Chapter 1 - Recent Advances in the C-2 Regioselective Direct Arylation of Indoles

Abstract

Publisher Summary This chapter describes recent methods adopted for the synthesis of 2-arylindoles via arylation at C-2. Three main strategies are adopted to date for the C-2 arylation of indoles. All these approaches rely on the use of a transition metal as a catalyst and vary depending on the level of pre-functionalization on the substrate starting materials. First, there are processes that involve a traditional cross-coupling reaction between two pre-functionalized substrates, usually a metallated indole and a haloarene. Second, there are direct arylation methodologies, where only the arene coupling partner is pre-functionalized either as a haloarene or as an organometallic reagent. Third, oxidative couplings can be used, where neither the indole nor the arene coupling partner is pre-functionalized, representing the most atom- and step-efficient methodologies. However, there is no room for complacency, because more efficient methodologies using lower catalyst loadings, milder conditions, avoiding the pre-functionalization of the substrates, compatible with unprotected functional groups are still necessary and their development will undoubtedly occupy the minds of many synthetic chemists in the future.