Transition-metal-free Coupling Reactions of Aryl Halides

Abstract

Transition metal catalysis plays a leading role in C(sp 2 )C(sp 2 ) bond formation through substitution reactions. On the other hand, a similar type of substitution reaction has recently been achieved without the aid of transition-metal catalysts. In this review, recent transition-metal-free coupling reactions of aryl halides with arenes, alkenes, or aryl Grignard reagents are summarized in view of S RN 1 reaction. Ç IntroductionAryl halides (ArX), readily available aryl electrophiles, do not undergo S N 2 nor S N 1 reaction. Instead, they are usually activated by reduction to participate in substitution reactions, even though the overall processes are not reduction or oxidation. Transition metal catalysis plays a dominant role to make use of ArX for substitution reactions in such a way.1,2 In particular, palladium is versatile to catalyze the coupling reaction of ArX with nucleophiles such as arenes, alkenes, and aryl Grignard reagents (Scheme 1).3 The generally accepted catalytic cycle consists of oxidative addition of ArX to a Pd(0) complex (i), reaction of the resulting ArPd II X with a nucleophile (ii), and reductive elimination to give the coupling product with regeneration of the Pd(0) complex (iii). ArX is activated by two electron reduction in step i, whereas two electron oxidation takes place in step iii.Single electron reduction also is effective for activation of aryl halides, 4 leading them to the substitution reaction (S RN 1 reaction) with anionic nucleophiles (R ¹ ) (Scheme 2). 5 Radical anion [ArX] •¹ , produced by single electron transfer (SET) from single electron donor Y in the initiation step (a), is converted into an aryl radical (Ar •¹ to ArX gives the coupling product (ArR) and regenerates [ArX] •¹ (e). S RN 1 reaction includes reduction of ArX (steps a and e) and oxidation giving coupling products (step e), as same as the palladium-catalyzed reaction. A major difference between these is the number of electrons involved in the redox processes. S RN 1 reaction features high efficiency that such a small unit as a single electron works as a catalyst, avoiding the use of expensive transition-metal catalysts. Although S RN 1 reaction is expected to have ability to connect the aryl group of aryl halides to sp 2 -carbons as same as transition metal catalysis, 6,7 the scope on anionic nucleophiles has been limited mainly to heteroatom anions and sp 3 -carboanions such as enolates. No reports are available for use of arenes, alkenes, or aryl Grignard reagents as (pro)nucleophiles in S RN 1 reaction.We have recently developed the transition-metal-free coupling reactions of aryl halides with arenes, alkenes, or aryl Grignard reagents (Scheme 1: ac). All the reactions are considered to proceed within the boundary of S RN 1 mechanism. In this Highlight Review, we summarize our work on the transition-metal-free coupling reactions in addition to related reactions reported by others. Ç tert-Butoxide-mediated Coupling with ArenesDuring the course of our studies on the iron-catalyzed coupling r...

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