Letter Cite This: Org. Lett. 2018, 20, 3225−3228
pubs.acs.org/OrgLett
Visible-Light-Driven Decarboxylative Alkylation of C−H Bond Catalyzed by Dye-Sensitized Semiconductor Li Ren†,‡ and Huan Cong*,†,‡ †
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China ‡ School of Future Technology, University of Chinese Academy of Sciences, Beijing, 100190, China S Supporting Information *
ABSTRACT: A decarboxylative alkylation of benzylic C(sp3)−H bonds of N-aryl tetrahydroisoquinolines under the irradiation of blue light is reported, featuring a broad substrate scope, low cost, heavy-metal-free, and mild conditions. A preliminary mechanistic study indicated that radical intermediates are involved during the course of the reaction.
Scheme 1. Functionalizations of C(sp3)−H Bonds in N-Aryl Tetrahydroisoquinolines
V
isible light photocatalysis has emerged as an attractive strategy to meet the increasing demand for the development of selective chemical transformations.1 Compared to the intensively studied homogeneous photoredox catalysts such as Ru or Ir complexes2 and organic dyes,3 heterogeneous semiconductor photocatalysts have been relatively underdeveloped to date. Although many semiconductor materials have already exhibited proven photocatalytic activity in areas, including solar energy conversion4 and pollutant degradation,5 applications of these large band gap catalysts in selective organic synthesis remain limited due to their weak absorption of visible light.6 Inspired by the success of dye-sensitized solar cells, we reasoned that the combination of organic dyes and semiconductors would become versatile photocatalysts by promoting electron transfer processes under visible light irradiation.7 Indeed, our previous work has established that dye-sensitized titanium dioxide can serve as effective and userfriendly catalysts for a number of radical-based reactions.8 Here, we report the development of visible-light-driven decarboxylative alkylation of tetrahydroisoquinoline derivatives using erythrosine B sensitized TiO2 as a catalyst. Though functionalizations of benzylic C(sp3)−H bonds in N-aryl tetrahydroisoquinolines have been intensively investigated,9 most of these reactions, including but not limited to Mannich,9a aza-Henry,9b cyanation,9d and phosphonylation,9g proceed through two-electron oxidation processes entailing nucleophilic addition to the in situ generated iminium intermediates (Scheme 1a). We speculated that if the single electron transfer (SET) mechanism could be operative, the less studied, radical-based functionalizations of tetrahydroisoquinoline derivatives could likely open the door to the discovery of new reactivity (Scheme 1b).10 Our approach toward this goal features the use of the dye-sensitized semiconductor catalyst system to facilitate visible-light-induced SET and the use of N-hydroxyphthalimide esters11 as precursors for unactivated alkyl radicals (Scheme 1c). © 2018 American Chemical Society
In order to evaluate the feasibility of the proposed catalytic alkylation, N-phenyl tetrahydroisoquinoline 1a and N-acyloxyphthalimide 2a were selected as the model substrates for extensive screening of the reaction parameters (Table 1).12 To our delight, the desired product 3aa could be obtained under the irradiation of blue LED light with almost quantitative yield, catalyzed by the combination of erythrosine B and P25-type titanium dioxide (Table 1, entry 1). Control experiments indicated that visible light irradiation and either catalyst component (entries 2−4) were necessary. Notably, the choices of solvents played critical roles in optimizing the reaction outcome. Protic solvents prove to be superior, and the use of Received: April 6, 2018 Published: May 21, 2018 3225
DOI: 10.1021/acs.orglett.8b01077 Org. Lett. 2018, 20, 3225−3228
Letter
Organic Letters Table 1. Reaction Optimizationa
Scheme 2. Substrate Scopea
entry
variation from the standard condition
conv (%)
yield (%)
1 2 3 4 5 6 7 8 9 10 11
none no light no TiO2(P25) no erythtosine B CH2Cl2 instead of TFE toluene instead of TFE CH3CN instead of TFE DMF instead of TFE EtOH instead of TFE ZnO instead of TiO2(P25) CeO2 instead of TiO2(P25)
95 11 93 45 58 49 63 97 49 82 89
93
