Diastereoselective Synthesis of Spiro[pyrazolone-4,3′-tetrahydrothiophenes] via a Sulfa-Michael/Aldol Domino Reaction

Abstract

A new approach for the diastereoselective synthesis of spiro[pyrazolone-4,3′-tetrahydrothiophenes] was developed. The N,N-diisopropylethylamine-catalyzed reaction of arylidenepyrazolones with in situ generated 2-sulfanylacetaldehyde provides the corresponding spiro-heterocycles via a domino sulfa-Michael/aldol reaction in 42–98% yield and 3:2:1 to 20:1 d.r. under mild reaction conditions.

Key words

spiro compounds - domino reaction - tetrahydrothiophene - pyrazolone - sulfa-Michael addition

The development of new and efficient synthetic routes to access bioactive heterocyclic compounds is fundamental for the synthesis of valuable natural products, pharmaceuticals and agrochemicals. Tetrahydrothiophenes are present in many natural products and pharmaceuticals,[1] such as the essential coenzyme biotin[2] or analogues of penicillin.[3] In addition, bioactive compounds bearing a pyrazolone moiety display a wide range of biological and pharmaceutical properties, and especially spiro-pyrazolones,[4] such as the spiro compounds A,[5] with antimicrobial activity, B, a phosphodiesterase inhibitor,[6] C, with antitumor activity,[7] and D, with antibacterial activity,[8] have attracted much interest in medicinal chemistry (Figure [1]).

Figure 1 Typical examples of bioactive spiro-pyrazolone compounds

Recently, arylidenepyrazolones have been recognized as very good substrates to provide new pyrazole and pyrazolone derivatives.[9] 1,4-Dithiane-2,5-diol, the dimer of 2-sulfanylacetaldehyde, emerged as an excellent precursor for the development of domino sulfa-Michael/aldol reactions to provide tetrahydrothiophene rings (Scheme [1]).[10] Similar domino transformations of 1,4-dithiane-2,5-diol resulted in the construction of spiro-tetrahydrothiophenes containing oxindole,[11a] [c] 1,3-indanedione,[11e] and chromanone cores.[11b,d] However, to the best of our knowledge, there is no report in the literature on the formation of spiro-tetrahydrothiophenes bearing a pyrazolone moiety.

Scheme 1 Synthetic catalytic approaches to spirocyclic tetrahydrothiophenes

Herein we report a diastereoselective sulfa-Michael/ aldol­ domino reaction of arylidenepyrazolones 1 and 1,4-dithiane-2,5-diol (2) to provide spiro[pyrazolone-4,3′-tetrahydrothiophenes] 3 (Scheme [1]). In our initial investigations, different organic and inorganic bases were tested (Table [1]). The first attempt using DMAP (10 mol%) in CH₂Cl₂ at room temperature afforded the spirocyclic product 3a in 83% yield and 12:2:1 d.r (entry 1). The product was acetylated in situ to ease the analysis of the NMR spectra. The screening of other organic bases such as Et₃N, DABCO, or DBU provided 3a in moderate to very good yields and good diastereomeric ratios, but the reaction time extended to 19 hours when the base DABCO was used (entries 2–4). The sulfa-Michael/aldol domino reaction proceeded well when the inorganic base K₂CO₃ was used, to afford 3a in 97% yield and 9:2:1 d.r., but in a longer reaction time (entry 5).

Table 1 Catalyst and Solvent Screening^a

Entry	Catalyst	Solvent	Reaction time	Yield (%)b	d.r.c
1	DMAP	CH2Cl2	55 min	83	12:2:1
2	Et3N	CH2Cl2	50 min	73	7:2:1
3	DABCO	CH2Cl2	19 h	93	10:2:1
4	DBU	CH2Cl2	90 min	81	12:2:1
5	K2CO3	CH2Cl2	48 h	97	9:2:1
6	DBN	CH2Cl2	3.5 h	83	11:2:1
7	HMTAd	CH2Cl2	4 h	77	13:2:1
8	TMEDA	CH2Cl2	30 min	98	12:2:1
9	DIPEA	CH2Cl2	15 min	98	12:2:1
10	DIPEA	DCE	30 min	79	15:2:1
11	DIPEA	toluene	5 h	96	15:2:1
12	DIPEA	THF	20 min	74	6:1:1
13e	DIPEA	CH2Cl2	7 d	n.d.	n.d.
14f	DIPEA	CH2Cl2	20 min	37	17:2:1
15g	DIPEA	CH2Cl2	25 min	55	16:2:1
16h	DIPEA	CH2Cl2	15 min	98	15:2:1

^a Reaction conditions: 1a (0.25 mmol), 2 (0.15 mmol), cat. (10 mol%), solvent (2.5 mL, 0.1 M).

^b Yield of 3a after flash chromatography.

^c The diastereomeric ratio was determined by ¹H NMR.

^d HMTA = hexamethylenetetramine.

^e The reaction was carried out at 0 °C.

^f The reaction was carried out with DIPEA (30 mol%) at 0 °C.

^g The reaction was carried out with DIPEA (1 mol%).

^h The reaction was carried out with DIPEA (5 mol%).

After further screening of organic bases, DIPEA was found to be the best catalyst, providing the spirocyclic product 3a in 98% yield and 12:2:1 d.r. within 15 minutes (Table [1], entry 9). The reaction was further optimized by conducting the reaction in different solvents and varying the catalyst loading to determine the optimal reaction conditions. We found that DIPEA (5 mol%) in CH₂Cl₂ at room temperature provided 3a in the best yield of 98% and a d.r. of 15:2:1 within 15 minutes (entry 16).

The optimized reaction conditions were then used to probe the general applicability of the domino sequence (Scheme [2]). The sulfa-Michael/aldol reaction of arylidene­pyrazolones bearing electron-donating (1a–f) and electron-withdrawing groups (1g–j) provided the spirocyclic compounds 3a–j in good to excellent yields and moderate to excellent diastereomeric ratios. Good results in terms of yield and d.r. were also obtained by using a thionyl substituent at the arylidenepyrazolone, showing the presence of heterocyclic substituents in this reaction. The substrate scope was extended by varying the substituents at the N-1 and C-3 positions of the alkylidenepyrazolone. The reaction with different aryl substituents at the N-1 position provided good yields and moderate to very good diastereomeric ratios (3l–n). Moderate to good yields and moderate to excellent diastereomeric ratios were achieved by varying the alkyl substituent at C-3 (3o–q). It was observed that an increase in the steric hindrance at C-3 resulted in a lower yield (3n–p).

Furthermore, an enantioselective sulfa-Michael/aldol domino sequence was investigated, catalyzed by different chiral bifunctional organocatalysts such as squaramides[12] and thioureas.[13] Initially different squaramide and thiourea catalysts (Table [2,] I–IV) were tested to provide the product 3a. In all approaches good to excellent yields could be achieved with good diastereomeric ratios, but the best enantioselectivity of only 19% ee was obtained with catalyst I. The reaction was then conducted in different solvents and at low temperature employing catalyst I, but so far the ee value could not be increased beyond 23% (entry 6).

Scheme 2 Substrate scope of the sulfa-Michael/aldol domino reaction

The relative cis-configuration of the spiro[pyrazolone-4,3′-tetrahydrothiophenes] was determined by X-ray crystal structure analysis of compound 3i (Figure [2]).[14]

Table 2 Test of an Enantioselective Sulfa-Michael/Aldol Domino Reaction^a

Entry	Catalyst	Solvent	Reaction time	Yield (%)b	ee (%)c	d.r.d
1	I	CH2Cl2	1 h	98	19	10:2:1
2	II	CH2Cl2	2.5 h	88	4	12:2:1
3	III	CH2Cl2	5.5 h	98	18	8:2:1
4	IV	CH2Cl2	5.5 h	98	14	10:2:1
5	I	toluene	3 d	97	17	6:1:1
6	I	THF	24 h	66	23	12:3:1
7e	I	THF	2 d	45	21	13:3:1

^a Reaction conditions: 1a (0.25 mmol), 2 (0.15 mmol), cat. (5 mol%), solvent (2.5 mL, 0.1 M).

^b Yield of 3a after flash chromatography.

^c The enantiomeric excess was determined by HPLC on a chiral stationary phase.

^d The diastereomeric ratio was determined by ¹H NMR.

^e The reaction was carried out at –65 °C.

In conclusion, we have developed a diastereoselective sulfa-Michael/aldol domino reaction of arylidenepyrazo­lones with 1,4-dithiane-2,5-diol to afford spiro[pyrazolone-4,3′-tetrahydrothiophenes] in moderate to excellent yields and diastereomeric ratios. An attempt to develop an enan­tioselective variant of this protocol has also been carried out, but so far only 23% ee could be reached.

Figure 2 X-ray crystal structure of spiro[pyrazolone-4,3′-tetrahydrothiophene] 3i. Interestingly, one enantiomer of 3i was obtained after crystallization from n-hexane–ethyl acetate (1:1).

Unless otherwise noted, all commercially available chemicals were used without purification. All solvents were distilled and purified according to standard procedures. Analytical TLC was performed using SIL G-25 UV₂₅₄ from Macherey & Nagel (particle size 0.040–0.063 nm; 230–240 mesh flash) and visualized with UV radiation at 254 nm. ¹H, ¹³C, and ¹⁹F NMR spectra were recorded at ambient temperature on a Varian Innova 400 or Innova 600 instrument. Chemical shifts of the major diastereomer for the ¹H NMR and ¹³C NMR spectra are reported in ppm with coupling constants given in Hz. Melting points were measured on a LLG MPM-H2 melting point instrument. Mass spectra were acquired on a Finnigan SSQ7000 (EI, 70 eV) spectrometer and on a ThermoFinnigan LCQ Deca XP plus (ESI) spectrometer, and high resolution ESI spectra were obtained on a ThermoFisher Scientific LTQ Orbitrap XL. Analytical HPLC was performed on a Agilent 1260 instrument by using chiral stationary phases (Daicel Chiralpak IA column). The alkylidenepyrazolones 1 were prepared according to known procedures.[15]

Compounds rac-3a–q; General Procedure

1,4-Dithiane-2,5-diol (2; 0.15 mmol) and DIPEA (5 mol%) were added to a solution of 1 (0.25 mmol) in CH₂Cl₂ (2.5 mL). The reaction mixture was stirred at r.t. until 1 was completely consumed as indicated by TLC. The solution of the crude product was cooled to 0 °C and treated with Ac₂O (0.30 mmol), DMAP (0.05 mmol), and pyridine (0.30 mmol). The crude product was then subjected to flash chromatography (silica gel, n-pentane–Et₂O, 20:1 to 6:1); this afforded the spiro product 3.

1-Methyl-4-oxo-3,6-diphenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3a)

Yield: 93 mg (98%); colorless solid; mp 78–80 °C; R_f = 0.60 (n-pentane–Et₂O, 1:1).

IR (ATR): 1750, 1709, 1595, 1495, 1452, 1401, 1364, 1323, 1292, 1216, 1148, 1053, 918, 839, 798, 758, 696 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.70 (m, 2 H, Ar-H), 7.39–7.33 (m, 4 H, Ar-H), 7.25–7.15 (m, 4 H, Ar-H), 5.75 (t, J = 8.5 Hz, 1 H, CHOAc), 5.14 (s, 1 H, CHAr), 3.81 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.19 (dd, J = 11.1, 8.8 Hz, 1 H, SCHH), 2.38 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.9 (C=O), 169.3 (C=O), 157.5 (C_q), 137.4 (C_q), 133.1 (C_q), 128.9 (2 C, Ar-C), 128.8 (Ar-C), 128.6 (2 C, Ar-C), 127.2 (2 C, Ar-C), 125.5 (Ar-C), 119.2 (2 C, Ar-C), 79.3 (CHOAc), 69.2 (C_q), 54.3 (CHAr), 33.0 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 381.3 (7) [M + H]⁺, 380.1 (33) [M]⁺, 320.1 (55) [M – OAc]⁺, 263.1 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₂₁N₂O₃S: 381.1267; found: 381.1268.

6-(4-Methoxyphenyl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3b)

Yield: 83 mg (81%); yellow solid; mp 38–40 °C; R_f  = 0.47 (n-pentane–Et₂O, 1:1).

IR (ATR): 2944, 1719, 1596, 1493, 1363, 1216, 1044, 918, 829, 753, 692 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.72 (d, J = 8.6 Hz, 2 H, Ar-H), 7.36 (m, 2 H, Ar-H), 7.29–7.23 (m, 2 H, Ar-H), 7.17 (m, 1 H, Ar-H), 6.74 (t, J = 7.7 Hz, 2 H, Ar-H), 5.72 (t, J = 8.5 Hz, 1 H, CHOAc), 5.09 (s, 1 H, CHAr), 3.80 (dd, J = 11.0, 8.5 Hz, 1 H, SCHH), 3.72 (s, 3 H, OCH₃), 3.17 (m, 1 H, SCHH), 2.40 (s, 3 H, CH₃), 1.97 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 171.0 (C=O), 169.3 (C=O), 159.7 (C_q), 157.6 (C_q), 137.4 (C_q), 129.6 (C_q), 128.8 (2 C, Ar-C), 128.4 (2 C, Ar-C), 125.4 (Ar-C), 119.1 (2 C, Ar-C), 113.9 (2 C, Ar-C), 79.2 (CHOAc), 69.2 (C_q), 55.2 (OCH₃), 53.9 (CHAr), 33.0 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 411.1 (16) [M + H]⁺, 410.1 (62) [M]⁺, 350.1 (50) [M – HOAc]⁺, 293.1 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₄SNa: 433.1193; found: 433.1192.

1-Methyl-4-oxo-3-phenyl-6-p-tolyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3c)

Yield: 91 mg (92%); colorless solid; mp 35–37 °C; R_f = 0.68 (n-pentane–Et₂O, 1:1).

IR (ATR): 2951, 1750, 1709, 1596, 1497, 1434, 1402, 1364, 1291, 1216, 1146, 1052, 920, 821, 798, 757, 727, 689 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.72 (m, 2 H, Ar-H), 7.36 (m, 2 H, Ar-H), 7.22 (d, J = 8.1 Hz, 2 H, Ar-H), 7.18 (m, 1 H, Ar-H), 7.01 (d, J = 7.9 Hz, 2 H, Ar-H), 5.73 (t, J = 8.5 Hz, 1 H, CHOAc), 5.11 (s, 1 H, CHAr), 3.80 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.17 (dd, J = 11.1, 8.8 Hz, 1 H, SCHH), 2.39 (s, 3 H, CH₃), 2.25 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 171.0 (C=O), 169.3 (C=O), 157.6 (C_q), 138.6 (C_q), 137.5 (C_q), 129.9 (C_q), 129.3 (2 C, Ar-C), 128.8 (2 C, Ar-C), 127.0 (2 C, Ar-C), 125.4 (Ar-C), 119.1 (2 C, Ar-C), 79.4 (CHOAc), 69.2 (C_q), 54.1 (CHAr), 33.0 (SCH₂), 21.1 (CH₃), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 395.2 (11) [M + H]⁺, 394.2 (31) [M]⁺, 334.1 (64) [M – HOAc]⁺, 277.1 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₃SNa: 417.1243; found: 417.1240.

6-(3-Methoxyphenyl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3d)

Yield: 92 mg (90%); brown oil; R_f = 0.55 (n-pentane–Et₂O, 1:1).

IR (ATR): 2951, 1751, 1709, 1595, 1493, 1458, 1433, 1402, 1366, 1270, 1216, 1153, 1045, 923, 872, 756, 713, 692 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.72 (d, J = 7.8 Hz, 2 H, Ar-H), 7.34 (t, J = 7.9 Hz, 2 H, Ar-H), 7.19–7.08 (m, 2 H, Ar-H), 6.93 (d, J = 7.5 Hz, 1 H, Ar-H), 6.84 (s, 1 H, Ar-H), 6.75 (d, J = 8.4 Hz, 1 H, Ar-H), 5.72 (t, J = 8.6 Hz, 1 H, CHOAc), 5.09 (s, 1 H, CHAr), 3.78 (dd, J = 11.0, 8.3 Hz, 1 H, SCHH), 3.56 (s, 3 H,OCH₃), 3.16 (dd, J = 10.9, 9.0 Hz, 1 H, SCHH), 2.36 (s, 3 H, CH₃), 1.96 (s, 3 H, CH₃).

¹³C NMR (101 MHz, CDCl₃): δ = 171.0 (C=O), 169.2 (C=O), 159.6 (C_q), 157.5 (C_q), 137.4 (C_q), 134.6 (C_q), 129.6 (Ar-C), 128.8 (2 C, Ar-C), 125.4 (Ar-C), 119.3 (Ar-C), 119.0 (2 C, Ar-C), 114.8 (Ar-C), 112.2 (Ar-C), 79.3 (CHOAc), 69.1 (C_q), 55.0 (OCH₃), 54.1 (CHAr), 33.0 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 411.0 (9) [M + H]⁺, 410.0 (21) [M]⁺, 350.0 (38) [M – HOAc]⁺, 292.9 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₄SNa: 433.1193; found: 433.1193.

1-Methyl-4-oxo-3-phenyl-6-o-tolyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3e)

Yield: 69 mg (70%); colorless solid; mp 127–129 °C; R_f = 0.59 (n-pentane–Et₂O, 1:1).

IR (ATR): 2958, 2312, 2093, 1724, 1476, 1361, 1212, 1025, 737 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.75–7.65 (m, 3 H, Ar-H), 7.35–7.28 (m, 2 H, Ar-H), 7.17–7.09 (m, 3 H, Ar-H), 7.02 (m, 1 H, Ar-H), 5.73 (t, J = 8.3 Hz, 1 H, CHOAc), 5.41 (s, 1 H, CHAr), 3.82 (dd, J = 11.2, 8.1 Hz, 1 H, SCHH), 3.21 (dd, J = 11.2, 8.5 Hz, 1 H, SCHH), 2.53 (s, 3 H, CH₃), 2.26 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (101 MHz, CDCl₃): δ = 170.9 (C=O), 169.2 (C=O), 157.8 (C_q), 137.5 (C_q), 137.3 (C_q), 131.6 (C_q), 131.0 (Ar-C), 128.8 (2 C, Ar-C), 128.5 (Ar-C), 128.1 (Ar-C), 125.9 (Ar-C), 125.3 (Ar-C), 118.8 (2 C, Ar-C), 79.6 (CHOAc), 68.2 (C_q), 50.3 (CHAr), 33.4 (SCH₂), 20.7 (CH₃), 19.6 (CH₃), 18.6 (CH₃).

MS (EI, 70 eV): m/z (%) = 395.2 (1) [M + H]⁺, 335.0 (1) [M – OAc]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₃SNa: 417.1243; found: 417.1226.

6-(Benzo[d][1,3]dioxol-5-yl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3f)

Yield: 69 mg (65%); orange solid; mp 42–44 °C; R_f = 0.63 (n-pentane–Et₂O, 1:1).

IR (ATR): 2902, 1717, 1598, 1488, 1362, 1221, 1037, 922, 758 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.73 (m, 2 H, Ar-H), 7.40–7.34 (m, 2 H, Ar-H), 7.18 (m, 1 H, Ar-H), 6.91 (d, J = 1.8 Hz, 1 H, Ar-C), 6.80 (dd, J = 8.2, 1.9 Hz, 1 H, Ar-H), 6.62 (d, J = 8.1 Hz, 1 H, Ar-H), 5.90 (dd, J = 12.0, 1.5 Hz, 2 H, -OCH₂O-), 5.70 (t, J = 8.6 Hz, 1 H, CHOAc), 5.05 (s, 1 H, CHAr), 3.79 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.17 (dd, J = 11.1, 8.9 Hz, 1 H, SCHH), 2.42 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.8 (C=O), 169.2 (C=O), 157.5 (C_q), 147.9 (C_q), 147.8 (C_q), 137.4 (C_q), 128.9 (2 C, Ar-C), 126.6 (C_q), 125.5 (Ar-C), 121.0 (Ar-C), 119.2 (2 C, Ar-C), 108.2 (Ar-C), 107.5 (Ar-C), 101.3 (-OCH₂O-), 79.1 (CHOAc), 69.2 (C_q), 54.2 (CHAr), 33.0 (SCH₂), 20.6 (CH₃), 17.9 (CH₃).

MS (EI, 70 eV): m/z (%) = 425.3 (2) [M + H]⁺, 424.2 (7) [M]⁺, 364.2 (16) [M – HOAc]⁺, 307.1 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₀N₂O₅SNa: 447.0985; found: 447.0984.

6-(4-Chlorophenyl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3g)

Yield: 81 mg (78%); colorless solid; mp 37–39 °C; R_f = 0.50 (n-pentane–Et₂O, 1:1).

IR (ATR): 2939, 2291, 2083, 1715, 1596, 1491, 1361, 1213, 1043, 917, 828, 751, 691 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.74–7.70 (m, 2 H, Ar-H), 7.37 (m, 2 H, Ar-H), 7.31–7.27 (m, 2 H, Ar-H), 7.22–7.18 (m, 3 H, Ar-H), 5.73 (t, J = 8.6 Hz, 1 H, CHOAc), 5.09 (s, 1 H, CHAr), 3.81 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.19 (dd, J = 11.1, 8.9 Hz, 1 H, SCHH), 2.37 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.7 (C=O), 169.2 (C=O), 157.2 (C_q), 137.3 (C_q), 134.6 (C_q), 131.8 (C_q), 128.9 (2 C, Ar-C), 128.8 (2 C, Ar-C), 128.6 (2 C, Ar-C), 125.6 (Ar-C), 119.1 (2 C, Ar-C), 79.2 (CHOAc), 69.1 (C_q), 53.5 (CHAr), 33.1 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 416.1 (16) [M, ³⁷Cl]⁺, 414.1 (39) [M, ³⁵Cl]⁺, 356.0 (17) [M – HOAc, ³⁷Cl]⁺, 354.0 (65) [M – HOAc, ³⁵Cl]⁺, 299.1 (31) [M – C₄H₅O₂S, ³⁷Cl]⁺, 297.0 (100) [M – C₄H₅O₂S, ³⁵Cl]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₉ClN₂O₃SNa: 437.0697; found: 437.0698.

6-(4-Bromophenyl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3h)

Yield: 90 mg (78%); colorless solid; mp 38–40 °C; R_f = 0.53 (n-pentane–Et₂O, 1:1).

IR (ATR): 1750, 1708, 1595, 1492, 1430, 1398, 1365, 1279, 1214, 1147, 1105, 1054, 1009, 955, 920, 881, 827, 793, 757, 725, 691 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.74–7.70 (m, 2 H, Ar-H), 7.40–7.33 (m, 4 H, Ar-H), 7.24–7.17 (m, 3 H, Ar-H), 5.73 (t, J = 8.6 Hz, 1 H, CHOAc­), 5.07 (s, 1 H, CHAr), 3.80 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.19 (dd, J = 11.1, 8.9 Hz, 1 H, SCHH), 2.37 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.7 (C=O), 169.2 (C=O), 157.1 (C_q), 137.3 (C_q), 132.3 (C_q), 131.8 (2 C, Ar-C), 128.9 (2 C, Ar-C), 128.9 (2 C, Ar-C), 125.6 (Ar-C), 122.8 (C_q), 119.1 (2 C, Ar-C), 79.2 (CHOAc), 68.98 (C_q), 53.5 (CHAr), 33.1 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 460.1 (34) [M, ⁸¹Br]⁺, 458.0 (33) [M, ⁷⁹Br]⁺, 400.0 (62) [M – OAc, ⁸¹Br]⁺, 398.0 (60) [M – OAc, ⁷⁹Br]⁺, 343.1 (94) [M – C₄H₆O₂S, ⁸¹Br]⁺, 341.0 (100) [M – C₄H₆O₂S, ⁷⁹Br]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₉N₂O₃S⁷⁹BrNa: 481.0192; found: 481.0193.

6-(3-Chlorophenyl)-1-methyl-4-oxo-3-phenyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3i)

Yield: 87 mg (84%); colorless solid; mp 119–121 °C; R_f = 0.59 (n-pentane–Et₂O, 1:1).

IR (ATR): 2950, 1728, 1589, 1489, 1361, 1219, 1041, 913, 768, 698 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.72–7.66 (m, 2 H, Ar-H), 7.43 (m, 1 H, Ar-H), 7.39–7.32 (m, 2 H, Ar-H), 7.23–7.10 (m, 4 H, Ar-H), 5.71 (t, J = 8.6 Hz, 1 H, CHOAc), 5.07 (s, 1 H, CHAr), 3.79 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.18 (dd, J = 11.1, 8.9 Hz, 1 H, SCHH), 2.36 (s, 3 H, CH₃), 1.97 (s, 3 H, CH₃).

¹³C NMR (101 MHz, CDCl₃): δ = 170.7 (C=O), 169.2 (C=O), 157.1 (C_q), 137.2 (C_q), 135.4 (C_q), 134.6 (C_q), 129.9 (Ar-C), 129.0 (Ar-C), 128.9 (2 C, Ar-C), 127.3 (Ar-C), 125.7 (Ar-C), 125.5 (Ar-C), 119.3 (2 C, Ar-C), 79.1 (CHOAc), 69.0 (C_q), 53.5 (CHAr), 33.1 (SCH₂), 20.6 (CH₃), 17.7 (CH₃).

MS (EI, 70 eV): m/z (%) = 415.9 (14) [M, ³⁷Cl]⁺, 414.0 (35) [M, ³⁵Cl]⁺, 356.0 (19) [M – HOAc, ³⁷Cl]⁺, 354.0 (48) [M – HOAc, ³⁵Cl]⁺, 298.9 (29) [M – C₄H₅O₂S, ³⁷Cl]⁺, 297.0 (100) [M – C₄H₅O₂S, ³⁵Cl]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₉N₂O₃SClNa: 437.0697; found: 437.0696.

1-Methyl-4-oxo-3-phenyl-6-[4-(trifluoromethyl)phenyl]-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3j)

Yield: 107 mg (95%); colorless solid; mp 40–42 °C; R_f = 0.53 (n-pentane–Et₂O, 1:1).

IR (ATR): 2101, 1712, 1600, 1497, 1322, 1219, 1119, 1053, 921, 846, 755, 688 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.70 (m, 2 H, Ar-H), 7.48 (m, 4 H, Ar-H), 7.37 (m, 2 H, Ar-H), 7.20 (t, J = 7.4 Hz, 1 H, Ar-H), 5.75 (t, J = 8.6 Hz, 1 H, CHOAc), 5.16 (s, 1 H, CHAr), 3.83 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.21 (dd, J = 11.1, 8.9 Hz, 1 H, SCHH), 2.37 (s, 3 H, CH₃), 1.99 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.6 (C=O), 169.2 (C=O), 157.0 (C_q), 137.46 (C_q), 137.2 (C_q), 130.9 (q, J = 32.7 Hz, C_q), 128.9 (2 C, Ar-C), 127.7 (2 C, Ar-C), 125.7 (Ar-C), 125.6 (2 C, Ar-C), 123.7 (q, J = 272.3 Hz, CF₃), 119.1 (2 C, Ar-C), 79.3 (CHOAc), 69.0 (C_q), 53.5 (CHAr), 33.1 (SCH₂), 20.6 (CH₃), 17.7 (CH₃).

¹⁹F NMR (376 MHz, CDCl₃): δ = –62.78 (s).

MS (EI, 70 eV): m/z (%) = 449.0 (7) [M + H]⁺, 447.9 (31) [M]⁺, 387.9 (33) [M – HOAc]⁺, 330.6 (100) [M – C₄H₆O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₁₉N₂O₃S F₃Na: 471.0961; found: 471.0961.

1-Methyl-4-oxo-3-phenyl-6-(2-thienyl)-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3k)

Yield: 82 mg (85%); orange solid; mp 39–41 °C; R_f = 0.46 (n-pentane–Et₂O, 1:1).

IR (ATR): 3073, 2953, 1750, 1708, 1595, 1495, 1431, 1363, 1274, 1215, 1141, 1050, 919, 849, 800, 757, 697 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.81–7.77 (m, 2 H, Ar-H), 7.40–7.35 (m, 2 H, Ar-H), 7.19 (m, 1 H, Ar-H), 7.16 (m, 1 H, Ar-H_2-Thienyl), 6.97 (m, 1 H, Ar-H_2-Thienyl), 6.85 (m, 1 H, Ar-H_2-Thienyl), 5.69 (t, J = 8.6 Hz, 1 H, CHOAc), 5.32 (s, 1 H, CHAr), 3.80 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.21 (dd, J = 11.0, 9.0 Hz, 1 H, SCHH), 2.47 (s, 3 H, CH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.4 (C=O), 169.2 (C=O), 157.4 (C_q), 137.5 (C_q), 136.6 (C_q), 128.9 (2 C, Ar-C), 127.1 (Ar-C), 126.4 (Ar-C), 125.8 (Ar-C), 125.5 (Ar-C), 119.1 (2 C, Ar-C), 78.8 (CHOAc), 69.0 (C_q), 49.3 (CHAr), 33.3 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 387.0 (10) [M + H]⁺, 385.9 (36) [M]⁺, 325.8 (38) [M – HOAc]⁺, 268.7 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₈N₂O₃S₂Na: 409.0651; found: 409.0651.

3-(2-Chlorophenyl)-1-methyl-4-oxo-6-phenyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3l)

Yield: 78 mg (75%); colorless solid; mp 153–155 °C; R_f = 0.50 (n-pentane–Et₂O, 1:1).

IR (ATR): 3016, 2969, 2040, 1740, 1592, 1486, 1443, 1366, 1218, 1052, 919, 763, 701 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.43 (m, 3 H, Ar-H), 7.31–7.25 (m, 5 H, Ar-H), 7.08–7.04 (m, 1 H, Ar-H), 5.76 (t, J = 8.6 Hz, 1 H, CHOAc), 5.14 (s, 1 H, CHAr), 3.78 (dd, J = 11.0, 8.3 Hz, 1 H, SCHH), 3.20 (dd, J = 11.0, 8.9 Hz, 1 H, SCHH), 2.39 (s, 3 H, CH₃), 2.02 (s, 3 H, CH₃).

¹³C NMR (101 MHz, CDCl₃): δ = 169.7 (C=O), 168.9 (C=O), 156.5 (C_q), 133.9 (C_q), 133.8 (C_q), 131.9 (C_q), 130.3 (Ar-C), 129.8 (Ar-C), 128.7 (4 C, Ar-C), 128.5 (2 C, Ar-C), 127.3 (Ar-C), 75.8 (CHOAc), 66.5 (C_q), 49.6 (CHAr), 30.9 (SCH₂), 20.7 (CH₃), 13.7 (CH₃).

MS (EI, 70 eV): m/z (%) = 356.1 (11) [M – HOAc, ³⁷Cl]⁺, 354.1 (27) [M – HOAc, ³⁵Cl]⁺, 299.1 (35) [M – C₄H₅O₂S, ³⁷Cl]⁺, 297.1 (100) [M – C₄H₅O₂S, ³⁵Cl]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₉N₂O₃SClNa: 437.0697; found: 437.0685.

3-(4-Chlorophenyl)-1-methyl-4-oxo-6-phenyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3m)

Yield: 92 mg (89%); yellow oil; R_f = 0.61 (n-pentane–Et₂O, 1:1).

IR (ATR): 2951, 1723, 1595, 1490, 1357, 1215, 1143, 1044, 929, 825, 769, 697 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.70–7.64 (m, 2 H, Ar-H), 7.29 (m, 4 H, Ar-H), 7.23–7.17 (m, 3 H, Ar-H), 5.72 (t, J = 8.5 Hz, 1 H, CHOAc), 5.10 (s, 1 H, CHAr), 3.79 (dd, J = 11.2, 8.3 Hz, 1 H, SCHH), 3.17 (dd, J = 11.2, 8.7 Hz, 1 H, SCHH), 2.36 (s, 3 H, CH₃), 1.96 (s, 3 H, CH₃).

¹³C NMR (101 MHz, CDCl₃): δ = 170.9 (C=O), 169.2 (C=O), 157.8 (C_q), 135.9 (C_q), 132.9 (C_q), 130.5 (C_q), 128.8 (3 C, Ar-C), 128.6 (2 C, Ar-C), 127.1 (2 C, Ar-C), 120.1 (2 C, Ar-C), 79.3 (CHOAc), 69.3 (C_q), 54.5 (CHAr), 33.1 (SCH₂), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 416.0 (14) [M, ³⁷Cl]⁺, 414.0 (36) [M, ³⁵Cl]⁺, 356.0 (18) [M – HOAc, ³⁷Cl]⁺, 354.0 (47) [M – HOAc, ³⁵Cl]⁺, 299.0 (31) [M – C₄H₅O₂S, ³⁷Cl]⁺, 297.0 (100) [M – C₄H₅O₂S, ³⁵Cl]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₉N₂O₃SClNa: 437.0697; found: 437.0697.

1-Methyl-4-oxo-6-phenyl-3-p-tolyl-7-thia-2,3-diaza­spiro[4.4]non-1-en-9-yl Acetate (3n)

Yield: 85 mg (86%); brown solid; mp 37–39 °C; R_f = 0.56 (n-pentane–Et₂O, 1:1).

IR (ATR): 3479, 2940, 2655, 2333, 2099, 1719, 1613, 1510, 1362, 1215, 1044, 919, 814, 698 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.59–7.54 (m, 2 H, Ar-H), 7.36–7.33 (m, 2 H, Ar-H), 7.24–7.20 (m, 3 H, Ar-H), 7.17–7.14 (m, 2 H, Ar-H), 5.74 (t, J = 8.5 Hz, 1 H, CHOAc), 5.13 (s, 1 H, CHAr), 3.81 (dd, J = 11.1, 8.3 Hz, 1 H, SCHH), 3.18 (dd, J = 11.1, 8.8 Hz, 1 H, SCHH), 2.37 (s, 3 H, CH₃), 2.33 (s, 3 H, ArCH₃), 1.98 (s, 3 H, CH₃).

¹³C NMR (151 MHz, CDCl₃): δ = 170.7 (C=O), 169.3 (C=O), 157.3 (C_q), 135.3 (C_q), 135.0 (C_q), 133.1 (C_q), 129.3 (2 C, Ar-C), 128.7 (Ar-C), 128.6 (2 C, Ar-C), 127.2 (2 C, Ar-C), 119.2 (2 C, Ar-C), 79.3 (CHOAc), 69.1 (C_q), 54.2 (CHAr), 33.0 (SCH₂), 21.0 (CH₃), 20.6 (CH₃), 17.8 (CH₃).

MS (EI, 70 eV): m/z (%) = 395.2 (10) [M + H]⁺, 394.2 (26) [M]⁺, 334.1 (21) [M – HOAc]⁺, 277.1 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₃SNa: 395.1424; found: 395.1423.

1-Isopropyl-4-oxo-3,6-diphenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3o)

Yield: 55 mg (54%); yellow solid; mp 101–103 °C; R_f = 0.63 (n-pentane–Et₂O, 1:1).

IR (ATR): 2973, 1749, 1710, 1596, 1495, 1452, 1355, 1217, 1148, 1051, 979, 921, 883, 753, 693 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.79 (m, 2 H, Ar-H_Diast), 7.52 (m, 2 H, Ar-H), 7.47–7.43 (m, 2 H, Ar-H, Ar-H), 7.39 (m, 2 H, Ar-H_Diast), 7.33 (m, 2 H, Ar-H, Ar-H_Diast), 7.30–7.25 (m, 4 H, Ar-H, Ar-H_Diast), 7.24–7.19 (m, 4 H, Ar-H, Ar-H_Diast), 7.17 (m, 1 H, Ar-H_Diast), 7.11 (m, 1 H, Ar-H), 5.75 (dd, J = 10.1, 7.8 Hz, 1 H, CHOAc_Diast), 5.68 (dd, J = 9.9, 7.1 Hz, 1 H, CHOAc), 5.19 (s, 1 H, CHAr_Diast), 4.95 (s, 1 H, CHAr), 3.99 (t, J = 9.7 Hz, 1 H, SCHH), 3.75 (dd, J = 10.6, 7.8 Hz, 1 H, SCHH_Diast), 3.44 (dd, J = 9.5, 7.1 Hz, 1 H, SCHH), 3.23 (t, J = 10.3 Hz, 1 H, SCHH _Diast), 3.12 (m, 1 H, CH(CH₃)_2Diast), 2.91 (m, 1 H, CH(CH₃)₂), 1.98 (s, 3 H, CH₃), 1.96 (s, 3 H, CH_3Diast), 1.43 (d, J = 6.8 Hz, 3 H, CH₃ ( ⁱ Pr)), 1.31 (d, J = 6.8 Hz, 3 H, CH₃ ( ⁱ Pr)_Diast), 1.21 (d, J = 6.8 Hz, 3 H, CH₃ ( ⁱ Pr)), 0.80 (d, J = 6.7 Hz, 3 H, CH₃ ( ⁱ Pr)_Diast).

¹³C NMR (151 MHz, CDCl₃): δ = 171.0 (C=O_Diast), 169.9 (C=O), 169.1 (C=O), 168.7 (C=O_Diast), 165.4 (C_{q Diast}), 163.6 (C_q), 137.7 (C_{q Diast}), 137.3 (C_q), 134.0 (C_{q Diast}), 133.8 (C_q), 128.8 (2 C, Ar-C_Diast), 128.7 (2 C, Ar-C), 128.6 (2 C, Ar-C_Diast), 128.5 (2 C, Ar-C), 128.3 (2 C, Ar-C), 127.3 (2 C, Ar-C_Diast), 125.4 (2 C, Ar-C_Diast), 125.2 (2 C, Ar-C), 119.3 (2 C, Ar-C), 119.1 (2 C, Ar-C_Diast), 79.8 (CHOAc_Diast), 76.5 (CHOAc), 69.5 (C_{q Diast}), 67.7 (C_q), 53.0 (CHAr_Diast), 49.7 (CHAr), 32.3 (SCH_{2 Diast}), 30.7 (SCH₂), 29.7 (CH(CH₃)_{2 Diast}), 27.2 (CH(CH₃)₂), 22.8 (CH_{3 Diast}), 22.3 (CH₃), 20.8 (2 C, CH(CH₃)_{2 Diast}), 20.6 (2 C, CH(CH₃)₂).

MS (EI, 70 eV): m/z (%) = 408.1 (3) [M]⁺, 348.1 (13) [M – HOAc]⁺, 291.2 (67) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₂₄N₂O₃SNa: 409.1580; found: 409.1573.

1-tert-Butyl-4-oxo-3,6-diphenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3p)

Yield: 44 mg (42%); orange solid; mp 155–157 °C; R_f = 0.70 (n-pentane–Et₂O, 1:1).

IR (ATR): 2965, 1721, 1596, 1490, 1373, 1218, 1044, 967, 849, 748 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.45 (m, 4 H, Ar-H), 7.28–7.24 (m, 2 H, Ar-H), 7.21 (m, 2 H, Ar-H), 7.17–7.12 (m, 1 H, Ar-H), 7.09 (m, 1 H, Ar-H), 5.91 (dd, J = 9.7, 7.2 Hz, 1 H, CHOAc), 5.32 (s, 1 H, CHAr), 4.01 (t, J = 9.6 Hz, 1 H, SCHH), 3.43 (dd, J = 9.5, 7.2 Hz, 1 H, SCHH), 1.98 (s, 3 H, CH₃), 1.47 (s, 9 H, ^t Bu).

¹³C NMR (151 MHz, CDCl₃): δ = 170.0 (C=O), 168.9 (C=O), 163.6 (C_q), 137.1 (C_q), 134.3 (C_q), 128.5 (Ar-C), 128.5 (2 C, Ar-C), 128.4 (2 C, Ar-C), 128.1 (2 C, Ar-C), 125.2 (Ar-C), 119.2 (2 C, Ar-C), 77.0 (CHOAc), 68.4 (C_q), 48.5 (CHAr), 37.1 (C(CH₃)₃), 30.5 (SCH₂), 29.8 (3 C, ^t Bu), 20.7 (CH₃).

MS (EI, 70 eV): m/z (%) = 423.2 (36) [M + H]⁺, 422.2 (18) [M]⁺, 362.1 (89) [M – HOAc]⁺, 305.0 (100) [M – C₄H₅O₂S]⁺.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₄H₂₇N₂O₃S: 423.1737; found: 423.1736.

1-Ethyl-4-oxo-3,6-diphenyl-7-thia-2,3-diazaspiro[4.4]non-1-en-9-yl Acetate (3q)

Yield: 74 mg (76%); colorless oil; R_f = 0.65 (n-pentane–Et₂O, 1:1).

IR (ATR): 2978, 2940, 2106, 1751, 1708, 1596, 1495, 1453, 1353, 1218, 1142, 1049, 957, 913, 837, 800, 757, 728, 696 cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.74 (m, 2 H, Ar-H), 7.39–7.31 (m, 5 H, Ar-H), 7.24–7.20 (m, 3 H, Ar-H), 5.73 (t, J = 8.6 Hz, 1 H, CHOAc), 5.13 (s, 1 H, CHAr), 3.79 (dd, J = 11.0, 8.2 Hz, 1 H, SCHH), 3.17 (dd, J = 10.9, 9.1 Hz, 1 H, SCHH), 2.68–2.58 (m, 2 H, CH ₂CH3), 1.97 (s, 3 H, CH₃), 1.12 (t, J = 7.2 Hz, 3 H, CH₂CH ₃).

¹³C NMR (151 MHz, CDCl₃): δ = 171.0 (C=O), 169.3 (C=O), 161.3 (C_q), 137.6 (C_q), 133.3 (C_q), 128.8 (2 C, Ar-C), 128.7 (Ar-C), 128.5 (2 C, Ar-C), 127.2 (Ar-C), 125.4 (2 C, Ar-C), 119.1 (2 C, Ar-C), 79.3 (CHOAc), 69.2 (C_q), 54.2 (CHAr), 33.1 (SCH₂), 24.5 (CH₂), 20.7 (CH₃), 9.0 (CH₂ CH₃).

MS (EI, 70 eV): m/z (%) = 394.0 (3) [M]⁺, 333.9 (12) [M – HOAc]⁺, 77.2 (100) [C₆H₅]⁺.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂N₂O₃SNa: 417.1243; found: 417.1242.

Acknowledgment

Financial support from the European Research Council (ERC Advanced Grant 320493 ‘DOMINOCAT’) is gratefully acknowledged.

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• 14 CCDC 1484545 (3i) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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