Читать книгу Methodologies in Amine Synthesis - Группа авторов - Страница 31

As ubiquitous fundamental linkages, C—N bonds prevalently exist in various value‐added compounds such as natural products, pharmaceutical agents, functional materials, synthetic intermediates, and coordinating ligands. Thus, developing efficient methodologies for the construction of C—N bonds has always been a hot research goal in synthetic chemistry [1]. Among the existing approaches toward C—N bonds, cross‐dehydrohalogenative couplings of C—H/N—X (X = halide or pseudo‐halide) bonds or C—X/N—H bonds are generally well established, highly efficient, and consequently widely used, including the classical Buchwald–Hartwig amination and Ullman amination. However, from the perspective of green chemistry, these methods are not the ideal choices because the requirement for prefunctionalization of the coupling substrates considerably lowers their atom and step economy.

During the past few decades, cross‐dehydrogenative coupling (CDC) has emerged as an attractive technique, in which preinstallation of a reactive group in either of the coupling precursors is avoided, thus featuring higher atom and step economy in synthetic chemistry. Accordingly, CDC amination, which furnishes C—N bonds directly from unfunctionalized C—H bonds and N—H bonds, is acknowledged as one of the most straightforward approaches for C—N bond construction. In this field, transition‐metal‐mediated CDC aminations have been more extensively investigated, as summarized in the reviews by Patureau and coworker [2] and Chang and coworker [3]. Generally, these protocols depend on the interaction of the metal catalysts with the preinstalled directing groups on the substrates to facilitate the following amination. However, both the installation and the removal of such groups are tedious work that makes these strategies practically compromised. While, in other C–H aminations without chelation, the substrate scopes of carbon moieties are mostly limited to certain acidic C—H bonds that are more prone to activation. Nevertheless, these limitations have been overcome, wherein the direct conversion of unfunctionalized N—H and C—H bonds into C—N bonds have been achieved via reactive metal‐nitrenoid species [4]. Apart from metal chemistry, metal‐free direct oxidative C–H aminations have also been realized by the groups of Antonchick, Deboef, Chang, etc., via the mediation of hypervalent iodine reagents [5].

Scheme 3.1 C—N bond formation applying N—H bonds via photo/electrochemical methods.

Radical chemistry is reviving in organic synthesis owing to its inherently advantageous properties and has provided various alternative approaches for C—N bond formation. As is documented in one review on nitrogen‐centered radical amination, apart from some metal‐coordinated aminations, considerable progress has been advanced on photocatalytic strategies in the past years [6]. Moreover, remarkable achievements in direct electrochemical amination have also been witnessed more recently. On the basis of the active radical intermediates involved, pathways of oxidative radical aminations can be classified into three major patterns: N‐radical addition (Scheme 3.1, path A), N‐atom nucleophilic addition (Scheme 3.1, path B), and radical cross‐coupling (Scheme 3.1, path C), which have enriched the methodology of C—N bond formation and broadened the substrate scope to some extent.

Accordingly, this chapter will highlight the recent advances in the photo/electrochemically mediated, radical‐involved cross‐coupling reactions of unfunctionalized N—H bonds with diverse C—H bonds, among which several cyclization or hydroamination examples with certain unsaturated carbon‐centered moieties are also included. To stimulate the design and development of more versatile and practical amination protocols, extra emphasis is put on the reaction mechanisms. The key radical intermediates involved in these transformations are highlighted in yellow boxes.