Lithium Compounds in Cross‐Coupling Reactions

Abstract

IntroductionTransition-metal-catalyzed cross-coupling reactions of organic halides with organometallic compounds have been recognized as one of the most powerful, practical, and versatile methods for carbon-carbon bond formation [1]. Various organometallic reagents such as organomagnesium (Grignard reagents), -zinc, -tin, -boron, and -silicon compounds are extensively studied and applied to the concise synthesis of natural products, biologically active substances, and functional materials [2]. On the other hand, the cross-coupling reactions of organolithium compounds are less developed compared to those of the organometals listed above probably because the high reactivity of lithium can cause side reactions such as halogen-lithium exchange and deprotonation of organic halides seriously and result in the narrow compatibility of functional groups [3]. Organolithium compounds are often used as typical precursors of the other organometallic reagents. Accordingly, it is highly desirable to use organolithium compounds as nucleophiles directly for transition-metal-catalyzed cross-coupling reactions in view of atom economy as well as the reduction of chemical waste, money, and time. As shown in Scheme 16.1, this chapter is divided into four sections based on the types of lithium compounds that participate in the cross-coupling reactions: (i) organolithium reagents in which a lithium atom is attached to a carbon atom, (ii) lithium enolates, (iii) lithium amides, and (iv) lithium thiolates. Described in Section 16.2 are cross-coupling reactions of aryl-, alkenyl-, and alkyllithiums with halogenated compounds. Section 16.3 summarizes the coupling reactions of lithium enolates with organic halides. Amination of aryl halides with lithium amides is reviewed in Section 16.4. Finally, thioether synthesis by coupling reaction using lithium thiolates as nucleophiles is described in Section 16.5. Throughout this chapter, molecular structures of lithium compounds, their precursors, and the molecular fragments originating from the lithium compounds in the products are drawn with thick bonds and atom labels in bold.