Electron-Donor–Acceptor Complex-Enabled Flow Methodology for the Hydrotrifluoromethylation of Unsaturated β-Keto Esters

Abstract

A novel electron-donor–acceptor (EDA) complex-enabled flow photochemical hydrotrifluoromethylation of unsaturated β-keto esters is described. The developed protocol has an easy experimental procedure and does not require the use of transition-metal-based photocatalysts, allowing the isolation of 14 new compounds in up to 86% yield. Control experiments and computational studies revealed that the reaction proceeds through a Michael-type 1,4-addition of a trifluoromethyl radical, followed by a proton transfer step. Furthermore, the reaction could be scaled up to 1 mmol, and the final product could be employed in the preparation of an isoxazolone and a pyrazolone as trifluoro-substituted heterocycles.

Discovery of EDA-Complex Photocatalyzed Reactions Using Multidimensional Image Processing: Iminophosphorane Synthesis as a Case Study

“…27 In this study, we have explored EDA complex-mediated reactions, where the substrates (electron donor and acceptor) are mixed and submitted to visible-light irradiation to undergo chemical transformations. 5,6,8 Other approaches, which use sacri cial electron donor-or acceptor-species for EDA complex formation, and subsequent trapping of the target radical with a third substrate, 7,11 were not covered in this study. The analysis of new products after visible-light irradiation of the "EDA-hit" solutions could select potential EDA complex-promoted reactions (reaction-based screening).…”

“…6 Recently, the synthetic community has recognized the potential of this photochemical approach, mainly for dispensing the use of exogenous photoredox catalysts 6 . Examples of the synthetic potential of this approach include hetero-arene arylations, 4,5,[7][8][9] αalkylation of aldehydes, 10 hydrotri uoromethylation of unsaturated β-keto esters, 11 hydroalkylation of 1,7-enynes 12 and other chemical transformations. 6 Similar to the discovery of the EDA complex-mediated reactions, many other important chemical reactions have also been discovered serendipitously, such as the Friedel-Crafts and Wittig reactions.…”

“…The 50 substrates, where 4 (pyridine, 4-methoxybenzenediazonium tetra uoroborate, Umemoto's reagent, and N,N-dimethylaniline) were intentionally added as a positive control, 5,11 were selected by a randomized computer driven manner from our organic compounds laboratory stockroom list (details shown in the SI). Although the formation of EDA complexes requires two groups of compounds, one electron-donor and other electron-acceptor, this substrate separation was not considered during the choice of compounds.…”

Progress in Photoinduced Radical Reactions using Electron Donor‐Acceptor Complexes

“…The target alkynyl ketones might be further converted into alcohol, ketone and cyclic α , β ‐unsaturated compound through chemoselective reduction, hydrogenation and TfOH‐catalyzed cyclization reactions, respectively. Recently, Amarante et al further described a EDA complex‐enabled flow photochemical hydrotrifluoromethylation of unsaturated β ‐keto esters without the use of transition‐metal photocatalysts, involving a Michael‐type 1,4‐addition of a trifluoromethyl radical process and a proton transfer step [58b] …”

Starting from Styrene: A Unified Protocol for Hydrotrifluoromethylation of Diversified Alkenes

“…6 Elegant as it is, the near-room-temperature melting point and offensive odor of the thiophenol used can reduce its practicability in certain circumstances. Meanwhile, despite the fact that several methods concerning the hydrotrifluoromethylation of acrylates, 7 acrylamides, 8 and vinyl phosphate esters 9 were reported, a universal protocol that can break through the limits of the previously mentioned alkenes to realize hydrotrifluoromethylation has never been realized.…”