Letter pubs.acs.org/OrgLett
Photocatalytic α‑Acylation of Ethers Zhongdong Sun, Naoya Kumagai,* and Masakatsu Shibasaki* Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan S Supporting Information *
ABSTRACT: Direct coupling of ethers and acyl halides was promoted by a binary catalytic system comprising an Ir-based photocatalyst and a Ni complex under blue-light irradiation. Photocatalysts with high triplet energy directed the catalysis, and the reaction likely proceeded by triplet−triplet energy transfer from the excited photocatalysts. Chlorine radicals generated from an excited Ni complex bearing a Ni−Cl bond would be responsible for generating α-oxy radicals leading to the α-acylated ethers.
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Scheme 1. Visible-Light-Mediated Acylation Reactions with Ni/Ir
isible-light photoredox catalysis has profoundly advanced over the last several years, demonstrating the high versatility of reaction manifolds harnessed with photoirradiation in a wide variety of C−C and C−heteroatom bond-forming reactions.1 Direct photoexcitation of organic substrates by visible light is unlikely to be manifested, however, as organic substrates only barely absorb visible light. On the other hand, photosensitizers are amenable to converting the photoenergy of visible light into chemical energy to activate organic molecules via single-electron transfer (SET) or energy transfer, which is attracting growing interest for the development of unprecedented chemical transformations. The broad compatibility of photocatalytic cycles with organocatalysis and metal-based catalysis further extends the scope of the synthetically versatile reactions empowered by visible-light irradiation. These dual catalytic systems allow for a diverse array of C(sp2)−C(sp3) and C(sp3)−C(sp3) bond-forming reactions using stable pronucleophile carboxylates,2 trifluoroborates,3 and silicates4 instead of organometallic nucleophiles, where photocatalytic generation of an active nucleophile plays a critical role in driving the catalysis. The light-driven Ir/Ni catalysis strategy has been intensively studied, and its particular utility in photocatalytic installation of acyl units has been proven. MacMillan et al. documented a decarboxylative coupling reaction of carboxylic acids and acyl chlorides via Ir photoredox and Ni catalysis (Scheme 1a).5 Subsequently, the light-mediated direct α-acylation of amines using anhydride as the acylation reagent has been achieved by Doyle et al. (Scheme 1b).6 Molander et al. recently developed a protocol accessing dialkyl ketone from organotrifluoroborate and acyl chloride using synergistic photoredox/Ni catalysis (Scheme 1c).3h However, photocatalytic α-acylation of ethers has not been disclosed despite its potential synthetic utility. Direct α-C(sp3)−H functionalization of ethers has been a sustained topic in photocatalytic systems, revealing that αarylation of ethers is feasible where radicals play a key role in activation.7−11 We reasoned that this prior work could also be valid for the coupling with acyl chlorides to afford synthetically © 2017 American Chemical Society
versatile α-oxygenated ketones. Herein, we report the direct αC(sp3)−H acylation of ethers via Ir/Ni synergistic catalysis (Scheme 1d). At the outset, we selected benzoyl chloride 1a as an archetypal acyl chloride in the reaction with THF. Based on the proficiency of the precedent Ir/Ni binary catalytic system in αarylation of ethers using aryl halides reported independently by Molander and Doyle,10,11 we examined a combined catalytic system comprising Ir[dF(CF3)ppy]2(dtbbpy)PF6 (dF(CF3)ppy = 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine, dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine) and Ni complexes at room temperature under visible-light irradiation (blue LED, 21 W). Received: May 22, 2017 Published: July 11, 2017 3727
DOI: 10.1021/acs.orglett.7b01552 Org. Lett. 2017, 19, 3727−3730
Letter
Organic Letters With readily available NiCl2 as the Ni source, a brief survey of ligands and bases indicated that the reported combination of the Ir photocatalyst and L2 was optimal with K3PO4, affording 2a in 66% yield (Table 1, entries 1−9). Concentrated conditions partially improved the yield (entry 6 vs 10). Table 1. Conditions Screening of α-Benzoylation of THFa
entry
ligand
concn (M)
base
yieldb (%)
1 2 3 4 5 6 7 8 9 10
L1 L1 L1 L1 L1 L2 L3 L4 L5 L2
0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.2
K2CO3 CS2CO3 K3PO4 DBU Et3N K3PO4 K3PO4 K3PO4 K3PO4 K3PO4
31
