ACS catalyst: copper catalyzed radical mediated Suzuki miyaara coupling reaction

Suzuki miyaara coupling reaction is one of the most powerful methods to construct C SP2 − C SP2 bond The reaction mechanism is as follows: the oxidation addition of PD (0) to C sp2-x bond yields C sp2-pd-x, and the conversion metallization between PD (0) and boron reagent yields C sp2-pd-c ′ SP2, and further reduction elimination yields C sp2-c ′ SP2 However, due to the slow oxidation and addition rate of alkyl halides and the easy β - hydrogen elimination of σ - alkyl metal intermediates, Suzuki miyaara coupling reaction is difficult to occur On the other hand, the electroneutrality of free radicals allows them to combine with organic metal intermediates, such as the bifunctional reactions of alkenes or alkynes reported by the Nevada group (J am Chem SOC 2017, 139, 6835; chem Commun 2009, 7336; angel Chem Int ed 2016, 55, 12270) However, the cross coupling reaction between metal catalyzed radicals and organometallic intermediates is still challenging Recently, the research team of Professor Takashi nishikata of Yamaguchi University in Japan has developed a copper catalyzed Suzuki miyaara cross coupling reaction of three-stage alkyl bromide and alkenylborate The reaction can be used to construct alkenylated carbon centers The mechanism research shows that alkenyl copper species may be the key intermediate of the reaction (ACS catalyst 2018, 8, 6791) (source: ACS catalyst.) firstly, the reaction conditions were screened with ethyl 2-bromoisobutyrate 1a and pinacol styrene borate 2A as substrates (Table 1) Under the action of 10 mol%CuI, 1.5 equivalent two isopropylamine, 2 equivalent six fluoroisopropanol and ligand L5, the target compound 3A (entry 13) can be obtained in 78% yield Furthermore, when Pt (DBA) 2 was added to the reaction system as a cocatalyst, the yield could be increased to 92% (entry 15) (source: ACS catalyst.) then, the author studied the substrate application scope of the reaction (Table 2) Both electron rich or electron deficient styrene and heterocyclic substituted alkenylborate pinacol ester 2 can react with 2-bromoester 1 with large steric hindrance, including 4-membered, 5-membered, 6-membered ring and chain 2-bromoester The substrate containing boron, alkynyl, amides and amino groups can only obtain medium yield under standard conditions, but the yield is significantly improved when Pt (DBA) 2 is added as a cocatalyst (source: ACS catalyst.) because the reaction has very good activity for alkenyl borate and is inert for aryl borate, the substrate 4 containing aryl borate and 2-bromo-1b are coupled under standard conditions, and then the compound 6 (scheme 2) can be further derived through Suzuki miyaara coupling reaction catalyzed by palladium (source: ACS catalyst.) the author proposed a possible mechanism (scheme 4): Cu (I) reacts with 2a to obtain alkenyl copper intermediate a, which reacts with 1a to obtain target product 3A via intermediate B or C (source: ACS catalyst.) in order to verify the mechanism, the author synthesized alkenyl copper compound 12, whose structure was confirmed by X-ray single crystal diffraction (scheme 5) 12 can react successfully with 1a in the presence of ligand L5 to obtain 3a The addition of Pt (DBA) 2 can significantly improve the yield of the reaction (Table 3) It shows that PT plays a key role in the reaction When free radical inhibitors were added to the system, the target transformation was inhibited, which indicated that alkyl radical species should be involved in the system (source: ACS catalyst.) in addition, the author tries to use 12 instead of Cui to catalyze the reaction, and can obtain 3A (scheme 6) in 61% yield (source: ACS catalyst.) conclusion: Professor Takashi nishikata, Yamaguchi University, Japan, has developed a copper catalyzed Suzuki miyaara cross coupling reaction of tertiary alkyl bromide and alkenylborate The reaction conditions are mild and the substrate range is wide It can be used to construct alkenyl quaternary carbon center Adding PT to the reaction system is of great significance to improve the yield of the reaction The mechanism study indicated that alkenyl copper species may be the key intermediate of the reaction.