Synthetic Application of Intramolecular Cyanoboration on the Basis of Removal and Conversion of a Tethering Group by Palladium-Catalyzed Retro-Allylation

Abstract

A new synthetic strategy, involving utilization of a tethered intramolecular reaction with a removable tether, was demonstrated by the intramolecular cyanoboration-retro-allylation sequence.

Key words

alkenes - arylation - nitriles - palladium - retro-allylation

References and Notes

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9

General Procedure for the Palladium-Catalyzed Retro-Allylative Coupling of 2 with 3 (Tables 1-3): Cesium carbonate was dried in vacuo by heating with a heat gun prior to use. Under a nitrogen atmosphere, a mixture of Pd(OAc)₂ (0.010 mmol), PCy₃ or PPh₃ (0.020 mmol), Cs₂CO₃ (0.24 mmol), 2 (0.20 mmol), and 3 (0.24 mmol) was heated at 110 °C. The reaction was monitored by GC. Heating was stopped as soon as 2 was consumed, since prolonged heating led to a drop in the product yield. Volatiles were removed and the crude product was purified by PTLC.
(E)-3-(4-Methoxyphenyl)-4-(4-methylphenyl)but-2-enenitrile (4a): ¹H NMR (400 MHz, CDCl₃): δ = 7.38 (d, J = 8.8 Hz, 2 H), 7.02-7.12 (m, 4 H), 6.83 (d, J = 8.8 Hz, 2 H), 5.65 (s, 1 H), 4.16 (s, 2 H), 3.80 (s, 3 H), 2.28 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 161.6, 161.2, 136.3, 134.0, 129.5, 129.4 (2 × C), 128.20 (2 × C), 128.18 (2 × C), 118.0, 114.1 (2 × C), 94.8, 55.3, 39.0, 21.0. IR (neat): 2211 (CN), 1605 (C=C) cm^-1. LRMS (EI): m/z = 263 (100) [M⁺], 248 (18), 158 (38), 133 (40), 105 (41). HRMS (EI): m/z [M⁺] calcd for C₁₈H₁₇NO: 263.1310; found: 263.1311. The geometry of the double bond was assigned as E by NOE experiments.
(E)-4-(2,6-Dimethylphenyl)-3-(4-methoxyphenyl)but-2-enenitrile (4b): ¹H NMR (400 MHz, CDCl₃): δ = 7.06-7.11 (m, 3 H), 6.98-7.03 (m, 2 H), 6.78 (d, J = 8.8 Hz, 2 H), 5.49 (t, J = 1.2 Hz, 1 H), 4.17 (d, J = 1.2 Hz, 2 H), 3.78 (s, 3 H), 2.29 (s, 6 H). ¹³C NMR (126 MHz, CDCl₃): δ = 162.7, 160.6, 137.5 (2 × C), 133.5, 131.1, 128.3 (2 × C), 127.8 (2 × C), 127.1, 116.6, 113.7 (2 × C), 96.3, 55.2, 35.7, 20.5 (2 × C). IR (KBr): 2207 (CN), 1605 (C=C) cm^-1. LRMS (EI): m/z = 277 (80) [M⁺], 237 (100), 119 (40). HRMS (EI): m/z [M⁺] calcd for C₁₉H₁₉NO: 277.1467; found: 277.1474. The geometry of the double bond was assigned as E by NOE experiments.

10

General Procedure for the Palladium-Catalyzed Protonative Retro-Allylation of 2 (Entry 9 in Table 1 and Table 4): Cesium carbonate was dried in vacuo by heating with a heat gun prior to use. Under a nitrogen atmosphere, a mixture of Pd(OAc)₂ (0.010 mmol), P(OPh)₃ (0.020 mmol), Cs₂CO₃ (0.24 mmol), and 2 (0.20 mmol) was heated at 110 °C. The reaction was monitored by GC. After consumption of 2, volatiles were removed and the crude product was purified by PTLC.
(E)-3-(4-Methoxyphenyl)but-2-enenitrile (5a): ¹H NMR (400 MHz, CDCl₃): δ = 7.41-7.45 (m, 2 H), 6.89-6.93 (m, 2 H), 5.55 (d, J = 0.8 Hz, 1 H), 3.85 (s, 3 H), 2.45 (d, J = 0.8 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 161.3, 158.8, 130.4, 127.3 (2 × C), 118.1, 114.1 (2 × C), 93.2, 55.4, 20.0. IR (KBr): 2205 (CN), 1603 (C=C) cm^-1. LRMS (EI): m/z = 173 (100) [M⁺], 158 (41), 103 (35). HRMS (EI): m/z [M⁺] calcd for C₁₁H₁₁NO: 173.0841; found: 173.0841. The geometry of the double bond was assigned as E by NOE experiments.