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Synthesis 2024; 56(21): 3307-3313
DOI: 10.1055/a-2326-6416
paper
Special Issue PSRC-10 (10th Pacific Symposium on Radical Chemistry)

Sodium-Mediated Reductive anti-Dimagnesiation of Diarylacetyl­enes with Magnesium Bromide

Haruka Yamaguchi 
,
Fumiya Takahashi 
,
Takashi Kurogi 
,
Hideki Yorimitsu  ∗

This work was supported by Japan Science and Technology Agency (JST) Core Research for Evolutional Science and Technology (CREST, Grant Number JPMJCR19R4) as well as Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers JP19H00895 and JP24H02208 to H.Y.
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This paper is dedicated to Professor Dr. Thorsten Bach on his 60th birthday.

Abstract

Diarylacetylenes undergo anti-dimagnesiation using magnesium bromide and sodium dispersion to afford (E)-1,2-dimagnesioalkenes. This dimagnesiation utilizes simple magnesium bromide as a reduction-resistant electrophile, contrasting with the previously reported dimagnesiation using tricky organomagnesium halides. The resulting vicinal double Grignard reagents react with various electrophiles to yield multisubstituted alkenes stereoselectively.


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Key words

organomagnesium compounds - sodium dispersion - alkynes - electron transfer - multisubstituted alkenes

Since the discovery of the Barbier reaction[1] and the Grignard reaction,[2] organomagnesium species have served as versatile reagents for various bond formations in organic synthesis for over a century.[3] Naturally, methods to generate Grignard reagents have also been an important subject of investigation.[4] Typical approaches to the reagents include reduction of organic halides with magnesium metal[5] and halogen–magnesium exchange[6] (Scheme [1]A). However, these approaches rely on organic halide precursors, thereby limiting accesses to certain organomagnesium compounds such as vicinal dimagnesio species due to inevitably rapid β-elimination from 1-magnesio-2-halo intermediates (Scheme [1]B). While a handful of examples of 1,2-dimagnesioalkanes[7] and -alkenes[7] [8] have been reported, the methods require intricately designed magnesium complexes to achieve the addition of Mg(I)–Mg(I) complexes across C–C multiple bonds and are hence practically inconvenient for organic synthesis (Scheme [1]C).

Recently, we reported the synthesis of (E)-1,2-dimagnesioalkenes A-R via electron injection to alkynes from sodium metal in the presence of alkylmagnesium halide, RMgX (Scheme [1]D).[9] The coordination of the alkyl ligand R has been considered to make the magnesium center electron-rich to suppress its reduction with sodium metal. The reductive dimagnesiation process to generate A-R includes the transient formation of organosodium intermediates from alkynes through single-electron reduction and the subsequent transmetalation to the coexisting RMgX electrophile. Very recently, we have achieved reductive anti-dizincation of alkynes using ZnCl2(tmeda) as a reduction-resistant zinc electrophile (Scheme [1]E).[10] Encouraged by the success of the dizincation using a simple zinc halide, we decided to revisit the investigation of magnesiation reagents, despite the intuition that simple magnesium halides readily undergo reduction by sodium metal to form Rieke magnesium.[11] Herein, we report reductive anti-dimagnesiation of alkynes by the use of a simple magnesium salt.

Zoom Image
Scheme 1 Generation of organomagnesium species: A) Common methods for generation of organomagnesium halides. B) β-Elimination from 1-magnesio-2-halo species. C) Addition of Mg(I)–Mg(I) complex to alkenes and alkynes. D) Reductive anti-1,2-dimagnesiation of alkynes with RMgX as an electrophile. E) Reductive anti-1,2-dizincation using a zinc halide.

Our study commenced with screening magnesium salts for the model dimagnesiation of tolane (1a) with the aid of Na dispersion.[12] [13] [14] The resulting dimagnesioalkene A-X, formed through sequential reduction and transmetalation processes similar to those of A-R in Scheme [1]D, was treated with D2O to yield dideuterated stilbene (2a-d 2). Following our previous dimagnesiation with alkylmagnesium halides,[9] the reductive dimagnesiation of 1a was performed using 2 equivalents of simple magnesium salts and Na dispersion (Table [1]). The reactions using Mg(OTf)2, MgF2, and MgCl2 afforded only trace amounts of 2a (entries 1–3). In these cases, upon the addition of Na dispersion to the mixture of 1a and a magnesium salt in THF, the mixture immediately turned into a black suspension, indicating the formation of Rieke magnesium. Interestingly, dimagnesiation using MgBr2 led to formation of a reddish-orange suspension (entry 4), similar to the orange-colored 1,2-dimagnesioalkene A-R.[9] Quenching the resulting orange suspension with D2O afforded 2a in 71% yield with a high deuterium incorporation and an E/Z ratio of 89:11. However, a 14% remainder of 1a implied that the reduction of MgBr2 with sodium metal competitively proceeded, resulting in fruitless consumption of both MgBr2 and sodium metal. To address the deficiency of MgBr2 and sodium metal, larger amounts, 2.5 equivalents, of MgBr2 and Na dispersion were used, improving the yield of 2a (entry 5). High E selectivity and 97% deuterium incorporation were observed, suggesting the intermediacy of anti-dimagnesiated species A-Br. When MgI2 was investigated as a magnesium electrophile, a much darker brown suspension was formed to eventually give 2a in low yield with poor stereoselectivity (entry 6).

Table 1 Screening Magnesium Electrophiles for Dimagnesiation of 1a

Entry

MgX2

Yield (%) of 2a a

%Db

E/Z a

1

Mg(OTf)2

<1

–

–

2

MgF2

<1

–

–

3

MgCl2

<1

–

–

4

MgBr2

71

98

89:11

5

MgBr2 (2.5 equiv)c

98

97

87:13

6

MgI2

37

–d

62:38

a Yields and E/Z ratios were determined by FID-GC analysis using tetradecane as an internal standard.

b Deuterium incorporations in (E)-2a were determined by 1H NMR spectroscopy.

c With Na dispersion (2.5 equiv).

d Deuterium incorporation in (E)-2a could not be determined due to overlapping with 1H NMR signals of other products.

With the optimal conditions for anti-selective dimagnesiation with MgBr2 (Table [1], entry 5), we have examined vic-double Grignard reactivity of 1,2-dimagnesioalkene A-Br (Scheme [2]A). In our previous study,[9a] the reaction of dimagnesioalkene A-cPent prepared from cyclopentylmagnesium bromide required 6.0 equivalents of isopropoxypinacolborane (iPrOBpin) due to a side reaction by the cyclopentylmagnesium moiety. In contrast, fewer equivalents of iPrOBpin were needed for A-Br to afford 1,2-diborylalkene 3. Dimagnesioalkene A-Br also reacted with benzaldehyde. However, Oppenauer-type oxidation[15] of the resulting magnesium alkoxide subsequently took place to yield 1,2-dibenzoylalkene 4. To our surprise, exposure of A-Br to an atmosphere of CO2 resulted in formation of diphenylmaleic anhydride (5) in 68% yield, while expected diphenylfumaric acid was not obtained. After the reaction of A-Br with 1 equivalent of CO2, stereoinversion of the remaining alkenylmagnesium moiety[8] [16] in intermediate B could preferentially occur to introduce a second CO2 molecule in a syn fashion and then to form 5 (Scheme [2]B). It is noteworthy that the addition of CO2 to dimagnesioalkene A-cPent afforded only a trace amount of 5, along with a significant amount of cPentCO2H. Reaction of A-Br with tert-butyl isocyanate afforded diphenylfumaramide 6 in 74% yield with an E/Z ratio of 71:29.

Zoom Image
Scheme 2 vic-Double Grignard reactivity of A-Br: A) Substrate scope with respect to electrophiles. B) Plausible mechanism for stereoinversion of B.

With the aid of a copper catalyst, CuCN·2LiCl,[17] 1,2-dimagnesioalkene A-Br reacted with other electrophiles (Scheme [3]). Reactions with isobutylene oxide, allyl chloride, and methoxymethyl chloride (MOMCl) gave the corresponding tetrasubstituted alkenes 7a, 8a, and 9, respectively, in good yields.

Zoom Image
Scheme 3 Synthesis of tetrasubstituted alkenes via transmetalation to copper; Ans = 4-MeOC6H4.

This dimagnesiation method with MgBr2 also accommodates diarylacetylene with a π-extended naphthyl group to give 7b. Even under the strongly reducing and basic conditions for dimagnesiation, silyl (7c), methoxy (8d and 7e), and thioether (7f) were well tolerated. Unfortunately, dimagnesiation of alkylarylacetylenes with MgBr2 was not successful because the reduction of MgBr2 would predominate over that of substrates that have electron-donating alkyl groups.

Transmetalation of A-Br to zinc chloride and subsequent Negishi coupling with aryl iodide afforded tetraarylethylene 10. In our previous study on transmetalation of 1,2-dimagnesioalkene to zinc for Negishi coupling,[9b] it was troublesome that the organic moiety R (R = Me, cPent, tBu, Me3SiCH2) in A-R from the magnesium electrophile RMgX was also transmetalated to zinc and involved in the cross-coupling reaction. To avoid such unwanted transmetalation events, preparation of A-(Me3Si)2CH from an elaborate organomagnesium halide, (Me3Si)2CHMgCl, was required. To our delight, the dimagnesiation method using MgBr2 allowed the subsequent Negishi coupling to efficiently yield the product without using such a dummy alkyl ligand.

In summary, we have developed reductive anti-dimagnesiation of alkynes with simple magnesium bromide and Na dispersion. The choice of magnesium bromide is crucial to suppress the reduction of magnesium(II) species. This reductive dimagnesiation using MgBr2 provides 1,2-dimagnesioalkenes A-Br, vic-double Grignard reagents. The vic-double nucleophiles reacted with various electrophiles to give multisubstituted alkenes. Further exploration of reductive dimetalation is in progress.

1H NMR (600 MHz), 11B NMR (192 MHz), and 13C NMR (151 MHz) spectra were recorded on a JEOL ECZ-600 spectrometer. Chemical shifts in 1H NMR spectra were recorded in delta (δ) units, parts per million (ppm) relative to residual CHCl3 (δ = 7.26 ppm) or CD3COCHD2 (δ = 2.05 ppm). Chemical shifts in 13C NMR spectra were recorded in δ units, ppm relative to CDCl3 (δ = 77.16 ppm) or CD3COCD3 (δ = 29.84 ppm). For 11B NMR spectra, BF3·OEt2 (δ = 0.00 ppm) was used as an external standard. Mass spectra were determined on a Bruker micrOTOF II spectrometer. TLC analyses were performed on commercial glass plates bearing a 0.25-mm layer of Merck silica gel 60F254. Purification was done by column chromatography using silica gel (KANTO CHEMICAL CO., INC.; silica gel 60 N, spherical neutral, particle size 100–210 μm) or a monolithic silica column.[18] Preparative recycling gel permeation chromatography (GPC) was done on a JAI LC-9260 II NEXT system using CHCl3 as the eluent. FID-GC analysis was carried out using a Shimadzu GC-2025 system equipped with a Shimadzu SH-Rtx-5 GC column (30 m × 0.25 mm × 0.25 μm). Anhydrous THF was purchased from KANTO CHEMICAL CO., INC. and stored under an atmosphere of nitrogen. Mg(OTf)2, MgF2, MgCl2, MgBr2, and MgI2 were purchased from Aldrich and dried under vacuum at 150 °C prior to use. Alkynes 1b, 1d, 1e, and 1f were prepared according to the literature.[9a] iPrOBpin, isobutylene oxide, allyl chloride, and MOMCl were purchased from commercial suppliers and distilled prior to use. CO2 gas (99.5%) was purchased from Nippon Sanso Holdings Corporation. Unless otherwise noted, materials obtained from commercial suppliers were used without further purification. Na dispersion (ca. 10 M suspension in mineral oil) was provided by KOBELCO ECO-Solutions Co., Ltd. The concentration of the Na dispersion was determined by acid–base titration. Reactions were carried out under an atmosphere of nitrogen.


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Screening Magnesium Electrophiles (Table [1]); General Procedure

An oven-dried 20-mL Schlenk tube was charged with MgX2 (2.0 mmol), 1a (178 mg, 1.00 mmol), and THF (6.3 mL) under nitrogen atmosphere. The mixture was heated at 60 °C for 10 min to dissolve MgX2. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.20 mL, 2.0 mmol) was added dropwise and the resulting suspension was stirred at 0 °C for 30 min. D2O (1.0 mL) was then added and the resulting biphasic solution was stirred additionally for 10 min. After addition of aqueous HCl (1 M; 2.5 mL), the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The yield and E/Z ratio of 2a-d 2 were determined by FID-GC analysis with tetradecane as an internal standard.


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1,2-Diphenyl-1,2-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethene (3) (Scheme [2])

An oven-dried 20-mL Schlenk tube was charged with MgBr2 (0.4 M in THF; 6.3 mL, 2.5 mmol) and 1a (178 mg, 1.00 mmol) under nitrogen atmosphere. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.25 mL, 2.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. After the addition of iPrOBpin (0.81 mL, 4.01 mmol), the mixture was warmed to 60 °C and stirred for an additional 2 h. The reaction was then quenched with aqueous HCl (1 M; 2.5 mL) and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The yield of 3 was determined as 63% NMR yield (E/Z = 90:10) by 1H NMR measurement with dibromomethane as an internal standard. Purification by column chromatography on silica gel (hexane/EtOAc, 40:1 to 20:1) gave a white solid (264 mg); Rf = 0.2 (hexane/EtOAc, 10:1). The 1H NMR spectrum of the obtained showed a mixture of (E)-3 and its reduced form, diborylalkane 3′,[14a] in an 88:12 ratio. The yield of (E)-3 after column chromatography was calculated as 54% (232 mg, 0.537 mmol) by 1H NMR analysis of the obtained mixture.

1H NMR (600 MHz, CDCl3): δ [(E)-3] = 7.35 (d, J = 7.2 Hz, 4 H), 7.28 (t, J = 7.2 Hz, 4 H), 7.22 (t, J = 7.2 Hz, 2 H), 1.08 (s, 24 H).

13C NMR (151 MHz, CDCl3): δ [(E)-3] = 147.7, 143.3, 128.2, 128.0, 126.8, 83.6, 24.6.

11B NMR (192 MHz, CDCl3): δ [(E)-3] = 30.4.

All the resonances in the 1H and 13C NMR spectra were consistent with the reported values.[9a]


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(E)-1,2,3,4-Tetraphenylbut-2-ene-1,4-dione (4) (Scheme [2])

An oven-dried 20-mL Schlenk tube was charged with MgBr2 (0.4 M in THF; 6.3 mL, 2.5 mmol) and 1a (178 mg, 0.996 mmol) under nitrogen atmosphere. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.25 mL, 2.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. After the addition of benzaldehyde (0.510 mL, 5.05 mmol), the mixture was warmed to 60 °C and stirred for an additional 4 h. The reaction was then quenched with aqueous HCl (1 M; 2.5 mL) and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (hexane, Rf = 0.1) and then GPC (CHCl3) gave 4 as a white solid (186 mg, 0.479 mmol, 48%).

1H NMR (600 MHz, CDCl3): δ = 7.52 (d, J = 6.9 Hz, 4 H), 7.28–7.21 (m, 12 H), 7.17–7.16 (m, 4 H).

13C NMR (151 MHz, CDCl3): δ = 147.8, 133.3, 131.0, 130.5, 128.50, 128.48, 127.4, 127.3, 126.0, 125.2.

All the resonances in the 1H and 13C NMR spectra were consistent with the reported values.[19]


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2,3-Diphenylmaleic Anhydride (5) (Scheme [2])

An oven-dried 20-mL Schlenk tube was charged with MgBr2 (0.4 M in THF; 19 mL, 7.6 mmol) and 1a (536 mg, 3.08 mmol) under nitrogen atmosphere. After the mixture was cooled to 0 °C, Na dispersion (9.8 M; 0.77 mL, 7.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. The headspace of the Schlenk tube was evacuated, and then an atmosphere of CO2 (1 atm) was introduced. The mixture was warmed to room temperature and stirred for an additional 1 h. The reaction was then quenched with aqueous HCl (2 M; 3.5 mL) and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (hexane/EtOAc, 3:1 to 0:1) gave 5 as a white solid (508 mg, 2.03 mmol, 68%); Rf = 0.1 (hexane/EtOAc, 10:1).

1H NMR (600 MHz, acetone-d 6): δ = 7.52 (d, J = 7.2 Hz, 4 H), 7.42–7.41 (m, 6 H).

13C NMR (151 MHz, acetone-d 6): δ = 169.4, 137.5, 136.8, 129.4, 129.2, 128.9.

All the resonances in the 1H and 13C NMR spectra were consistent with the reported values.[20]


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N,N′-Di-tert-butyl-2,3-diphenylfumaramide (6) (Scheme [2])

An oven-dried 20-mL Schlenk tube was charged with MgBr2 (0.4 M in THF; 6.3 mL, 2.5 mmol) and 1a (179 mg, 1.00 mmol) under nitrogen atmosphere. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.25 mL, 2.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. After the addition of tert-butyl isocyanate (0.480 mL, 4.07 mmol), the mixture was warmed to room temperature and stirred for an additional 1 h. The reaction was then quenched with aqueous HCl (1 M; 2.0 mL) and sat. aqueous NH4Cl (0.5 mL), and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The yield of 6 was determined as 76% NMR yield (E/Z = 64:36) by 1H NMR measurement with dibromomethane as an internal standard. Purification by column chromatography on silica gel (hexane/EtOAc, 20:1 to 4:1) gave 6 as a white solid (282 mg, 0.745 mmol, 74%); E/Z = 71:29; Rf = 0.2 (hexane/EtOAc, 3:1).

1H NMR (600 MHz, CDCl3): δ [(E)-6] = 7.56 (d, J = 7.8 Hz, 4 H), 7.39–7.33 (m, 6 H), 5.17 (s, 2 H), 1.07 (s, 18 H); δ [(Z)-6] = 7.18–7.12 (m, 10 H), 5.80 (s, 2 H), 1.38 (s, 18 H).

13C NMR (151 MHz, CDCl3): δ [(E)-6] = 167.7, 138.7, 136.1, 129.5, 128.6, 128.32, 51.6, 28.2; δ [(Z)-6] = 168.5, 138.4, 135.9, 128.6, 128.3, 127.9, 52.0, 28.6.

HRMS (APCI-MS, positive): m/z [M + H]+ calcd for C24H31O2N2: 379.2380; found: 379.2377.


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2,7-Dimethyl-4,5-diphenyloct-4-ene-2,7-diol (7a); Typical Procedure for Cu-Catalyzed Synthesis of Tetrasubstituted Alkenes 7–9 (Scheme [3])

The synthesis of 7a is representative. An oven-dried 20-mL Schlenk tube was charged with MgBr2 (0.4 M in THF; 6.3 mL, 2.5 mmol) and 1a (178 mg, 0.998 mmol) under nitrogen atmosphere. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.25 mL, 2.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. After the addition of CuCN·2LiCl (1.0 M in THF; 0.10 mL, 0.10 mmol) and isobutylene oxide (0.360 mL, 3.99 mmol), the mixture was allowed to warm to room temperature and stirred for an additional 1 h. The reaction was then quenched with aqueous HCl (1 M; 2.5 mL) and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The yield of 7a was determined as 63% NMR yield (E/Z >99:1) by 1H NMR measurement with dibromomethane as an internal standard. Purification by column chromatography on silica gel (hexane/EtOAc, 10:1 to 3:1) gave 7a as a white solid (201 mg, 0.617 mmol, 62%); E/Z >99:1; Rf = 0.2 (hexane/EtOAc, 3:1).

1H NMR (600 MHz, CDCl3): δ = 7.40 (t, J = 7.3 Hz, 4 H), 7.32 (d, J = 7.3 Hz, 4 H), 7.28 (t, J = 7.3 Hz, 2 H), 2.68 (s, 4 H), 1.41 (s, 2 H), 0.94 (s, 12 H).

13C NMR (151 MHz, CDCl3): δ = 142.9, 137.9, 129.3, 128.7, 127.0, 71.9, 47.9, 29.8.

All the resonances in the 1H and 13C NMR spectra were consistent with the reported values.[9a]


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4,5-Diphenylocta-1,4,7-triene (8a)

Compound 8a was formed in 71% NMR yield (E/Z = 98:2) from 1a (178.0 mg, 0.999 mmol) and allyl chloride (0.330 mL, 4.05 mmol). Purification by column chromatography on silica gel (hexane, Rf = 0.2) and then GPC (CHCl3) gave 8a as a white solid (168 mg, 0.644 mmol, 65%); E/Z = 98:2.

1H NMR (600 MHz, CDCl3): δ [(E)-8a] = 7.36 (t, J = 7.8 Hz, 4 H), 7.29–7.25 (m, 6 H), 5.63 (ddt, J = 6.0, 10.8, 17.4 Hz, 2 H), 4.87 (dd, J = 1.8, 10.8 Hz, 2 H), 4.82 (d, J = 1.8, 17.4 Hz, 2 H), 2.96 (d, J = 6.0 Hz, 4 H); δ [(Z)-8a] = 7.07 (t, J = 7.5 Hz, 4 H), 7.02 (t, J = 7.5 Hz, 2 H), 6.99 (d, J = 7.5 Hz, 4 H), 5.85–5.80 (m, 2 H), 5.11 (m, 2 H), 5.02 (m, 2 H), 3.33 (d, J = 6.1 Hz, 4 H).

13C NMR (151 MHz, CDCl3): δ [(E)-8a] = 142.2, 137.1, 136.4, 128.9, 128.1, 126.7, 115.6, 40.4; δ [(Z)-8a] = 143.0, 136.7, 135.8, 129.7, 127.6, 126.0, 39.1.

All the resonances in the 1H and 13C NMR spectra of (E)-8a were consistent with the reported values.[9a] The rest of the 13C NMR resonances of (Z)-8a could not be assigned due to overlapping with the resonances of (E)-8a.


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1,4-Dimethoxy-2,3-diphenylbut-2-ene (9)

Compound 9 was formed in 69% NMR yield (E/Z >99:1) from 1a (177.7 mg, 0.997 mmol) and MOMCl (0.300 mL, 3.99 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 20:1; Rf = 0.2) gave 9 as a white solid (167 mg, 0.623 mmol, 62%); E/Z >99:1.

1H NMR (600 MHz, CDCl3): δ = 7.41–7.36 (m, 8 H), 7.34–7.31 (m, 2 H), 4.03 (s, 4 H), 3.14 (s, 6 H).

13C NMR (151 MHz, CDCl3): δ = 140.0, 139.2, 128.7, 128.1, 127.2, 73.6, 57.9.

All the resonances in the 1H and 13C NMR spectra were consistent with the reported values.[9a]


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2,7-Dimethyl-4-(naphthalen-2-yl)-5-phenyloct-4-ene-2,7-diol (7b)

Compound 7b was formed in 73% NMR yield (E/Z = 94:6) from 2-(phenylethynyl)naphthalene (228 mg, 1.00 mmol) and isobutylene oxide (0.360 mL, 3.99 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 20:1 to 2:1) gave 7b as a white solid (237 mg, 0.631 mmol, 63%); E/Z >99:1; Rf = 0.2 (hexane/EtOAc, 3:1).

1H NMR (600 MHz, CDCl3): δ = 7.89 (d, J = 8.4 Hz, 1 H), 7.86–7.85 (m, 2 H), 7.77 (s, 1 H), 7.53–7.48 (m, 2 H), 7.46 (dd, J = 8.4, 1.8 Hz, 1 H), 7.44–7.41 (m, 2 H), 7.37 (d, J = 6.6 Hz, 2 H), 7.30 (t, J = 7.2 Hz, 1 H), 2.78 (s, 2 H), 2.73 (s, 2 H), 1.36 (s, 2 H), 0.94 (s, 6 H), 0.92 (s, 6 H).

13C NMR (151 MHz, CDCl3): δ = 142.9, 140.6, 138.5, 137.9, 133.3, 132.3, 129.4, 128.7, 128.3, 128.0, 127.81 (2 C), 127.79, 127.0, 126.4, 126.1, 72.03, 71.98, 48.1, 48.0, 30.0, 29.9.

HRMS (ESI-MS, positive): m/z [M + NH4]+ calcd for C26H34O2N: 392.2584; found: 392.2571.


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2,7-Dimethyl-4-phenyl-5-(4-(trimethylsilyl)phenyl)oct-4-ene-2,7-diol (7c)

Compound 7c was formed in 53% NMR yield (E/Z = 95:5) from 1-(phenylethynyl)-4-(trimethylsilyl)benzene (250 mg, 0.997 mmol) and isobutylene oxide (0.360 mL, 3.99 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 10:1 to 3:1) gave 7c as a white solid (198 mg, 0.499 mmol, 50%); E/Z >99:1; Rf = 0.2 (hexane/EtOAc, 3:1).

1H NMR (600 MHz, CDCl3): δ = 7.53 (d, J = 7.8 Hz, 2 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.32–7.27 (m, 5 H), 2.69 (s, 2 H), 2.66 (s, 2 H), 0.95 (s, 12 H), 0.27 (s, 9 H).

13C NMR (151 MHz, CDCl3): δ = 143.1, 142.8, 138.8, 137.83, 137.75, 133.6, 129.3, 128.5 (2 C), 126.8, 71.9 (2 C), 47.9, 47.8, 29.8, 29.7, –1.0.

HRMS (ESI-MS, positive): m/z [M + NH4]+ calcd for C25H40O2NSi: 414.2823; found: 414.2827.


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4-(4-Methoxyphenyl)-5-phenylocta-1,4,7-triene (8d)

Compound 8d was formed in 39% NMR yield (E/Z = 98:2) from 1-methoxy-4-(phenylethynyl)benzene (208 mg, 0.999 mmol) and allyl chloride (0.330 mL, 4.05 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 1:0 to 40:1) and then GPC (CHCl3) gave 8d as a white solid (91.6 mg, 0.315 mmol, 32%); E/Z = 98:2; Rf = 0.4 (hexane/EtOAc, 10:1).

1H NMR (600 MHz, CDCl3): δ [(E)-8d] = 7.35 (t, J = 7.8 Hz, 2 H), 7.28–7.23 (m, 3 H), 7.18 (d, J = 8.4 Hz, 2 H), 6.90 (d, J = 8.4 Hz, 2 H), 5.67–5.60 (m, 2 H), 4.88–4.81 (m, 4 H), 3.83 (s, 3 H), 2.98 (d, J = 6.6 Hz, 2 H), 2.94 (d, J = 6.6 Hz, 2 H); δ [(Z)-8d] = 7.08 (t, J = 7.5 Hz, 2 H), 7.04–7.02 (m, 1 H), 6.99 (d, J = 7.5 Hz, 2 H), 6.61 (d, J = 8.9 Hz, 2 H), 5.84–5.78 (m, 2 H), 5.12–5.08 (m, 2 H), 5.02–4.99 (m, 2 H), 3.70 (s, 3 H), 3.32–3.30 (m, 4 H).

13C NMR (151 MHz, CDCl3): δ [(E)-8d] = 158.4, 142.4, 137.0, 136.64, 136.61, 136.5, 134.5, 130.0 (2 C), 128.9, 128.1, 126.6, 115.6, 113.5, 55.3, 40.4 (2 C); δ [(Z)-8d] = 130.9, 129.7, 113.0.

All the resonances in the 1H and 13C NMR spectra of (E)-8d were consistent with the reported values.[9a] The rest of the 1H and 13C NMR resonances of (Z)-8d could not be assigned due to overlapping with the resonances of (E)-8d.


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4-(3-Methoxyphenyl)-2,7-dimethyl-5-phenyloct-4-ene-2,7-diol (7e)

Compound 7e was formed in 58% NMR yield (E/Z = 94:6) from 1-methoxy-3-(phenylethynyl)benzene (209 mg, 1.00 mmol) and isobutyl­ene oxide (0.360 mL, 3.99 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 10:1 to 3:1) gave 7e as a white solid (182 mg, 0.514 mmol, 51%); E/Z >99:1; Rf = 0.2 (hexane/EtOAc, 3:1).

1H NMR (600 MHz, CDCl3): δ = 7.39 (t, J = 7.8 Hz, 2 H), 7.33–7.27 (m, 4 H), 6.90 (d, J = 7.8 Hz, 1 H), 6.86–6.85 (t, J = 2.1 Hz, 1 H), 6.82 (dd, J = 8.4, 2.4 Hz, 1 H), 3.84 (s, 3 H), 2.68 (s, 2 H), 2.66 (s, 2 H), 0.96 (s, 6 H), 0.95 (s, 6 H).

13C NMR (151 MHz, CDCl3): δ = 159.6, 144.3, 142.7, 137.9, 137.6, 129.6, 129.2, 128.5, 126.8, 121.5, 115.2, 112.0, 71.8 (2 C), 55.2, 48.0, 47.8, 29.8, 29.7.

HRMS (ESI-MS, positive): m/z [M + NH4]+ calcd for C23H34O3N: 372.2533; found: 372.2535.


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2,7-Dimethyl-4-(3-(methylsulfanyl)phenyl)-5-phenyloct-4-ene-2,7-diol (7f)

Compound 7f was formed in 68% NMR yield (E/Z = 89:11) from 1-(methylsulfanyl)-3-(phenylethynyl)benzene (215 mg, 0.957 mmol) and isobutylene oxide (0.360 mL, 3.99 mmol). Purification by column chromatography on silica gel (hexane/EtOAc, 3:1; Rf = 0.2) gave 7f as a white solid (209 mg, 0.564 mmol, 59%); E/Z >99:1.

1H NMR (600 MHz, CDCl3): δ = 7.40 (t, J = 7.5 Hz, 2 H), 7.33–7.27 (m, 4 H), 7.20 (t, J = 1.7 Hz, 1 H), 7.16 (dd, J = 9.3, 1.7 Hz, 1 H), 7.09 (d, J = 7.5 Hz, 1 H), 2.66 (s, 4 H), 2.51 (s, 3 H), 1.27 (s, 2 H), 0.95 (s, 6 H), 0.94 (s, 6 H).

13C NMR (151 MHz, CDCl3): δ = 143.5, 142.6, 138.7, 138.2, 137.3, 129.2, 128.8, 128.5, 127.1, 126.8, 126.0, 124.6, 71.7 (2 C), 48.0, 47.8, 29.8 (2 C), 15.7.

HRMS (ESI-MS, positive): m/z [M + NH4]+ calcd for C23H34O2NS: 388.2305; found: 388.2295.


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1,2-Bis(4-methoxyphenyl)-1,2-diphenylethene (10) via Negishi Coupling (Scheme [3])

An oven-dried 20-mL Schlenk tube was charged with MgBr2 (464 mg, 2.52 mmol), 1a (178 mg, 1.00 mmol), and THF (6.3 mL) under nitrogen atmosphere. The mixture was heated at 60 °C for 10 min to dissolve MgBr2. After the mixture was cooled to 0 °C, Na dispersion (10 M; 0.25 mL, 2.5 mmol) was added dropwise and the resulting reddish-orange suspension was stirred at 0 °C for 30 min. After the addition of ZnCl2 (1.0 M in THF; 2.5 mL, 2.5 mmol), the mixture was warmed to room temperature and stirred for 30 min. PdCl2(PPh3)2 (14.3 mg, 0.0204 mmol) and 4-iodoanisole (519 mg, 2.22 mmol) were then added and the mixture was stirred at 60 °C for 3 h. The reaction was then quenched with aqueous HCl (1 M; 2.5 mL) and the resulting biphasic solution was extracted with EtOAc (3 × 4 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The yield of 10 was determined as 82% NMR yield (E/Z = 91:9) by 1H NMR measurement with dibromomethane as an internal standard. Purification by column chromatography on silica gel (hexane/EtOAc, 40:1 to 20:1) and then GPC (CHCl3) gave 10 as a white solid (274 mg, 0.698 mmol, 70%); E/Z = 78:22; Rf = 0.3 (hexane/EtOAc, 10:1).

1H NMR (600 MHz, CDCl3): δ [(E)-10] = 7.13–7.10 (m, 6 H), 7.04 (d, J = 6.9 Hz, 4 H), 6.91 (d, J = 7.5 Hz, 4 H), 6.62 (d, J = 8.9 Hz, 4 H), 3.73 (s, 6 H); δ [(Z)-10] = 6.94 (d, J = 6.9 Hz, 4 H), 6.65 (d, J = 8.9 Hz, 4 H), 3.75 (s, 6 H).

13C NMR (151 MHz, CDCl3): δ [(E)-10] = 158.0, 144.4, 139.7, 136.4, 132.64, 131.49, 127.8, 126.3, 113.1, 55.15; δ [(Z)-10] = 158.0, 144.3, 139.7, 136.5, 132.62, 131.51, 127.7, 126.3, 113.2, 55.18.

All the resonances in the 1H and 13C NMR spectra of (E)-10 were consistent with the reported values.[10] The rest of the 1H NMR resonances of (Z)-10 could not be assigned due to overlapping with the resonances of (E)-10.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We thank KOBELCO ECO-Solutions Co., Ltd. for providing Na dispersion.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2326-6416.
  • Supporting Information

Corresponding Author

Hideki Yorimitsu
Department of Chemistry, Graduate School of Science, Kyoto University
Sakyo-ku, Kyoto 606-8502
Japan   

Publication History

Received: 28 April 2024

Accepted after revision: 14 May 2024

Accepted Manuscript online:
14 May 2024

Article published online:
28 May 2024

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Scheme 1 Generation of organomagnesium species: A) Common methods for generation of organomagnesium halides. B) β-Elimination from 1-magnesio-2-halo species. C) Addition of Mg(I)–Mg(I) complex to alkenes and alkynes. D) Reductive anti-1,2-dimagnesiation of alkynes with RMgX as an electrophile. E) Reductive anti-1,2-dizincation using a zinc halide.
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Scheme 2 vic-Double Grignard reactivity of A-Br: A) Substrate scope with respect to electrophiles. B) Plausible mechanism for stereoinversion of B.
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Scheme 3 Synthesis of tetrasubstituted alkenes via transmetalation to copper; Ans = 4-MeOC6H4.