Sequential olefination–dimerisation of benzylic dithioacetals by the nickel-catalysed reaction with methyl Grignard or zinc reagent

Abstract

Products of main group elements from cross-coupling reactions have been shown to serve as Lewis acids, mediating further reactions of organic coupling products. Thus, the nickel-catalysed olefination of benzylic dithioacetal with MeMgI in benzene in a sealed Schlenk tube at 130 °C generates magnesium mercaptide which regioselectively converts 2-arylpropene into a dimer in good yield. Aryl iodide reacts with 2-propenylmagnesium bromide in the presence of 1,2-ethanedithiol and NiCl₂(PPh₃)₂ to yield the same dimer. Replacement of the Grignard reagent by an organozinc reagent gives the dimers in a better yield.

---

Introduction

Transition metal-catalysed cross coupling reactions have significantly contributed to the formation of carbon–carbon bonds.^1–3 In general, these reactions require an organic electrophile, a transition-metal catalyst, and a main group organometallic compound as a nucleophile. After the reaction is complete, the main group element is converted into the corresponding inorganic salt or equivalent. To illustrate this, Mg(II) and Zn(II) are produced from Kumada–Corriu–Tamao² and Negishi³ reactions, respectively. These in situ generated inorganic salts can serve as a Lewis acid catalyst⁴ or a reagent to mediate further reactions of the cross-coupling product. In particular, these Lewis catalysed reactions can even take place in strong basic conditions. For example, the regioselective ring-opening of acetals of contiguous polyols, such as monosaccharides or inositols, by a Grignard regent is well documented (eqn (1)).⁵

Dimerisation of α-methylstyrene 1 under various conditions, leading to different kinds of products 2–4, has been extensively studied (eqn (2)).^6–8 Under strong acidic conditions or longer reaction times, indane derivative 2 is obtained predominantly, if not exclusively.⁶ Regioisomers 3 and 4 are occasionally isolated as a mixture under acid-catalysed conditions.^6a–c,7 Notably, these pentene derivatives are industrially important to serve as chain-transfer agents or molecular weight regulators for styrene-based polymers or copolymers.^6–8

Compound 1 can readily be obtained by the nickel-catalysed olefination^9,10 of benzylic dithioacetals 5 with excess MeMgI under conditions similar to those of the Kumada–Corriu–Tamao reaction (eqn (3)).² As previously mentioned, Mg(II) salt will be generated from this reaction. Compound 1 may be vulnerable to further transformation under these reaction conditions. Since Mg(II) can be considered as a mild Lewis acid, it is envisaged that dimerisation might take place to give 3 and/or 4, but not the Friedel–Crafts product 2. In this paper, we wish to report for the first time the direct conversion of 5 to 6 regioselectively under cross-coupling reaction conditions.

Results and discussion

NiCl₂(PPh₃)₂MeMgI catalysed olefination–dimerisation reactions with 5a

Treatment of 5a with MeMgI in the presence of 10 mol% of NiCl₂(PPh₃)₂ in refluxing benzene gave 67% of the corresponding dimer 6a. The isolation of 6a from the reaction under the conditions of the Kumada–Tamao reaction^2a is striking. The reaction mixture may contain a Grignard reagent or a Mg(II), Ni(II) or Ni(0) catalyst, Ph₃P, and ⁻SCH₂CH₂S⁻. It seems likely that some of these components might be responsible for promoting the formation of 6 from 1. Our initial aim was to find suitable conditions to give 6 predominantly, if not exclusively.

Effect of halide X in MeMgX on the dimerisation step

The halogen atom in the Grignard reagent has been shown to play an important role in the reactivity of the reaction (eqn (4)). A sealed Schlenk tube was chosen for the reaction of 5a with the Grignard reagent in benzene and the reaction tube was immersed in an oil bath at 130 °C for 24 h. When MeMgCl was employed, the ratio of 1a to 6a was 87/13. The ratio changed to 37/63 if MeMgBr was used. MeMgI, on the other hand, gave excellent selectivity with 1a/6a = 4/96. The magnesium ion liberated during the course of the cross-coupling reaction would interact with the negatively charged halide and/or sulfide moieties. Apparently, when these softer anions are associated with magnesium ion, the reactivity of the magnesium ion would be enhanced and dimer 6a would be formed preferentially.

Effect of ⁻SCH₂CH₂S⁻ on the reactivity of dimerisation of 1a

Since ⁻SCH₂CH₂S⁻ would be generated from the olefination of dithiolanes, it seems likely that the sulfide moiety might also bind to the magnesium ion that might promote the formation of dimer 6. Dimerisation of 1a to 6a has been carefully examined. Notably, there is no sulfur atom in 1a. In the absence of 1,2-ethanedithiol, no dimerisation took place. Interestingly, a benzene solution of 1a, MeMgI, and HSCH₂CH₂SH (1 : 3 : 1) in a sealed Schlenk tube was heated to 130 °C for 24 h. Only 23% of conversion of 1a was observed and the ratio of dimer 6a versus unreacted 1a was 22 to 78. When 10 mol% of NiCl₂(PPh₃)₂ was added to the reaction mixture, only 3% of the starting 1a was recovered and the yield of 6a was improved to 67%. It is worth mentioning that no dimer 6a was detected from the mixture without MeMgI. In other words, NiCl₂(PPh₃)₂-HSCH₂CH₂SH alone does not catalyse the dimerisation of 1a at all. Presumably, the direct displacement of the chloride by a mercaptan would generate HCl that would not be a favored process.

Examples of sequential olefination–dimerisation reactions

Being successful in this transformation shown in eqn (5), we tested the generality of this catalyst system for sequential olefination–dimerisation. The reaction mixture consists of excess Grignard reagent and the medium should, therefore, be basic. The Lewis acidity of magnesium may not be active enough to promote the dimerisation process. It is envisaged that zinc might be a stronger Lewis acid. Accordingly, the reactivity of the organozinc reagent obtained by the addition of ZnI₂ to the above Grignard reagent was also examined and the results are compared in Table 1.

Table 1 A comparison of the yields of 6 from the NiCl₂(PPh₃)₂-catalysed reactions of 5 with MeMgI in benzene in the absence or presence of ZnI₂^a

Ar in dithioacetal 5	% yield of 6 (without ZnI2)	% yield of 6 (With ZnI2)
a Conditions: a sealed Schlenk tube containing 3, NiCl2(PPh3)2 (10 mol%) and MeMgI (4 equiv.), with or without ZnI2 (4 equiv.), was heated at 130 °C for 24 h, unless otherwise specified.b Reaction for 48 h.
4-Me2NC6H4 (5a)	88	76
4-HOC6H4 (5b)	82	89
4-MeOC6H4 (5c)	52^b	81
4-^tBuC6H4 (5d)	48^b	67
4-^iPrC6H4 (5e)	43^b	78
4-MeC6H4 (5f)	21	74
C6H5 (5g)	10	64
4-CF3C6H4 (5h)	—	—

---

Substrates with highly electron-donating substituents gave the corresponding 6 in a much better yield than those with alkyl substituents. The compound with an electron withdrawing group, such as the CF₃ group, gave the corresponding olefination product 1h only. These results imply that the dimerisation reaction may proceed via a carbocation-like mechanism. Notably, organozinc reagent appears to be more potent than the corresponding Grignard reagent in these sequential olefination–dimerisation reactions.

Nickel-catalysed sequential cross coupling-dimerisation of aryl iodide 7 with H₂C=C(Me)MgBr/ZnI₂

Dimer 6a could also be obtained from the reaction of 7a with 7 equiv. each of the 2-propenyl Grignard reagent and ZnI₂ in the presence of 10 mol% of NiCl₂(PPh₃)₂, and 1 equiv. of 1,2-ethanedithiol at rt for 6 h. The temperature was then raised to 130 °C for 42 h to give, after workup, 6a in 72% yield (eqn (6)). When 1,2-ethanedithiol was replaced by 2 equiv. of propanethiol, otherwise under the same conditions, dimer 6a and monomer 1a were obtained in 15 and 44% yield, respectively.

Without 1,2-ethanedithiol, the reaction stopped at the 1a stage and no dimer 6a was detected. These results suggest that the presence of bismercaptan is essential to facilitate the formation of dimer 6a. Representative examples are tabulated in Table 2.

Table 2 A comparison of the yields of 6 from the NiCl₂(PPh₃)₂-catalysed reactions of 7 or 8 with H₂C=C(Me)MgBr, ZnI₂ and HSCH₂CH₂SH in benzene^a

Aryl halide	6 (% yield)	1 (% yield)
a Conditions: in a sealed Schlenk tube, a mixture of 7, NiCl2(PPh3)2 (10 mol%), H2C=C(Me)MgBr (7 equiv.), ZnI2 (7 equiv.) and HSCH2CH2SH (1 equiv.) was stirred at rt for 6 h and then heated at 130 °C for 42 h.
7a	6a (72)	1a (7)
7c	6c (47)	1c (16)
7d	6d (37)	1d (30)
8a	6a (56)	1a (17)
8b	6e (55)	1e (34)

---

As can be seen from Table 2, the yield of 6 is no more than moderate, a significant amount of the intermediate product 1 being obtained. In addition, the reaction is much longer than those starting with dithioacetals shown in Table 1. As shown in eqn (4), the nature of the halide in the Grignard reagent may exhibit different reactivity in the overall sequential reaction.

Possible nature of the Lewis acid catalyst for the dimerisation step

In the reaction mixture, there are two (Column 2 of Table 1 and eqn (6)) or three (Column 3 of Table 1) kinds of divalent metallic species that can serve as a Lewis acid catalyst for the dimerisation step. They are Mg(II), Ni(II) and/or Zn(II). As can be seen from Table 1, the yields of reactions in the presence of ZnI₂ (Column 3) are, in general, much higher than those without the ZnI₂ additive (Column 2). It seems likely that Zn(II) might be a more active catalyst than Mg(II) for the dimerisation step.

As shown in eqn (5), the addition of NiCl₂(PPh₃)₂ to the MeMgI–HSCH₂CH₂SH mixture will significantly accelerate the dimerisation of 1a. Grignard reagent is known to reduce Ni(II) to Ni(0). The role of the nickel species rendering the dimerisation of 1a is not clear.

Another interesting feature in this sequential reaction is the regioselectivity for the formation of the double bond in 6. In other words, no double bond migration (like 4) would take place under the reaction conditions. Whether the nickel catalyst would be involved in the regioselective formation of the double bond in 6 remains to be clarified.

Conclusions

In summary, we have demonstrated the first example of using the main-group by-product from the transition-metal catalysed cross-coupling reaction as the second catalyst to mediate further reaction of the main coupling product. Thus, under Kumada–Corriu–Tamao reaction conditions,² the cascade olefination–dimerisation of benzylic dithioacetals derived from acetophenones affords the corresponding dimers 6 via 2-arylpropenes 1. Incorporation of ZnI₂ has been shown to significantly improve the yield of the reaction. An extension of this reaction to aryl iodide 7 by applying the catalytic system NiCl₂(PPh₃)₂-H₂C=C(Me)MgBr–ZnI₂–HSCH₂CH₂SH to promote the cross-coupling and dimerisation leads to the same dimeric products 6. The Lewis acid character of the product of the main group element [Mg(II) or Zn(II)] from the transition metal catalysed cross-coupling reaction may play a critical role for the dimerisation process of the organic coupling products. The presence of 1,2-ethanedithiol is also crucial for the success of these sequential reactions. Presumably, chelation of the sulfur moiety to Mg(II) or Zn(II) may tune the catalytic activity for the dimerisation step. Indeed, the involvement of this dithiol for the dimerisation of 2-arylpropenes can be understood within this framework. The application of this strategy to other cross-coupling reactions is in progress in our laboratories.

Experimental section

General information

All melting points were measured on an SGW X-4A apparatus and were uncorrected. ¹H and ¹³C NMR nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Advance 400 MHz spectrometer at ambient temperature. Chemical shifts (δ) and coupling constants (J) were expressed in units of ppm and Hz, respectively. Samples for measurements were dissolved in CDCl₃. The residual peak of CHCl₃ at δ 7.26 was used as the reference for ¹H NMR chemical shifts and the central peak at δ 77.16 of CDCl₃ was used as the reference for ¹³C NMR chemical shifts. Infrared spectra were taken on a Nicolet 700 FT infrared spectrophotometer using a KBr plate for solid samples or forming a film on an NaCl window.

Materials

Compounds 5b, 5e, 5f and 5g were prepared according to a literature procedure.⁷

General procedure for the synthesis of dithioacetals

To a chloroform solution (50 mL) of acetophenone derivative (20 mmol) and 1,2-ethanedithiol (density = 1.123 g cm⁻³, 22–44 mmol), boron trifluoride etherate (density = 1.15 g cm⁻³, 14–34 mmol) was added. The mixture was stirred at rt overnight. The solution was washed twice with 10% aqueous sodium hydroxide (30 mL) and the aqueous layer was extracted twice with DCM (20 mL). The combined organic layers were washed twice with water (50 mL), dried (Na₂SO₄) and filtered. The solvent was removed in vacuo and the residue was chromatographed on silica gel using petroleum ether and ethyl acetate as the eluent to give the corresponding dithioacetals.

2-[4-(Dimethylamino)phenyl]-2-methyl-1,3-dithiolane (5a). In a manner similar to that described in the general procedure, a mixture of 4-(dimethylamino)acetophenone (3.26 g, 20 mmol), 1,2-ethanedithiol (density = 1.123 g cm⁻³, 1.8 mL, 22 mmol), and boron trifluoride etherate (density = 1.15 g cm⁻³, 4.2 mL, 34 mmol) was converted to 5a (4.20 g, 88%) as a yellow solid: mp 47–48 °C; ¹H NMR (CDCl₃, 400 MHz) δ 7.63–7.60 (m, 2H), 6.68–6.66 (m, 2H), 3.52–3.36 (m, 4H), 2.94 (s, 6H), 2.15 (s, 3H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 149.6, 132.8, 127.7, 111.8, 68.4, 40.6, 40.4, 33.9 ppm; HRMS (ESI, m/z): [M + H]⁺ calculated for C₁₂H₁₈S₂: 240.0875, found 240.0869.

2-Methyl-2-(4-t-butylphenyl)-1,3-dithiolane (5d). In a manner similar to that described in the general procedure, a mixture of 4-t-butylacetophenone (3.53 g, 20 mmol), 1,2-ethanedithiol (density = 1.123 g cm⁻³, 1.8 mL, 22 mmol), and boron trifluoride etherate (density = 1.15 g cm⁻³, 1.7 mL, 14 mmol) was converted to 5d (4.13 g, 81%) as a white solid: mp 73–74 °C; ¹H NMR (CDCl₃, 400 MHz) δ 7.74 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 3.57–3.38 (m, 4H), 2.22 (s, 3H), 1.38 (s, 9H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 149.9, 142.8, 126.5, 125.0, 68.4, 40.5, 34.5, 34.1, 31.4 ppm; IR (KBr, cm⁻¹): 2961, 1499, 1396, 1363, 1267, 1111, 1071, 1012, 829, 729; HRMS (ESI, m/z): [M + H]⁺ calculated for C₁₄H₂₁S₂: 253.1079, found 253.1085.

2-Methyl-2-(4-isopropylphenyl)-1,3-dithiolane (5e). In a manner similar to that described in the general procedure, a mixture of 4-propylacetophenone (3.25 g, 20 mmol), 1,2-ethanedithiol (density = 1.123 g cm⁻³, 1.8 mL, 22 mmol), and boron trifluoride etherate (density = 1.15 g cm⁻³, 1.7 mL, 14 mmol) was converted to 5e (4.17 g, 87%) as a colourless oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.58–7.56 (m, 2H), 7.08–7.06 (m, 2H), 3.41–3.17 (m, 4H), 2.80 (d, J = 6.9 Hz, 1H), 2.06 (s, 3H), 1.15 (d, J = 6.9 Hz, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 147.7, 143.2, 126.8, 126.1, 68.5, 40.4, 34.1, 33.7, 24.0 ppm; IR (KBr, cm⁻¹): 2959, 1503, 1411, 1275, 1075, 1016, 833, 698; HRMS (APCI, m/z): [M + H]⁺ calculated for C₁₃H₁₉S₂: 239.0923, found 239.0917.

General procedure for the NiCl₂(PPh₃)₂-catalysed reaction of dithioacetal 5 with MeMgX

In a sealed Schlenk tube, a benzene solution of dithioacetal (0.5 mmol), NiCl₂(PPh₃)₂ (0.05 mmol), and MeMgI (3 M in ether, 2–3 mmol) was immersed in an oil bath at 130 °C for 24 or 48 h. The mixture was then poured into saturated Na₂CO₃ solution. The organic layer was separated and the aqueous layer was extracted twice (10 mL) with diethyl ether. The combined organic portions were washed twice each (10 mL) with 10% NaOH and brine (10 mL), and dried (Na₂SO₄). The solvent was removed in vacuo and the residue was chromatographed on silica gel (petroleum ether and EtOAc) to give the product.

2,4-Bis-(4-dimethylaminephenyl)-4-methylpent-1-ene (6a). In a manner similar to that described in the general procedure, a mixture of 5a (120 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 24 h. After workup, the product 6a (71 mg, 88%) was obtained as a colourless solid: mp 47–48 °C; ¹H NMR (CDCl₃, 400 MHz) δ 7.15–7.11 (m, 4H), 6.61–6.53 (m, 4H), 5.04–5.00 (br, 1H), 4.58 (br, 1H), 2.84 (s, 6H), 2.82 (s, 6H), 2.67 (s, 2H), 1.10 (s, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 149.7, 148.6, 146.3, 138.6, 131.9, 127.3, 126.5, 113.9, 112.6, 112.2, 49.4, 40.9, 40.7, 37.9, 28.9 ppm; IR (KBr, cm⁻¹): 3290, 1610, 1512, 1435, 1362, 1222, 1177, 895, 829; HRMS (ESI, m/z): [M + H]⁺ calculated for C₂₂H₃₁N₂: 323.2482, found 323.2480.

2,4-Bis-(4-hydroxypheny)-4-methylpent-1-ene (6b). In a manner similar to that described in the general procedure, a mixture of 5b (104 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgI (1 mL, 3 M in ether, 3 mmol) was immersed in an oil bath at 130 °C for 24 h. After workup, the product 6b (61 mg, 82%) was obtained as a white solid: mp 130–131 °C (lit^7b 127.8 °C); ¹H NMR (CDCl₃, 400 MHz) δ 7.12–7.07 (m, 4H), 6.68–6.66 (m, 4H), 5.07 (d, J = 1.6 Hz, 1H), 4.97 (br, 1H), 4.85 (s, 1H), 4.72 (s, 1H), 2.74 (s, 2H), 1.20 (s, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 154.3, 153.0, 146.2, 141.6, 136.0, 127.8, 127.2, 115.4, 114.8, 114.5, 50.1, 37.9, 28.9.; IR (KBr, cm⁻¹): 3291, 1611, 1513, 1435, 1367, 1222, 1179, 895, 829, HRMS (ESI, m/z): [M + Na]⁺ calculated for C₁₈H₂₀NaO₂: 291.1356, found 291.1361. The spectroscopic properties of 6b were identical to those reported in the literature.^7b

2,4-Bis-(4-methoxyphenyl)-4-methylpent-1-ene (6c). In a manner similar to that described in the general procedure, a mixture of 5c (113 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 48 h. After workup, the product 6c (39 mg, 52%) was obtained as a brown oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.21–7.14 (m, 4H), 6.79–6.73 (m, 4H), 5.08 (d, J = 2.0 Hz, 1H), 4.70 (br, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 2.76 (s, 2H), 1.19 (s, 6H); ¹³C NMR (CDCl₃, 101 MHz) δ 158.6, 157.3, 146.1, 141.7, 136.0, 127.6, 126.9, 115.4, 113.4, 113.1, 55.2, 49.8, 38.1, 28.9, ppm; IR (KBr, cm⁻¹): 2959, 1607, 1509, 1463, 1243, 1179, 1034, 892, 827; HRMS (ESI, m/z): [M + Na]⁺ calculated for C₂₀H₂₄NaO₂: 319.1669, found 319.1657. The spectroscopic properties of 6c were identical to those reported in the literature.^7b

2,4-Bis-(4-t-butylphenyl)-4-methylpent-1-ene (6d). In a manner similar to that described in the general procedure, a mixture of 5d (126 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 10 mol%), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 48 h. After workup, the product 6d (42 mg, 48%) was obtained as a yellow oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.18–7.08 (m, 8H), 5.09 (br, 1H), 4.71 (br, 1H), 2.72 (s, 2H), 1.24–1.19 (m, 18H), 1.14 (s, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 149.7, 148.0, 146.7, 146.4, 140.4, 126.1, 125.5, 124.8, 124.6, 116.2, 49.4, 38.2, 34.4, 34.2, 31.5, 31.4, 28.7; IR (KBr, cm⁻¹): 2959, 1736, 1459, 1173, 832; HRMS (APCI, m/z): [M + H]⁺ calculated for C₂₆H₃₄N: 366.3155, found 366.3149. The spectroscopic properties of 6d were identical to those reported in the literature.^7b

2,4-Bis-4-isopropylphenyl-4-methylpent-1-ene (6e). In a manner similar to that described in the general procedure, a mixture of 5e (119 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 48 h. After workup, the product 6e (34 mg, 43%) was obtained as a yellow oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.35–7.26 (m, 4H), 7.22–7.15 (m, 4H), 5.27 (br, 1H), 4.91 (br, 1H), 3.07–2.87 (m, 4H), 1.46–1.28 (m, 18H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 147.4, 146.6, 145.7, 140.8, 126.35, 125.9, 125.8, 125.7, 116.1, 49.6, 38.2, 33.8, 33.5, 28.7, 24.0, 24.0; IR (KBr, cm⁻¹) 2959, 1510, 1460, 1362, 1053, 1016, 896, 828, 700; HRMS (APCI, m/z): [M + NH]⁺ calculated for C₂₄H₃₆N: 338.2842, found 338.2838. The spectroscopic properties of 6e were identical to those reported in the literature.^7b

2,4-Bis-(4-methylphenyL)-4-methylpent-1-ene (6f). In a manner similar to that described in the general procedure, a mixture of 5f (137 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgI (1 mL, 3 M in ether, 3 mmol) was immersed in an oil bath at 130 °C for 24 h. After workup, the product 6f (14 mg, 21%) was obtained as a yellow oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.21–7.17 (m, 4H), 7.07–7.05 (m, 4H), 5.14 (d, J = 1.9 Hz, 1H), 4.75 (br, 1H), 2.80 (s, 2H), 2.33 (s, 3H), 2.31 (s, 3H), 1.20 (s, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 146.8, 146.5, 140.7, 136.5, 134.8, 128.7, 128.5, 126.4, 125.8, 116.1, 49.6, 38.4, 28.8, 21.1, 20.8.; IR (KBr, cm⁻¹): 2922, 1512, 1019, 897, 815, 733; HRMS (APCI, m/z): [M + NH]⁺ calculated for C₂₀H₂₈N: 282.2216, found 282.2209. The spectroscopic properties of 6f were identical to those reported in the literature.^7b

2,4-Diphenyl-4-methylpent-1-ene (6g). In a manner similar to that described in the general procedure, a mixture of 5g (98 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 10 mol%), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 24 h. After workup, the product 6g (6 mg, 10%) was obtained as a colourless oil: ¹H NMR (CDCl₃, 400 MHz) δ 7.25–7.07 (m, 10H), 5.06 (d, J = 1.9 Hz, 1H), 4.70 (d, J = 1.9 Hz, 1H), 2.75 (s, 2H), 1.14 (s, 6H) ppm; ¹³C NMR (CDCl₃, 101 MHz) δ 149.4, 146.7, 143.5, 128.0, 127.9, 126.9, 126.5, 126.0, 125.5, 116.9, 49.6, 38.7, 28.8; IR (KBr, cm⁻¹): 2963, 1260, 1112, 1015, 795; HRMS (APCI, m/z): [M + H]⁺ calculated for C₁₈H₂₁: 237.1638, found 237.1632. The spectroscopic properties of 6g were identical to those reported in the literature.^7b

General procedure for the nickel-catalysed reaction of dithioacetal with organozinc reagent

In a manner of the same procedure as described above except ZnI₂ (0–3 mmol) was added to the reaction mixture, which was heated at 130 °C for 24 h.

Compound 6a. In a manner similar to that described in the general procedure, a mixture of 5a (120 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (638 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6a (61 mg, 76%).

Compound 6b. In a manner similar to that described in the general procedure, a mixture of 5b (104 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (957 mg, 3 mmol), and MeMgI (1 mL, 3 M in ether, 3 mmol) was converted to 6b (66 mg, 89%).

Compound 6c. In a manner similar to that described in the general procedure, a mixture of 5c (113 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (638 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6c (60 mg, 81%).

Compound 6d. In a manner similar to that described in the general procedure, a mixture of 5d (126 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 10 mol%), ZnI₂ (638 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6d (58 mg, 67%).

Compound 6e. In a manner similar to that described in the general procedure, a mixture of 5e (119 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (638 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6e (62 mg, 78%).

Compound 6f. In a manner similar to that described in the general procedure, a mixture of 5f (137 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (957 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6f (49 mg, 74%).

Compound 6g. In a manner similar to that described in the general procedure, a mixture of 5g (98 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 10 mol%), ZnI₂ (638 mg, 2 mmol), and MeMgI (0.7 mL, 3 M in ether, 2.1 mmol) was converted to 6g (38 mg, 64%).

General procedure for the reaction of aryl halides with 2-propenylmagnesium bromide in the presence of NiCl₂(PPh₃)₂, ZnI₂ and 1,2-ethanedithiol

THF was removed from the solution of 2-propenylmagnesium bromide (3.5 mL, 1 M in THF, 3.5 mmol) and benzene (1 mL) was then added. To a Schlenk tube containing aryl halide (0.5 mmol), NiCl₂(PPh₃)₂ (0.05 mmol), ZnI₂ (3.5 mmol) and 1,2-ethanedithiol (0.5 mmol) in benzene (1 mL), the benzene solution of 2-propenyl Grignard reagent was added. The mixture was then poured into saturated Na₂CO₃ solution. The organic layer was separated and the aqueous layer was extracted twice (10 mL) with diethyl ether. The combined organic portions were washed twice each (10 mL) with 10% NaOH and brine (10 mL), and dried (Na₂SO₄). The solvent was removed in vacuo and the residue was chromatographed on silica gel (petroleum ether and EtOAc) to give the product.

Reaction of 7a. In a manner of the general procedure as described above, to a mixture of 2-propenylmagnesium bromide (3.5 mmol), 4-iodo-N,N-dimethylaminebenzene 7a (124 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (1.11 g, 3.5 mmol) and 1,2-ethanedithiol (0.04 mL, 0.5 mmol) in benzene (1 mL), the benzene solution of 2-propenyl Grignard reagent was added. The mixture was stirred for 6 h at rt and the temperature was raised to 130 °C and the mixture was stirred for 42 h. After workup, the mixture compound was chromatographed on silica gel (petroleum ether : EtOAc = 9 : 1) to give 1a (6 mg, 7%) and 6a (58 mg, 72%).

Reaction of 7c. In a manner of the general procedure as described above, a mixture of 2-propenylmagnesium bromide (3.5 mmol), 4-iodoanisole 7c (117 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (1.11 g, 3.5 mmol) and 1,2-ethanedithiol (0.04 mL, 0.5 mmol) in benzene was stirred for 6 h at rt and the temperature was raised to 130 °C and the mixture was stirred for 42 h. After workup, the mixture compound was chromatographed on silica gel (petroleum ether) to give 1c (12 mg, 16%) and 6c (35 mg, 47%).

Reaction of 7d. In a manner of the general procedure as described above, a mixture of 2-propenylmagnesium bromide (3.5 mmol), 4-tert-butyliodobenzene 7d (130 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (1.11 g, 3.5 mmol) and 1,2-ethanedithiol (0.04 mL, 0.5 mmol) in benzene was stirred for 6 h at rt and the temperature was raised to 130 °C and the mixture was stirred for 42 h. After workup, the mixture compound was chromatographed on silica gel (petroleum ether) to give 1d (26 mg, 30%) and 6d (32 mg, 37%).

Reaction of 8a. In a manner of the general procedure as described above, a mixture of 2-propenylmagnesium bromide (3.5 mmol), 4-bromo-N,N-dimethylaminebenzene 8a (100 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (1.11 g, 3.5 mmol) and 1,2-ethanedithiol (0.04 mL, 0.5 mmol) in benzene was stirred for 6 h at rt and the temperature was raised to 130 °C and the mixture was stirred for 42 h. After workup, the mixture compound was chromatographed on silica gel (petroleum ether : EtOAc = 9 : 1) to give 1a (14 mg, 17%) and 6a (45 mg, 56%).

Reaction of 8b. In a manner of the general procedure as described above, a mixture of 2-propenylmagnesium bromide (3.5 mmol), 4-isopropylbromobenzene 8b (100 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), ZnI₂ (1.11 g, 3.5 mmol) and 1,2-ethanedithiol (0.04 mL, 0.5 mmol) in benzene was stirred for 6 h at rt and the temperature was raised to 130 °C and the mixture was stirred for 42 h. After workup, the mixture compound was chromatographed on silica gel (petroleum ether) to give 1e (44 mg, 55%) and 6e (27 mg, 34%).

Effect of the halide in MeMgX on the product distribution of the reaction of 5a in the presence of NiCl₂(PPh₃)₂. A mixture of 5a (120 mg, 0.5 mmol), NiCl₂(PPh₃)₂ (33 mg, 0.05 mmol), and MeMgCl (0.7 mL, 3.0 M in ether, 2.1 mmol) was immersed in an oil bath at 130 °C for 24 h. After workup, the ratio of 1a to 6a was 87 to 13. The ratio was changed to 37 to 63 when the same amount of MeMgBr was used. When MeMgI was employed, the ratio of 1a to 6a changed to 4 to 96.

Author's contributions

T.-Y. L. and G.-Q. L. contributed to the conception and design of this study in addition to the data analysis. P. Z. and Z. L. contributed intellectually and took the responsibility to supervise L. Y., a graduate student, working on this project in the laboratory. All co-authors actively participated in writing the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

T.-Y. L. thanks the Ministry of Science and Technology (Taipei) for partial support. P. Z. thanks the Hangzhou Normal University for a start-up research fund.

Notes and references

1. (a) A. de Meijere and F. Diederich, Metal-catalyzed cross coupling reactions; 2nd completely revised and enlarged edition, vol. 1 and 2, Wiley-VCH, Mannheim, 2004; (b) Y. Nishihara, Applied cross coupling reactions, Springe, 2013; (c) J. Cossy, Grignard reagents and transition metal catalysts: formation of C-C Bonds by Cross Coupling, de Gruyter, 2016.
2. (a) K. Tamao, K. Sumotani and M. Kumada, J. Am. Chem. Soc., 1972, 94, 4374; (b) R. J. P. Corriu and J. P. Masse, J. Chem. Soc., Chem. Commun., 1973, 144.
3. (a) E.-i. Negishi and L. Anastasia, Chem. Rev., 2003, 103, 1979–2017; (b) E.-i. Negishi, Angew. Chem., Int. Ed., 2011, 50, 6738.
4. Y. Motoyama and H. Nishiyama, in Lewis Acids in Organic Synthesis, ed., H. Yamamoto, Wiley-VCH, 2000, ch. 3.
5. (a) Y.-H. Chen, T.-Y. Luh, G.-H. Lee and S.-M. Peng, J. Chem. Soc., Chem. Commun., 1994, 2369; (b) S.-M. Yeh, G.-H. Lee, Y. Wang and T.-Y. Luh, J. Org. Chem., 1997, 62, 8315.
6. (a) C. Peppe, E. S. Lang, F. M. de Andrade and L. B. de Castro, Synlett, 2004, 10, 1723; (b) M. Higashimura, K. Imamura, Y. Yokogawa and T. Sakakibara, Chem. Lett., 2004, 33, 728; (c) Q. H. Cai, J. Li, F. X. Bao and Y. K. Shan, Appl. Catal., A, 2005, 279, 139; (d) H.-B. Sun, B. Lin, R. Hua and Y. W. Yin, Eur. J. Org. Chem., 2006, 4231; (e) F. Howard, S. Sawadjoon and J. S. M. Samec, Tetrahedron Lett., 2010, 51, 4208; (f) A. Tarlani, M. P. Zarabadi, J. Muzart, E. Lotfalipour and F. Darkhosh, Catal. Commun., 2011, 14, 89; (g) B. V. Ramulu, L. Mahendar and G. Satyanarayana, Asian J. Org. Chem., 2016, 5, 207.
7. (a) H. M. Wang, P. Cui, G. Zou, F. Yang and J. Tang, Tetrahedron, 2006, 62, 3985; (b) Y. Miyake, T. Moriyama, Y. Tanabe, G. Onodera and Y. Nishibayashi, Organometallics, 2011, 30, 5972.
8. (a) E. Bergmann, H. Taubadel and H. Weiss, Ber., 1931, 64, 1493; (b) J. Hukki, Acta Chem. Scand., 1949, 3, 279; (c) A. Zwierzak and H. Pines, J. Org. Chem., 1963, 28, 3392; (d) N. H. Werstiuk and G. Timmins, Can. J. Chem., 1988, 33, 2309–2312; (e) B. Chaudhuri, Org. Process Res. Dev., 1999, 3, 220–223; (f) N. G. Grigor’eva, R. R. Galyautdinova, A. V. Vosmerikov, L. L. Korobitsina, B. I. Kutepov and U. M. Dzhemilev, Pet. Chem., 2008, 48, 366.
9. (a) T.-Y. Luh, Acc. Chem. Res., 1991, 24, 257; (b) T.-Y. Luh and C.-F. Lee, Eur. J. Org. Chem., 2005, 3875.
10. (a) Z.-J. Ni and T.-Y. Luh, J. Chem. Soc., Chem. Commun., 1987, 1515; (b) Z.-J. Ni, P.-F. Yang, D. N. P. Ng, Y.-L. Tzeng and T.-Y. Luh, J. Am. Chem. Soc., 1990, 112, 9356; (c) Z.-J. Ni, N.-W. Mei, X. Shi, Y.-L. Tzeng, M.-C. Wang and M. T.-Y. Luh, J. Org. Chem., 1991, 56, 4035.

---

Footnotes

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d2ra00841f

‡ Contributed equally.

---