Cationic Palladium(II)-Catalyzed Synthesis of 2-Substituted 3-Hydroxymethylbenzo[b]furans

Abstract

A tandem reaction involving an intramolecular oxypalladation of an alkyne and an addition to the carbonyl group to quench the carbon-palladium bond to complete the catalytic cycle was developed. The reaction was catalyzed with the cationic palladium(II) species without the necessity of a redox system.

aldehyde - alkyne - cationic palladium(II) complex - 3-hydroxymethylbenzofuran - oxypalladation

References and Notes

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General Procedure for the Synthesis of 2-Substituted 3-Hydroxymethylbenzofuran Catalyzed by [Pd(dppp)(H ₂ O) ₂ ](BF ₄ ) ₂
A dried small tube with screw-cap was charged with [Pd(dppp)(H₂O)₂](BF₄)₂ (1.2 mg, 0.002 mmol), 4 Å MS
(20 mg), THF (0.5 mL), then substrates 1 (0.1 mmol) and aldehydes 2 (0.2 mmol, 2 equiv) were added to the mixture, and the solution was stirred at 45 ˚C until complete consumption of substrates 1 (monitored by TLC). Then,
the mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel
using EtOAc and PE as the eluent to afford the product.
Compound 3aa: solid; mp 87-89 ˚C. ^¹H NMR (400 MHz, CDCl₃): δ = 8.16 (d, J = 8.8 Hz, 2 H), 7.77 (d, J = 6.8 Hz, 2 H), 7.65 (d, J = 8.4 Hz, 2 H), 7.52-7.45 (m, 4 H), 7.28-7.23 (m, 1 H), 7.19 (d, J = 7.6 Hz, 1 H), 7.08 (t, J = 7.6 Hz, 1 H), 6.39 (s, 1 H), 2.61 (d, J = 3.6 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 154.3, 153.5, 149.1, 147.1, 129.7, 129.5, 129.0, 127.7, 126.9, 124.9, 123.0, 121.0, 116.2, 111.4, 67.7. IR (KBr): ν = 3349, 3065, 1600, 1518, 1453, 1344, 1027, 834, 746 cm^-¹. MS (EI): m/z (%) = 345 (100) [M⁺], 328, 223, 165, 105, 77, 57. HRMS (EI): m/z calcd for C₂₁H₁₅NO₄: 345.1001; found: 345.1005.