Temporary or removable directing groups enable activation of unstrained C–C bonds

Abstract

Carbon−carbon (C-C) bonds constitute basic skeletons in most organic molecules. One can imagine that selective manipulation of C-C bonds would provide a direct approach to edit or alter molecular scaffolds but has been an ongoing challenge. Due to the kinetic inertness of C-C bonds, the common strategies of activating these bonds by transition metals rely on either the use of highly strained substrates or the assistance of a permanent directing group (DG), in which strain relief or formation of stable metallocycles becomes the driving force. To allow more common and less strained compounds utilized as substrates for C-C activation, the use of temporary and removable DGs has emerged as an attractive strategy in the past two decades. A variety of C−C bonds in unstrained or less strained organic molecules now can be converted to more reactive metal-carbon bonds, and further downstream transformations have led to diverse synthetic methods. This review highlights the development of catalytic approaches that can activate unstrained C-C bonds enabled by temporary or removable DGs. The content is mainly divided based on the nature of the DGs: temporary and removable. Applications of these methods in syntheses of natural products or bioactive molecules are also discussed.

“Broken-hearted” carbon bowl via electron shuttle reaction: energetics and electron coupling

“…Such ring opening is unprecedented in the literature and has not been observed for pristine p-bowls (e.g., corannulene) to date (with the exception of uncontrollable brute force vacuum pyrolysis 22 ). PAH hydrogenation has been previously observed under harsh experimental conditions (e.g., high hydrogen pressure or extreme temperatures above 1000 C), [38][39][40][41][42][43][44] therefore the formation of P-C 20 H 14 in a one-pot synthesis under relatively mild conditions is an unexpected and remarkable result. Through employment of Marcus theory, optical spectroscopy, and crystallographic analysis, we estimated the electron coupling between "open" corannulene and a strong electron acceptor, TCNQ.…”

“…37 The literature precedent for C-C bond scission primarily relies on the assistance of transition metal catalysts, high hydrogen pressure, elevated temperatures, or a combination of all three parameters. [38][39][40][41][42][43][44] Therefore, unexpected C-C bond cleavage (discovered from photophysical studies of alignment of electron donor (corannulene) and acceptor (7,7,8,TCNQ) in the solid state) reported herein led us to probe mechanistic pathways to determine the feasibility for p-bowl planarization and factors that could affect such a transformation including strain energy (E s ) and released energy (E 0 , Scheme 1, see more details in the ESI †). The electron coupling and charge transfer (CT) rates between "open" corannulene (or parent corannulene) and TCNQ were evaluated by applying Marcus theory.…”

Recent Advances on Synthetic Methodology Merging C–H Functionalization and C–C Cleavage

“…The scission of C–C bonds in acyclic carbon skeletons is a challenging topic since these processes lack the release of the strain present in small carbocyclic structures as a driving force. Nevertheless, this fact has not precluded the development of synthetic methods where unstrained C–C bonds are cleaved [ 22 , 118 , 119 , 120 ]. Furthermore, in some cases these processes have been engaged with the functionalization of C–H bonds either intra- or intermolecularly.…”

“…A powerful strategy to merge C–H and C–C cleavage relies on the use of properly designed coordinating groups to assist either the cleavage of the C–C or the C–H bond, or both [ 120 ]. In 2016, Dong’s group reported the Rh-catalyzed synthesis of tetralones 379 via the selective proximal C–C cleavage of cyclopentanones cores 3 78 [ 134 ].…”

Reversible C–C Bond Formation Using Palladium Catalysis

“…16 The relief of steric strain via a β-carbon elimination, as seen in the Catellani reaction, rely on the build-up of increasing steric encumbrance during the course of the reaction (Scheme 1b). 17,21,22 Other strategies to enable β-carbon eliminations rely on the formation of a strong π-bond (Scheme 1c). 17,19,[23][24][25][26][27][28][29] These biased systems make it difficult to study the effects of different parameters on the β-carbon elimination process, and thus an unbiased system would not only be conceptually novel, but allow for the examination of other parameters on reversible C-C bond cleavage.…”