Site-Selective Sequential Coupling Reactions Controlled By “Electrochemical Reaction Site Switching”: A Straightforward Approach to 1,4-Bis(diaryl)Buta-1,3-Diynes

Recently, π-conjugated compounds have received considerable attention because they are known to be key building blocks for pharmaceuticals and candidates for electrochemical and optical materials. One of the most straightforward and powerful ways to construct π-skeletons is through transition-metal catalysed cross-coupling reactions using aryl halides or triflates and organometallic species such as in Suzuki–Miyaura coupling. Alternatively, transition metal-catalysed oxidative homo-coupling reactions of aryl metal species (e.g., arylboronic acids and esters) or terminal alkynes have also been shown to be convenient methods for building symmetrical π-structures. In these oxidative homo-coupling reactions, a stoichiometric amount of an oxidant is usually required. One way to overcome this drawback is to use electro-oxidation instead of a stoichiometric oxidant. The electrochemical method is advantageous, not only because it does not require excess oxidant, but also because the system can be switched between oxidative and neutral conditions by the on/off application of electricity. We considered that this feature could make it possible to realize a site selective coupling reaction controlled by the on/off application of electricity, and we call this strategy “Electrochemical Reaction Site Switching (e-RSS)”. This idea prompted us to design a novel integrated sequential reaction that consisted of an oxidative homo-coupling reaction and a typical coupling reaction.

  As the first example of the construction of π-conjugated compounds by a sequential coupling reaction controlled by e-RSS, we chose π-conjugated compounds that include a diyne moiety as a target; they are of interest due to their unique optical and electrochemical characteristics. The sequential reactions consist of two coupling reactions (Scheme 1). The first step is a Pd/Cu-catalysed electrochemical homo-coupling of p-bromophenylacetylene to give bis(p-bromophenyl)butadiyne (1st step: electricity ON), and the second step is a sequential Suzuki–Miyaura coupling reaction to build up 1,4-bis(diaryl)butadiynes (2nd step: electricity OFF). First, we optimized the reaction conditions of Pd/Cu-catalyzed electro-oxidative homo-coupling of p-bromophenylacetylene (1) (1st step) and we obtained diyne 2 in good yield. With the optimized conditions for the first step in hand, we next carried out the sequential reactions, including the electrooxidative homo-coupling of 1 and subsequent Suzuki–Miyaura coupling with several arylboronic acids on the basis of the e-RSS strategy. After the electro-oxidative homo-coupling of p-bromophenylacetylene, the electricity was turned off and to the resulting mixture were added p-tolylboronic acid, P(t-Bu)₃·HBF₄, Cs₂CO₃, and DME, then refluxed to give 1,4-bis(p-tolylphenyl)butadiyne 3a in 95% yield. In a similar manner, i-Pr- or t-Bu-substituted 1,4-bis(diaryl)butadiyne 3b and 3c were obtained in 79 and 86% yields, respectively. Anisole and aniline skeletons can also be introduced (3d and 3e). Arylboronic acids bearing electronwithdrawing functional groups could also be used in the reactions. 1,4-Bis-(diaryl)butadiynes with fluoro (3f), acetyl (3g), and cyano (3h) groups at the p-position can be synthesized by the sequential coupling reactions in respective yields of 68%, 65%, and 47%. The synthesis of aryl-substituted diynes with much greater π-conjugation was achieved by the use of 2-naphthylboronic acid or 2-phenylethenylboronic acid to afford 3i and 3j in 72% and 70% yields, respectively. We will discuss the details of the reactions and further transformations of 1,4-bis(diaryl)buta-1,3-diynes.