Application of the Fluorous-Biphase Concept to Palladium-Catalyzed Sonogashira Couplings

Abstract

Dedicated to Professor Wolfgang Pfleiderer on the occasion of his 75th birthday Sonogashira C,C couplings in a fluorous biphasic system by application of three differently perfluorotagged Pd complexes are reported. All three complexes were probed in the coupling of four bromoarenes to three alkynes. The parallel workup procedure allowed for straightforward product isolation and catalyst recovery by simple extraction steps. In particular, the coupling of electron-deficient bromoarenes proceeded with good yields and allowed for the catalyst to be used up to three times.1. Introduction. ± According to the alchemists rule similia similibus solvuntur, highly fluorinated compounds show greatly enhanced solubility in perfluorinated alkanes even in the presence of a second organic phase. This principle can be applied in catalytic processes as well as in combinatorial strategies. Horva¬th and Ra¬bai [1] were the first to point out that this allows for a perfluoro-tagged catalyst to remain in the fluorous phase, while other reactants dissolve in the organic phase. Furthermore, the temperature-dependent miscibility of such fluorous biphasic systems (FBS) [2] provides an option to homogenize the phases at elevated temperatures. Workup is essentially straightforward, as the two phases reform after lowering the temperature again. Simple phase-separation suffices to recover the perfluoro-tagged catalyst. At the same time, product isolation can be reduced to an extraction protocol.Syntheses in the nonpolar reaction medium scCO 2 represent a further application of perfluoro-tags where they can be used to mediate sufficient solubility [3]. Hence, there is currently a great deal of interest in perfluoro-tagged catalysts. So far, a number of reactions have been successfully evaluated under FBS conditions, including hydroformylation [4], hydroboration [5], hydrosilylation [6], epoxidation [7] [8], and the Rh-catalyzed cyclopropanation of alkenes [9], oxidations of aldehydes [7], thioesters [7], and alkanes [10], as well as Wacker oxidations [11], Pdcatalyzed allylic substitutions [12], and Negishi [13] and Heck reactions [14].Among the transition-metal catalyzed reactions, C,C couplings are of particular importance, as they allow construction of molecule skeletons. We have previously reported on highly efficient protocols for Stille [15] and Suzuki [16] cross-coupling

Palladium‐Based Catalytic Systems for the Synthesis of Conjugated Enynes by Sonogashira Reactions and Related Alkynylations

“…Three phosphane ligands with fluorinated side chains (Scheme 48) have been investigated in the Sonogashira cross‐coupling of aryl bromides with various alkynes in a fluorous biphasic system 116. Good to excellent conversions were observed with electronically activated bromides (NO 2 ‐, COMe‐, CO 2 Et‐substituted bromobenzene) and were maintained over two recycling experiments irrespective of the ligand used (2 mol % Pd/fluorinated phosphane, 5 mol % CuI, 100 °C, 4 h).…”

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

“…[91] A bimetallic rhodium catalyst was used in the cyclopropanation of alkenes and recovered by fluorous extraction. [100] The Suzuki coupling of five different aryl bromides 21 with phenylboronic acid (22) was carried out with four different palladium complexes (17 a ± d, Scheme 18). [100] The Suzuki coupling of five different aryl bromides 21 with phenylboronic acid (22) was carried out with four different palladium complexes (17 a ± d, Scheme 18).…”

Side chain fluorination and anion effect on the structure of 1-butyl-3-methylimidazolium ionic liquids

“…14 In this context, Horváth and Rábai introduced the term fluorous biphasic system (FBS) and described the hydroformylation of olefins in FBS. 15 Several applications a) Electronic mail: kirchner@thch.uni-bonn.de of fluorine-containing functionalities followed, including perfluorinated solvents as reaction media, 16,17 perfluoro-tagged catalysts, [18][19][20][21][22][23][24][25][26] perfluoro-tagged reagents, 27 and perfluorotagged products. 28 The principle of these applications is the tendency of fluorous media to form a separate phase.…”