Phenyl-Acetylene Bond Assembly: A Powerful Tool for the Construction of Nanoscale Architectures

This microreview summarises fundamental strategies and basic considerations for the design and synthesis of nanoscale architectures assembled through the formation of acetylene‐phenyl bonds. Since its first appearance in 1975 the Sonogashira–Hagihara reaction has allowed the formation of bonds between sp1 and sp2 carbon centres under mild conditions. This palladium‐catalysed cross‐coupling quickly found application in almost every area of synthetic organic chemistry. The biggest impact of this new method was probably observed in nanoscale architectures, giving rise to the new field of “acetylene scaffolding”. Here we present a summary of the underlying concepts and important strategies for the formation of acetylene‐phenyl bonds geared towards the assembly of nanoscale architectures illustrated with a few beautiful examples from the literature. It is not meant to be a comprehensive overview of the Sonogashira cross‐coupling reaction nor of the area of acetylene scaffolding but should serve as guide to the those new to the field. Starting with a short discussion of the reaction mechanism, appropriate choice of precursors is discussed. Introduction of chemoselectivity through the use of various leaving groups or by masking of their reactivity follows. The most common acetylene protection groups are summarised and compared in terms of their functional group tolerances and strategic concepts including orthogonality, sequential deprotection and in situ deprotection. Strategies for quick access to highly functionalised building blocks such as chemoselective halogenations and symmetry breaking are considered. Finally, the potential of the strategies discussed is documented with a few examples from the current literature. This microreview describes synthetic strategies for the formation of phenyl–acetylene bonds through Sonogashira cross‐couplings. Chemoselectivity, masking, protecting group strategies and statistical reactions are presented as synthetic techniques for the formation of building blocks,geared towards the design and assembly of larger molecular architectures.