‘Evans Auxiliary’ Based P–N Ligands for Pd-Catalyzed Asymmetric Allylic Alkylation Reactions

Abstract

A new type of chiral P–N ligands has been prepared which incorporates the Evans auxiliary as chiral ligand. They were found to act as effective ligands in the Pd-catalyzed allylic alkylation reactions. Using these ligands with allylpalladium chloride dimer as catalyst, the coupling of 1,3-diphenyl-3-acetoxyprop-1-ene and dimethyl malonate proceeded smoothly at –10 °C providing the desired product with enantiomeric excess up to 87% and excellent yield.

Key words

asymmetric allylic alkylation - palladium catalysis - P–N ligand - Evans auxiliary

• References

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• 12 Typical Procedure for the Preparation of 1a The reaction mixture of 6a (1.75 g, 6.89 mmol) and ZnCl₂ (0.188 g, 1.378 mmol) and 4 Å MS (2.0 g) in THF (34.4 mL) was added 7 (2.00 g, 6.90 mmol) and stirred for 12 h at r.t. After that, the reaction mixture was filtered and diluted with CH₂Cl₂. The organic phase was washed 3 times with H₂O and brine and then separeted and dried over Na₂SO₄. Organic phase was then concentrated and chromatographed on silica gel, eluted with hexane–EtOAc (2:1) which afford 1a (2.358 g, 65% yield) as a yellowish solid; mp 144–145 °C; [α]_D ²⁵ +224 (c 0.76, CHCl₃). ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.90 (d, J = 5.0 Hz, 1 H), 8.27 (dd, J = 3.6, 7.4 Hz, 1 H), 7.62 (t, J = 7.5 Hz, 1 H), 7.52 (t, J = 7.4 Hz, 1 H), 7.42 (d, J = 3.3 Hz, 6 H), 7.36–7.16 (m, 11 H), 7.16–7.03 (m, 2 H), 6.93 (dd, J = 4.8, 7.5 Hz, 1 H), 6.40 (d, J = 7.5 Hz, 1 H), 5.50 (t, J = 8.4 Hz, 1 H), 4.81 (t, J = 8.7 Hz, 1 H), 4.16 (t, J = 8.3 Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 160.2 (d, J = 22 Hz), 156.7, 148.6, 139.1 (d, J = 5 Hz), 138.8 (d, J = 4 Hz), 138.5, 136.4 (d, J = 5 Hz), 136.3 (d, J = 6 Hz), 134.2 (d, J = 3 Hz), 134.0 (d, J = 3 Hz), 133.6, 132.1, 130.3, 130.0, 129.8, 129.46 (d, J = 1 Hz), 129.4 (d, J = 1 Hz), 129.1, 128.9, 127.9, 126.6, 119.3, 70.5, 62.2. ³¹P NMR (162 MHz, DMSO-d ₆): δ = –14.4 (s). ESI-MS: m/z = 526.2 [M + H⁺]. ESI-HRMS: m/z calcd for C₃₄H₂₈N₂O₂P [M + H⁺]: 527.1888; found: 527.1882. Compound 1b: 54%; mp 125–126 °C. [α]_D ²⁵ +174 (c 1.0, CHCl₃). ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.92 (d, J = 5.0 Hz, 1 H), 8.12 (dd, J = 3.6, 6.9 Hz, 1 H), 7.68–7.53 (m, 1 H), 7.49 (t, J = 7.4 Hz, 1 H), 7.42 (d, J = 2.0 Hz, 6 H), 7.37 (dd, J = 3.5, 5.8 Hz, 1 H), 7.33–7.19 (m, 6 H), 6.89 (dd, J = 5.0, 6.8 Hz, 1 H), 6.46 (dd, J = 3.5, 5.8 Hz, 1 H), 4.53–4.30 (m, 2 H), 4.18 (dd, J = 4.6, 7.2 Hz, 1 H), 1.78–1.53 (m, 1 H), 0.79 (d, J = 6.8 Hz, 3 H), 0.74 (d, J = 6.8 Hz, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 159.4 (d, J = 22 Hz), 156.3, 148.1, 138.5, 138.3, 138.2, 135.7 (d, J = 9 Hz), 135.6 (d, J = 9 Hz), 133.6 (d, J = 8 Hz), 133.4 (d, J = 8 Hz), 132.9, 131.5, 130.0, 129.3, 129.2, 128.8 (d, J = 7 Hz), 128.1 (d, J = 4 Hz), 126.2, 119.0, 63.5, 61.2, 54.8, 28.6, 17.1, 14.8. ³¹P NMR (162 MHz, DMSO-d ₆): δ = –14.3 (s). ESI-MS: m/z = 493.2 [M + H⁺]. ESI-HRMS: m/z calcd for C₃₁H₃₀N₂O₂P [M + H⁺]: 493.2044; found: 493.2048
• 13 General Procedure for the Asymmetric Allylic Alkylation To a Schlenk tube containing allyl palladium(II) chloride dimer (2.90 mg, 0.008 mmol), 1b (15.3 mg, 0.032 mmol), and LiOAc (2.62 mg, 0.040 mmol) were evacuated and backfilled with nitrogen for 3 times, after that, THF (2 mL) was added and stirred for 0.5 h at r.t. Then (E)-1,3-diphenylallyl acetate (100 mg, 0.396 mmol) was added, and the mixture was stirred for another 10 min, dimethyl malonate (157 mg, 1.189 mmol) was added to the reaction mixture followed by BSA (242 mg, 1.189 mmol). The resultant mixture was stirred at –10 °C for 10 h. The reaction was diluted with CH₂Cl₂ and quenched by sat. aq NH₄Cl. The organic layer was washed by H₂O and brine 3 times, concentrated and purified with silica gel (EtOAc–hexane, 1:10) afforded 10a (121 mg, 99% yield) as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.34–7.20 (m, 10 H), 6.51–6.46 (d, J = 15.6 Hz, 1 H), 6.37–6.29 (dd, J = 8.4, 15.9 Hz, 1 H), 4.30–4.24 (dd, J = 8.7, 10.8 Hz, 1 H), 3.98–3.94 (d, J = 10.8 Hz, 1 H), 3.71–3.70 (d, J = 3.0 Hz, 3 H), 3.52–3.51 (d, 3 H, J = 3.3 Hz, 3 H). The ee value was determined by SFC (Daicel CHIRALCEL AD-H, column size: 0.46 cm I.D. × 25 cm L, liquid CO₂/MeOH = 85:15, flow rate: 2.0 mL/min, λ = 254 nm): t _R (major) = 8.0 min; t _R (minor) = 16.77 min; 87% ee