Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Synthesis of β‑Sulfonyl Amides through a Multicomponent Reaction with the Insertion of Sulfur Dioxide under Visible Light Irradiation Yu Zong,†,‡ Yimin Lang,‡ Min Yang,† Xiaofang Li,§ Xiaona Fan,*,† and Jie Wu*,‡ †
Gannan Medical University Collaborative Innovation Center for Gannan Oil-tea Camellia Industrial Development, 1 Yixueyuan Road, Ganzhou, Jiangxi 341000, China ‡ Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China § School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China Org. Lett. Downloaded from pubs.acs.org by WASHINGTON UNIV on 03/06/19. For personal use only.
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ABSTRACT: A multicomponent reaction of styrenes, aryldiazonium tetrafluoroborates, sulfur dioxide, nitriles, and water in the presence of a photocatalyst at room temperature is performed. This vicinal aminosulfonylation of styrenes with the insertion of sulfur dioxide under visible light irradiation proceeds efficiently with excellent chemoselectivity, giving rise to the corresponding β-sulfonyl amides in moderate to good yields. Scheme 1. A Proposed Route to β-Hydroxy Sulfones with an Unexpected Result
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o far, multicomponent reactions have been used as a powerful tool in organic synthesis for the construction of multibonds.1,2 In the meantime, continuous interest has been focused on the photoinduced reactions, because many transformations could be achieved under visible light irradiation in the presence of photoredox catalysis under mild conditions.3,4 Usually, a radical process would be involved in photoredox catalysis through a single electron transfer (SET). Currently, photoinduced multicomponent reactions have been developed, which show the advantages of a green process, atom economy, and mild conditions.5 As part of a program for the synthesis of sulfonyl-containing drugs, we are interested in the transformations by using sulfur dioxide as the source of the sulfonyl group.6 This strategy would avoid the utilization of odorous thiol substrates with harsh reaction conditions, which had to be employed for the generation of sulfonyl precursors.7 So far, many reports have described the insertion of sulfur dioxide catalyzed by transition metals or through a radical process.8 Generally, the sulfur dioxide surrogates include 1,4-diazabicyclo[2.2.2]octane-sulfur dioxide [DABCO·(SO2)2]9,10 and inorganic sulfites,11 which avoid the use of gaseous sulfur dioxide. Among the approaches developed, we have demonstrated that the combination of aryldiazonium tetrafluoroborates with DABCO·(SO2)2 provides an efficient pathway for generating an arylsulfonyl radical intermediate.9 During the studies of the synthesis of a marketed drug of bicalutamide, we designed a radical process for the vicinal difunctionalization of alkenes with the insertion of sulfur dioxide under photoinduced conditions (Scheme 1). We hypothesized that a four-component reaction of alkenes, aryldiazonium tetrafluoroborates, sulfur dioxide, and water in the presence of a photocatalyst would afford β-hydroxy sulfones, thus providing a facile pathway to bicalutamide. We proposed that the arylsulfonyl radical generated in situ would attack the © XXXX American Chemical Society
terminal position of alkene, thus giving rise to a carbon radical intermediate. After an oxidative SET, a cation would be formed, which would react with water to produce the desired β-hydroxy sulfone. Initial exploration was performed for the reaction of styrene 1a, 4-methylphenyldiazonium tetrafluoroborate 2a, DABCO· (SO2)2, and water promoted by a photocatalyst under visible light irradiation. However, we failed to observe the formation of β-hydroxy sulfone. Instead, a small amount of product (
