Synthesis of 1-Stannylated and 1-Iodinated 1-Chloroalkenes as Versatile Synthetic Intermediates

Abstract

An efficient and convenient synthesis of 1-stannylated and iodinated 1-chloroalkenes is described based on MoBI₃-catalyzed hydrostannations of 1-chloroalkynes, followed by a tin-­iodine exchange. The 1-chloro-1-iodoalkenes are suitable substrates for further modification, for example, via cross-coupling reactions.

Key words

chloroalkynes - cross-coupling - hydrostannation - molybdenum - vinyl halides

References and Notes

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21

The slight excess of Bu₃SnH was used to allow complete conversion, because during transition-metal-catalyzed hydrostannations in general a certain amount of the tin hydride decomposes towards Bu₃SnSnBu₃.

23

General Procedure for MoBI ₃ -Catalyzed Hydrostannations In an oven-dried Schlenk tube the corresponding chloroalkyne (1 mmol) and Mo(CO)₃(CNt-Bu)₃ (MoBI₃, 12.9 mg, 30 µmol) were dissolved together with hydro-quinone (10 mg, 91 µmol) in dry THF (2 mL) under argon. The solution was heated to 60 ˚C for 10 min before Bu₃SnH (435 mg, 1.5 mmol) was added. The reaction mixture was stirred for 16-24 h. After completion, the reaction mixture was cooled to r.t., and the solvent was evaporated in vacuo. The crude product was purified by flash chromatography on silica gel (neutralized with Et₃N) using pentane or hexane as an eluent.
Tributyl(1-chloro-1-pentenyl)stannane (2a) Colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.92 (t, J = 7.0 Hz, 12 H, CH₃), 1.01-1.05 (m, 6 H, CH₂), 1.28-1.37 (m, 8 H, CH₂), 1.52-1.58 (m, 6 H, CH₂), 2.30 (dt, J = 6.9 Hz, J _Sn-H = 14.2 Hz, 2 H, CHCH ₂), 5.79 (t, J = 6.9 Hz, J _Sn-H = 32.4 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 10.3 (J _Sn-C = 342.6 Hz), 13.6, 13.7, 21.8, 27.2 (J _Sn-C = 60.2 Hz), 28.7 (J _Sn-C = 22.7 Hz), 30.8, 136.8, 142.0 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -31.9 ppm. HRMS:
m/z calcd for C₁₃H₂₆ClSn [M - C₄H₉]⁺: 337.0740; found: 337.0729.
Tributyl(1-chloro-1-octenyl)stannane (2d) Colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.92 (t, J = 7.2 Hz, 12 H, CH₃), 1.01-1.05 (m, 6 H, CH₂), 1.31-1.38 (m, 14 H, CH₂), 1.50-1.56 (m, 6 H, CH₂), 2.32 (dt, J = 6.9 Hz, J _Sn-H = 14.5 Hz, 2 H, CHCH ₂), 5.80 (t, J = 6.4 Hz, J _Sn-H = 32.1 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 10.3 (J _Sn-C = 341.8 Hz), 13.6, 14.1, 22.6, 27.2, (J _Sn-C = 57.2 Hz), 28.6, 28.8, 28.9, 31.7, 136.6, 142.3 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -32.0 ppm. HRMS: m/z calcd for C₁₆H₃₂ClSn [M - C₄H₉]⁺: 365.1053; found: 365.1033.
( E )-Tributyl(1-chloro-3-methoxypropenyl)stannane [( E )-2g] Colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.92 (t, J = 7.3 Hz, 9 H, CH₃), 1.06-1.11 (m, 6 H, CH₂), 1.31-1.40 (m, 6 H, CH₂), 1.52-1.60 (m, 6 H, CH₂), 3.38 (s, 3 H, OCH₃), 4.23 (d, J = 5.3 Hz, J _Sn-H = 14.5 Hz, 2 H, CHCH ₂), 5.27 (t, J = 5.3 Hz, J _Sn-H = 31.1 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 10.4, 13.6, 27.2, 28.7, 58.1, 69.4, 138.6, 142.2 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -28.3 ppm. HRMS: m/z calcd for C₁₂H₂₄OClSn [M - C₄H₉]⁺: 339.0533; found: 339.0525.
( Z )-Tributyl(1-chloro-3-methoxypropenyl)stannane [( Z )-2g] Colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.93 (t, J = 7.1 Hz, 9 H, CH₃), 1.06-1.11 (m, 6 H, CH₂), 1.31-1.40 (m, 6 H, CH₂), 1.52-1.60 (m, 6 H, CH₂), 3.34 (s, 3 H, OCH₃), 3.87 (d, J = 6.5 Hz, J _Sn-H = 14.5 Hz, 2 H, CHCH ₂), 6.64 (t, J = 6.5 Hz, J _Sn-H = 75.3 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 11.6 (J _Sn-C = 348.0 Hz), 13.6, 27.2
(J _Sn-C = 60.8 Hz), 28.7 (J _Sn-C = 19.8 Hz), 57.9, 71.6
(J _Sn-C = 14.7 Hz), 139.7, 142.1 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -32.21 ppm. HRMS: m/z calcd for C₁₂H₂₄OClSn [M - C₄H₉]⁺: 339.0533; found: 339.0525.
( E )-Tributyl(1-methoxymethylvinyl)stannane (11g) Colorless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 0.89-0.95 (m, 15 H, CH₂ and CH₃), 1.31-1.36 (m, 6 H, CH₂), 1.48-1.56 (m, 6 H, CH₂), 3.32 (s, 3 H, OCH₃), 4.05 (d, J = 1.5 Hz, J _Sn-H = 34.6 Hz, 2 H, CH₂), 5.28 (dt, J = 2.7, 1.7 Hz,
J _Sn-H = 62.2 Hz, 1 H, CH), 5.88 (dt, J = 2.7, 1.7 Hz, J _Sn-H = 131.0 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 9.5, 13.7, 27.3, 29.1, 57.7, 79.7, 124.6, 153.0 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -45.4 ppm. HRMS: m/z calcd for C₁₂H₂₅OSn [M - C₄H₉]⁺ 305.0922; found: 305.0920.

24

Representative Procedure for the Synthesis of 1-Chloro-1-iodoalkenes A solution of iodine (280 mg, 1.1 mmol) in CH₂Cl₂ (8.0 mL) was added dropwise (up to 1 h) to the solution of tributyl(1-chlorohex-1-enyl)stannane (2b, 408 mg, 1 mmol) in CH₂Cl₂ (7.0 mL) at 0 ˚C. After addition of the iodine solution the cooling bath was removed, and the reaction mixture was stirred at r.t. for 1 h, before the reaction mixture was stirred with sat. KF solution (15 mL) for 2 h. The organic layer was separated, and the aqueous layer was extracted with CH₂Cl₂ (10 mL). The combined organic layers were dried over Na₂SO₄. After evaporation of the solvent, the crude product was purified by flash chromatography using hexane as eluent to yield 1-chloro-1-iodo-1-hexene (4b) as colorless oil.
1-Chloro-1-iodo-1-hexene (4b) ^¹H NMR (400 MHz, CDCl₃): δ = 0.93 (t, J = 7.8 Hz, 3 H, CH₃), 1.34-1.42 (m, 4 H, CH₂), 2.18 (q, J = 7.5 Hz, 2 H, CH₂), 6.45 (t, J = 7.5 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 13.8, 22.1, 30.0, 31.4, 66.3, 144.4 ppm. HRMS (CI): m/z calcd for C₆H₁₀ClI [M]⁺: 243.9516; found: 243.9556.

25

Representative Procedure for Sonogashira Couplings In an oven-dried Schlenk tube CuI (17.0 mg, 10 mol%) was added to a solution of Pd(PPh₃)₄ (44.0 mg, 5 mol%) in benzene (2 mL) under Ar. To this mixture 1-chloro-1-iodo-1-heptene (4c, 223 mg, 0.87 mmol) and piperidine (178 µL, 1.74 mmol) were added before it was warmed up to 60 ˚C. Phenyl acetylene was added dropwise (over 1 h), and the reaction mixture was heated at this temperature for addi-tional 4 h. After the reaction was complete (TLC), the mixture was cooled to r.t. and diluted with Et₂O (20 mL). The organic layer was washed with sat. NH₄Cl solution and H₂O (20 mL each). The organic layer was separated, dried over Na₂SO₄ and evaporated to dryness. The crude product obtained was purified by flash chromatography using hexane as eluent.
( Z )-1-Phenyl-3-chloro-3-nonen-1-yne (6c)
^¹H NMR (400 MHz, CDCl₃): δ = 0.93 (t, J = 7.3 Hz, 3 H, CH₃), 1.34-1.39 (m, 4 H, CH₂), 1.47-1.51 (m, 2 H, CH₂), 2.33 (q, J = 7.5 Hz, 2 H, CH₂), 6.22 (t, J = 7.5 Hz, 1 H, CH), 7.33-7.37 (m, 3 H, ArH), 7.47-7.50 (m, 2 H, ArH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 13.9, 22.4, 27.8, 29.3, 31.4, 86.5, 88.2, 113.7, 122.2, 128.3, 128.8, 131.7, 137.9 ppm. ^¹¹9Sn NMR (150 MHz, CDCl₃): δ = -28.96 ppm. HRMS: m/z calcd for C₁₅H₁₇ [M - Cl]⁺: 197.1325; found: 197.1296.

26

Representative Procedure for Stille Couplings In an oven-dried Schlenk tube PdCl₂(PhCN)₂ (3.8 mg, 5 mol%) was dissolved in DMF (2.0 mL) under Ar. To this solution 1-chloro-1-iodo-1-octene (4d, 54.0 mg, 0.2 mmol) was added, followed by the dropwise addition of vinyl tributyltin (70 µL, 0.22 mmol) at r.t. After 30 min the reaction was complete (TLC), and the reaction mixture was diluted with Et₂O, washed with sat. NH₄Cl solution and H₂O. The organic layer was separated and dried over Na₂SO₄ and the crude product obtained after evaporation of the solvent was purified by silica gel column chromatography using hexane as eluent.
( Z )-3-Chloro-1,3-decadiene (7d) ^{²8 ¹}H NMR (400 MHz, CDCl₃): δ = 0.91 (t, J = 6.3 Hz, 3 H, CH₃), 1.29-1.37 (m, 6 H, CH₂), 1.40-1.46 (m, 2 H, CH₂), 2.33 (q, J = 7.3 Hz, 2 H, CH₂), 5.16 (d, J = 11.8 Hz, 1 H, CH), 5.57 (d, J = 15.8 Hz, 1 H, CH), 5.79 (t, J = 7.3 Hz, 1 H, CH), 6.39 (dd, J = 11.8, 15.8 Hz, 1 H, CH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 22.6, 28.4, 28.8, 28.9, 31.6, 115.0, 131.9, 132.4, 134.6 ppm.

27

Representative Procedure for Suzuki Couplings A solution of phenylboronic acid (26.4 mg, 0.22 mmol) in EtOH (0.2 mL) was added to a Schlenk tube containing a solution of Pd(PPh₃)₄ (11.5 mg, 5 mol%) and 1-chloro-1-iodo-1-octene (4d, 54.0 mg, 0.2 mmol) in DME (1.0 mL) under argon. A solution of Na₂CO₃ (64 mg, 0.6 mmol) in degassed H₂O (0.5 mL) was added to the reaction mixture, and the mixture was heated under reflux for 24 h. The reaction mixture was then cooled to r.t., diluted with H₂O (10 mL) and Et₂O (10 mL). The layers were separated, and the aqueous layer was extracted with Et₂O (10 mL). The combined organic layers were washed with H₂O and dried over anhyd Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product obtained was purified by flash chromatography on silica gel using hexanes to yield 19.0 mg (45%) of monoarylated product 8d and 9.6 mg (16%) of diarylated product 9d.
( Z )-1-Chloro-1-phenyl-1-octene (8d) ^¹H NMR (400 MHz, CDCl₃): δ = 0.92 (t, J = 7.0 Hz, 3 H, CH₃), 1.29-1.42 (m, 6 H, CH₂), 1.50-1.56 (m, 2 H, CH₂), 2.41 (q, J = 7.1 Hz, 2 H, CH₂), 6.16 (t, J = 6.6 Hz, 1 H, CH), 7.31-7.38 (m, 3 H, ArH), 7.57-7.60 (m, 2 H, ArH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 22.6, 28.5, 29.0, 29.6, 31.7, 126.3, 128.1, 128.2, 128.8, 132.6, 138.4 ppm. HRMS: m/z calcd for C₁₄H₁₉ [M - Cl]⁺: 187.1481; found: 187.1482.
1,1-Diphenyl-1-octene (9d) ^¹H NMR (400 MHz, CDCl₃): δ = 0.89 (t, J = 6.8 Hz, 3 H, CH₃), 1.23-1.44 (m, 6 H, CH₂), 1.46-1.48 (m, 2 H, CH₂), 2.14 (q, J = 7.3 Hz, 2 H, CH₂), 6.11 (t, J = 7.5 Hz, 1 H, CH), 7.19-7.41 (m, 6 H, ArH), 7.45-7.49 (m, 2 H, ArH), 7.61-7.64 (m, 2 H, ArH) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 22.6, 28.9, 29.7, 29.9, 31.7, 126.7, 126.8, 127.2, 127.3, 128.0, 128.1, 128.8, 129.9, 130.4, 140.3, 141.2, 141.4, 142.9 ppm. HRMS: m/z calcd for C₂₀H₂₄ [M]⁺: 264.1873; found: 264.1843.