Dual Ligand-Enabled Late-Stage Fujiwara–Moritani Reactions

Abstract

In this study, we describe the use of dual ligand-based palladium catalysts for the late-stage olefination of arenes. Building upon a method previously developed for simple arenes, a variety of complex arene substrates were functionalized. Importantly, the method uses the arene as a limiting reactant and is therefore suitable for valuable starting materials that cannot be used in excess. The regioselectivity of the transformation is controlled by the steric and electronic properties of the substrate, providing access to regioisomers that would be challenging to prepare through other synthetic approaches.

Key words

C–H bond activation - late-stage functionalization - palladium catalysis - arenes - Fujiwara–Moritani reaction - olefination

Publication History

Received: 02 December 2020

Accepted after revision: 23 December 2020

Article published online:
18 January 2021

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• 13 Ethyl (2E)-3-(3,5-Diisopropyl-4-methoxyphenyl)acrylate (2a); Typical Procedure An oven-dried 10 mL Schlenk tube was charged with Pd(OAc)₂ (4.5 mg, 0.020 mmol, 10 mol%), L1 (9.4 mg, 0.040 mmol, 20 mol%), N-acetylglycine (7.0 mg, 0.060 mmol, 30 mol%), AgOAc (100.2 mg, 0.6000 mmol, 3 equiv), propofol methyl ether (38.5 mg, 0.200 mmol, 1 equiv), and HFIP (2 mL). The mixture was stirred at rt for 2 min. Ethyl acrylate (0.600 mmol, 3 equiv) was added, and the reaction vessel was tightly sealed and placed in an aluminum block with a tightly fitting recess on a magnetic stirrer at 90 °C. The mixture was stirred at 90 °C for 24 h, then allowed to cool to rt, filtered through silica, transferred into a 100 mL round-bottomed flask, and concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel, pentane–EtOAc (80:1 to 60:1)] to give a colorless solid; yield: 35.5 mg (61%). ¹H NMR (400 MHz, CDCl₃): δ = 7.58 (d, J = 16.0 Hz, 1 H), 7.20 (s, 2 H), 6.29 (d, J = 16.0 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 3.67 (s, 3 H), 3.25 (hept, J = 6.9 Hz, 2 H), 1.27 (t, J = 7.1 Hz, 3 H), 1.17 (d, J = 6.9 Hz, 12 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 167.2, 156.7, 144.9, 142.4, 130.7, 124.3, 116.8, 62.3, 60.4, 26.5, 23.9, 14.4 ppm. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₈H₂₆NaO₃ ⁺: 313.1780; found: 313.1771.