Palladium-Catalyzed Reactions of Allylic Boronic Esters with Nucleophiles: Novel Umpolung Reactivity

Dedicated to Professor K. Peter C. Vollhardt with deep appreciation, where science and art combine

Abstract

Oxidative palladium-catalyzed reaction conditions have been developed to allow for regioselective and stereoselective coupling of allylic boronic esters with a range of carbon-, oxygen-, and nitrogen-based nucleophiles. Studies into the mechanism of the reaction have shown that the key transmetalation step occurs with retention of stereochemistry, since overall inversion is observed.

Key words

palladium - boronic ester - umpolung - allylation - oxidative coupling

• References and Notes

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• 20 General Procedure Allylic boronic ester (0.50 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.50 mol%), tri(2-furyl) phosphine (2.0 mol%), and the nucleophile (1.3 equiv) were weighed into a dry flask and placed under argon [for reactions with nitrogen nucleophile 6, EtN(i-Pr)₂ (5.0 mol%) was also added to the flask at this stage]. A solution of 2,6-dimethylbenzoquinone (1.3 equiv) in DMF (5.0 mL) was added in one portion, and the mixture was stirred at r.t for 16 h, or until the reaction was complete as determined by GC–MS analysis. 20% aq NaHSO₃ (10 mL) was added, and the mixture was stirred vigorously for 5 min. Et₂O (10 mL) was added, and the layers were separated. The aqueous phase was extracted with Et₂O (2 × 10 mL), and the combined organic phases were washed with brine (10 mL), dried (MgSO₄), and concentrated in vacuo. Purification by flash column chromatography (pentane–EtOAc) yielded the allylation product. Dimethyl (E)-2-(4-Phenylpent-2-en-1-yl)malonate Yield 53%; E/Z >95:5; linear to branched >95:5; R_f = 0.25 (pentane–EtOAc, 15:1); IR (neat): ν_max = 2958, 1733 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29 (3 H, d, J = 7.0 Hz), 2.56–2.62 (2 H, m), 3.39 (1 H, app p, J = 7.0 Hz), 3.41 (1 H, t, J = 7.6 Hz), 3.65 (3 H, s), 3.68 (3 H, s), 5.40 (1 H, dtd, J = 15.3, 7.0, 1.3 Hz), 5.68 (1 H, ddt, J = 15.3, 7.0, 1.3 Hz), 7.10–7.21 (3 H, m), 7.21–7.32 (2 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 21.3, 32.0, 42.3, 52.0, 52.5, 52.5, 124.1, 126.2, 127.3, 128.5, 138.8, 145.8, 169.5. HRMS (ESI⁺): m/z calcd for C₁₆H₂₁O₄Na [M + Na⁺]: 299.1254; found: 299.1246. (E)-4-Phenylpent-2-en-1-yl Benzoate Yield 92%; E/Z >95:5; linear to branched >95:5; R_f = 0.30 (pentane–EtOAc, 30:1). IR (neat): ν_max = 2966, 1715 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40 (3 H, d, J = 7.1 Hz), 3.53 (1 H, qd, J = 7.1, 6.6 Hz), 4.82 (2 H, m), 5.73 (1 H, dtd, J = 15.5, 6.2, 1.4 Hz), 6.05 (1 H, ddt, J = 15.5, 6.6, 1.3 Hz), 7.19–7.25 (3 H, m), 7.29–7.35 (2 H, m), 7.41–7.46 (2 H, m), 7.54 (1 H, m), 8.05-8.09 (2 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 21.1, 42.1, 65.6, 123.0, 126.4, 127.3, 128.4, 128.6, 129.7, 130.5, 133.0, 140.4, 145.2, 166.5. HRMS (ESI⁺): m/z calcd for C₁₈H₁₈O₂Na [M + Na⁺]: 289.1199; found: 289.1186. Methyl (E)-(4-Phenylpent-2-en-1-yl)(tosyl)carbamate Yield 81%; E/Z >95:5; linear to branched >95:5; R_f = 0.30 (pentane–EtOAc, 6:1). IR (neat): ν_max = 2961, 1732 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.38 (3 H, d, J = 7.0 Hz), 2.42 (3 H, s), 3.50 (1 H, app p, J = 6.8 Hz), 3.68 (3 H, s), 4.47 (2 H, app dt, J = 6.4, 1.2 Hz), 5.58 (1 H, dtd, J = 15.4, 6.4, 1.4 Hz), 5.98 (1 H, ddt, J = 15.4, 6.9, 1.2 Hz), 7.19–7.25 (5 H, m), 7.30–7.35 (2 H, m), 7.73–7.83 (2 H, m Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 21.2, 21.7, 42.1, 48.5, 53.8, 123.3, 126.3, 127.2, 128.6, 128.6, 129.3, 136.5, 140.1, 144.5, 145.3, 152.7. HRMS (ESI⁺): m/z calcd for C₂₀H₂₃O₄NNaS [M + Na⁺]: 396.1240; found: 396.12430.