Highly Stereoselective Synthesis of 2-Methyl-1,3-dienes by Palladium-Catalyzed Cross-Coupling Reaction with Trimethylaluminum

This work is dedicated to Dr. Masanori SAKAMOTO, Professor Emeritus of Meiji Pharmaceutical University, on the occasion of his 77^th birthday (KIJU).

Abstract

Palladium-catalyzed cross-coupling reaction using tricyclohexylphosphine can be used to convert a range of 2-bromo-1,3-dienes efficiently and selectively to the corresponding methyl-branched conjugated dienes.

Key words

palladium catalyst - alkylation - isomerization - cross-coupling - conjugated diene

• References and Note

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• 10 Typical Procedure for the Synthesis of ( E,E )-5e: A mixture of Pd₂(dba)₃CHCl₃ (26 mg, 0.025 mmol) and PCy₃ (28 mg, 0.100 mmol) was dissolved in THF (5 mL) under a nitrogen atmosphere. To the resultant red solution was added a solution of (1Z,3E)-2-bromo-1-cyclohexyl-4-phenyl-1,3-butadiene (4e; 146 mg, 0.501 mmol) in THF (10 mL). After stirring at r.t. for 5 min, Me₃Al (1.05 M hexane solution, 1.0 mL, 1.0 mmol) was added to the solution and the mixture was refluxed for 3 h. The reaction mixture was allowed to cool to r.t. and quenched with diluted cold HCl. The aqueous layer was extracted with Et₂O (3 ×). The combined organic layers were washed with aq sat. NaHCO₃ solution and brine, dried over MgSO₄, and concentrated under reduced pressure. The residue was purified by silica gel column chromatog-raphy using hexane as eluent to afford the title compound [107 mg, 95%, (E,E)-5e/(Z,E)-5e >95:<5]. (1E,3E)-1-Cyclohexyl-2-methyl-4-phenylbuta-1,3-diene (E,E-5e): ¹H NMR (600 MHz, CDCl₃): δ = 7.37–7.42 (m, 2 H), 7.27–7.32 (m, 2 H), 7.16–7.20 (m, 1 H), 6.78 (dd, J = 16.1, 0.7 Hz, 1 H), 6.45 (d, J = 16.1 Hz, 1 H), 5.48 (d, J = 9.2 Hz, 1 H), 2.36 (dtt, J = 9.1, 11.1, 3.7 Hz, 1 H), 1.88 (d, J = 1.1 Hz, 3 H), 1.73 (dquint, J = 13.4, 3.4 Hz, 2 H), 1.63–1.71 (m, 3 H), 1.31 (tq, J = 3.3, 12.7 Hz, 2 H), 1.20 (tq, J = 3.3, 12.5 Hz, 1 H), 1.11 (dq, J = 3.0, 12.2 Hz, 2 H). ¹³C (75 MHz, CDCl₃): δ = 140.30, 138.03, 134.29, 131.92, 128.50 (2 × C), 126.76, 126.10 (2 × C), 125.62, 37.40, 33.02 (2 × C), 26.03, 25.92 (2 × C), 12.56. IR (neat): 3079, 3058, 3026, 2924, 2849, 1629, 1598, 1494, 1447, 958, 746, 691 cm^–1. MS (EI): m/z = 226 (64%). HRMS (EI): m/z [M⁺] calcd for C₁₇H₂₂: 226.1722; found: 226.1731. (1E,3Z)-1-Cyclohexyl-2-methyl-4-phenylbuta-1,3-diene (Z,E-5e): ¹H NMR (600 MHz, CDCl₃): δ = 7.43–7.49 (m, 2 H), 7.31–7.37 (m, 2 H), 7.19–7.24 (m, 1 H), 7.19 (d, J = 16.1 Hz, 1 H), 6.54 (d, J = 16.1 Hz, 1 H), 5.31 (d, J = 9.5 Hz, 1 H), 2.54 (dtt, J = 9.2, 11.1, 3.7 Hz, 1 H), 1.92 (d, J = 1.1 Hz, 3 H), 1.74 (dquint, J = 13.6, 3.4 Hz, 2 H), 1.65–1.71 (m, 3 H), 1.34 (tq, J = 3.3, 12.7 Hz, 2 H), 1.19 (tq, J = 3.5, 12.7 Hz, 1 H), 1.10 (dq, J = 3.0, 12.3 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 138.51, 138.10, 130.06, 128.56 (2 × C), 128.10, 127.12, 126.37, 126.35 (2 × C), 36.52, 33.53 (2 × C), 26.01, 25.93 (2 × C), 20.60. IR (neat): 3080, 3058, 3036, 3024, 2923, 2849, 1632, 1597, 1494, 1446, 957, 747, 691 cm^–1. MS (EI): m/z = 226 (83%). HRMS (EI): m/z [M⁺] calcd for C₁₇H₂₂: 226.1722; found: 226.1742.