Convenient Synthesis of 4-Methylenecyclobutenones and Their Synthetic Utility as Allenylketene Precursors

Abstract

Thermal reaction of alkynyl propargyl sulfides 1 in the presence of n-BuN₃ followed by moist silica gel treatment afforded 4-methylenecyclobutenones 4 in moderate yields. Photogeneration of allenylketenes 5 from 4 in the presence of amine or methanol gave 3,4-pentadienamides 6 or methyl 3,4-pentadienates 7, respectively. Similar reaction in the presence of aldimines afforded unsaturated δ-lactams 9 in good yields.

Key words

alkynyl propargyl sulfides - 4-methylenecyclobutenones - allenylketenes - [4+2]-cycloaddition - unsaturated δ-lactams

References and Notes

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7

A benzene solution (20 mL) of 1a (500 mg, 2.01 mmol) and n-BuN₃ (598 mg, 6.04 mmol) was heated to reflux for 14 h. Decantation (hexane) of the residue after removal of solvent and excess amount of n-BuN₃ followed by evaporation afforded 3a; yield: 4.87 mg (84%); pale yellow oil. MS: m/z = 287 (95) [M⁺], 230 (100) [M⁺ - n-Bu]. IR (neat): 2957, 2930, 1708, 1444, 1361, 867, 764, 691 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, J = 7.3 Hz, 3 H), 1.51-1.61 (m, 2 H), 1.71-1.76 (m, 2 H), 3.81 (t, J = 7.2 Hz, 2 H), 5.09 (d, J = 1.5 Hz, 1 H), 5.17 (d, J = 1.5 Hz, 1 H), 7.32-7.47 (m, 6 H), 7.61-7.65 (m, 2 H), 7.90-7.94 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.9 (q), 20.5 (t), 33.7 (t), 51.6 (t), 98.5 (dd), 127.2 (d), 127.8 (d), 128.1 (d), 128.2 (d), 128.7 (d), 129.1 (d), 129.3 (s), 130.8 (s), 151.1 (s), 151.8 (s), 157.8 (s), 161.9 (s). Anal. Calcd for C₂₁H₂₁N: C, 87.76; H, 7.36; N, 4.87. Found: C, 87.44; H, 7.41; N, 4.67.

8

A benzene solution (20 mL) of 1a (500 mg, 2.01 mmol) and n-BuN₃ (598 mg, 6.04 mmol) was heated to reflux for 14 h. The resulting solution was subjected to column chromatography on silica gel (hexane-EtOAc = 20:1) to yield 4a (337 mg, 72%) as a pale yellow oil. UV (hexane): λ_max = 332 (ε = 10500), 283 (ε = 13500) nm. MS: m/z = 232 (100) [M⁺], 204 (79) [M⁺ - CO]. IR (neat): 3062, 1773, 1751, 1445, 1360, 722, 692 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 5.02 (d, J = 1.7 Hz, 1 H), 5.27 (d, J = 1.7 Hz, 1 H), 7.35-7.37 (m, 3 H), 7.50-7.51 (m, 3 H), 7.76-7.78 (m, 2 H), 7.82-7.85 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 95.7 (dd), 127.5 (d), 127.83 (d), 128.78 (d), 129.1 (d), 129.4 (s), 130.1 (d), 131.0 (s), 131.5 (d), 155.5 (s), 157.0 (s), 172.4 (s), 188.2 (s). Anal. Calcd for C₁₇H₁₂O: C, 87.90; H, 5.21. Found: C, 87.81; H, 5.33.

11

A THF solution (20 mL) of 4h (300 mg, 1.31 mmol) and BnNH₂ (703 mg, 6.57 mmol) was irradiated using high pressure Hg lamp at r.t. for 8 h under N₂. The residue after removal of solvent was subjected to column chromatog-raphy on silica gel (hexane-EtOAc = 5:1) to give 6h-Bn (317 mg, 72%) as a pale yellow oil. MS: m/z = 335 (3) [M⁺], 262 (51) [M⁺ - Me₃Si], 91 (100) [Bn]. IR (neat): 3304, 3062, 3031, 2956, 1938, 1636, 1515, 1495, 1249, 846, 733, 696 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.08 (s, 9 H), 2.97 (s, 1 H), 4.31 (d, J = 2.1 Hz, 1 H), 4.33 (d, J = 2.1 Hz, 1 H), 5.04 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 6.14 (br s, 1 H), 7.00-7.03 (m, 2 H), 7.07-7.14 (m, 3 H), 7.17-7.22 (m, 3 H), 7.27-7.30 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = -1.5 (q), 41.2 (d), 43.4 (t), 79.9 (t), 103.1 (s), 126.0 (d), 127.0 (d), 127.1 (d), 127.3 (d), 128.3 (d), 128.4 (d), 136.5 (s), 138.4 (s), 171.7 (s), 210.0 (s). Anal. Calcd for C₂₁H₂₅NOSi: C, 75.18; H, 7.51; N, 4.17. Found: C, 75.11; H, 7.50; N, 4.27.

12

A MeOH solution (20 mL) of 4h (300 mg, 1.31 mmol) was irradiated using high pressure Hg lamp at r.t. for 5 h under N₂. The residue after removal of excess amount of MeOH was subjected to column chromatography on silica gel (hexane-EtOAc = 7:1) to provide 7h (322 mg, 94%) as a pale yellow oil. MS: m/z = 260 (44) [M⁺], 245 (77) [M⁺ - Me], 187 (65) [M⁺ - Me₃Si], 73 (100) [Me₃Si]. IR (neat): 2952, 1948, 1731, 1715, 1251, 1154, 850, 695 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.18 (s, 9 H), 3.19 (s, 1 H), 3.69 (s, 3 H), 5.17 (d, J = 11.8 Hz, 1 H), 5.27 (d, J = 11.8 Hz, 1 H), 7.18-7.21 (m, 1 H), 7.25-7.30 (m, 2 H), 7.32-7.39 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = -1.7 (q), 38.8 (d), 51.5 (q), 79.5 (t), 101.4 (s), 126.0 (d), 126.7 (d), 128.4 (d), 137.4 (s), 173.3 (s), 173.3 (s), 210.9 (s). Anal. Calcd for C₁₅H₂₀O₂Si: C, 69.19; H, 7.74. Found: C, 69.28; H, 7.96.

15

To an ethereal solution (50 mL) of 8c prepared from piperidine (335 mg, 3.94 mmol) according to the reported procedure,¹³ 4h (300 mg, 1.31 mmol) was added and the mixture was irradiated using high pressure Hg lamp at r.t. for 8 h under N₂. The residue after removal of solvent was subjected to column chromatography on silica gel (hexane-EtOAc = 5:1) to give 9c (291 mg, 71%) as a colorless oil. MS: m/z = 311 (10) [M⁺], 296 (100) [M⁺ - Me]. IR (neat): 2939, 1623, 1462, 1442, 1269, 1251, 878, 843 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = -0.15 (s, 9 H), 1.49-1.57 (m, 1 H), 1.67-1.74 (m, 3 H), 1.79-1.87 (m, 1 H), 1.95-1.99 (m, 1 H), 2.58 (td, J = 2.6, 12.8 Hz, 1 H), 4.14 (br d, 1 H), 4.64-4.71 (m, 1 H), 4.68 (s, 1 H), 5.18 (s, 1 H), 7.11-7.12 (m, 2 H), 7.33-7.36 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 0.93 (q), 25.1 (t), 25.7 (t), 36.2 (t), 43.9 (dd), 61.8 (d), 118.6 (d), 127.8 (d), 129.0 (d), 129.7 (d), 133.8 (s), 138.8 (s), 144.9 (s), 155.2 (s), 165.6 (s). Anal. Calcd for C₁₉H₂₅NOSi: C, 73.26; H, 8.09; N, 4.50. Found: C, 73.08; H, 8.15; N, 4.44.