowledgements

This work was supported by the Russian Science Foundation (Grant 14-23-00150).

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Footnote

† Electronic supplementary information (ESI) available: NMR spectra of all synthesized compounds. See DOI: 10.1039/c6ra19190h

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